Diabetology doi: 10.3390/diabetology7100192

Authors: Takao Kimura

The prevalences of overweight, obesity, prediabetes, and diabetes are rapidly increasing worldwide, accompanied by increased insulin resistance (IR). Although the proportions of these populations vary greatly by region, a common trend across all areas is the increasing the prevalence of overweight, obesity, impaired glucose tolerance (IGT)/prediabetes and diabetes throughout all income levels. Based on the international baseline standards provided by the World Health Organization, national health and hygiene agencies and local expert organizations are implementing more proactive screening protocols tailored to local circumstances. These indicators are based on anthropometric measurements and do not include measurements of blood or urine biomarkers. However, evidence-based screening methods utilizing measurements of blood biomarkers, such as blood glucose levels and hemoglobin A1c, generally target individuals aged 40 and older. Therefore, screening based on anthropometric indices, adjusted for regional and racial characteristics and targeting individuals under 40 years old, can fail to identify individuals at relatively high risk for metabolic disorders, such as IGT or prediabetes, even when their measurements fall within the reference range. There are important points to consider regarding the measurement and interpretation of biomarkers used for diabetes screening. This review outlines the limitations and key considerations associated with biomarker measurement for screening IGT/prediabetes, diabetes, and elevated IR.

Diabetology doi: 10.3390/diabetology7100191

Authors: Hideaki Kaneto Tomohiko Kimura Yuichiro Iwamoto Junpei Sanada Masashi Shimoda Kohei Kaku

PDX-1 and MafA are insulin gene transcription factors and maintain mature pancreatic β-cell function. After chronic exposure to hyperglycemia, however, the expression levels of PDX-1 and MafA are substantially suppressed by provoked oxidative stress and the activation of the JNK/c-Jun pathway, which further aggravates β-cell function. In addition, glucocorticoids are often used to treat a variety of diseases, but they often induce hyperglycemia, not only by increasing insulin resistance, but also by directly impairing insulin biosynthesis in β-cells. Glucocorticoids bind and activate the glucocorticoid receptor in β-cells, while PDX-1 and MafA expression levels are substantially suppressed through the activation of the JNK/c-Jun pathway, which could explain the molecular mechanism behind glucocorticoid-induced β-cell dysfunction. There are similarities in the molecular mechanism for β-cell dysfunction induced by chronic hyperglycemia and glucocorticoid administration. On the other hand, a GLP-1 receptor agonist rapidly enhances microvascular flow in pancreatic islets in a NO-dependent manner. Such phenomena show that the islet microenvironment is substantially regulated by GLP-1 receptor signaling. Also, based on these data, it is likely that rapid microvascular adaptation contributes to the maintenance of β-cell function under diabetic conditions.

Diabetology doi: 10.3390/diabetology7100190

Authors: Pavlina Andreeva-Gateva Milen Hristov Dragomira Nikolova Ilyan Bogdanov Zafer Sabit Ivanka Dimova

Background/Objectives: This study aimed to assess the effect of tirzepatide on systemic inflammation in a diabetic neuropathy (DN) model in mice. Methods: Type 1 diabetes was induced with streptozotocin 180 mg/kg i.p. One month later, we injected two doses of tirzepatide (5 or 15 mcg/kg BW s.c. e3d) over the next 4 weeks, then performed a battery of neurological tests and measured blood cytokines with the Simple Plex® platform CE-IVD version. Data were compared with naïve controls with or without diabetes induction. Results: Tirzepatide treatment failed to improve both glycemia and neuropathic behavior post-streptozotocin treatment. Higher-dose tirzepatide-treated mice had significantly decreased grip strength (p = 0.013) and higher cold (p = 0.04) and mechanical (p < 0.001) sensitivity, despite substantially lower systemic inflammation, as assessed by TNF-α and IL-6. An exploratory composite inflammatory index (ECII) derived from IL-6 and TNF-α showed statistically significantly lower systemic inflammation in the group treated with a higher tirzepatide dose vs. the treatment-naïve control (p < 0.05), the diabetic group (p < 0.05), and the diabetic group treated with lower-dose tirzepatide (p < 0.05). Conclusions: Tirzepatide failed to improve DN in a streptozotocin-induced murine nonobese model of type 1 diabetes, although it substantially decreased systemic inflammation. Testing tirzepatide for potential protection against DN in non-streptozotocin-based DN animal models is warranted.

Diabetology doi: 10.3390/diabetology7100189

Authors: Robert Matson Karthik Murugadoss A. J. Venkatakrishnan Venky Soundararajan

Background: Semaglutide and tirzepatide are not approved for type 1 diabetes (T1D), and their real-world effects on insulin requirements, metabolic outcomes, and safety are uncertain. Methods: Using de-identified electronic health record data from a federated U.S. network (2018–2025), adults with T1D who initiated semaglutide (n = 1447) or tirzepatide (n = 568) were matched 1:1 to unexposed adults with T1D on demographics, comorbidities, glycated hemoglobin (HbA1c), body mass index (BMI), estimated glomerular filtration rate (eGFR), T1D duration, healthcare utilization, and calendar year (Cohort A). Insulin total daily dose (TDD) was analyzed in a second cohort additionally matched on baseline TDD and insulin delivery modality (Cohort B; 337 semaglutide and 117 tirzepatide pairs). Results: At 12 months, TDD changed by −12.9% with semaglutide versus −2.6% in matched controls (difference −10.4 percentage points [pp]; p < 0.001) and by −10.4% with tirzepatide versus +13.3% (difference −23.7 pp; p = 0.02); a ≥10% TDD reduction was reached by 41% versus 21% of patients with semaglutide and 47% versus 11% with tirzepatide (both p < 0.001). Among semaglutide-treated patients, 6-month-TDD reduction was −24.1%, −12.6%, and −5.6% with ≥10% weight loss, 0 to <10% loss, and weight gain (p < 0.001), but did not vary with HbA1c change (p = 0.95) or semaglutide dose (p = 0.50). At 12 months, HbA1c fell 0.31 pp more with semaglutide than in controls (p < 0.001) and 0.19 pp more with tirzepatide (p = 0.07); body weight fell 3.3 pp and 5.1 pp more with semaglutide and tirzepatide, respectively (both p < 0.001). Relative to matched controls, the 365-day risk of nausea or vomiting rose 8.6 pp after semaglutide or tirzepatide initiation (p < 0.001) and constipation rose 3.4 pp (p = 0.003), whereas diabetic ketoacidosis (+0.3 pp; p = 0.63) and severe hypoglycemia (−0.8 pp; p = 0.39) did not change significantly. Conclusions: In routine care, adjunctive semaglutide and tirzepatide were associated with lower insulin requirements, modest HbA1c improvement, and weight loss in adults with T1D, with a gastrointestinal-predominant adverse-event profile. Randomized trials are needed to establish efficacy and safety.

Diabetology doi: 10.3390/diabetology7100188

Authors: Maxwell J. Latshaw Aaron J. Gillespie Hasan Pracha Shawn J. Yates Anoop Sunkara Arun K. Movva Albert T. Anastasio

Diabetes mellitus is increasingly recognized as a disorder of skeletal quality in addition to metabolic dysregulation. Both type 1 and type 2 diabetes are associated with increased fracture risk, impaired fracture healing, and higher rates of orthopedic complications despite preserved or even elevated bone mineral density, highlighting the limitations of conventional densitometric assessment alone. Diabetic bone disease arises through complex and interconnected mechanisms involving osteoblast, osteocyte, and osteoclast dysfunction, accumulation of advanced glycation end products, oxidative stress, chronic inflammation, impaired insulin and insulin-like growth factor-1 signaling, and disruption of bone–pancreas and bone–adipose crosstalk. Here, we review the cellular, molecular, genetic, and epigenetic mechanisms that contribute to diabetic skeletal fragility and examine how these abnormalities impair bone remodeling, fracture healing, and orthopedic outcomes. Particular emphasis is placed on the disconnect between bone mineral density and bone quality, describing how alterations in bone microarchitecture and matrix integrity contribute to skeletal fragility beyond the conventional measures of bone mass. We further review emerging strategies for fracture risk assessment, including advanced imaging modalities and biomarkers that more accurately characterize diabetic bone disease, and discuss the influence of antidiabetic therapies, perioperative glycemic optimization, and emerging biologic and epigenetic therapeutic approaches on fracture healing and musculoskeletal outcomes. By integrating molecular mechanisms with clinical and orthopedic evidence, this review provides a comprehensive overview of diabetic bone disease while highlighting priorities for future research and clinical translation.

Diabetology doi: 10.3390/diabetology7100187

Authors: Anna Arecco Grazia Piras Francesco Cocchiara Davide Carlo Maggi Alessandra Puddu

Type 1 diabetes (T1D) is an autoimmune disease in which genetic susceptibility interacts with environmental and immunometabolic factors. Growing evidence implicates gut dysbiosis, impaired intestinal barrier integrity, and altered microbial metabolites in the loss of immune tolerance and β-cell autoimmunity. Microbiota-derived metabolites regulate enteroendocrine glucagon-like peptide-1 (GLP-1) secretion, epithelial barrier function, and immune responses. Conversely, GLP-1 signaling and incretin-based therapies may modify the intestinal environment and microbial composition. Overall, the GLP-1–gut microbiota axis is a promising therapeutic target. Activation of the GLP-1 receptor suppresses pro-inflammatory pathways while promoting anti-inflammatory ones; all these effects may protect β-cells. Caveolin-1 may represent a molecular hub linking the GLP-1–gut microbiota–autoimmunity axis in T1D. This narrative review examines the bidirectional relationship between GLP-1 signaling and the gut microbiota and its potential relevance to T1D.

Diabetology doi: 10.3390/diabetology7090186

Authors: Marija Macesic Katarina Lalic Ljiljana Lukic Tanja Milicic Gorana Mandic Stojmenovic Tanja Stojkovic Jelena Stanarcic Gajovic Milica Stoiljkovic Jelena Milin Mina Bozic Djurdja Rafailovic Stefan Maric Milica Vujasevic Aleksandra Jotic

Background/Objectives: Insulin resistance (IR) and metabolic Syndrome (MSy) have been linked to cognitive decline, but their presence in mild cognitive impairment (MCI) and Alzheimer disease (AD) remains unclear. We evaluated MSy and IR in nonobese, nondiabetic older adults with cognitive dysfunction. Methods: The cross-sectional study included 143 participants aged 65–90 years: 62 with AD, 41 with MCI, and 40 cognitively preserved controls. Anthropometric measures, blood pressure, fasting glucose, insulin, and lipid levels were assessed. Diabetes was excluded by oral glucose tolerance testing. IR was estimated using HOMA-IR, and MSy was diagnosed according to International Diabetes Federation (IDF) criteria. Group differences and associations with cognitive impairment were assessed using analysis of variance and regression analyses. Results: Fasting insulin increased from controls to MCI and AD (7.18 ± 4.32, 13.76 ± 6.89, and 18.58 ± 8.19 mU/L), as did HOMA-IR (1.49 ± 0.98, 3.35 ± 1.72, and 4.59 ± 2.19, p < 0.05). Compared with controls, both cognitively impaired groups had higher fasting glucose, TCh, LDL-ch and lower HDL-ch (all p < 0.05), whereas triglycerides did not differ (p = 0.266). MSy prevalence was 22.5% in controls, 46.3% in MCI, and 35.5% in AD; however, the overall difference was not statistically significant (p = 0.079). In binary logistic regression analysis, sex, age, LDL-ch, and HOMA-IR were independently associated with cognitive impairment (all p < 0.05). Conclusions: Increased IR was more consistently associated with cognitive impairment than the presence of MSy, with the highest degree of IR observed in AD. These findings support an association between metabolic dysfunction and cognitive impairment and suggest that IR may represent a potential target for preventive and therapeutic strategies.

Diabetology doi: 10.3390/diabetology7090185

Authors: Takako Ikeda Ikuo Kimura

Recently, a subset of G protein-coupled receptors (GPCRs) has been deorphanized as nutrient-sensing receptors activated by free fatty acids (FFAs). These GPCRs, termed free fatty acid receptors (FFARs), change their conformation in response to fatty acid binding and transmit extracellular signals into cells to maintain physiological homeostasis. Therefore, FFAs serve a dual role as energy substrates for most body tissues and as signaling molecules. Signaling through FFARs affects various physiological functions, such as metabolic and immune responses. In particular, their role in metabolic regulation has been extensively studied. Thus, FFARs have gained attention as key therapeutic targets for the treatment of obesity and type 2 diabetes. To date, many synthetic agonists for FFARs have been designed and have entered clinical trials, but no agonists have received approval for clinical use. In this review, we summarize and discuss the current knowledge of nutrient signaling mediated by FFARs. We also review the biological importance of FFARs in maintaining metabolic health and recent advances in the translational research of FFAR1 agonists. A better understanding of how FFARs maintain metabolic health may help address global public health problems such as obesity and type 2 diabetes.

Diabetology doi: 10.3390/diabetology7090184

Authors: Antony Arumairaj Poojaben Dhorajiya Jayesh Mittal Manikya Kuriti Vimala Sravanthi Vajjala Divya Korpu Dili Dhanani

Background: Diabetes mellitus (DM) is highly prevalent in the United States and increases the risk of severe illness in patients with COVID-19. We compared outcomes among adult COVID-19 hospitalizations with and without DM. Methods: We compared the National Inpatient Sample (2020–2022), using multivariate regression to adjust for potential confounders. Results: Among 5,934,565 hospitalizations for COVID-19, 2,155,978 (36.3%) had concomitant DM. The DM group had higher unadjusted in-hospital mortality (13.5% vs. 10.1%) and was associated with higher mortality after adjustment (aOR 1.17; 95% CI, 1.15–1.19; p < 0.001). DM was also independently associated with higher odds of acute respiratory failure (46.1% vs. 42.3%; aOR 1.12; 95% CI, 1.11–1.13; p < 0.001), greater use of invasive mechanical ventilation (aOR 1.35; 95% CI, 1.33–1.37; p < 0.001) and non-invasive ventilation (NIV; aOR 1.42; 95% CI, 1.40–1.45; p < 0.001). COVID-19 hospitalizations with DM also had higher rates of acute respiratory distress syndrome, acute kidney injury, renal replacement therapy, sepsis, septic shock, and vasopressor use, along with longer length of hospital stay and higher total hospitalization charges. In-hospital mortality among COVID-19 hospitalizations with DM was lower in 2022 than in 2020 and 2021. Conclusions: DM was associated with higher in-hospital mortality and greater respiratory, renal, and hemodynamic complications and hospital resource utilization.

Diabetology doi: 10.3390/diabetology7090183

Authors: Aashish Kumar Amanda Zahumensky Rahima Habibullah Jana Waldmann Mahesh Ramanan

Objective: To perform a systematic literature review summarising current evidence of the incidence and clinical outcomes of thiamine deficiency in patients with diabetic ketoacidosis (DKA). Due to inconsistent and variable measurement of thiamine levels, hyperlactataemia in DKA was included as a potential surrogate for thiamine deficiency. Methods: The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO). MEDLINE, EMBASE, Cochrane, CINAHL and ClinicalTrials.gov were searched using medical subject headings from database inception to 26 June 2026. Two independent reviewers screened results, and studies were included if they were original research that assessed lactate and/or thiamine in DKA, with subsequent forward citation searching. Risk of bias was assessed using the Cochrane Risk of Bias 2 Tool and the Newcastle-Ottawa Scale, and the data was analysed using a systematic review without meta-analysis (SWIM) approach. Results: Of 2122 screened studies, 31 were included in the final manuscript. Six studies assessed thiamine levels and deficiency, one assessed thiamine replacement, and the remainder assessed hyperlactataemia in patients with DKA. The incidence of thiamine deficiency ranged from 23.8–78%, with two studies demonstrating an inverse correlation between thiamine levels and lactate. The incidence of hyperlactataemia in patients with DKA ranged from 37.5–92%, with inconsistent findings regarding clinical outcomes. Conclusions: The available evidence suggests that thiamine deficiency and hyperlactataemia are common among patients with DKA. However, the association of both with clinical outcomes remains uncertain, with limited data making it difficult to draw significant conclusions, highlighting the need for further research.

Diabetology doi: 10.3390/diabetology7090182

Authors: Satoru Yamada

Medical nutrition therapy is a cornerstone of type 2 diabetes mellitus (T2DM) management. Current guidelines emphasize individualized nutrition therapy rather than a single universal dietary approach. This narrative review summarizes current dietary strategies for T2DM and examines moderate carbohydrate restriction and the Japanese LOCABO® approach, which combines meal-based carbohydrate targets (20–40 g/meal), a daily target (70–130 g/day), and limited discretionary carbohydrate intake. Research was identified from major diabetes guidelines and peer-reviewed publications, including randomized controlled trials and long-term observational studies. Evidence supporting moderate carbohydrate restriction in general is substantially broader than evidence specifically evaluating LOCABO®. LOCABO®-specific evidence comprises one small RCT and several observational or uncontrolled studies conducted in Japan. These studies provide preliminary signals regarding glycemic efficacy and longer-term metabolic outcomes and have also examined restaurant availability of compatible meals and renal function. However, validated evidence regarding dietary adherence, acceptability, nutritional adequacy, adverse events, long-term cardiovascular outcomes, and international generalizability remains insufficient. Moderate carbohydrate restriction may therefore be considered one evidence-based option within individualized medical nutrition therapy for T2DM, whereas LOCABO® should be regarded as a pragmatic meal-based implementation that requires independent, multicenter, and long-term validation.

Diabetology doi: 10.3390/diabetology7090181

Authors: Anca Cristina Ferician Timea Claudia Ghitea Mihaela Simona Popoviciu

Background: Diabetes mellitus is frequently complicated by cardiovascular, neurological, and limb-threatening conditions, yet these complications are often evaluated separately. Heart failure, peripheral neuropathy, and lower-limb amputation may coexist in patients with advanced diabetes and may define a clinically severe cardio-neurovascular multimorbidity phenotype. This study evaluated the real-world overlap between these complications. Methods: This retrospective hospital-based study used four routinely generated patient-level exports from the electronic diabetes registry/clinical information system of the Clinical County Emergency Hospital Bihor, Oradea, Romania. The primary cohort comprised 2246 unique patients with diabetes and a recorded heart failure diagnosis; linked exports identified peripheral neuropathy and below- or above-ankle amputation. Results: Peripheral neuropathy was documented in 1028 patients (45.8%). Patients with neuropathy were older (median 70 [IQR 63–76] vs. 67 [IQR 59–73] years, p < 0.001) and had longer diabetes duration (15 [IQR 9–21] vs. 6 [IQR 1–11] years, p < 0.001) than patients without neuropathy. Any lower-limb amputation occurred in 35 patients (1.6%) and was more frequent among patients with neuropathy than among those without neuropathy (2.6% vs. 0.7%, p < 0.001). In the adjusted analysis, male sex, diabetes duration, and insulin therapy were independently associated with lower-limb amputation, whereas the association with neuropathy was attenuated. Conclusions: In this hospital-based retrospective cohort, peripheral neuropathy was common and identified a subgroup with longer-standing diabetes, more intensive therapy, and greater amputation burden. The findings indicate associations within a selected clinical population and should not be interpreted as causal or population-based estimates.

Diabetology doi: 10.3390/diabetology7090180

Authors: Zandra Overgaard Pedersen Bryan Cleal Kristoffer Marsaa

Contemporary diabetes care is largely organised around one-to-one clinical consultations and the regulation of biomedical outcomes. While such approaches remain essential, they may be insufficient for addressing the social and behavioural aspects of chronic disease management. Based on this conceptual perspective, we propose the Friendly Neighbourhood Hospital as an approach to supporting peer contact and self-management, complementing clinical care. Drawing on affordance theory, social architecture, and urban social geography, we argue that hospital environments can shape participation, learning, and behavioural change through mechanisms including peer interaction, tacit knowledge, situated learning, and institutional trust. We illustrate this approach using five settings: communal cooking, movement and social interaction, public and cultural events, flexible access, and digital participation. These examples are illustrative and not evaluated interventions, and their anticipated effects, ranging from immediate participation and belonging to longer-term behavioural change, remain hypotheses for future testing. From this perspective, we do not advocate for replacing individual consultations but rather for repositioning them within a broader social and spatial context.

Diabetology doi: 10.3390/diabetology7090179

Authors: Shelley Spurr Jill M. G. Bally Kali McNair Helen Tootoosis

Background/Objectives: Type 2 diabetes (T2D) is one of the fastest growing chronic pediatric conditions worldwide. Indigenous children tend to be diagnosed younger, have severe progression of disease, and poorer health outcomes. While biomedical advancements have yielded more effective treatment outcomes, few resources have been implemented to prevent T2D in Indigenous youth. Therefore, an exploratory pilot study was conducted in one Canadian province with an overall purpose of co-creating, pilot-testing, and evaluating an Indigenous community-led T2D education resource called the wîcihitowin: Helping Each Other with Type 2 Diabetes Education Program. Methods: Data for this analysis were derived from a pre- and post-test evaluation of the digital education resource with a purposeful sample of Indigenous youth (n = 87) from two Cree communities living in a western Canadian province. Descriptive statistics, paired t-tests, and correlations were used to measure the differences from pre- to post-participation in the education program. Results: The youth had moderate knowledge baseline scores of diabetes, nutrition, and physical activity. Participants reported improved knowledge on all the education topics after participating in the wîcihitowin: Helping Each Other with Type 2 Diabetes Program. Significant positive correlations were found between all knowledge areas. Conclusions: The digital education resource effectively enhanced youths’ knowledge of diabetes, nutrition, and physical activity. Additionally, these findings highlighted the importance of culturally safe teachings for Indigenous peoples, emphasizing the need for T2D education to be community and culturally driven. These results are particularly important given the lack of existing evidence evaluating the effectiveness of T2D education among Indigenous youth.

Diabetology doi: 10.3390/diabetology7090178

Authors: Kwaku Karikari Manu Seth Appiah-Opoku Cassandra Ford Joe Weber Selima Sultana Amobichukwu Chukwudi Amanambu

Diabetes disproportionately affects African American and Native American populations in the United States; however, diabetes disparities are frequently examined either collectively across minority populations or within individual groups, limiting understanding of the distinct mechanisms that drive inequities. This narrative review compares differences in diabetes diagnosis, culturally grounded management, diabetes self-management education and support (DSMES), and diabetes-related complications among African American and Native American adults in the United States to identify both shared and population-specific pathways contributing to disparities. A narrative review of peer-reviewed literature published between 2010 and 2025 was conducted using PubMed, Scopus, and Google Scholar. Studies addressing diabetes diagnosis, management, diabetes education, or complications among African American and Native American adults were included and synthesized using a comparative thematic approach. Disparities were evident across the continuum of diabetes care, but their underlying drivers differed substantially between populations. Among African Americans, diagnostic challenges reflected both structural inequities and limitations of commonly used glycemic markers such as hemoglobin A1c. Among Native Americans, delayed diagnosis was more closely associated with geographic isolation and under-resourced healthcare systems. Culturally grounded management also differed, with Native American communities demonstrating greater integration of Indigenous frameworks and traditional practices, whereas African American communities relied more heavily on family- and faith-based support systems. DSMES remained underutilized in both populations because of referral gaps, structural barriers, and limited cultural tailoring, with access barriers particularly pronounced in rural and tribal settings. Both populations experienced disproportionately high rates of diabetes-related complications, although Native Americans frequently exhibited earlier onset while African Americans often experienced greater severity of outcomes. Findings suggest that similar diabetes disparities emerge through different structural, cultural, and healthcare system pathways. Recognizing these differences can inform the development of more targeted clinical interventions, community-based programs, and health policies aimed at reducing diabetes inequities in underserved populations.

Diabetology doi: 10.3390/diabetology7090177

Authors: Roberto Da Ros Enrica Barro Andrea Michelli Roberta Assaloni Barbara Brunato Marta Nardi Cesare Miranda

Background: Calcaneal osteomyelitis is a severe form of diabetic foot osteomyelitis associated with poor healing, major amputation, and increased mortality. Evidence on the use of bone graft substitutes in this setting remains limited. Methods: We conducted a retrospective single-center cohort study including 103 consecutive patients with diabetic calcaneal osteomyelitis treated at a tertiary diabetic foot center. In total, 29 patients received bone graft substitutes following surgical debridement, while 74 underwent conventional surgical treatment. Outcomes included healing, time to healing, major amputation, and mortality for all-cause. Results: Overall healing rates were similar between the bone graft and control groups (58.6% vs. 54.1%; p = 0.83). However, healing within one year was more frequent in patients treated with bone graft substitutes (65.4% vs. 45.8%). In multivariable analysis, bone graft substitute treatment was independently associated with healing within one year (OR 4.96, 95% CI 1.18–20.79; p = 0.029). Median healing time was significantly shorter in the bone graft group (90 [IQR 60–120] vs. 210 [IQR 150–370] days; p < 0.001), corresponding to a 67% reduction after adjustment. Major amputation rates were low and comparable between groups (10.3% vs. 13.5%; p = 0.75). Observed three-year mortality was lower in the bone graft group (33.3% vs. 54.8%), and bone graft substitute treatment remained independently associated with reduced 3-year mortality (OR 0.29, 95% CI 0.09–0.88; p = 0.028). Conclusions: In diabetic calcaneal osteomyelitis, bone graft substitutes were associated with faster healing, improved 1-year healing outcomes, and lower long-term mortality, while maintaining high limb-salvage rates. These findings suggest that bone graft substitutes may represent a promising adjunct to surgical treatment and warrant confirmation in prospective studies.

Diabetology doi: 10.3390/diabetology7090176

Authors: Sidhartha D. Ray Lining Liang He Stratton Rottersmann Christina Hand Maria Di Leo Alec Chunilall Ian G. Gray Ngo Tsun Siu Sonia Jong Nigel Sirois Kaitlin M. McNeely Margarett A. Costes

Several decades of intensive research into antidiabetic therapeutics have yielded an expansive, mechanism-driven pharmacopeia. Yet, the clinical endpoint for these diverse agents remains singular and superficial: the reduction in glycated hemoglobin (HbA1c). By focusing primarily on downstream glucose lowering, current therapeutic paradigms treat the symptom rather than the etiology. This approach persists despite definitive consensus that the foundational pathology of type 2 diabetes is much more complex which paves the way to insulin resistance, not merely the spillover of glucose into the bloodstream. This systemic misalignment raises a critical question for the scientific community: are we collectively “agreeing to disagree” on a biological fact or a clinical myth? The Myth is that ‘Persistent hyperglycemia’ is the disease itself, but the fact is: hyperglycemia is a late-stage biomarker of systemic insulin resistance. By managing the biomarker rather than the root cause, clinical medicine has normalized an incomplete treatment model. This review aims to deliberately provoke a shift in rational thinking. We challenge the comfortable status quo of accepting hyperglycemia as the primary definition of diabetes. True therapeutic innovation requires moving past this consensus of convenience. We must reorient basic and clinical science toward reversing the cellular mechanisms of insulin resistance itself, rather than settling for the cosmetic management of blood glucose levels. Rather than merely recounting established therapeutic mechanisms, this review systematically bridges classical antidiabetic pharmacology with the specific pharmacogenomic determinants likely driving hyperglycemia and phenotypic insulin resistance. Mechanisms of action and pharmacogenomic perspectives of α-glucosidase inhibitors, Sulfonylureas, SGLT2 inhibitors, GLP-1 agonists, Meglitinides, Insulins, Metformin, Thiazolidinediones, and DPP4 inhibitors are discussed in this review. In conclusion, mapping the pharmacogenetic landscape of antidiabetic therapies reveals how distinct genetic variations likely dictate drug metabolism and insulin receptor kinetics. Decoding these patient-specific mechanisms is essential to reverse tissue-specific insulin resistance and transition from empirical prescribing to precise, genotype-directed diabetes management.

Diabetology doi: 10.3390/diabetology7090174

Authors: Luisa V. Gracia Mazuca Bibiana Mancera

Background/Objective: Prediabetes is increasingly recognized as a state of chronic, low-grade inflammation that contributes to early β-cell dysfunction, insulin resistance, and progression to type 2 diabetes (T2D). This review synthesizes mechanistic and clinical evidence to characterize the inflammatory landscape of prediabetes, evaluate the consistency of candidate biomarkers, and assess potential for clinical translation. Methods: We conducted a structured narrative review and assessed 22 studies investigating inflammatory and metabolic biomarkers for prediabetes across experimental animal models, human pancreatic islets, and clinical cohorts. Biomarkers included cytokines, oxidative stress indicators, microRNAs, and immune-cell-associated factors. Studies included cross-sectional, longitudinal, and mechanistic designs. Results: Clinical studies generally reported higher CRP and hsCRP. In several cohorts, IL-6 and other inflammatory mediators were increased in individuals with prediabetes. However, inflammatory responses were not uniform across studies. One study reported elevated IL-10 and IL-4 in addition to hsCRP, while TNF-α and IL-6 were not significantly different. Overall, CRP and hsCRP demonstrated the strongest clinical translational evidence, with findings replicated across multiple cohorts and longitudinal evidence linking higher baseline hsCRP or CRP with increased risk of progression to T2D. Other candidates, including IL-6, TNF-α, adiponectin, SFRP4, oxidative stress markers, and microRNAs, remain promising but have more limited or inconsistent evidence for clinical application. Conclusions: Prediabetes is characterized by a multifaceted inflammatory response involving innate and adaptive immune pathways, altered cytokine and microRNA profiles, oxidative stress, and adipose–pancreatic interactions. Although inflammatory biomarkers may enhance conventional metabolic measures for risk stratification, current evidence does not establish any inflammatory marker as a standalone diagnostic test for prediabetes.

Diabetology doi: 10.3390/diabetology7090175

Authors: Emanuele Maria Merlo

Type 1 diabetes mellitus (T1DM) is increasingly recognized as a condition in which psychological processes play an important role in disease management, adaptation, and clinical outcomes. Although research has identified a growing number of relevant psychological constructs, these have largely been investigated independently, limiting understanding of their interactions with behavioral and biological processes. This contribution discusses the principal conceptual gaps that currently constrain theoretical integration and proposes an integrative psychobiological framework in which individual and contextual factors, psychological processes, self-management behaviors, and biological and metabolic dimensions are conceptualized as components of a dynamic and temporally embedded system. The framework emphasizes potentially mediated, moderated, and reciprocal pathways whose relative contribution may vary across individuals, life stages, and the disease trajectory. By providing a structure through which these processes can be jointly operationalized and empirically investigated, this perspective may support more coherent research strategies and help identify individual and evolving assessment and intervention priorities in diabetes care.

Diabetology doi: 10.3390/diabetology7090173

Authors: Isaki Hanamura Norio Abiru Toshifumi Sakamoto Akie Moriuchi Nobuko Sera

Objective: This study aimed to evaluate how using personal health records (PHRs; Health2Sync®) impacts long-term glycemic management and body weight in people with type 2 diabetes (T2DM) and to identify factors associated with glycated hemoglobin (HbA1c) changes. Methods: This single-center, retrospective observational study included 154 patients with T2DM (76 PHR users and 78 non-users [control]; mean age: 57.9 and 65.0 years, respectively) between April 2022 and June 2024. Clinical parameters (HbA1c, body weight; BW), nutritional support, and antidiabetic medications were collected at the index date and at 3, 6, and 12 months. The between-group difference in HbA1c change (ΔHbA1c) from the index date to 12 months was the primary outcome, and the between-group difference in body weight change (ΔBW) was the secondary outcome. Factors associated with ΔHbA1c were explored using multivariate analysis in the PHR group. Results: In the PHR group, ΔHbA1c from the index date showed a significant reduction as early as 3 months, and this decrease was sustained at 6 and 12 months (p < 0.001). Furthermore, a similar trend was observed for ΔBW (p < 0.001). Moreover, multivariable regression analysis revealed an independent association between nutritional support and improvement in HbA1c. Conclusions: PHR use was associated with improved glycemic control and weight reduction in people with T2DM, and together with nutritional support, it may further enhance self-management and clinical outcomes.

Diabetology doi: 10.3390/diabetology7090172

Authors: Stavroula-Panagiota Lontou Ioanna A. Anastasiou Nikolitsa Kafasi Anestis Chanos Vasiliki Mamakou Paraskevas Stamopoulos Dimitrios Chronopoulos Maria Tektonidou Helen Gogas Nikolaos Papanas Aris Polyzos Nikolaos Tentolouris

Background/Objectives: Antiphospholipid antibodies (aPL) comprise anticardiolipin antibodies (aCL), antibodies against β2 glycoprotein I (anti-β2GPI) and lupus anticoagulant (LA). LA is an established risk factor for thrombosis and pregnancy morbidity in the general population. In people with type 1 diabetes (T1D), aPL have been proposed as potential predictors of microvascular and macrovascular diabetes-related complications. The aim of the present prospective, observational study was to investigate the prevalence of aPL in a well-defined cohort of adults presenting with uncomplicated T1D compared with healthy controls. In addition, we prospectively examined whether aPL titers or positivity were potentially associated with the subsequent development of diabetes-related complications. Methods: Two hundred (200) adults with T1D and without microvascular or macrovascular complications participated (mean age, 37.9 ± 10.6 years; mean diabetes duration, 21.00 ± 9.20 years). We also included 200 age- and sex-matched healthy controls (mean age, 37.7 ± 10.1 years) without diabetes mellitus or other autoimmune diseases. The aPL panel, including aCL ΙgG/IgM, anti- β2GPI IgG/IgM, and LA, was assessed using standardized laboratory methods. Participants with T1D were re-evaluated after a mean follow-up of 7.6 years. Results: Titers of aCL IgG/IgM and anti-β2GPI IgG, as well as positivity of aCL-IgG and aCL-IgM, were higher in participants with T1D compared with healthy controls, whereas LA positivity was very low in both groups. In the T1D group, aCL-IgG titers significantly correlated with age and diabetes duration. Neither aCL-IgG titers nor positivity was associated with the development of microvascular or macrovascular complications or with all-cause mortality during follow-up. Conclusions: In adults with long-standing, uncomplicated T1D, most aPL titers and positivity rates were higher than those observed in healthy controls. However, aCL-IgG titers and positivity were not associated with the subsequent development of diabetes-related complications. Larger prospective studies are required to determine whether aPL have predictive value for diabetes-related complications and to identify subgroups of people with T1D who may benefit from aPL testing.

Diabetology doi: 10.3390/diabetology7090171

Authors: Eugene Feigin Hussein Zaitoon

Background: Individuals with diabetes have an increased risk of infection-related hospitalization; however, whether type 1 diabetes (T1D) and type 2 diabetes (T2D) differentially influence outcomes following hospitalization remains unclear. We compared mortality, metabolic complications, and hospital outcomes among adults with T1D, T2D, or no documented diabetes admitted with urinary tract infection (UTI) or pneumonia. Methods: We performed a retrospective cohort study using electronic health records from a tertiary 1500-bed medical center (2018–2026). Eligible adult hospital admissions for UTI or pneumonia were classified according to documented T1D, T2D, or no diabetes. The study included 22,475 UTI admissions (211 with T1D, 9230 with T2D, and 13,034 without diabetes) and 32,703 pneumonia admissions (208 with T1D, 15,112 with T2D, and 17,383 without diabetes). Multivariable logistic regression was used to evaluate the association between diabetes status and 30-day mortality, with adjustment for age, sex, BMI, CCI, and MEWS. Because individuals could contribute multiple eligible admissions, the primary mortality models used patient-level cluster-robust standard errors to account for within-patient correlation. Results: T1D admissions involved substantially younger individuals than T2D or non-diabetes admissions but were associated with the greatest metabolic instability during hospitalization. Hypoglycemia occurred in 41.2% of T1D admissions for UTI and 19.7% for pneumonia, compared with 19.6% and 4.1% in T2D, respectively (both p < 0.001). Hyperglycemia was also markedly more frequent in T1D, affecting 88.6% of UTI and 72.6% of pneumonia admissions. ICU transfer was nearly threefold higher in T1D than T2D during UTI hospitalization (10.0% vs. 3.5%, p < 0.001). After adjustment, T1D was not independently associated with 30-day mortality, whereas T2D was associated with modestly lower adjusted odds of 30-day mortality compared with patients without documented diabetes. No significant mortality differences were observed between T1D and T2D. Conclusions: Diabetes type was not independently associated with higher short-term mortality following hospitalization for UTI or pneumonia after adjustment for measured confounders. However, T1D was associated with substantially greater glycemic instability and increased intensive care utilization, suggesting that diabetes type may influence the metabolic complexity and intensity of inpatient management more than short-term survival.

Diabetology doi: 10.3390/diabetology7090170

Authors: Hiroaki Kataoka Takuo Nomura Hiroyuki Oka Yukio Ikeda

Background/Objectives: Telerehabilitation for physiotherapy programs (TelePhysio) has been shown to improve knee extension force (KEF) in older patients with type 2 diabetes mellitus (T2DM), but factors associated with responsiveness remain unclear. This exploratory secondary analysis investigated whether baseline eating behaviors modified the effectiveness of TelePhysio in KEF. Methods: This secondary analysis included 74 older patients with T2DM enrolled in a randomized controlled trial. The participants were assigned to the TelePhysio (n = 39) or non-intervention group (n = 35). Baseline eating behaviors were assessed using an Eating Behavior Questionnaire. Multiple regression analysis was performed using 6-month KEF as the dependent variable, adjusting for baseline KEF, age, sex, body mass index, diabetic polyneuropathy, intervention group, baseline eating behavior score, and their interactions. The original trial was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; UMIN000024416; registered on 15 October 2016). Results: A significant interaction was found between the intervention group and baseline eating behavior score (B = −0.0064, p = 0.0352). Estimated TelePhysio effects on eating behavior scores corresponding to mean − 1 standard deviation (SD), mean, and mean + 1 SD were +0.36, +0.12, and −0.12 Nm/kg, respectively. None of the seven domain-specific group-by-domain interactions reached statistical significance. Sensitivity analyses using KEF changes showed a similar directional trend but were not statistically significant (p = 0.2913). Conclusions: Baseline eating behaviors may be associated with differential responsiveness to TelePhysio in older adults with T2DM. The estimated effect of TelePhysio on KEF was smaller at higher baseline Eating Behavior Questionnaire scores. These findings should be cautiously interpreted because the interaction was not confirmed using sensitivity analysis regarding changes in the KEF.

Diabetology doi: 10.3390/diabetology7090169

Authors: Laura Palacios-Abril Aroa Tardáguila-García Francisco Javier Álvaro-Afonso Sol Tejeda-Ramírez Yolanda García-Álvarez José Luis Lázaro-Martínez

Background and objectives: Diabetic microangiopathy is a frequent complication of diabetes mellitus, and its early identification remains challenging, particularly in resource-limited settings. This study aimed to develop a simple clinical scoring system based on cutaneous manifestations to estimate the risk of microangiopathy. Methods: An observational cross-sectional pilot study was conducted in 30 adults with diabetes mellitus attending a specialized diabetic foot unit. Lower-limb cutaneous manifestations (xerosis, absence of hair, hyperpigmentation, nail-plate thickening, skin atrophy and hypertrophy) were assessed during physical examination. Cutaneous findings significantly associated with clinically established microangiopathy were incorporated into a preliminary clinical screening index. Its discriminative ability was evaluated using receiver operating characteristic (ROC) analysis. As a secondary exploratory analysis, the relationship between the index and transcutaneous oxygen pressure (TcPO2) was investigated. Results: Five cutaneous manifestations were included in the final clinical screening index. The index demonstrated excellent discriminative ability for identifying clinically established microangiopathy (AUC = 0.95; 95% CI: 0.88–1.00). A cut-off value of ≥4 points yielded a sensitivity of 76.2% and a specificity of 100%. Higher index scores showed a trend towards lower TcPO2 values and a greater frequency of reduced tissue oxygenation, although these exploratory associations were not statistically significant. Conclusions: The proposed score shows promising discriminative performance. Although physiological associations were not statistically significant, observed trends support its potential clinical relevance. Further validation in larger cohorts is required.

Diabetology doi: 10.3390/diabetology7090168

Authors: Eugenia Vlachou Anastasia Ntikoudi Dimitra Anna Owens Despoina Rizikou Afroditi Tsalkitzi Eleni Evangelou Athanasios N. Tsartsalis

Background: Type 1 diabetes (T1D) is increasingly recognized as a condition associated with impaired skeletal health and increased fracture risk. Although osteoporosis is usually considered more clinically relevant after menopause, diabetes-related skeletal alterations may begin earlier in life. This scoping review aimed to map the available evidence on bone-health outcomes in premenopausal women with T1D. Methods: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Scopus, Web of Science, CINAHL and the Cochrane Library were searched, supplemented by Google Scholar and manual screening of reference lists. Eligible studies examined bone mineral density (BMD), fracture history or fracture risk, bone turnover markers, quantitative ultrasound parameters, bone microarchitecture, or other skeletal outcomes in premenopausal women or women with T1D. Results: Seven studies met the eligibility criteria. The included studies were mainly observational and varied in sample size, age range, diabetes duration, skeletal sites assessed, and bone-assessment methods. Most studies reported lower BMD or less favorable skeletal parameters in premenopausal women with T1D compared with women without diabetes, particularly at peripheral or hip-related skeletal sites. Quantitative ultrasound studies suggested impaired peripheral skeletal properties, while one MRI-based study identified trabecular microarchitectural deficits. Several studies also reported altered bone turnover markers and associations between poorer glycemic control, adverse health behaviors or diabetes-related complications, and poorer bone outcomes. Fracture data were limited and were based on previous or self-reported fractures. Potential determinants of skeletal health were variably reported across studies, with more consistent consideration of body mass index and selected lifestyle or reproductive factors than of autoimmune, nutritional, medication-related, and detailed reproductive variables. Conclusions: Available evidence indicates that premenopausal women with T1D may exhibit early alterations in skeletal health, including differences in BMD, peripheral bone measures, bone turnover, and microarchitecture. These findings highlight the potential importance of considering bone health before the menopausal transition. However, prospective data on fragility fractures remain limited, and further longitudinal studies incorporating detailed reproductive, metabolic, and clinical factors are needed to clarify the long-term skeletal implications and inform future risk-assessment strategies.

Diabetology doi: 10.3390/diabetology7090167

Authors: Geoffrey Ezama Marc Sam Opollo Bosco Opio Felix Bongomin Francis Kiweewa Beth Namukwana Solomon Icel Gasthony Alobo Bernard Omech

Background: Hypertension commonly complicates Type 2 diabetes mellitus (T2DM), contributing significantly to increased morbidity and mortality. This study determined the prevalence and factors associated with hypertension among people with T2DM at a tertiary health facility in Northern Uganda. Methods: A hospital-based cross-sectional study was conducted from 18 July to 24 October 2024. Participants with confirmed T2DM were selected through systematic random sampling at Lira Regional Referral Hospital (LRRH) in Lira City, Uganda. Data were collected using a structured questionnaire adapted from the WHO STEPS (2022) tool. Patient charts and registers were used to verify information. Data were analyzed using STATA version 16. Multivariable logistic regression was performed, and p-values < 0.05 were considered statistically significant. Results: A total of 340 participants were enrolled in the study; the median age was 55 years; 244 (71.8%) were female; and nearly half of the participants (163, 47.9%) had attained primary education. Overall, 67.1% (228/340) of the participants with T2DM had hypertension. Factors independently associated with higher odds of hypertension were as follows: age 61+ years (aOR = 5.55, 95% CI: 1.34–23.1, p = 0.018), being overweight (aOR = 3.77, 95%CI: 1.05–13.57, p = 0.042), T2DM duration of more than five years (aOR = 2.51, 95% CI: 1.41–4.67, p = 0.002), and being widowed (aOR = 8.04, 95% CI: 1.87–34.61, p = 0.005). Earning UGX 50,001–100,000 per month (aOR = 0.35, 95% CI: 0.13–0.93, p = 0.037) was associated with 65% lower odds of having hypertension. Conclusions: Two-thirds of patients with T2DM had hypertension, and factors such as older age, being overweight, a longer T2DM duration, and marital status significantly increased hypertension risk; meanwhile, moderate-income status offered a protective effect. The high burden of hypertension among patients with T2DM demonstrates the necessity for targeted public health interventions such as comprehensive lifestyle modification programs, routine screening for hypertension, early detection, and its management among patients with T2DM through enhanced healthcare access. These interventions should focus on integrated care approaches that monitor and manage T2DM alongside hypertension.

Diabetology doi: 10.3390/diabetology7090166

Authors: Djenane Cristovam Souza Rejane Cristiany Lins de França Pereira Rogério Fabiano Gonçalves Paulo Adriano Schwingel Manoel da Cunha Costa

Background/Objectives: The ankle–brachial index (ABI) is a low-cost, non-invasive screening tool for peripheral artery disease (PAD) and an independent predictor of cardiovascular events, which makes it suitable for primary care. Peripheral haemodynamic data across body mass index (BMI) gradients remain scarce, and BMI and diabetes are seldom modelled together despite their frequent co-occurrence. We investigated their associations with peripheral haemodynamic parameters. Methods: We performed a cross-sectional study in 147 primary care users, twenty-seven of whom had a self-reported diagnosis of diabetes mellitus (DM). Systolic pressure was obtained by auscultation, with Doppler being unavailable. The ABI was calculated per leg from unrounded pressure, and the lower index was adopted and classified according to American Heart Association thresholds (abnormal: ≤0.90; borderline: 0.91–0.99; normal: 1.00–1.40; elevated: >1.40). Nested linear models with robust standard errors estimated the adjusted association of DM with each outcome. Results: The DM group was older (62 vs. 44 years; p < 0.001), with greater rates of excess weight (77.8% vs. 54.2%), hypertension (59.3% vs. 25.8%), dyslipidaemia (48.1% vs. 11.7%), and smoking (30.8% vs. 10.1%). Crude upper-limb systolic pressure was 10.1 mmHg higher in the DM group (95% confidence interval [CI]: −0.5 to 20.6) but fell to 1.3 mmHg upon adjustment for age (p = 0.82 fully adjusted). The ABI did not differ between the groups (mean difference of 0.02, 95%CI: −0.06 to 0.11; p = 0.59) and showed no gradient across BMI. An abnormal ABI was present in 14.4% of participants and a borderline ABI in 18.5%, so that 32.9% had an ABI below 1.00. Conclusions: The crude blood pressure difference was attenuated after adjustment, chiefly for age, and DM was not independently associated with any outcome; residual confounding cannot be excluded. No ABI difference was detected, but power reached 80% only for a difference of about 0.12 units. The fact that one-third of participants had an ABI below 1.00 warrants further investigation of risk-based vascular peripheral assessment in primary care.

Diabetology doi: 10.3390/diabetology7090165

Authors: Elitsa Hadzhieva Mila Boyadzhieva Zornitsa Zlatarova Violeta Iotova Lidiya Zaduryan Natalya Usheva Sevim Shefket Yoto Yotov

Introduction: Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus (DM). Among the established risk factors for DR, “metabolic memory” plays a key role. Its development is mainly driven by advanced glycation end-products (AGEs), some of which possess characteristic fluorescent properties. Aims: To examine the relationship between skin AGEs, noninvasively assessed through skin autofluorescence (SAF), and the presence and severity of DR in subjects with long-standing type 1 DM (T1DM) and no history of atherosclerotic cardiovascular disease. Methods: 81 subjects with T1DM and 45 healthy controls were included. All individuals underwent SAF measurements and fundus photographs were taken in subjects with T1DM. Associations between SAF, its change over time and the presence and severity of DR were analyzed. Results: A significant positive correlation was found between SAF and the severity of DR. Only SAF and renal parameters showed a significant positive association with the presence of sight-threatening DR (STDR). There was a statistically significant increase in SAF levels over 3 years in STDR. Conclusions: SAF, but not HbA1c or diabetes duration, was associated with the severity of DR. SAF may therefore represent a promising, rapid, and non-invasive biomarker for identifying individuals at increased risk of STDR.

Diabetology doi: 10.3390/diabetology7090164

Authors: Sandro Gentile Raffaella Fiorentino Maddalena Lettieri Giuseppina Guarino Giampiero Marino Elisabetta Tommasi Vera Frison Ersilia Satta Maria Chiarello Giuseppe Caccavale Emilia Masuccio Felice Strollo

This response letter addresses criticisms from a recent commentary regarding a real-world survey on insulin pen needle preferences. The authors clarify that their study was purposefully designed as an observational survey to capture genuine patient perceptions under routine clinical conditions, rather than functioning as a randomized controlled trial. Consequently, methodological constraints such as blinding were fundamentally inapplicable. Furthermore, the authors emphasize the limited relevance of the Hawthorne effect in this context. While originally described in industrial settings, recent systematic reviews in the medical literature indicate that its magnitude and impact on modern clinical research are highly uncertain and generally modest. Ultimately, the study effectively highlights real-world patient experiences with the shortest and thinnest needles currently available, aligning with advances in injection technology.

Diabetology doi: 10.3390/diabetology7090163

Authors: David C. Klonoff Mandy M. Shao Agatha F. Scheideman

We read with interest a recent article in Diabetology titled “Enhancing Insulin Therapy Adherence Through Technology: Which Needles Do People with Diabetes Prefer [...]

Diabetology doi: 10.3390/diabetology7090162

Authors: Laura A. M. Konings Weiwei Xu Vivian D. de Jong Marco Alings Jean-Claude Tardif Abraham M. Lincoff Gregory G. Schwartz Diederick E. Grobbee Manuel Castro Cabezas

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2DM) have been associated with dyslipidemia. This study aimed to investigate the association between lipid values and markers of hepatic steatosis and fibrosis in patients with T2DM. Methods: This is a post hoc analysis of the AleCardio randomized controlled trial in patients with T2DM and recent acute coronary syndrome. Risk of liver steatosis was estimated with the Hepatic Steatosis Index (HSI), risk of liver fibrosis with the NAFLD Fibrosis Score (NFS). Results: Of 7226 participants, 526 were untreated with lipid-lowering medication and formed the analysis cohort. Mean age was 61 ± 10 years, and body mass index (BMI) was 28.5 ± 5.8 kg/m2. A total of 75% of individuals had an HSI score > 36, associated with high risk of liver steatosis, elevated NFS scores > 0.67, associated with high risk of liver fibrosis, were present in 15%. Patients with elevated HSI scores had higher BMI, HOMA IR, triglycerides, remnant cholesterol, and lower high-density lipoprotein compared to those with lower scores. Patients with elevated NFS scores had greater BMI and HOMA IR, and had lower triglycerides, remnant cholesterol, and apolipoprotein B in linear regression analyses. Conclusion: Patients with T2DM, cardiovascular disease, and blood-based indices suggesting liver steatosis or fibrosis differed significantly with respect to the lipid profile. An elevated HSI score, suggesting steatosis, was associated with dyslipidemia, an elevated NFS score, suggesting fibrosis, was not. A possible explanation for the latter findings is reduced very-low-density lipoprotein (VLDL-C) synthesis or secretion accompanying advanced hepatocellular dysfunction.

Diabetology doi: 10.3390/diabetology7090161

Authors: Hikmet Erhan Güven Lara Kavasoğlu George Theodorakopoulos

Background: Necrotizing fasciitis complicating diabetic foot infection requires rapid source control and is associated with substantial morbidity. A topical desiccating agent (TDA) may assist debridement by dehydrating necrotic tissue and potentially disrupting biofilm, but comparative clinical evidence is limited. Methods: We conducted a retrospective, single-center cohort study of 87 patients who underwent emergency surgery for diabetic foot-related necrotizing fasciitis between July 2023 and February 2026. Nineteen patients received a single application of TDA at the index operation in addition to standard care, and 68 received standard care without TDA. Treatment allocation was non-random and occurred in routine clinical practice. The primary outcome was the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score at Day 7. The primary analysis used linear regression adjusted for baseline LRINEC score and baseline septic status, with heteroskedasticity-consistent type 3 (HC3) standard errors. LRINEC was treated as a laboratory-based surrogate rather than as a validated treatment-response measure. C-reactive protein (CRP), white blood cell count, and glucose at Day 0 and Day 7 were summarized descriptively. Secondary clinical outcomes were 30-day major amputation and all-cause mortality. Results: The mean LRINEC score decreased from 8.58 to 2.95 in the TDA group and from 7.51 to 5.51 in the control group. The mean change was −5.63 in the TDA group and −2.00 in the control group, an unadjusted between-group difference of −3.63 points (95% confidence interval [CI], −4.83 to −2.43; p < 0.001). Baseline sepsis was more frequent in the TDA group than in the control group (89.5% vs. 51.5%). After adjustment for baseline LRINEC score and septic status, TDA exposure was associated with a 3.01-point lower Day-7 LRINEC score (95% CI, −4.00 to −2.02; p < 0.001). At Day 7, 18 of 19 TDA-treated patients (94.7%) and 34 of 68 controls (50.0%) had an LRINEC score below 6; this threshold analysis was exploratory. CRP, white blood cell count, and glucose decreased descriptively in both groups, with numerically larger reductions in the TDA group. No major amputations or deaths occurred within 30 days in either group. No TDA-related adverse event was documented in the retrospective clinical records. Conclusions: Adjunctive TDA use was associated with a lower Day-7 LRINEC score and a greater reduction from baseline. Because treatment was not randomized, baseline severity differed between groups, LRINEC is not a validated longitudinal treatment-response measure, and assessment of clinical outcomes was limited, the findings should be interpreted as exploratory associations and confirmed in prospective multicenter studies.

Diabetology doi: 10.3390/diabetology7080160

Authors: Saverio D’Elia Rosa Franzese Ettore Luisi Mariarosaria Morello Gisella Titolo Chiara Serpico Achille Solimene Granata Matteo Acampora Benito Francesco Loffredo Paolo Golino Francesco Natale Giovanni Cimmino

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a global epidemic strongly associated with an increased risk of heart failure, independent of coronary artery disease or hypertension. This condition, historically termed diabetic cardiomyopathy (DCM) and recently redefined as “diabetic myocardial disorder,” remains frequently underdiagnosed in its subclinical stages. The objective of this non-systematic review is to synthesize current evidence on the pathophysiological mechanisms, diagnostic advancements, and evolving therapeutic strategies for diabetic myocardial involvement. Methods: A comprehensive review of contemporary literature was conducted, focusing on recent consensus statements from the ESC and AHA, large-scale epidemiological data (IDF/WHO), and pivotal clinical trials (EMPA-REG, DAPA-HF, and LEADER). We analyzed the role of multimodal imaging—specifically speckle-tracking echocardiography (STE) and multiparametric cardiac magnetic resonance (CMR)—and circulating biomarkers in early phenotyping. Results: Pathophysiological drivers include lipotoxicity, oxidative stress, and AGE-mediated fibrosis. Advanced imaging techniques, such as global longitudinal strain (GLS) and CMR T1-mapping/ECV quantification, demonstrate superior sensitivity over LVEF in detecting early subendocardial dysfunction and diffuse fibrosis. Furthermore, NT-proBNP serves as a robust prognostic marker for the HFpEF-like trajectory typical of diabetes. Clinically, the therapeutic landscape has shifted with SGLT2 inhibitors and GLP-1 receptor agonists, which provide significant cardioprotection and reduction in heart failure hospitalizations through mechanisms beyond glycemic control. Conclusions: Diabetic myocardial disorder represents a complex continuum within the cardiometabolic spectrum. Early detection through multimodal imaging and biomarkers is essential for risk stratification. Integrating novel glucose-lowering therapies with proven cardiovascular benefits is now mandatory to alter the natural history of the disease and prevent progression to overt heart failure.

Diabetology doi: 10.3390/diabetology7080159

Authors: Rachid Aithammou Mohamed Ben-El-Caid

Background/Objectives: Diabetes mellitus is associated with cognitive impairment, but evidence from southern Morocco remains limited. This study examined the associations of diabetes status, HbA1c, and diabetes duration with Mini-Mental State Examination (MMSE) performance among adults aged 45 years or older in Dakhla. Methods: This hospital-based comparative cross-sectional study included 100 participants (50 with diabetes and 50 without diabetes). Data were collected through a structured bilingual questionnaire and medical records. MMSE scores below 27 defined MMSE-based cognitive impairment. Crude and age-, sex-, and education-adjusted linear regression models with HC3 robust standard errors were complemented by correlation, subgroup, chi-square, and odds-ratio analyses. Results: Mean MMSE scores were lower in participants with diabetes than in those without diabetes (24.4 ± 5.39 vs. 28.8 ± 2.08). After adjustment, diabetes remained associated with a 4.13-point lower score (β = −4.13; 95% CI: −5.57 to −2.69; p < 0.001). MMSE-defined impairment occurred in 54% and 14% of the diabetic and non-diabetic groups, respectively (OR = 7.21; 95% CI: 2.72–19.05; p < 0.001). Within the diabetic group, MMSE scores correlated inversely with diabetes duration (r = −0.523; p < 0.001) and HbA1c (r = −0.393; p = 0.005), but neither remained independently associated after adjustment. Participants with type 1 diabetes had lower median MMSE scores and longer disease duration than those with type 2 diabetes, although this subgroup comparison was exploratory. Conclusions: Diabetes was strongly associated with lower MMSE performance and a higher prevalence of MMSE-defined impairment in this hospital-based sample. The cross-sectional design precludes causal interpretation, and the findings require confirmation in larger prospective studies.

Diabetology doi: 10.3390/diabetology7080158

Authors: Kinfe G. Bishu Andrew D. Schreiner David J. Taber Matvey Tsivian Mulugeta Gebregziabher

Background: Accurate diagnosis and cause of death ascertainment are essential for effective disease surveillance and epidemiological research. This study aimed to validate prostate cancer diagnostic accuracy (PCa) and the accuracy of cause of death information among veterans with type 2 diabetes mellitus (T2DM). Methods: We conducted a retrospective cohort study of veterans with T2DM diagnosed during the baseline period (2008–2009) and followed from 2010 to 2019 using data from the Veterans Health Administration (VHA) Corporate Data Warehouse (CDW). Diagnostic codes and cause of death data were obtained from the Prostate Cancer Data Core (PCDC) and the National Death Index (NDI), which served as the gold standards for validating PCa diagnosis and mortality information in the CDW. Concordance between data sources was assessed using Cohen’s Kappa statistic. Results: Among 763,424 veterans with T2DM, 37,048 (4.9%) were diagnosed with PCa in the CDW and 36,861 (4.8%) in the PCDC, with a concordance rate of 36,361 (98.6% of patients diagnosed in the PCDC). Mortality data from the NDI identified 2723 deaths with PCa listed as the underlying cause of death, of whom 75.4% had a corresponding PCa diagnosis recorded in the CDW. For all-cause mortality, 328,165 veterans were identified as deceased in the CDW Vital Status File (VSF), compared with 326,707 deaths recorded in the NDI. Of these, 324,567 deaths were concordant between the two sources, representing 99.3% of NDI-recorded deaths. Compared with the PCDC, the CDW demonstrated high accuracy for identifying incident PCa diagnosis, with a sensitivity of 98.6% and a specificity of 99.9%. Conclusions: The findings demonstrated a high level of concordance in key outcomes, including PCa diagnosis between the CDW and PCDC, and all-cause mortality between the CDW VSF and NDI.

Diabetology doi: 10.3390/diabetology7080157

Authors: Cesare Miranda Valerio Velardi Roberto Da Ros

Background: Diabetic foot ulcer (DFU) recurrence remains a primary challenge in diabetes care. Although wound closure is the conventional therapeutic endpoint, it does not equate to risk resolution. Despite the implementation of evidence-based preventive strategies, a significant proportion of patients experience recurrent ulceration, highlighting an efficacy gap in current management. Objectives: This narrative review aims to quantify the residual recurrence risk and to provide a clinical framework for risk stratification in patients in remission. Methods: A structured narrative review of PubMed and Google Scholar (up to May 2026) was conducted to evaluate the residual burden associated with standard preventive interventions. Only English-language publications were considered. Results: Our analysis reveals that even with optimal adherence to established preventive protocols, a substantial residual risk persists, ranging from 16.7% to 41.4%. Clinical data indicate that the frequency of podiatric follow-up is a critical determinant of outcomes, with a 4-week screening interval limiting residual risk to 18.4%, significantly outperforming less frequent assessments. Conclusions: The persistence of residual risk mandates a paradigm shift in diabetic foot management: from a “healing-centered” approach to a “remission-focused” model. We propose an integrated, multidisciplinary strategy—anchored by 4-week podiatric surveillance—to mitigate the multifactorial drivers of recurrence and narrow the efficacy gap in clinical practice.

Diabetology doi: 10.3390/diabetology7080156

Authors: Lara Osama Al Hartany Marya Aref Alghorab Maya Faissal Alhomieed Reema Saleh Albalawi A’laa Abdullah Almowallad Abdulaziz Alsharif Ayesha Shrouq Amin Saud Faisal Alamri Taif Khalid Aljabal Abdulrhman Abdulaziz Alkthiry

Background/Objectives: Prediabetes is a highly prevalent metabolic condition associated with an increased risk of progression to type 2 diabetes mellitus (T2DM) and related cardiometabolic complications. Although lifestyle modification remains the cornerstone of diabetes prevention, long-term adherence is often challenging in routine clinical practice. This systematic review and meta-analysis aimed to evaluate the effect of metformin therapy on progression from prediabetes to T2DM and its impact on glycemic and metabolic outcomes. Methods: A systematic literature search was conducted in PubMed, MEDLINE, and Web of Science in accordance with the PRISMA 2020 guidelines. Studies involving adults with prediabetes that evaluated metformin therapy and reported diabetes-related outcomes were eligible for inclusion. Risk of bias was assessed using the RoB 2 tool and the NOS. Where appropriate, quantitative meta-analysis was performed using a random-effects model. Results: Forty-one publications were included in the systematic review, with eligible subsets contributing to the quantitative analyses. Overall, the available evidence suggested that metformin was associated with a reduced risk of progression from prediabetes to T2DM compared with placebo, usual care, or lifestyle intervention alone. Long-term follow-up studies demonstrated sustained preventive effects extending beyond 10 years. Meta-analysis demonstrated a significant reduction in BMI among metformin-treated participants (MD = −2.06, 95% CI −2.53 to −1.60; I2 = 0%; p < 0.001). Findings for glycated hemoglobin and fasting plasma glucose were variable across studies and did not consistently reach statistical significance. Some studies reported additional improvements in insulin sensitivity and other cardiometabolic outcomes, although these findings were not consistently reported across the evidence base. Conclusions: The available evidence supports metformin as an effective adjunctive pharmacological strategy for reducing progression from prediabetes to T2DM, particularly among selected high-risk adults. When used alongside lifestyle modification, metformin may provide additional benefits in body weight and metabolic health. However, lifestyle intervention should remain the first-line preventive strategy. Further high-quality studies are needed to optimize patient selection, dose, treatment duration, and long-term clinical outcomes.

Diabetology doi: 10.3390/diabetology7080155

Authors: Dimitrios Raptis Natalia Nazarenko Raksheeth Agarwal Mandar Kalpesh Shah Yiqi Gao Panagiotis Theodoropoulos Pawel Borkowski Maisha Maliha Maria Alyssa Yee Policarpio Shreyas Yakkali Yi-Yun Chen Jason Leider Preeti Kishore Naomi Friedman

Background/Objectives: People living with HIV (PLWH) who undergo prolonged antiretroviral therapy (ART) may experience weight gain as a potential side effect. Many of these individuals are prescribed glucagon-like peptide 1 (GLP-1) receptor agonists (RAs), or dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) RAs, which are known for their weight-reducing effects and positive impact on metabolic health. However, studies investigating their effects on PLWH are limited. Methods: We conducted a retrospective study at a public hospital in the Bronx, New York, among PLWH with obesity and/or type 2 diabetes mellitus (T2DM) prescribed GLP-1 or dual GLP-1/GIP RAs between August 2020 to March 2024. We collected baseline measurements of weight, body mass index (BMI), glycated hemoglobin (HbA1c), and lipid panel, before and after initiation of treatment, to assess the potential metabolic changes associated with the therapy. Logistic regression was used to analyze the factors associated with reductions in HbA1c and weight. Results: A total of 202 patients were included in the final study, with a mean duration of 24.2 months of GLP-1 or GLP-1/GIP RA therapy. A mean HbA1c reduction of 1.0% (p < 0.001), a mean BMI reduction of 0.7 kg/m2 (p < 0.001), and an average mean weight loss of 3.55% were observed. In the univariate analysis, the duration of GLP-1 or GLP-1/GIP RA use was the only factor independently associated with HbA1c reduction greater than 1% (p = 0.027). However, no correlation was found between the duration of their use and the percentage of weight loss (p = 0.126). Insulin use was associated with less weight loss (p = 0.048), while younger age was associated with greater weight loss (p = 0.048). No significant differences in weight loss were observed when the population was stratified by sex, race, comorbidities, type of GLP-1 RA therapy, or other antidiabetic or ART regimens. Conclusions: Use of GLP-1 RAs among PLWH with obesity and/or T2DM is associated with reductions in HbA1c and BMI. In this diverse cohort, which predominantly consists of Black and Hispanic individuals, longer duration of treatment was associated with reductions in HbA1c greater than 1%. These findings encourage GLP-1 RA-related treatment for PLWH with obesity and/or T2DM. Further prospective studies with larger cohorts are needed to confirm these benefits and better define their effects on long-term metabolic health.

Diabetology doi: 10.3390/diabetology7080154

Authors: Monica Verdoia Matteo Nardin Giuseppe Ciliberti Marta Leverone Jari Paternoster Aron Faraguna Emanuel Barnoffi Domenico Lorusso Gennaro Ciliberti Tommaso Piva Elisa Nicolini Marco Marini Antonio Dello Russo Rocco Mollace Gaia Gasparini Eligio Miccichè Roberto Bonmassari Orazio Viola Davide Cao Andrea Rognoni Filippo Zilio

Background: The most appropriate management of glucose-lowering therapies in patients exposed to iodinated contrast media (ICM) is still debated. The recent development of antidiabetic drugs that improve cardiovascular and renal outcomes leads to questions regarding their impact on the risk of contrast-associated acute kidney injury (CA-AKI). The present study aimed to assess the effect of different glucose-lowering therapies on the rate of CA-AKI among patients undergoing coronary angiography and/or angioplasty. Methods: Diabetic patients exposed to ICM for coronary procedures were retrospectively identified and divided according to the strategy for the management of diabetes mellitus. The use of a new antidiabetic drug (NAD) was defined for patients treated with SGLT2-I, DDP4-I or GLP-1 receptor agonists on admission. The primary endpoint was the occurrence of CA-AKI within 72 h after contrast medium exposure. Results: We included 462 patients with diabetes mellitus, 51.5% treated with insulin, 44.4% treated with metformin and 50.9% receiving NAD. Among them, 48 (10.4%) experienced CA-AKI. Patients experiencing acute renal injury were more often treated with calcium channel blockers (p = 0.04) and diuretics (p = 0.004), and less often P2Y12 inhibitors (p = 0.04), and presented lower levels of hemoglobin (p = 0.02). Patients receiving NADs displayed a significantly lower occurrence of CA-AKI (33.3% vs. 53.6%, p = 0.009), mainly for those treated with SGLT2-I. On the contrary, patients treated with sulfonylureas and meglitinides displayed a significant increase in the rate of CA-AKI (10.4% vs. 3.9%, p = 0.05). The results were confirmed via multivariable analysis, with NADs and diuretics emerging as the only independent predictors of CA-AKI (NAD: adjusted OR = 0.42 [0.21–0.81], p = 0.01; diuretics: adjusted OR = 2.22 [1.14–4.35], p = 0.02). The independent predictors of CA-AKI were the use of NADs (adjusted OR = 0.45 [0.24–0.86], p = 0.02) and diuretics (adjusted OR = 2.57 [1.33–4.97], p = 0.005). Conclusions: Among patients with diabetes mellitus undergoing coronary angiographic procedures, the use of diuretics, sulfonylureas and meglitinides is associated with an increased occurrence of CA-AKI, whereas the rate of events was significantly lower among users of new antidiabetic drugs and especially SGLT2-I.

Diabetology doi: 10.3390/diabetology7080153

Authors: Ekaterina Nesterova Maria Gladkikh Inna Burakova Olga Korneeva Polina Morozova Mikhail Syromyatnikov

Metabolic diseases, including obesity and type 2 diabetes mellitus, represent a major global health burden and are closely linked to the composition and function of the gut microbiota. Advances in molecular methods have enabled detailed characterization of microbial communities and their interactions with diet, medications, and host physiology, positioning the microbiome as an active metabolic organ. However, the field faces persistent challenges in distinguishing causal relationships from associations, largely owing to substantial biological, exposure-related, and methodological heterogeneity. This review systematizes the principal lines of evidence connecting the gut microbiome to metabolic disorders and critically examines the sources of variability that limit reproducibility and cross-cohort transferability of these findings. We discuss the taxonomic, functional, and metabolite-based levels of microbiome analysis, evaluate the strengths and limitations of cross-sectional, case–control, cohort, and interventional study designs, and consider approaches for establishing causality, including fecal microbiota transplantation, Mendelian randomization, mediation analysis, causal diagrams, and triangulation of evidence. We conclude that only a comprehensive, standardized, and causally informed approach will allow reliable discrimination between true microbiota-driven effects and methodological artifacts, thereby advancing the integration of microbiome science into the management of metabolic diseases and diabetes.

Diabetology doi: 10.3390/diabetology7080152

Authors: Kirill Berezhnoi Ilan Merdler Adam Folman Maguli Barel Rami Abu-Fanne Ariel Roguin Ofer Kobo

Background/Objectives: Obesity and diabetes mellitus coexist, but the association of obesity with invasive management and in-hospital outcomes in acute myocardial infarction (AMI) complicated by cardiogenic shock is uncertain. We evaluated these associations among adults with diabetes mellitus. Methods: We performed a retrospective discharge-level analysis of the National Inpatient Sample for 2016–2021. Obesity was identified from ICD-10-CM codes. Survey-design logistic regression accounted for weights, strata, hospital clusters, and prespecified covariates. Results: The cohort comprised 19,399 discharges, representing 96,995 hospitalizations; 24.1% had obesity. Angiography and coronary artery bypass grafting (CABG) were more frequent with obesity, whereas percutaneous coronary intervention (PCI) was less frequent. After adjustment, obesity was associated with higher odds of angiography (adjusted odds ratio [aOR] 1.12, 95% confidence interval [CI] 1.03–1.21) and CABG (aOR 1.49, 95% CI 1.35–1.63), lower odds of PCI (aOR 0.90, 95% CI 0.84–0.97), and similar odds of circulatory support (aOR 1.00, 95% CI 0.93–1.07). Adjusted odds were lower for major adverse cardiovascular and cerebrovascular events (aOR 0.88, 95% CI 0.82–0.95), in-hospital mortality (aOR 0.90, 95% CI 0.83–0.98), acute ischemic stroke (aOR 0.78, 95% CI 0.64–0.95), and major bleeding (aOR 0.86, 95% CI 0.76–0.98). Procedure adjustment attenuated mortality and major bleeding. Conclusions: Obesity was associated with a different invasive-management pattern and lower adjusted odds of several short-term outcomes, consistent with an apparent in-hospital obesity paradox in this high-risk population.

Diabetology doi: 10.3390/diabetology7080151

Authors: Reza Fahimi Abdulaziz Alrubayyi Habibullah Muhammad Kamal Ibrahim Khalil Ja’afar Mohanad Alhothify Thomas M. Barber Olalekan A. Uthman

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a growing burden in low- and middle-income countries, and non-invasive risk tools have been proposed where laboratory screening is not feasible. Fast-and-frugal decision trees (FFDTs) are transparent, non-compensatory rules that make sensitivity–specificity trade-offs explicit. We asked how far five routinely collected sociodemographic cues can go for classifying self-reported diabetes status and benchmarked FFDTs against the simplest possible alternatives. Methods: A cross-sectional secondary analysis of the 2016 South Africa Demographic and Health Survey Adult Health recode (N = 10,292; 459 self-reported cases, 4.46%) was carried out. Five binary cues were derived: age category, household wealth, employment, education and sex. Data were split 70/30 into development and a locked hold-out set. Three purpose-specific FFDTs were selected by 5 × 10-fold cross-validation within the development data only, frozen, and then evaluated once on the hold-out set. Comparators were a pre-specified age-only rule and logistic regression using the same five predictors at a development-derived Youden threshold. We report survey-weighted estimates, internal–external cross-validation across nine provinces, external validation in 12 further DHS, subgroup performance, and a log–log analysis of error against training sample size. Results: On the hold-out set the balanced screening FFDT achieved sensitivity 0.920 (95% CI 0.862–0.959), specificity 0.585 (0.567–0.602) and balanced accuracy 0.752 (0.727–0.776). The pre-specified age-only rule achieved balanced accuracy 0.751 (0.724–0.775), while logistic regression at the development-derived Youden threshold achieved 0.766 (0.735–0.797). Across 50 independent splits, the case-finding FFDT was arithmetically identical to the age-only rule in every split; the balanced FFDT exceeded it by a median of 0.001 (95% range −0.004 to +0.025); the referral-minimisation FFDT was worse by a median of 0.124. Performance was stable across provinces (balanced accuracy 0.731–0.801) but degraded across countries (0.508–0.724), with referral rate ranging from 0.225 to 0.806. Error scaled with training size as beta = −0.044 (95% CI −0.063 to −0.025). Conclusions: Transparent decision trees built from non-invasive sociodemographic cues classify self-reported diabetes status no better than a single question about age, do not transport reliably across countries, and are unlikely to be materially improved by simply increasing the training sample size. Their value lies in auditability rather than accuracy. Progress in low-burden risk stratification for T2DM in these settings will require cues that carry a biological rather than health system signal.

Diabetology doi: 10.3390/diabetology7080150

Authors: César Mauricio Baracaldo Barrera Martha Cecilia Jiménez Martínez Sandra Rojas Vega

Background: Type 2 Diabetes Mellitus (T2DM) is associated with cognitive decline, potentially mediated by neuroinflammatory processes and altered neuroplasticity. This study investigated cerebrospinal fluid (CSF) biomarkers of neuroinflammation and neuroplasticity in T2DM individuals versus controls, and their relationship with cognitive performance. Methods: This cross-sectional study included 56 T2DM individuals and 26 controls (aged 37–70 years; 48% male). CSF concentrations of leptin, IL-6, VEGF, BDNF, TNF-α, IGF-1, and IL-1β were measured using ELISA. Cognitive function was assessed using MMSE, the Stroop test, SDMT, RCFT, and TAAV. Group comparisons used Mann–Whitney U or t-tests; Spearman correlations examined variable relationships. Results: No statistically significant differences in CSF biomarkers were observed between groups. However, T2DM patients showed lower word recall (4.66 ± 1.48 vs. 5.81 ± 1.52; p = 0.002), reduced Symbol–Digit performance (17.82 ± 12.16 vs. 24.92 ± 12.10; p = 0.016), and higher Complex Figure Test scores (19.94 ± 9.32 vs. 15.94 ± 5.02; p = 0.009). IL-6 was negatively correlated with MMSE (r = −0.33, p = 0.005). Significant correlations emerged between MMSE and Symbol–Digit scores (r = 0.40, p < 0.001) and among biomarkers. Conclusions: “No statistically significant differences in CSF biomarkers were observed between groups and unadjusted CSF biomarker concentrations did not differ significantly between groups; however, after adjustment for age and BMI, IL-6 was significantly elevated in T2DM patients, indicating that covariate-adjusted analyses may be more sensitive for detecting subtle neuroinflammatory differences in this population.

Diabetology doi: 10.3390/diabetology7080149

Authors: Thanapat Limpaarayakul Jakkrit Palapinyo Methavee Poochanasri Kasidid Lawongsa Chanittha Buakhao Thawee Songpatanasilp Parinya Samakkarnthai

Background: This study aimed to determine the prevalence of osteosarcopenia and evaluate the diagnostic performance of phase angle, derived from bioelectrical impedance analysis, in identifying osteosarcopenia among older adults with type 2 diabetes mellitus. Method: A cross-sectional study was conducted with 147 participants aged 60 years or older, recruited from an outpatient clinic in Thailand between during 2024. Osteosarcopenia was diagnosed when criteria for both sarcopenia, defined by low skeletal muscle mass and either reduced handgrip strength or impaired physical performance, and osteoporosis, defined by a T-score of −2.5 or lower on dual-energy X-ray absorptiometry, were met. Participant characteristics, physical function, laboratory values, and body composition data were collected. Univariable Firth’s penalized logistic regression identified low body mass index and a lower phase angle as independent predictors of osteosarcopenia. Results: The overall prevalence of osteosarcopenia was 7.5 percent. Receiver operating characteristic curve analysis showed strong diagnostic performance of phase angle, with an area under the curve of 0.865. A cutoff value of less than 4.0 degrees achieved 100% sensitivity, 62.5% specificity, and 100% negative predictive value. These findings suggest that phase angle may be a practical, noninvasive screening tool for identifying older adults with type 2 diabetes mellitus who are at risk for osteosarcopenia. Its application in routine clinical settings could enable earlier intervention and reduce long-term complications associated with musculoskeletal decline in this vulnerable population.

Diabetology doi: 10.3390/diabetology7080148

Authors: Gisela M. Vaitaitis Martin G. Yussman Dan M. Waid Ronald Brazg David H. Wagner

Background: Type 1 diabetes (T1D) is a complex autoimmune disease demonstrating substantial heterogeneity in age of onset, residual C-peptide levels, clinical outcomes, and therapeutic response. Although the autoimmune classification of T1D has traditionally relied on detection of autoantibodies indicating B-cell involvement, studies targeting total CD3+ T cells have underscored the importance of T-cell regulation. Th40 cells, a pathogenic subset of CD3+ T cells, first identified in NOD mice, become significantly increased during diabetogenesis. Human subjects with T1D exhibit variable but significantly elevated Th40 levels in peripheral blood. Methods: To target pathogenic effector Th40 cells, we developed OPT101, a 15-mer peptide, and found that it interacts with CD40 in association with an activated integrin, identifying a novel inflammatory receptor complex. We conducted a phase 1b, double-blind, first-in-human clinical trial to evaluate OPT101 and met the primary objectives of safety and tolerability. Results: OPT101 generated only Grade 1 and 2 adverse events. Across eight doses, administered over six weeks, no product-related immune suppression was observed. Secondary objectives included immunologic outcomes and potential efficacy. Subjects with higher Th40 levels had low or undetectable C-peptide, higher (>7.0%) HbA1c, and elevated inflammatory cytokines. Th40 levels were significantly higher in subjects diagnosed before age eighteen. OPT101 treatment significantly reduced Th40 percentages without cell ablation, increased Treg levels, and decreased inflammatory cytokines. Serum blood glucose levels and HbA1c were significantly reduced by visit 8 in treated subjects. In two subjects, 11 and 13 years post-diagnosis, with undetectable C-peptide at screening, C-peptide became detectable post-treatment. Conclusions: OPT101 proved safe and effective in human T1D subjects with only mild and a few moderate adverse events. In this short-term study, OPT101 improved beta cell functions thus warranting further exploration.

Diabetology doi: 10.3390/diabetology7080147

Authors: Ahmed W. Al-Humadi Claire H. Parker Marcela Rodríguez-Flores Daniah A. Alwash Charis Liapi

Background: Obesity has a significant genetic component, accounting for up to an estimated 70% of individual susceptibility. Advances in genome-wide association studies (GWASs) and next-generation sequencing (NGS) have enhanced identification and characterization of genetic forms of obesity, facilitating more precise and individualized treatment approaches. The phenotypic heterogenicity of the disease of obesity, along with the limited predictive value of clinical features, hinders the accurate identification of genetic forms of the disease. Therefore, genetic testing represents a critical diagnostic modality to confirm etiology and inform precision-based therapeutic strategies. Aim: To compare the clinical utility, interpretation and potential impact of direct-to-consumer (DTC-GT) and clinician-directed genetic testing for obesity in the context of type 2 diabetes. Methods: This case-based review evaluated a patient with severe obesity and type 2 diabetes who underwent both DTC-GT and clinician-directed genetic testing for obesity. A structured literature review using PubMed, Scopus, Web of Science, and Google was undertaken to identify the resources of both testing approaches. Tables and a schematic figure were developed to summarize the findings. Results: Neither testing approach identified clinically actionable obesity-associated genetic variants or a monogenic cause of obesity. However, the DTC-GT report concluded that the patient was at “high risk” of obesity and was provided to the patient without a referral to genetic counseling which contributed to patient misunderstanding. Conclusions: This case, interpreted alongside the reviewed literature, suggests that clinician-directed genetic testing may better support reliable interpretation of obesity-associated genetic findings and disease management than DTC-GT. Larger studies are warranted to confirm these observations.

Diabetology doi: 10.3390/diabetology7080146

Authors: Akifumi Kushiyama Haruka Ota Kaho Higashi Iori Yamazaki Momoka Kojima Takako Kikuchi

Background/Objectives: The prevalence of obesity is increasing among Japanese patients with type 2 diabetes (T2D); however, the impact of obesity history and severity on microvascular complications remains poorly understood. This study aimed to investigate the association of lifetime maximum body mass index (BMI) and BMI at the first clinical visit with the development and progression of diabetic nephropathy and retinopathy. Methods: This retrospective cohort study included T2D patients who first visited the clinic of the Institute for Medical Sciences, Asahi Life Foundation between 2005 and 2022. Patients were categorized into five groups based on both lifetime maximum and first-visit BMI: underweight, normal weight, class I obesity, class II obesity, and severe obesity. The primary endpoints were renal events (sustained increase in proteinuria or ≥40% decline in eGFR) and retinal events (worsening of diabetic retinopathy by ≥1 stage). Results: A history of severe obesity, based on the lifetime maximum BMI, was an independent risk factor for proteinuria progression. While a history of severe obesity was associated with all endpoints in unadjusted analyses, these associations with eGFR decline and retinopathy were not significant after adjusting for covariates. In contrast, the BMI at the first visit was significantly associated with retinal events but not with renal events. Conclusions: A history of maximum lifetime obesity is a critical predictor of the proteinuria progression. A history of obesity, a simple clinical metric, is a valuable tool for identifying high-risk patients and may contribute to more effective preventative strategies.

Diabetology doi: 10.3390/diabetology7080145

Authors: Madalina Ioana Moisi Cosmin Mihai Vesa Florica Ramona Dorobantu Corina Cinezan Timea Claudia Ghitea Roxana Daniela Brata

Background: Contemporary antidiabetic therapy has evolved from a glucose-centered approach toward integrated cardiometabolic risk reduction. However, real-world evidence regarding treatment patterns and their association with glycemic and cardiovascular–renal profiles remain limited. Methods: This retrospective observational study included 250 adults with type 2 diabetes mellitus receiving non-insulin glucose-lowering therapy in routine specialist clinical practice. Demographic, clinical, biochemical, and pharmacological data were extracted from medical records. Glycemic control was assessed using HbA1c levels and HbA1c variation, while cardiovascular–renal parameters included estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), lipid profile, blood pressure, and heart failure prevalence. Comparative analyses and multivariate logistic regression were performed. Results: The cohort had a mean age of 61.8 ± 11.3 years, and all patients had type 2 diabetes mellitus (100.0%). Obesity, metabolic syndrome, hypertension, ischemic heart disease, and chronic kidney disease were highly prevalent. Metformin was the most frequently prescribed therapy (58.8%), followed by GLP-1 receptor agonists (28.8%) and SGLT-2 inhibitors (27.6%). Patients receiving GLP-1 receptor agonists or SGLT-2 inhibitors showed numerically lower HbA1c values and greater HbA1c reductions compared with conventional therapies. However, differences in HbA1c, CRP, and eGFR were not statistically significant after correction for multiple comparisons. Longer diabetes duration independently predicted poor glycemic control, whereas increasing age was associated with a lower probability of HbA1c > 7%. Conclusions: Contemporary antidiabetic therapies were associated with favorable numerical cardiometabolic trends, although these associations did not remain statistically significant after multiple-comparison correction. The findings should therefore be considered exploratory and hypothesis-generating.

Diabetology doi: 10.3390/diabetology7080144

Authors: Kavita Batra Jagdish Khubchandani Ravi Batra Syed Aman Ali

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become first-line pharmacotherapy for eligible patients with type 2 diabetes mellitus and obesity. Soon after their broad uptake, spontaneous reports of suicidal ideation, depression, and anxiety prompted regulatory investigations and a contentious debate about the neuropsychiatric safety of the class. Objective: We aimed to synthesize emerging evidence on psychiatric adverse outcomes associated with GLP-1 RAs by integrating mechanistic, pharmacovigilance, observational, and regulatory data; to trace how the evidence and regulatory assessments evolved chronologically from initial signal detection toward subsequent controlled refutation; and to translate the current balance of evidence into practical clinical guidance. Methods: We conducted a narrative integrative synthesis of peer-reviewed pharmacovigilance studies, cohort and case–control analyses, systematic reviews and meta-analyses, mechanistic literature, and regulatory communications identified through targeted searches of the published record through early 2026. Results: Disproportionality analyses of spontaneous-reporting databases have generated modest, semaglutide-predominant signals for depression and suicidality, whereas liraglutide and tirzepatide have generally not. Anxiety signals parallel those for depression, and emerging data also indicate potential benefits for substance-use, binge-eating, and sleep-disordered breathing. In contrast, large propensity-matched cohort studies, a nationwide case–time–control analysis, an administrative-claims cohort exceeding two million users, and a meta-analysis of 91 placebo-controlled trials enrolling 107,910 participants found no increased risk and, in some analyses, lower risk of suicidal ideation. The principal exception is an amplified reporting signal among patients co-prescribed antidepressants or benzodiazepines, indicating effect modification by psychiatric vulnerability. Conclusions: The preponderance of controlled evidence has not demonstrated a causal relationship between GLP-1 RAs and suicidality or major psychiatric harm, a conclusion reflected in 2024–2026 regulatory determinations. Residual uncertainty persists for psychiatrically vulnerable subgroups, justifying continued individualized monitoring rather than restriction of access.

Diabetology doi: 10.3390/diabetology7080143

Authors: Rebecca Duarte Jeegan Parikh Ismael Hoare

Background: Physical activity is a crucial component of diabetes prevention and management, yet participation varies across populations. Differences by country of birth may reflect cultural, socioeconomic, and structural factors that influence health behaviors among individuals with diabetic conditions. Objective: To examine the relationship between country of birth, diabetes status, and physical activity, and to assess whether country of birth is associated with diabetes prevalence. Methods: A cross-sectional analysis was conducted using U.S.-nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Adults were categorized as having diabetes/prediabetes or no diabetes based on self-reported diagnosis. Physical activity was assessed using self-reported levels of moderate and vigorous leisure-time physical activity (LTPA). Sociodemographic characteristics were compared across groups. Stratified analyses were conducted to evaluate differences by country of birth and statistical tests were used to identify significant associations between diabetes status, physical activity, and sociodemographic variables. Results: Significant differences in sociodemographic characteristics were observed across diabetes status groups, particularly by age. There was no significant difference in physical activity levels between adults with diabetes compared to those without. Individuals with diabetes reported higher levels of sedentary time before adjustment for sociodemographic factors. Differences in physical activity behaviors were also observed in unadjusted analyses by country of birth, with foreign-born groups demonstrating lower levels of vigorous activity. Conclusions: Physical activity disparities exist among adults in the United States with diabetes and prediabetes and differ by country of birth, although they can be largely explained by sociodemographic factors. These findings highlight the need for culturally and socioeconomically tailored interventions to promote physical activity and support chronic disease management in diverse populations.

Diabetology doi: 10.3390/diabetology7080142

Authors: Scelo Khumalo Zamathombeni Duma Lizette Bekker Puleng Matatiele Lesibana Sethoga Sara Mosima Pheeha

Background: Type 2 diabetes mellitus (T2DM) is associated with altered gut microbiota and reduced short-chain fatty acid production, which may contribute to insulin resistance. However, evidence on fecal Short Chain Fatty Acid (SCFA) profiles in African populations remains limited. This study quantified fecal SCFAs in individuals with and without T2DM using Gas Chromatography–Mass Spectrophotometry (GC-MS) with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) derivatization. Methods: A cross-sectional study included 140 adults (92 non-diabetic and 48 T2DM). Fecal SCFAs were extracted, derivatized using BSTFA, and analysed by GC–MS. Associations between SCFAs, diabetes status, and HbA1c were evaluated using non-parametric statistics. Results: The GC–MS method demonstrated strong linearity (R2 = 0.9917–0.9978), acceptable recovery, and reproducibility. Acetic, propionic, butyric, pentanoic, hexanoic, and heptanoic acids were detected, with acetic acid being most abundant in both groups. T2DM participants had higher median SCFA levels, although only butyric acid differed significantly (p = 0.027). HbA1c was significantly higher in the T2DM group (p < 0.001). No significant associations were observed between SCFAs and HbA1c in either group. Age differed significantly between groups, with T2DM participants older than non-diabetic controls. Conclusions: Most fecal SCFA profiles were comparable between individuals with T2DM and healthy controls. However, butyric acid was significantly elevated in the T2DM group, indicating that not all SCFAs exhibited similar patterns between the study groups. These findings suggest that fecal SCFAs alone may not serve as reliable biomarkers of T2DM in this population and highlight the influence of complex host–microbiome–environment interactions suggesting that dietary and microbial factors may outweigh disease status in determining SCFA variability in this cohort setting.

Diabetology doi: 10.3390/diabetology7070141

Authors: Jong Han Lee

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus, and a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. It is characterized by proteinuria, mesangial expansion, glomerulosclerosis and progressive loss of renal function. Current therapeutic strategies of DN, including renin–angiotensin–aldosterone system (RAAS) blockade, glucagon-like peptide-1 receptor agonists, non-steroidal mineralocorticoid receptor, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, only slow the progression of the disease rather than reversing the pathology. Therefore, there is a growing interest in identifying alternative or complementary therapeutic agents, particularly those derived from natural products with multi-targeted activities. Psoralea corylifolia Linn (PCL) is a medicinal herb commonly used in traditional Asian medicine. It has known pharmacological properties on oxidative stress, inflammation, fibrosis and metabolic disorders. Accumulating recent studies indicated that PCL and its bioactive compounds, such as psoralen, bakuchiol, and corylin, mitigate pathological conditions in various diseases. Here, the current review will provide our current knowledge of major identified and characterized PCL focusing on their biological activity and function, particularly in DN.

Diabetology doi: 10.3390/diabetology7070140

Authors: Sathish Thirunavukkarasu Kai Wallens Gabrielli T. De Mello Yingting Cao Emma E. Thomas Natasha Reid Kavumpurathu Raman Thankappan Brian Oldenburg Elezebeth Mathews

Objectives: We assessed the test–retest reliability, criterion validity, and agreement of the Global Physical Activity Questionnaire (GPAQ) against accelerometry for estimating physical activity (PA) and sedentary behaviour (SB) among Indian adults at high risk of type 2 diabetes. Methods: We validated the original GPAQ in a subsample of 196 participants from the Kerala Diabetes Prevention Program. Participants were identified as being at high risk based on an Indian Diabetes Risk Score (IDRS) ≥ 60 and the absence of diabetes on an oral glucose tolerance test. To assess test–retest reliability, participants completed the GPAQ on two occasions, one week apart. Criterion validity and agreement were evaluated by comparing GPAQ responses with seven days of concurrent ActiGraph GT3X accelerometer data. Statistical analyses included intraclass correlation coefficients (ICCs) for reliability, Spearman’s correlation coefficients (ρ) for criterion validity, and Bland–Altman plots for agreement. Results: The mean (SD) age of participants was 47.0 (7.4) years, and 51% were female. ICCs for test–retest reliability ranged from 0.37 for moderate-intensity PA to 0.61 for vigorous-intensity PA. Spearman’s ρ for criterion validity ranged from 0.14 for SB to 0.38 for overall moderate-to-vigorous PA. Bland–Altman plots showed that the GPAQ consistently overestimated PA across all intensity levels while underestimating SB. Conclusions: The GPAQ demonstrated poor-to-moderate test–retest reliability, low criterion validity, and poor agreement with accelerometry for assessing PA and SB among Indian adults at high risk of type 2 diabetes.

Diabetology doi: 10.3390/diabetology7070139

Authors: Sirapat Khodseewong Thidarat Somdee Ploypailin Aneknan Rujira Nonsa-ard

Objectives: Type 2 diabetes mellitus (T2DM) is an increasing public health concern in Thailand, particularly in rural communities where dietary practices and contextual factors may influence glycemic control. This study aimed to assess nutritional knowledge, attitude, and eating behavior using the Knowledge–Attitude–Practice (KAP) framework and to compare nutritional intake profiles between patients with controlled and uncontrolled glycemic status. Methods: A cross-sectional study was conducted among 70 patients with T2DM attending a health-promoting hospital in northeastern Thailand. Participants were classified into glycemic-controlled (GC; HbA1c < 7%, n = 36) and glycemic-uncontrolled (UC; HbA1c ≥ 7%, n = 34) groups. Data were collected using a semi-structured questionnaire covering demographics, anthropometry, body composition, biochemical parameters, and KAP domains. Dietary intake was assessed using three-day food records (two weekdays and one weekend day) and analyzed with the INMUCAL Nutrients program. Statistical analyses included descriptive statistics, group comparisons, logistic regression, and Spearman’s correlation. Results: Overall, participants demonstrated high levels of nutritional knowledge (71.4%) and fair attitude (52.9%), but moderate levels of appropriate eating behavior (58.6%). Eating behavior differed significantly between GC and UC groups (p = 0.038). The UC group consumed significantly higher amounts of total energy, carbohydrates, simple carbohydrates, and protein than the GC group. HbA1c and fasting blood glucose were positively correlated with total energy, carbohydrate, simple carbohydrate, and zinc intake, while protein and phosphorus intake were positively associated with fasting blood glucose only. Logistic regression analysis showed no significant associations between KAP domains and glycemic control. Conclusions: Glycemic control among rural Thai patients with T2DM was more closely related to dietary intake patterns than to nutritional knowledge or attitude alone, highlighting the need for context-specific, community-based dietary interventions.

Diabetology doi: 10.3390/diabetology7070138

Authors: Lăcrămioara Aurelia Brîndușe Corina Vicol Maria Alexandra Cucu Eugenia Claudia Bratu

Background/Objectives: In Romania, diabetes mellitus remains a significant public health challenge, characterized by high prevalence and significant undiagnosed cases. This study assessed the prevalence of elevated glycated hemoglobin (HbA1c) levels within the adult population participating in the European Health Examination Survey (EHES) and examined their associations with major cardiometabolic risk factors, subjective health perception, and patient awareness of previously diagnosed chronic conditions. Methods: This cross-sectional study analyzed data from the EHES in Romania, including systematic, population-weighted sample of adults aged 25–64 years. Data were analyzed using the Complex Samples module in SPSS, version 29.0 (IBM Corp., Armonk, NY, USA). HbA1c levels were measured through standardized clinical examination, with values of 5.7–6.4% classified as at risk for diabetes mellitus, and values ≥6.5% as diabetes mellitus. Results: Among 5380 representative adults, the prevalence of elevated HbA1c (≥6.5%) was 7.1%, while prediabetes (HbA1c 5.7–6.4%) affected 35.4% of participants; both conditions were significantly more prevalent in men than in women. Elevated HbA1c and prediabetes were substantially more frequent among individuals with hypertension and hypercholesterolemia, and glycemic control among participants with previously diagnosed diabetes was generally poor (all p ≤ 0.05). Individuals who are aware of having a chronic health condition appear to engage more actively in self-care practices, including increased physical activity and more frequent monitoring of key biological parameters. Conclusions: Elevated HbA1c and prediabetes were more prevalent than estimates reported in other studies using HbA1c-based diagnostic criteria. These observations highlight the importance of early detection and timely diagnosis, as awareness of one’s health status may facilitate healthier behaviors that mitigate metabolic complications.

Diabetology doi: 10.3390/diabetology7070137

Authors: Laura Palacios-Abril Aroa Tardáguila-García Francisco Javier Álvaro-Afonso Sol Tejeda-Ramírez Mateo López-Moral José Luis Lázaro-Martínez

Background and Objectives: Physical inactivity is a modifiable risk factor for vascular complications in individuals with diabetes mellitus. The aim of this study was to evaluate the predictive capacity of physical activity level for peripheral arterial disease (PAD) in patients with diabetes. Methods: A multicentre cross-sectional study was conducted in adults with diabetes undergoing vascular screening. Physical activity was assessed using the Spanish short version of the Minnesota Leisure-Time Physical Activity Questionnaire (VREM), with energy expenditure expressed as metabolic equivalents (MET-min/14 days). PAD was defined according to standard vascular criteria. Analyses included bivariate tests, Spearman correlation, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis. Results: Fifty-four participants were included, with a mean energy expenditure of 4031.8 ± 3986.9 MET-min/14 days. Physical activity was inversely correlated with PAD (ρ = −0.380; p = 0.005). Participants without PAD had significantly higher activity levels than those with PAD (p = 0.006). After adjustment for age, body mass index, glycated haemoglobin, and diabetes duration, higher physical activity remained independently associated with lower odds of PAD (OR = 0.621; 95% CI: 0.392–0.983; p = 0.042). The model showed good discrimination (AUC = 0.840). Conclusions: Higher leisure-time physical activity is associated with a reduced likelihood of PAD in individuals with diabetes, although the findings should be interpreted cautiously due to the study design and sample size.

Diabetology doi: 10.3390/diabetology7070136

Authors: Nina L. Owen-Simon Geoffrey K. Dube Lloyd E. Ratner Kasi McCune

Background/Objectives: To determine the association between post-pancreas transplantation weight gain and graft dysfunction. Methods: Retrospective analysis of pancreas transplantation from 1 August 2008 to 1 November 2022. All patients > 18 years old who underwent simultaneous kidney pancreas transplant (SPK), pancreas after kidney transplant (PAK), and pancreas transplant alone (PTA) with at least one year of follow up were included. The association between post-transplant weight gain and graft dysfunction was assessed. Graft dysfunction was defined as HbA1c > 6.5% or use of antihyperglycemic medication. Results: Twenty-five percent of recipients had substantial weight gain (SWG), defined as >7% weight increase, by 1 year post-transplant. Recipients with T2D and SPK recipients were more likely to gain weight. SWG within the first year was significantly associated with the development of graft dysfunction at most recent follow up (Cox HR = 3.3, p = 0.005), but not at 1 year. Recipients with SWG in the first year had significantly higher HbA1C at most recent follow up (5.3 ± 0.7% vs. 5.9 ± 0.9%, p = 0.009), but not at 1 year. Among recipients with SWG occurring after 1 year, there were no differences in graft dysfunction or HbA1C at 1 year and no difference in graft dysfunction or HbA1C at most recent follow up. Conclusions: In this single-center study, SWG at 1 year post-transplant was associated with the development of graft dysfunction and elevated HbA1C in the long term.

Diabetology doi: 10.3390/diabetology7070135

Authors: Stella Stare Ema Šuligoj Melina Bešić Jernej Letonja Mojca Globočnik Petrovič Ines Cilenšek Daniel Petrovič

Background: Osteoprotegerin (OPG) is best known for regulating bone remodeling, vascular calcification, apoptosis, and immune responses. Recent studies also suggest that OPG may play an important role in diabetic microvascular complications such as diabetic retinopathy (DR). Objectives: The aim of our cross-sectional case–control study was to assess the relationship between the OPG variants (rs2073618 and rs3134069) and DR in a large cohort of subjects with type 2 diabetes (T2DM). Methods: A total of 1554 subjects with T2DM were enrolled in this cross-sectional case–control study: 577 with DR and 977 without DR. Genotyping was performed using StepOne Real-Time PCR with TaqMan genotyping assays. Results: Our data indicated that the prevalence of the C minor allele was significantly higher among patients with DR and type 2 diabetes in both polymorphisms. Furthermore, individuals carrying the CC genotype of the rs2073618 had a 1.42-fold increased likelihood of DR, while carriers of the CC or CA genotypes of the rs3134069 exhibited a 1.55-fold higher likelihood of DR. Conclusions: Taken together with existing evidence, these results suggest that OPG polymorphisms may be involved in the development of DR.

Diabetology doi: 10.3390/diabetology7070134

Authors: Mari Tanaka Hiroyuki Ito Erika Watanabe

Background/Objectives: Diabetes-related stigma decreases treatment motivation. While subjective financial burden is a known barrier, the impact of actual medical costs on stigma remains unclear. We investigated the relationship between annual outpatient medical costs (total and out-of-pocket) and stigma in type 2 diabetes to explore whether this association might be more closely related to direct financial hardship or underlying treatment complexity. Methods: In a cross-sectional study, we evaluated stigma in 232 outpatients using the Kanden Institute Stigma Scale (KISS). Patients scoring ≥20 formed the high stigma group (n = 59). Annual medical costs were extracted from electronic hospital claims. We examined associations between medical costs and high stigma using multivariable logistic regression and restricted cubic spline (RCS) models. Results: Adjusted for sex and age, higher total medical cost (per 10,000 JPY/year) was significantly associated with high stigma (odds ratio [OR] = 1.03, 95% confidence interval [CI]: 1.01–1.05, p < 0.01). However, this significance was attenuated after additionally adjusting for HbA1c and antidiabetic agent count (OR = 1.02, 95% CI: 1.00–1.04, p = 0.05). RCS analysis confirmed this dose–response association disappeared upon adjusting for treatment intensity. Notably, out-of-pocket costs showed no significant association with high stigma in any fully adjusted models (OR = 1.03, 95% CI: 0.95–1.11, p = 0.45). Conclusions: While total medical costs are associated with high stigma, the attenuation of this relationship after adjusting for clinical factors suggests that this association may be closely intertwined with the psychosocial burden of treatment complexity, such as polypharmacy and insulin injections, rather than acting solely through direct economic pain from out-of-pocket expenses. Clinicians should prioritize shared decision-making to mitigate psychological distress when intensifying treatment.

Diabetology doi: 10.3390/diabetology7070133

Authors: Kara Turner Denise Levy Jairo L. Arce-Morales Manasa Kanneganti Johanna P. Daily Alyson K. Myers

Introduction: Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes, and management by multidisciplinary foot teams has been shown to reduce serious sequelae, such as amputations. There are stark racial and ethnic disparities in morbidity and mortality from DFUs, and multidisciplinary care has been shown to reduce lower extremity amputations, length of hospital stays and readmissions. This is a review of the impact of multidisciplinary care on DFUs, particularly regarding social determinants of health, with an illustrative case. Case Presentation: This is a case of a 32-year-old African American male with Type 1 Diabetes, a history of poor glycemic control, attention deficit hyperactivity disorder, tobacco and marijuana use disorder, and multiple social and structural barriers to care. He presented with bilateral Wagner grade 3 DFUs with osteomyelitis to the emergency department, requiring hospitalization. Upon discharge, he was referred to a multidisciplinary diabetes clinic and received coordinated support from endocrinology, podiatry, vascular surgery, infectious disease, pedorthics, and behavioral health. Comprehensive evaluation, intensive wound care with adjuvant hyperbaric oxygen therapy, offloading, blood glucose management and medical source control of infection were established for his treatment plan. At the three-month follow-up, the patient’s wound beds had significantly improved, and his Hemoglobin A1c declined from 12.6% to 9.3%. The right plantar wound completely epithelialized, and the left foot wound showed 90% contracture. Review and Discussion: This case highlights the importance of integrated, multidisciplinary care for DFUs, particularly in addressing both the clinical and social drivers of complications from diabetes.

Diabetology doi: 10.3390/diabetology7070132

Authors: Despoina Rizikou Anastasia Ntikoudi Anastasia Papachristou Polyxeni Mangoulia Afroditi Tsalkitzi Eugenia Vlachou

Background/Objectives: Therapeutic education for children and adolescents with Type 1 Diabetes Mellitus (T1DM) is a continuous and essential process in the effective management of the disease. These programs consider the unique characteristics and developmental needs of each child or adolescent, aiming to empower them to take responsibility for their disease self-management, improve quality of life, and prevent complications. The purpose of this systematic review was to evaluate the impact of therapeutic education in children and adolescents with T1DM on self-management of their disease. Methods: International bibliography was reviewed using electronic databases such as PubMed, Cochrane Library, and Scopus. Key words such as “Therapeutic Education”, “Type 1 diabetes”, “children”, “self-management”, “glycemic control”, and “educational programs” in combination with Boolean operators (AND, OR) were used in English language to search for studies conducted during 2014–2024. Results: A total of 23 studies met the inclusion criteria. Most reported improvements in glycemic control, though not all showed statistically significant reductions in glycated hemoglobin (HbA1c). Enhanced treatment adherence and increased diabetes-related knowledge were common outcomes. Combined educational approaches incorporating psychoeducational interventions demonstrated greater effectiveness in promoting self-management. Digital tools, such as Continuous Glucose Monitoring (CGM), further supported adherence. Quality-of-life improvements were noted but were not always sustained long-term. Parental involvement appeared to improve children’s confidence in disease management. The critical role of interdisciplinary diabetes care teams, particularly nurses’ role, was also highlighted. Conclusions: Therapeutic education appears to support self-management among children and adolescents with T1DM, particularly when programs are individualized, family-centered, multidisciplinary, and supported by psychosocial or technological components. However, effects on glycemic control were not consistent across studies, and further research is needed to confirm long-term outcomes.

Diabetology doi: 10.3390/diabetology7070131

Authors: Stephanie M. Mueller Hannah D. Shi Aditi Kaveti Amy Du Devin J. Clegg Romi Wagner Dennis P. Orgill

Background: Diabetic foot ulcers (DFUs) are a major cause of morbidity and lower extremity amputation. Numerous advanced wound therapies with various mechanisms of action have been developed to improve healing outcomes; however, the comparative certainty of evidence supporting these interventions remains unclear. This study evaluates randomized controlled trials (RCTs) of DFU therapies using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Methods: A narrative synthesis of RCTs published between January 2016-January 2026 evaluating therapies for DFUs was performed. For studies that reported 12–week healing outcomes, risk of bias was assessed using the Cochrane Risk of Bias 2 tool and certainty of evidence for each therapy subgroup was evaluated using the GRADE framework. Results: A total of 143 RCTs were included with 45 RCTs undergoing GRADE assessment. The proportion of studies demonstrating statistically significant improvements in 12-week healing rates relative to controls varied and was not reflected in the GRADE assessment. Moderate-certainty evidence was assigned to the hyperbaric oxygen therapy subgroup. Low-certainty evidence was assigned to silver dressings, biosynthetic scaffolds, stem cell therapy, and negative pressure wound therapy. Very low-certainty evidence was assigned to topical oxygen, synthetic structural scaffolds, moisture-retaining dressings, local antimicrobial delivery, placental-derived skin substitutes, platelet-rich plasma, acellular dermal matrices, allografts/xenografts, and off-loading devices. No therapy subgroup was assigned high-certainty evidence. Conclusions: The certainty of evidence supporting DFU therapies varies substantially across intervention categories. These findings highlight the need for larger, methodologically rigorous comparative trials to clarify the effectiveness of DFU therapies and guide evidence-based wound care.

Diabetology doi: 10.3390/diabetology7070130

Authors: Kristoffer Marsaa Julie E. Stenvang Jonatan I. Bagger

Introduction: As diabetes care becomes increasingly digitalized, stratified, and differentiated, psychosocial vulnerability risks becoming less visible within routine care and documentation. To ensure that differentiated care pathways meaningfully incorporate psychosocial stratification, vulnerability must be identifiable, documented, and revisited as part of routine clinical practice. Aim: The aim of this study is to explore how healthcare professionals identify psychosocial vulnerability in routine diabetes care and how such vulnerability is documented and followed up in the electronic medical record (EMR). Methods: This quality improvement audit with a descriptive analysis component was conducted at Steno Diabetes Center Copenhagen as part of the development of a new differentiated outpatient pathway. Healthcare professionals across disciplines submitted cases of persons with diabetes whom they considered psychosocially vulnerable. Documentation from the preceding six months was reviewed descriptively in order to find patterns of identification, documentation, care planning, and follow-up. Results: A total of 334 referrals representing 275 unique persons with diabetes were submitted. Psychosocial vulnerability extended beyond predefined high-risk categories, as 37% of identified cases did not align with any of the six vulnerability groups described in the Danish VIVE framework. Vulnerability often reflected cumulative everyday-life strain rather than formal diagnoses. While healthcare professionals demonstrated substantial relational attentiveness to psychosocial concerns, this knowledge was not consistently evident in formal documentation. Explicit care plans and longitudinal follow-up were uncommon, and psychosocial concerns were frequently documented as isolated observations rather than as part of structured ongoing care. Conclusions: Psychosocial vulnerability was frequently identified through clinical dialogue and professional judgement and often extended beyond predefined vulnerability categories. The findings highlight the importance of developing shared approaches and a shared understanding of psychosocial vulnerability across professional groups. If psychosocial stratification is to become an operational component of differentiated diabetes care, information about what burdens matter to the person must be identifiable, documented, and carried forward across encounters alongside biomedical information.

Diabetology doi: 10.3390/diabetology7070129

Authors: Monique Resende Costa Machado Claudio Melibeu Bentes Claudia Cardoso Netto Letícia Baptista de Paula Barros Rafael Bizarelo Karina Ribeiro Silva Humberto Miranda Pablo B. Costa Lizanka Paola Figueiredo Marinheiro

Background/Objectives: Type 2 diabetes mellitus (T2DM) and menopause are associated with low levels of vitamin D (25[OH]D). Primary trials reported the effects of cholecalciferol supplementation on glycemia and T2DM incidence with conflicting results. This uncontrolled longitudinal prospective study aimed to evaluate changes in metabolic and cardiovascular parameters in postmenopausal women with T2DM during sequential cholecalciferol supplementation. Methods: Thirty-four postmenopausal women (mean of 63.8 ± 7.5 years) with T2DM received 1000 IU/day of cholecalciferol for 12 months, followed by 2000 IU/day for another 12 months. Fasting blood tests, anthropometric assessments, and physical examinations were performed at baseline, 12 months, and 24 months after the intervention. The levels of 25(OH)D, fasting glycemia, glycated hemoglobin, fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, HOMA of β-cell function (HOMA-β), total cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides, and C-reactive protein were evaluated. Systolic blood pressure (SBP), diastolic blood pressure, waist circumference (WC), waist-to-hip ratio, and body mass index were also assessed. Results: Serum 25(OH)D and HDL-c levels increased over time during the follow-up period. Lower WC and SBP values were observed across follow-up assessments. Although fasting blood glucose values showed a median of 120 mg/dL at baseline and 110 mg/dL after cholecalciferol supplementation, and HOMA-β values were approximately 35% higher at the end of follow-up, these differences were not statistically significant (p = 0.059 and p = 0.158, respectively). Conclusions: The long-term 25(OH)D dosing regimen had modest beneficial effects on glucose homeostasis, lipid profiles, and blood pressure in postmenopausal women with T2DM. This study contributes to the search for an optimal daily 25(OH)D dose in postmenopausal women with diabetes.

Diabetology doi: 10.3390/diabetology7070128

Authors: Niel Patel Miriam Soliman Amit Majithia Atul Malhotra

Obstructive sleep apnea (OSA) is a common condition defined by recurrent upper airway collapse, intermittent hypoxia, and sleep fragmentation that leads to sympathetic activation and adverse cardiometabolic effects. OSA and type 2 diabetes mellitus (T2DM) share a complex, bidirectional relationship driven in part by obesity, but also by overlapping pathophysiologic mechanisms. Diabetes may worsen upper airway collapsibility, while untreated OSA may exacerbate hyperglycemia, contributing to a self-perpetuating cycle of metabolic abnormalities. Continuous positive airway pressure (CPAP) remains the first-line therapy for OSA, and improves symptoms and some cardiometabolic parameters, although effects on glycemic control have been mixed and may depend on patient factors. Alternative therapies play important roles in some patients. Incretin-based therapies, particularly tirzepatide, have emerged as promising treatments for obesity-related OSA following the SURMOUNT-OSA trial, demonstrating significant reductions in apnea–hypopnea index and cardiometabolic risk factors, though their effect in patients with T2DM remains unclear. Considerations such as sarcopenia with weight loss and evolving pharmacologic and procedural strategies further shape management decisions. This review synthesizes current evidence on the pathophysiologic overlap, therapeutic approaches, and future directions in optimizing care for patients with coexisting OSA and diabetes.

Diabetology doi: 10.3390/diabetology7070127

Authors: Craig C. Teerlink Tyler J. Nelson Kathryn M. Pridgen Fatai Y. Agiri Mulugeta Gebregziabher Andrew D. Schreiner Kinfe G. Bishu Hermes J. Florez Richard L. Hauger Julie A. Lynch

Introduction: Previous research has suggested thiazolidinediones (TZDs) may be associated with certain solid tumors. We examined incidence rates over time for patients with solid tumors who received TZD treatment for diabetes. Methods: We identified medication use and diagnosis codes that were aggregated to phecode disease classifications derived from the nationwide Veterans Administration Health Record System from 2000 to 2021. We identified 148,139 patients who had ≥2 diabetes diagnoses and had no previous cancer diagnosis. Among these, 8981 subjects had ≥4 years of TZD exposure. We then identified subjects with ≥2 diagnosis codes for solid tumors including bladder (n = 3987), breast (n = 632), colorectal (n = 5139), esophageal (n = 482), glioma (n = 591), lung (n = 5142), melanoma (n = 1896), pancreatic (n = 726), prostate (n = 11,884), renal (n = 3145), testicular (n = 369), and thyroid (n = 513). We used multivariable Cox proportional hazards regressions to measure associations between TZD use and cancer incidence. TZD use was modeled as a time-varying covariate from the first to last prescription of TZD medication, and analyses were adjusted for age at diabetes diagnosis, self-reported race, self-reported ethnicity, sex, body mass index, and cancer site-specific polygenic risk scores. Results: Long-term (≥4 years) exposure to TZDs was significantly associated with increased risk of developing prostate cancer (HR = 1.24, p < 0.001) and decreased risk of developing lung (HR = 0.58, p < 0.001), bladder (HR = 0.51, p < 0.001), and renal cancer (HR = 0.75, p = 0.003). Conclusions: Decreased risk of developing several solid tumors (lung, bladder, and renal) indicate that TZDs may be strong candidates for drug repurposing strategies to manage these types of cancer. These results warrant replication attempts in external datasets.

Diabetology doi: 10.3390/diabetology7070126

Authors: Nadia Fehr Joan Walter Bojan Bojanic Thomas Sartoretti Moritz Schwyzer Katharina Binz Antonio G. Gennari Martin W. Huellner Michael Messerli Matthias Ernst

Background/Objectives: Patients with lymphoma are at increased risk of dysglycemia due to disease-related and treatment-associated metabolic alterations. This study aimed to characterize fasting capillary glucose patterns in patients with lymphoma undergoing routine capillary fasting blood glucose assessment before fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Materials and Methods: Consecutive patients with lymphoma undergoing clinically indicated FDG PET/CT at the University Hospital Zurich were included. Capillary fasting blood glucose (cFBG) was measured before tracer administration and categorized according to American Diabetes Association fasting glucose thresholds. Additional analyses were performed in patients examined before 11:00 AM and in patients without known diabetes mellitus. Multivariable linear regression was used to identify factors associated with cFBG. Results: The cohort included 210 consecutive patients with lymphoma (median age 64 years, IQR 48–73; 44% female, 92/210; median BMI 24 kg/m2, IQR 22–28). Known diabetes mellitus was present in 12% (25/210). Median cFBG was 104 mg/dL (IQR 95–115; 5.8 mmol/L, IQR 5.3–6.4). Overall, 64% (135/210) had cFBG values above the normal range (≥100 mg/dL; ≥5.6 mmol/L). Among patients examined before 11:00 AM, this proportion was 69% (81/117). After excluding patients with known diabetes mellitus, 60% (111/185) had cFBG values above the normal range, and 7% (13/185) had values ≥126 mg/dL (≥7.0 mmol/L). In multivariable analysis, BMI and regular exercise were independently associated with cFBG. Conclusions: Almost two-thirds of patients with lymphoma undergoing FDG PET/CT had cFBG values above the normal range, including 60% of those without known diabetes mellitus. These findings highlight the need for improved dysglycemia screening and management in lymphoma care.

Diabetology doi: 10.3390/diabetology7070125

Authors: Paloma López-Ros Aitor Gonzalez-Ibanez David Montoro-Cremades Laura Tabernero Grau Javier Marco-Lledo Vicenta Martínez-Córcoles Jonatan García-Campos

Background/Objectives: Diabetes mellitus (DM) is a group of chronic metabolic disorders characterised by persistent hyperglycaemia and an increasing global prevalence, imposing a significant socioeconomic and healthcare burden. Among its associated complications, the diabetic foot is a critical condition that doubles the risk of mortality. Although therapeutic footwear is an essential preventive strategy, research on treatment adherence has predominantly focused on quantitative parameters. This protocol aims to explore the experiences, needs, and perceived barriers of people with DM regarding therapeutic footwear use from a qualitative perspective. Methods: A qualitative focus group study will be conducted in the province of Alicante, Spain. Participants will be adults with a confirmed diagnosis of DM recruited across IWGDF foot risk categories 1–3 through purposive sampling. A total of 8–10 focus groups of 10–12 participants will be conducted in separate in-person and online modalities. Data will be analysed using reflexive thematic analysis within a constructivist epistemological framework, following the six-phase approach proposed by Braun and Clarke. The study adheres to the Consolidated Criteria for Reporting Qualitative Research (COREQ). Ethical approval will be obtained from the relevant Ethics Committee prior to data collection. Results/Expected Outcomes: The findings are anticipated to generate patient-centred, evidence-based insights into the psychosocial and experiential dimensions of therapeutic footwear adherence, informing the development of novel educational strategies and improvements in footwear design to optimise treatment adherence and clinical outcomes. Conclusions: This protocol provides a rigorous and transparent methodological framework for qualitative investigation of therapeutic footwear adherence in people with DM, contributing to a more comprehensive and person-centred approach to diabetic foot prevention.

Diabetology doi: 10.3390/diabetology7070124

Authors: Hiroaki Kataoka Masayuki Tanaka Kenichi Deguchi Kazuyuki Mori Ryota Shinomiya Fushi Higashine Takanori Kiso Shion Nagai Shinjiro Miyazaki

Background: Type 2 diabetes mellitus (T2DM) is associated with impaired skeletal muscle mass and function; however, respiratory muscle involvement has not been fully investigated, particularly in Japanese patients. This study aimed to evaluate respiratory muscle strength and identify its associated factors in Japanese patients with T2DM. Methods: This cross-sectional study included 55 patients with T2DM without respiratory disease. Maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) were measured and expressed as percentages of the predicted values (PImax %pred and PEmax %pred). Clinical variables, including age, sex, body mass index (BMI), diabetic polyneuropathy (DPN), skeletal muscle index (SMI), handgrip strength, and 6-min walk distance (6MWD), were assessed. Correlation and multiple regression analyses were performed to identify factors associated with PImax %pred. Results: PImax %pred was significantly lower than the predicted value (69.5% [95% CI: 63.1–75.9], p < 0.001), whereas PEmax %pred did not differ significantly from the predicted value (95.6% [95% CI: 86.8–104.3]). PImax %pred was significantly associated with age, BMI, SMI, handgrip strength, and 6MWD. In multiple regression analysis, age, sex, BMI, and handgrip strength were independently associated with PImax %pred, whereas DPN was not. These findings remained unchanged after adjusting for smoking habits. Conclusions: Inspiratory muscle strength was selectively reduced in Japanese patients with T2DM and was independently associated with general physical characteristics and overall muscle strength. Inspiratory muscle weakness may reflect generalized skeletal muscle dysfunction rather than solely a neuropathic impairment. This assessment of respiratory muscle strength may provide additional insights into the physical function of patients with T2DM.

Diabetology doi: 10.3390/diabetology7070123

Authors: Tokio Sanke Yuko Matsuoka Shoichi Yamada Yoshiki Kadoya

Background: Hypoglycemia has harmful effects on chronic complications of diabetes, and when it occurs at night, it is often asymptomatic. When oral hypoglycemic medications with different mechanisms of action that promote insulin secretion are used in combination in the individual with type 2 diabetes, hypoglycemia may occasionally occur. Therefore, we investigated blood glucose fluctuations with a focus on nocturnal hypoglycemia in the individuals with type 2 diabetes undergoing concomitant use of these medicines using continuous glucose monitoring (CGM) as a retrospective observational study. Methods: The participants consisted of 59 Japanese individuals with type 2 diabetes treated with a DPP-4 inhibitor and glimepiride (N = 30) or gliclazide (N = 29). Clinical factors including HbA1c were not significantly different between these groups. Blood glucose was monitored using CGM for 10 days. Hypoglycemia was defined as monitoring glucose less than 54 mg/dL for at least 15 min. Results: Asymptomatic nocturnal [from midnight to 6:00 AM (6 h)] hypoglycemia was observed more frequently in the glimepiride group (43.3%) than the gliclazide group (6.9%), p = 0.002. All hypoglycemia was unrecognized. Logistic regression analyses indicated that nocturnal hypoglycemia was significantly associated with concomitant use of a DPP-4 inhibitor and glimepiride. Conclusions: Among individuals with type 2 diabetes who had relatively good glycemic control, asymptomatic nocturnal hypoglycemia occurred more frequently in the group treated with a DPP-4 inhibitor and glimepiride than that treated with a DPP-4 inhibitor and gliclazide. Even when HbA1c levels were comparable, the use of CGM that could monitor nocturnal glucose fluctuation clearly identified this difference.

Diabetology doi: 10.3390/diabetology7070122

Authors: Michael Oraebosi Connor Baucom Ruifeng Cao

The global prevalence of type 2 diabetes continues to rise at an alarming pace, challenging existing strategies for disease prevention and management. Beyond traditional risk factors, increasing evidence indicates that glucose metabolism is temporally regulated by the body’s 24 h biological clock and oscillates based on the time of day. Disturbances of the circadian clock function are linked to impairments in glucose homeostasis and increased risk of obesity and diabetes. This review explores the intricate relationship between the circadian system and glucose homeostatic control. We begin with an introduction to the hierarchical organization of the circadian system. Next, we examine the role of the circadian clock in regulating organs and tissues that are involved in glucose metabolism, i.e., the pancreas, skeletal muscles, the liver and adipose tissue. We next review evidence that supports the involvement of circadian disturbances in the pathogenesis of diabetes. Finally, we discuss chronotherapy and its potential application in clinical intervention of diabetes. As type 2 diabetes becomes increasingly common worldwide, understanding how the body’s internal clock shapes this disease may open new and powerful opportunities for its prevention and treatment.

Diabetology doi: 10.3390/diabetology7070121

Authors: Víctor Eduardo Villalobos-Daniel Juan Espinosa-Montero Roberto Mendoza-Martinez Ruy López-Ridaura Eric Monterrubio-Flores Naiashell Agüero-Perez Dolores Ramírez-Villalobos Ismael Campos-Nonato

Background/Objectives: Type 2 diabetes (T2D) remission can be defined as a return to a HbA1c < 6.5% (<48 mmol/mol) sustained without ongoing treatment for at least 3 months. Prevalence estimates and factors associated remain unknown for LMIC and resource-limited settings. Methods: We conducted a retrospective observational analysis of electronic medical records from 8463 adults who received multidisciplinary care at Mexico’s primary care specialized units (UNEMES-EC) between 2015 and 2019 and who were referred for inadequate metabolic control. Remission was defined per 2021 ADA criteria as HbA1c <6.5% sustained for ≥3 months without glucose-lowering medications. After estimating the prevalence of T2D remission, logistic regression models were used to evaluate its sociodemographic and clinical predictors, with particular attention to weight change and baseline adiposity interactions. Results: RT2D prevalence was 0.87% (95% CI: 0.68–1.10) over a median 393-day follow-up. Weight loss ≥10% (adjusted OR 2.75; 95% CI: 1.21-6.27) and systolic blood pressure (tertile 3 vs tertile 1: OR 2.49; 95% CI: 1.17–5.26) were positively associated with RT2D, while elevated baseline HbA1c (tertile 3 vs. tertile 1: OR 0.09; 95% CI: 0.02–0.33), triglyceride levels (tertile 3 vs. tertile 1: OR 0.49; 95% CI: 0.24–0.98) and intensive pharmacotherapy were inversely associated with RT2D. No associations with HDL and total cholesterol were found. Age, sex, educational attainment, and income demonstrated no independent associations with remission. Among lifestyle-treated patients achieving ≥5% weight loss, remission prevalence reached approximately 11%. No significant interaction between baseline BMI and weight change was detected (p = 0.60). Conclusions: This first large-scale Mexican study establishes RT2D as an achievable endpoint in patients with poor baseline metabolic control. The findings suggest that remission could be achieved with equity-focused, weight-centered interventions even in resource-constrained health systems and populations.

Diabetology doi: 10.3390/diabetology7070120

Authors: Roberto Pippi Deborah Prete Michelantonio De Fano Daniela Fruttini Maurizio Caprai Maria Pia Mele Domenico Stabile Elisabetta Torlone Francesca Porcellati Giuseppe Rinonapoli Carmine Giuseppe Fanelli Efisio Puxeddu

Background: Sedentary behavior is a major modifiable risk factor for chronic metabolic disorders, particularly type 2 diabetes mellitus (T2DM). Despite recommendations promoting regular physical activity (PA), adherence remains low. DIA/01 is a multidisciplinary study designed to promote healthy lifestyles for the prevention and management of T2DM, supporting healthcare systems. Methods: A total of 123 adults with T2DM diagnosed will be enrolled at the Diabetes Center of the University Hospital of Perugia throughout 2025. Inclusion criteria are age 25–80 years, ability to walk independently, being inactive, and BMI 18.5–40 kg/m2. Exclusion criteria include severe cardiovascular, central nervous system, or musculoskeletal diseases contraindicating PA. Participants will be randomized into three groups: (1) standard care (SC); (2) SC plus theoretical PA counseling (TCPA); and (3) SC plus TCPA plus a 3-month supervised mixed exercise program. The assessment, conducted at baseline and at 6 and 12 months, includes total weekly PA (WPA) time, using IPAQ-SF and actigraphy. Moreover, glycated hemoglobin, sedentary time (ST), functional capacity, body composition, cardiometabolic risk factors, dietary adherence, perceived barriers and willingness to initiate PA, readiness to change, health-related quality of life, and sleep quality will be studied. This study is registered in the Clinical Trials Registry on 13 May 2026, with the identifier NCT07583355. Conclusions: Participants in groups (2) and (3) are expected to show greater improvements in WPA, reductions in ST, and favorable changes in metabolic and functional outcomes compared with SC. This approach may support long-term engagement in regular PA and contribute to improving the clinical management of T2DM.

Diabetology doi: 10.3390/diabetology7060119

Authors: Isabel Lavadinho Nídia Calado José Augusto Simões

Background: Type 2 Diabetes Mellitus (T2DM) is associated with a vascular-executive cognitive decline profile that early impacts complex daily tasks. Despite the increased risk of Mild Cognitive Impairment (MCI) in this population, there is a critical shortage of instruments specifically validated for this group. This scoping review aims to identify the instruments used to assess functionality in individuals with T2DM and MCI and to map their psychometric properties. Methods: We conducted a scoping review based on the JBI methodology and PRISMA-ScR guidelines. The search was performed across several electronic databases (PubMed, Cochrane Library, Web of Science, Scopus and SciELO), up to March 2026, focusing on the intersection of T2DM, mild cognitive impairment, and the psychometric properties of functional scales. Results: Our search identified only three studies meeting the eligibility criteria. The functional instruments evaluated across these publications were the ADCS-ADL scale, the A-FAQ, and a predictive nomogram including the Lawton-Brody scale. Methodological approaches, sample configurations and reported outcomes varied substantially within the included literature, with no comparative validation studies conducted among homogeneous T2DM cohorts. Conclusions: The notable scarcity and marked heterogeneity of the available literature prevent any definitive conclusions regarding the comparative diagnostic superiority of current functional scales. While gradated instruments show conceptual compatibility with the executive-vascular cognitive decline profile of T2DM, their psychometric properties remain unvalidated in this specific population. Future research should prioritize longitudinal validation designs in homogeneous diabetic cohorts to standardize screening protocols calibrated to metabolic and vascular variations.

Diabetology doi: 10.3390/diabetology7060118

Authors: Diana L. Baldenebro-Félix Alma Marlene Guadrón-Llanos Carla E. Angulo-Rojo Marco A. Valdez-Flores Claudia D. Norzagaray-Valenzuela Alberto K. De la Herrán-Arita Alexis M. Rodríguez-Rosas Loranda Calderón-Zamora Javier Magaña-Gómez

Background/Objectives: The Diabetes-Specific Dementia Risk Score (DSDRS) integrates clinical and metabolic markers to predict cognitive decline in Type 2 diabetes mellitus (T2DM), yet its association with key modifiable risk factors remains unvalidated in Latin American cohorts. This study aimed to assess the relationship between the DSDRS and clinical, biochemical, anthropometric, and neuropsychological variables in older adults with T2DM. Methods: A cross-sectional study of 291 Mexican adults aged ≥ 60 with T2DM was conducted, including assessments of cognitive function (MoCA), depression (BDI), sleep quality (AIS), and metabolic parameters. Results: Higher DSDRS correlated with lower cognitive scores, poorer sleep quality, reduced muscle mass, and smoking status. Multiple regression explained 32% of DSDRS variance, highlighting these factors as significant contributors. Conclusions: The DSDRS reflects multifactorial influences on dementia risk in older adults with T2DM and may aid early identification of individuals at increased cognitive vulnerability in this population.

Diabetology doi: 10.3390/diabetology7060117

Authors: Víctor Juan Vera-Ponce Jhosmer Ballena-Caicedo

Background/Objectives: Contemporary diabetes guidelines increasingly emphasize broader cardiometabolic risk stratification beyond glycemic control, but the national proportion of Peruvian adults with diagnosed diabetes who show obesity or hypertension is unknown. We estimated the prevalence of overweight/obesity, obesity, and hypertension; quantified the proportion meeting at least one cardiometabolic-profile criterion; and described recent acquisition of diabetes medications. Methods: We performed a cross-sectional analysis of the Peruvian Demographic and Family Health Survey (ENDES) 2022–2024. Adults aged ≥30 years with a prior medical diagnosis of diabetes were included (n = 2599; weighted population estimate = 1.51 million) from 49,363 eligible adults (weighted population estimate = 19.91 million). Survey-weighted prevalences of overweight (body mass index [BMI] ≥ 25 kg/m2), obesity (BMI ≥ 30 kg/m2), hypertension (primary definition: systolic blood pressure [SBP] ≥ 140 mmHg or diastolic blood pressure [DBP] ≥ 90 mmHg), and diabetes medication purchase in the previous 12 months were estimated. Results: Mean age was 60.0 years (95% confidence interval [CI]: 59.2–60.8), and 55.9% were women. Overall, 81.5% (95% CI: 79.2–83.7) had overweight/obesity, 41.1% (95% CI: 38.0–44.3) had obesity, and 31.8% (95% CI: 28.7–34.9) had hypertension by the primary survey definition. Among participants with complete data for obesity and hypertension (n = 2534; weighted population estimate = 1.45 million), 58.5% (95% CI: 55.4–61.6) met at least one cardiometabolic-profile criterion. Independently, 78.9% (95% CI: 76.4–81.3) reported purchasing diabetes medications, with lower proportions in rural populations and among uninsured adults. Conclusions: Nearly six in ten Peruvian adults with diagnosed diabetes had obesity or hypertension, a population-level profile consistent with substantial cardiometabolic complexity and the potential need for broader risk-oriented management beyond glucose alone. Persistent gaps in medication acquisition suggest that therapeutic modernization and equitable continuity of basic pharmacologic treatment should be addressed simultaneously.

Diabetology doi: 10.3390/diabetology7060116

Authors: Jinha Lee Hardik Sharma Geonsik Yu Zoran Obradovic Rozalina G. McCoy Daniel J. Rubin

Background/Objectives: Acute care use (ACU)—emergency department visits, inpatient hospitalizations, and observation stays—drives morbidity and costs among adults with diabetes. We developed and evaluated machine-learning models to predict 1-year ACU risk using electronic health record (EHR) data and neighborhood-level data. Methods: We performed a retrospective cohort study using de-identified EHR data from a large urban academic health center, including adults (≥18 years) with diabetes (N = 23,052). The index date was defined as one year before each patient’s last encounter, and ACU was assessed during the subsequent year. We modeled 180 predictors spanning demographics, Area Deprivation Index (ADI), prior healthcare utilization, vitals/BMI, comorbidities, medications, and laboratory results. Decision tree and gradient-boosted models (XGBoost, LightGBM, CatBoost) were tuned with Optuna using 8-fold stratified cross-validation, optimizing area under the receiver operating characteristic curve (AUC). To improve class-balanced classification performance under outcome imbalance, we selected post hoc probability thresholds that maximized Macro F1 and quantified interpretability with permutation feature importance. Results: ACU occurred in 30.53% of patients (7039/23,052). Boosted models achieved AUC ≈ 0.78, with LightGBM performing best (AUC = 0.7839). Macro F1–optimized thresholds (<0.5; typically 0.375–0.40) improved class-balanced performance versus a 0.5 cutoff. Across boosted models, prior utilization features dominated, followed by discharge-related factors and neighborhood deprivation; comorbidities and laboratory results contributed. Conclusions: In this single urban academic health-system cohort of adults with diabetes, EHRbased boosted models demonstrated moderate discrimination for predicting 1-year ACU and identified interpretable predictive signals. Threshold optimization improved class-balanced statistical performance. Prior utilization, care transitions, and neighborhood deprivation emerged as dominant predictive features. External and temporal validation are needed before broader application.

Diabetology doi: 10.3390/diabetology7060115

Authors: Monica Annemarie Selefon Claudiu Cobuz Corina Vernic Dragos Catalin Jianu Oana Milas Adrian Vlad

Background: Diabetic neuropathy (DN) is a common complication of diabetes mellitus that remains frequently undetected by conventional diagnostic methods. Sudomotor dysfunction, reflecting small-fiber impairment, has emerged as a potential early marker. SUDOSCAN, a rapid and non-invasive device measuring electrochemical skin conductance (ESC), has been proposed as a screening tool for early DN. The objective of this study was to systematically evaluate the diagnostic performance and clinical utility of SUDOSCAN in the early detection of DN. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Studies assessing SUDOSCAN-derived ESC in adults with diabetes were included. Data on diagnostic accuracy, correlations with established neuropathy measures, and clinical applicability were extracted. Where feasible, pooled sensitivity and specificity were estimated using a random-effects model. Results: Fifteen studies (n = 7343 participants) were included in the qualitative synthesis, with five of them contributing to the quantitative analysis. Reduced ESC values were consistently associated with DN, including early and asymptomatic cases. Pooled sensitivity and specificity for detecting DN were 0.81 (95% CI 0.73–0.87) and 0.73 (95% CI 0.57–0.85), respectively. ESC values correlated with neuropathy severity scores and autonomic dysfunction measures. However, substantial heterogeneity was observed due to variability in diagnostic criteria, ESC thresholds, and study populations. Conclusions: SUDOSCAN is a feasible, rapid, and non-invasive tool for detecting DN, particularly in the early-stage or small-fiber disease. It shows promise as a screening and adjunctive diagnostic modality, especially when combined with established clinical tools. Nevertheless, the lack of standardized thresholds limits its standalone use.

Diabetology doi: 10.3390/diabetology7060114

Authors: Niharika Mehta Lucia Larson

Gestational diabetes (GDM) is associated with long-term risk of diabetes and cardiovascular disease. Offspring of mothers with GDM also have elevated cardiometabolic risk in their lifetime. This article reviews risk factors that may predict progression to Type 2 or Type 1 diabetes after history of GDM, recurrence risk of GDM in a future pregnancy and discusses what evidence is available for risk mitigation in reducing long-term adverse health outcomes in both mothers with GDM and their children.

Diabetology doi: 10.3390/diabetology7060113

Authors: Miriam Longo Antonietta Maio Maria Tomasuolo Michela Di Nuzzo Daniela Forestiere Filomena Castaldo Paola Caruso Lorenzo Scappaticcio Maria Ida Maiorino Giuseppe Bellastella Katherine Esposito

Background/Objectives: Angiogenic T (Tang) cells support endothelial repair and vascular homeostasis. This cross-sectional study compared circulating Tang cell levels in young adults with T1DM vs. healthy controls, and assessed associations between Tang cells and continuous glucose monitoring (CGM) metrics. Methods: Sixty-five young adults with T1DM and 55 healthy controls were enrolled at the University of Campania “Luigi Vanvitelli,” Naples, Italy. Clinical and biochemical data were collected. Tang cells (CD3+CD31+CD184+) were quantified by flow cytometry as absolute counts and percentage of CD3+ T cells. In T1DM, CGM metrics from the preceding 14 days were analyzed, including time in range (TIR), time above range (TAR), and time below range (TBR). Results: Individuals with T1DM had higher fasting glucose and HbA1c than controls. Total CD3+ T cell counts were lower in T1DM. Tang cells were significantly reduced in T1DM both as absolute number and percentage (21% [10–31] vs. 48% [39–62]; p < 0.001). In multivariable analyses, Tang cell percentage was positively associated with TIR and inversely associated with HbA1c and TAR. Conclusions: Young adults with T1DM exhibit significantly reduced circulating Tang cells. Associations with CGM metrics support a link between real-world glucose control and endothelial vascular health.

Diabetology doi: 10.3390/diabetology7060112

Authors: Emily K. Mewborn Elizabeth A. Tolley James E. Bailey

Background/Objectives: Uncontrolled diabetes and associated comorbidities disproportionately affect African American (AA) adults. Medication adherence is key to diabetes control yet is often suboptimal, particularly among AA adults. This study examined associations between patient characteristics and adherence among AA adults with uncontrolled diabetes and compared two medication adherence instruments for predicting diabetes control. Methods: This cross-sectional analysis used baseline data from the Management of Diabetes in Everyday Life (MODEL) study, a clinical trial to improve diabetes self-care among AA adults with uncontrolled diabetes. Internal consistency of the 12-item Adherence to Medication Refills and Medications Scale for diabetes medications (ARMS-D) was evaluated by comparing its Cronbach α to the standardized Cronbach α calculated from MODEL data. Associations with variables were examined using correlations, t-tests, or ANOVA, as appropriate. Stepwise multiple regression identified predictors of diabetes control assessed by hemoglobin A1c (HbA1c). Results: Among 665 participants (mean age = 54 years, HbA1c = 10.24%; 67% female; 73% high health literacy), 75% reported perfect adherence on the Summary of Diabetes Self-Care Activities Medications Subscale (SDSCA-MS) versus 7.3% on ARMS-D. ARMS-D showed strong internal consistency (α = 0.81). Lower adherence by ARMS-D was associated with younger age, higher social complexity, and depression (all p ≤ 0.001). ARMS-D score, age, depression, and insulin, dipeptidyl peptidase 4 inhibitor, and sodium-glucose co-transporter 2 inhibitor use predicted baseline HbA1c. Conclusions: This study demonstrates that younger age, depression, and high social complexity are associated with lower medication adherence measured using the ARMS-D. Adherence gaps identified by ARMS-D may validly predict diabetes control and help guide interventions to improve diabetes care in AA adults with uncontrolled diabetes.

Diabetology doi: 10.3390/diabetology7060111

Authors: Subash Sapkota Miguel Leal Dani LaPreze Ya-Ching Huang

Background: Diabetes is the eighth-leading cause of death in the U.S. and poor blood glucose (BG) management is associated with serious long-term complications. While educational interventions have been shown to improve health outcomes among individuals with diabetes, evidence regarding the effectiveness of gamification remains inconsistent. The purpose of this study is to evaluate existing systematic reviews on the effectiveness of gamification interventions for blood glucose management among individuals with diabetes. Method: A systematic literature search was conducted using electronic databases including Medline, Embase, Cochrane library, APA PsycInfo, Web of Science, and Campbell systematic reviews. Studies published in English with gamification as the primary intervention and BG or HbA1c as primary outcomes were included in the review. Studies were excluded if they involved gestational diabetes, used gamification alongside other interventions, or were classified as gray literature. The quality of each review was assessed using a modified AMSTAR 2 tool. Results: Of 382 articles screened, eight systematic reviews were included in the final review. In the quality assessment, four reviews fulfilled 11 out of 13 (84.6%) of the critical appraisal items. All (100%) of the reviews demonstrated reduction in HbA1c; however, the reduction was statistically significant in only one review. Conclusions: Gamification shows potential in assisting with glycemic control, with reviews finding a decrease in HbA1c among patients with diabetes. More rigorous, large-scale studies need to be done to understand gamification as a method of diabetes management and long-term outcomes.

Diabetology doi: 10.3390/diabetology7060110

Authors: Ricardo E. T. Navarrete Joao Fernandes Isabel Fonseca José Luis Silvano Joao Roberto Sa La Salete Martins

Background: Kidney transplant recipients (KTRs) with diabetes mellitus (DM) are at high cardiovascular risk, and heart failure (HF) is a major concern. Dapagliflozin has proven benefits in HF, but data in KTRs are scarce. Methods: Retrospective analysis of adult KTRs with DM and HF who received dapagliflozin. Data were collected at baseline, defined as dapagliflozin initiation, and at the most recent follow-up (April 2024). Outcomes included changes in LVEF, renal function, metabolic and hemodynamic parameters, hospitalizations, and adverse events. Results: In 32 KTRs (median age 60.5 years, 66% male), after a median follow-up of 2.2 years, left ventricular ejection fraction (LVEF) did not change significantly (60% to 58%, p = 0.28). Systolic BP decreased by 5 mmHg (p < 0.001) and diastolic BP by 3 mmHg (p = 0.034). HbA1c decreased from 7.3 [6.6–8.1] to 6.8 [6.3–7.7]% (p = 0.034), while LDL-c and triglycerides decreased (p = 0.013 and p < 0.001). Body weight and BMI also decreased (both p < 0.001). Renal function, as assessed by eGFR, remained stable (p = 0.633), with no major renal safety signals. No deaths, severe hypoglycemia, or ketoacidosis occurred; urinary tract infections in 12%. Conclusions: In this exploratory cohort, dapagliflozin use was followed by stable graft function and changes in metabolic and hemodynamic parameters. No significant change in LVEF was observed. Given the observational design, small sample size, limited echocardiographic data, and absence of a control group, causal inference is not possible. These hypothesis-generating findings require confirmation in prospective controlled trials of KTRs with diabetes and heart failure.

Diabetology doi: 10.3390/diabetology7060109

Authors: Yuqing Zhang Tam Nguyen Hyeyeon Shin Shatha Al-Sabbah Lynn Warner Jing Kang Jie Hu

Background/Objectives: Family dyad-focused support plays an important role in health outcomes and has been incorporated in diabetes interventions to enhance diabetes self-management. The purpose of this meta-analysis was to examine the pooled efficacy of dyad-focused diabetes interventions on glycemic control for people with Type 2 diabetes (T2D). Methods: The PRISMA was used to guide the study. Four databases (PubMed, Embase, CINAHL, and Scopus) were searched from inception through 18 December 2025 to identify randomized controlled trials (RCTs) that tested glycemic control (A1C) of family-based diabetes interventions for people with T2D. Controlled vocabulary and key terms included “Diabetes, Mellitus, Type 2,” “type 2 diabetes,” “self-management,” “self-care,” “spouses,” “dyad,” “caregiver,” and “partner support”. Studies were excluded if they were not RCTs, contained peer-support dyads, lacked family/friend dyads, or did not measure glycemic control. Results: Nineteen eligible RCTs were included in this meta-analysis. Short-term efficacy (3–6 months) was reported in 17 studies with a total of 863 dyads; long-term efficacy (9–12+ months) was reported in 9 studies with a total of 707 dyads. Compared to the control groups, dyad-focused interventions showed a statistically significant reduction in A1C in both short-term (−0.50; 95% CI −0.72, −0.28) and long-term (−0.52; 95% CI −0.77, −0.27) measurement points (p < 0.001). The meta-analyses showed low or moderate detectable heterogeneity (I2 = 38%, 45%). The funnel plot suggested no obvious evidence of publication bias. Conclusions: Meta-analysis provided evidence on the efficacy of family dyad-focused diabetes intervention on improving glycemic control. Future large RCTs are warranted to explore innovative strategies to better incorporate family/friend dyad support in diabetes self-management.

Diabetology doi: 10.3390/diabetology7060108

Authors: Cristina-Elena Zbârcea Cristian-Daniel Marineci Andrei Văleanu Cornel Chiriță Oana-Cristina Șeremet

Background: The pharmacological management of type 2 diabetes mellitus has become increasingly complex due to expanding therapeutic options and the high prevalence of multimorbidity in affected patients. As a result, the risk of drug–drug and drug–disease interactions has grown significantly, with potential implications for glycemic control, safety, and treatment outcomes. Objective: This narrative review provides a comprehensive, class-based overview of clinically relevant interactions associated with antidiabetic medications, highlighting their mechanisms, clinical consequences, and practical management strategies. Methods: A targeted literature search was conducted using major medical databases to identify clinical studies, meta-analyses, pharmacovigilance reports, and evidence-based guidelines concerning interactions related to key antidiabetic drug classes. Interactions were categorized as pharmacokinetic, pharmacodynamic, or disease-related. Results: Significant variability exists across antidiabetic drug classes in terms of interaction profile and clinical relevance. Metformin presents interaction risks mainly through renal impairment or co-administration with drugs affecting lactate metabolism. Sulfonylureas and glinides are strongly associated with hypoglycemia-enhancing interactions. DPP-4 inhibitors generally exhibit a low interaction burden, whereas GLP-1 receptor agonists may interact through delayed gastric emptying. SGLT2 inhibitors require caution in patients with diuretics or conditions predisposing them to dehydration or ketoacidosis. Insulin remains highly sensitive to pharmacodynamic interactions with a broad spectrum of therapies. Underlying renal, hepatic, and cardiovascular conditions further modify the interaction risk. Conclusions: Understanding class-specific interaction profiles is essential for personalized and safe diabetes management. Careful medication review, close metabolic monitoring, and individualized dose adjustments can mitigate the risk of harmful interactions. Further research is needed to elucidate interactions in populations with advanced multimorbidity and polypharmacy.

Diabetology doi: 10.3390/diabetology7060107

Authors: Angela Claudia Paixão Soares de Magalhães Thatiana Lameira Maciel Amaral Maurício Teixeira Leite de Vasconcellos Gina Torres Rego Monteiro

Diabetes mellitus (DM) is increasing worldwide and places a substantial burden on health systems through its complications. Background/Objectives: To identify factors associated with DM-related complications in adults receiving primary care in Rio Branco, Acre, western Brazilian Amazon. Methods: Population-based cross-sectional study in 30 Family Health Strategy (FHS) units; 324 participants, weighted to represent 2245 adults with DM. Four binary outcomes were analyzed: self-reported stroke, electrocardiographic (ECG) abnormalities, microangiopathy, and any complication. Associations were estimated through using Poisson regression with robust variance. Results: About 72% of participants had at least one complication. Any complication was independently associated with male sex (PR = 1.23), age ≥ 60 years (PR = 1.25), hypertension (PR = 1.34), illiteracy (PR = 1.18), and ≤3 medical appointments in the previous 12 months (PR = 1.46). Distinct factors emerged for each individual outcome. Conclusions: DM complications were highly prevalent and associated with multifactorial determinants, supporting risk stratification, early detection, and targeted interventions in primary care.

Diabetology doi: 10.3390/diabetology7060106

Authors: Serpil Erşan İsmail Sarı Kürşad Ramazan Zor Esma Özmen Durmuş Ayan İsmail Abasıkeleş Ali Türker Çiftçi

Background/Objectives: Diabetic retinopathy (DR) is one of the most common microvascular complications in type 2 diabetes mellitus (T2DM), in which oxidative stress, inflammation and angiogenic pathways are associated with the development and progression beyond glycemic control. Serum trace element levels (Cu, Zn, Fe, Mg, Cr, Mn, Cd, and Se), antioxidant enzyme activities (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) were measured in patients with T2DM, with and without DR, as well as in healthy controls, and their associations with the presence and severity of DR were evaluated. Methods: 61 T2DM patients, 27 healthy controls. Patients with T2DM were classified into T2DM without DR (n = 30) and T2DM with DR (n = 31). Non-proliferative DR (NPDR, n = 19) and proliferative DR (PDR, n = 12) were classified as the T2DM with DR group. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to quantify serum trace elements. SOD and GSH-Px activities were measured using colorimetric assays. Results: Significant differences were observed in trace element levels and antioxidant enzyme activities among the study groups (p < 0.001 to 0.05). The DR subgroup had lower levels of Cr, Cu and Se compared to the T2DM without DR group; Cd, Zn and Mn were also higher in the T2DM with DR than in the T2DM without DR group. Fe levels were significantly higher in the PDR subgroup than in the T2DM without DR group (p < 0.001). The PDR group showed greater declines of Cr, Cu and GSH-Px compared to NPDR while higher values for Mn, Fe, and Zn were obtained (p < 0.001). Several biomarkers remained significantly associated with DR after adjustment for metabolic variables. Correlation analysis between trace elements, and antioxidant enzymes showed significant associations. Conclusions: Trace element imbalance, and reduced antioxidant enzyme activities may contribute to the development and progression of DR in T2DM. These findings suggest that oxidative stress and micronutrient imbalance may be linked to DR-related biochemical alterations.

Diabetology doi: 10.3390/diabetology7060105

Authors: Madalina Ioana Moisi Carmen Pantis Dorina Gabriela Dascăl Cosmin Mihai Vesa Timea Claudia Ghitea Nicolae Ovidiu Pop Roxana Daniela Brata

Background: Type 2 diabetes mellitus (T2DM) is strongly associated with atherosclerotic cardiovascular disease (ASCVD), yet the independent contribution of diabetes duration to cardiovascular burden remains incompletely understood. While prolonged disease exposure is presumed to increase vascular risk, the extent to which this association is independent of chronological aging and metabolic factors remains unclear. Methods: We conducted a real-world, cross-sectional study including 250 adults with T2DM followed in a tertiary outpatient clinic. Diabetes duration was analyzed both as a continuous variable and across four predefined strata (0–4, 5–9, 10–14, and ≥15 years). The primary outcome was the presence of a composite ASCVD endpoint. Logistic regression models were constructed in unadjusted, adjusted (age, sex, BMI, HbA1c), and extended forms including additional cardiometabolic variables. Interaction, nonlinear, and sensitivity analyses were also performed. Results: ASCVD prevalence increased numerically across duration strata (76.9%, 83.3%, 86.5%, and 93.8%, respectively), although the linear trend did not reach statistical significance (p = 0.118). In unadjusted analysis, each additional year of diabetes was associated with increased odds of ASCVD (OR 1.09; 95% CI 1.02–1.17; p = 0.012), but this association was attenuated after adjustment (OR 1.04; 95% CI 0.96–1.13; p = 0.328) and remained non-significant in extended models (OR 1.05; 95% CI 0.95–1.15; p = 0.347). Conclusions: In this high-risk clinical cohort, the association between diabetes duration and prevalent ASCVD was attenuated after multivariable adjustment, particularly after accounting for age and cardiometabolic covariates. These findings suggest substantial overlap between chronological aging, cumulative metabolic exposure, and cardiovascular burden in patients with T2DM. Due to the cross-sectional design and potential residual confounding, the results should be interpreted as hypothesis-generating.

Diabetology doi: 10.3390/diabetology7060104

Authors: Corinna Doege Jamschid Sedighi Mark Luedde Samuel Sossalla Karel Kostev

Background: Epilepsy is a frequent neurological comorbidity in type 2 diabetes. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) exert metabolic, vascular, and anti-inflammatory actions beyond glucose lowering, suggesting potential neuroprotective properties. We assessed whether SGLT2i use is associated with a reduced incidence of epilepsy compared with dipeptidyl peptidase-4 inhibitors (DPP-4i). Methods: We emulated a target trial using a retrospective observational cohort of adults with type 2 diabetes initiating SGLT2i or DPP-4i from a large real-world database. Propensity scores were estimated using a SuperLearner algorithm, and stabilized inverse probability of treatment weights were applied to balance baseline characteristics. Weighted Kaplan–Meier and Cox regression models were used to estimate hazard ratios (HRs) for incident epilepsy. Results: Among 176,728 patients (mean age 68 years; 39% women), 43% received SGLT2i. The weighted incidence of epilepsy was 2.05 versus 2.45 per 1000 person-years for SGLT2i and DPP-4i, respectively. SGLT2i treatment was associated with a significantly lower risk of epilepsy (HR 0.72, 95% CI 0.61–0.86; p < 0.001). Conclusions: In this large real-world study, initiation of SGLT2 inhibitors was associated with a lower incidence of epilepsy compared with DPP-4 inhibitors. The absolute difference in event rates was small (2.05 vs. 2.45 cases per 1000 person-years), and residual confounding cannot be excluded. These findings should therefore be regarded as hypothesis-generating and warrant prospective research to confirm causality and clarify potential mechanisms.

Diabetology doi: 10.3390/diabetology7060103

Authors: Andrea Issa Stephani Chaghoury Charbel Semaan Tatiana Youness Theresa Mazraani Rhiannon Boudeleh Ghassan Nabbout Hilda E. Ghadieh Mariam Isber Batoul Jaafar Sami Azar Nancy Nakhoul Frederic Harb

Background: The prevalence of GDM is increasing and is associated with maternal health and neonatal complications. Therapeutic intervention for this condition is important for the health of both mothers and their unborn children. Objective: The present meta-analysis evaluates the effects of pharmacological, nutritional, and physical activity interventions on maternal and neonatal outcomes in women with GDM, including glucometabolic control, weight gain, blood pressure, lipid profiles, and pregnancy complications. Methods: Multiple databases were systematically searched for studies investigating GDM interventions and their effects on maternal and neonatal outcomes, including at least one of the following endpoints: 2 h postprandial glycemia, FBG, HbA1c, triglycerides, cholesterol, weight gain, blood pressure, cesarean delivery, preeclampsia, gestational age at delivery, neonatal hypoglycemia, neonatal complications, birth weight, preterm birth, Apgar score at 5 min, macrosomia, and NICU admission. Initial screening identified 204 records, which were narrowed to 17 studies meeting the eligibility criteria for inclusion in the meta-analysis following multi-author relevance review. Six reviewers independently extracted data and resolved discrepancies through consensus. Study quality was appraised by two reviewers using the Cochrane Risk of Bias tool, and data were analyzed using the RevMan Web software with random-effects models. Results: Pharmacological, nutritional, and physical activity interventions in women with gestational diabetes mellitus demonstrated statistically significant reductions in gestational weight gain and cesarean delivery rates. No statistically significant effects were observed for HbA1c, fasting blood glucose, 2 h postprandial glucose, lipid profiles, or blood pressure. Several outcomes, including preeclampsia, neonatal hypoglycemia, neonatal complications, and NICU admission, showed non-significant trends toward benefit, but these findings were based on limited data and should be interpreted cautiously. No meaningful effects were observed for gestational age at delivery, neonatal birth weight, preterm birth, Apgar score, or macrosomia. Substantial heterogeneity was present across metabolic outcomes, limiting the interpretability of pooled estimates. Conclusions: Nutritional and physical activity interventions significantly reduce HbA1c, gestational weight gain, and cesarean delivery in women with GDM, with protective trends for preeclampsia and neonatal complications. However, effects on lipid profiles and blood pressure remain inconsistent. Personalized, multimodal strategies integrating pharmacological, nutritional, and lifestyle modifications are necessary for optimal GDM management.

Diabetology doi: 10.3390/diabetology7060102

Authors: Jeannette M. Beasley Andrea Leinberger-Jabari Emily A. Johnston Tamather Al Ameri Maryam Almarri Habiba Gaber Maheen Eatazaz Omar El Shahawy Scott E. Sherman

Background: Diabetes is a growing public health crisis across the Arab region, where rapid urbanization, dietary transitions, and physical inactivity have contributed to some of the highest diabetes rates globally. Despite a growing recognition of the problem, most diabetes prevention efforts in the region remain small-scale or insufficiently adapted to the sociocultural realities of adults living in the UAE. Evidence-based diabetes prevention strategies, such as the United States’ Centers for Disease Control Diabetes Prevention Program (DPP), reduce the risk of developing diabetes but remain underutilized. Methods: The objectives of this study were to (1) describe the systematic cultural adaptation of the Evidence-based Intervention for Diabetes Prevention (EID) using the Framework for Reporting Adaptations and Modifications–Expanded (FRAME), and (2) assess the preliminary acceptability of the adapted materials through formative focus groups. Results: Materials were culturally tailored to address both deep and surface structures. Deep structure adaptations incorporated Arab cultural values, social norms, and religious practices, including Ramadan-specific content. The original 26-session curriculum was condensed to 12 weekly sessions based on prior research and stakeholder input. Surface-level adaptations included translation into Arabic and development of culturally relevant educational videos. Three formative focus groups (n = 7 total participants) provided preliminary findings of strong acceptability of simplified, culturally relevant, and digitally supported materials. Conclusions: This work will inform the adaptation of an evidence-based lifestyle change program aimed at preventing type 2 diabetes in high-risk individuals to better meet the needs of adults living in the UAE. While some countries have created their own national diabetes prevention efforts, like the United Kingdom, there is notably no similar program in the Arab world.

Diabetology doi: 10.3390/diabetology7060101

Authors: Yuqing Zhang Suzanne G. Leveille Kimberly Berger Robert M. Cohen Tamilyn Bakas

Background: A bidirectional association between diabetes and oral health is well established, yet oral self-care is overlooked in diabetes management. Health Belief Model (HBM)-guided oral care interventions have exhibited promising outcomes in the literature but have not been used to guide oral self-care interventions designed for people with diabetes (PWD). Positioned at the early conceptualization and design stage of such a program, this developmental study was to identify self-perceived needs in oral self-care practices and to obtain preliminary feedback among PWD about the blueprint of a new program—DiaOral©. Methods: We conducted semi-structured interviews with 15 PWD recruited from a large healthcare system, with a goal to recruit patients from racially/ethnically diverse urban/suburban zip codes. Interviews explored participants’ oral self-care practices in relation to diabetes. Sample DiaOral© content and images on a blueprint were presented and feedback was solicited. Braun and Clarke’s reflexive thematic analysis was used to code and interpret transcripts, aligning emerging themes with HBM constructs through team-based consensus. Results: Three major themes and 27 sub-themes emerged: (1) lack of knowledge on optimal oral care, (2) low perceived importance of preventive care and oral health in diabetes, and (3) low self-efficacy for performing effective oral self-care. Participants expressed satisfaction with the content and their perceived confidence and interest potentially in using the DiaOral© program based on their preliminary review of the blueprint. Conclusions: Findings support the relevance of HBM constructs in shaping oral self-care among PWD. This developmental study suggests that the DiaOral© blueprint is ready to move forward to website prototype development. Future work will finalize the program and evaluate its efficacy among PWD.

Diabetology doi: 10.3390/diabetology7050100

Authors: Lily Popova Zhuhadar

Background: Pre-existing diabetes mellitus is prevalent among critically ill adults and can influence initial glycemic targets, therapeutic decisions, and early risk stratification in the intensive care unit (ICU). However, diabetes status may be distributed across heterogeneous electronic health record (EHR) sources and may be incomplete at the time of ICU admission, particularly for inter-facility transfers. Methods: Using the public WiDS Datathon 2021 tabular release derived from the Global Open-Source Severity of Illness Score (GOSSIS) initiative, we conducted a retrospective machine-learning benchmarking study for admission-time identification of documented diabetes status in ICU patients. Candidate predictors included demographics, admission characteristics, anthropometrics, day-1 physiologic and laboratory summaries, APACHE-related variables, comorbidity indicators, and site descriptors. We compared CatBoost, random forest, tuned XGBoost, tuned LightGBM, histogram-based gradient boosting, and a soft-voting ensemble combining XGBoost, LightGBM, and histogram-based gradient boosting. Because class imbalance was a central concern, the final workflow emphasized model-intrinsic class weighting and threshold-aware evaluation rather than synthetic oversampling. Results: In the primary leakage-mitigated random validation split, the voting ensemble achieved the highest overall balance, with AUROC 0.8539, precision 0.5671, recall 0.6690, and F1-score 0.6138. Tuned LightGBM was the most sensitivity-oriented individual model, achieving recall 0.7677 and AUROC 0.8537, although with lower precision and a less favorable Brier score. Ablation analyses clarified the source of this performance: removing leakage-prone and APACHE-related variables caused only modest decreases in discrimination, whereas the strict reduced model that also excluded glucose-like predictors produced a marked decline, with LightGBM AUROC falling to 0.7432 and the voting ensemble AUROC falling to 0.7448. These findings, together with SHAP analyses identifying day-1 glucose maximum, day-1 glucose minimum, BMI, age, hemoglobin, and related clinical variables as major contributors, indicate that glucose-related admission variables remained the dominant predictive signal. In grouped hospital validation, tuned LightGBM maintained recall of 0.7684 while AUROC decreased modestly to 0.8443, indicating preserved case detection under stricter site separation but reduced precision. Precision–recall analysis further showed that average precision decreased from 0.622 under random validation to 0.551 under grouped validation; at a high-sensitivity grouped-site operating point, a probability threshold of 0.4537 achieved recall of 0.8001 with precision of 0.4314. Calibration curves and Brier scores showed that predicted probabilities were imperfectly calibrated. Conclusions: Although the dominance of glucose-related predictors is clinically plausible for identifying documented diabetes status, early glycemic measurements in critically ill patients may also partly capture acute stress physiology, treatment-related effects, monitoring intensity, or other forms of acute dysglycemia rather than chronic diabetes status alone. Therefore, these findings support gradient-boosted and ensemble models as reproducible tools for ICU admission-time phenotyping of documented diabetes status, but the proposed system should be interpreted primarily as a screening-oriented phenotyping aid for chart review, cohort enrichment, or workflow support, not as a stand-alone diagnostic tool. Further external validation, recalibration, threshold selection matched to intended use, and clinical review are needed before deployment.

Diabetology doi: 10.3390/diabetology7050099

Authors: Mandy M. Shao Agatha F. Scheideman Casey Rand David C. Klonoff Juan Espinoza

The adoption of artificial intelligence (AI) tools for hospital insulin management is currently limited by data fragmentation and difficult integration into clinical workflows. This commentary examines the data infrastructure requirements for safe AI deployment in clinical settings. Device-mediated and clinician-administered dosing are the two methods by which insulin is managed in hospitals. In device-mediated dosing, glucose and insulin data often remain siloed within proprietary device ecosystems outside the electronic health record (EHR). In clinician-administered dosing, relevant data elements typically exist within the EHR but are distributed across workflows in ways that limit their usefulness for decision support. The Integration of Connected Diabetes Device Data into the Electronic Health Record (iCoDE) initiative is a standard for integrating device-generated diabetes data into clinical systems, which can lay the foundation for organizing hospital data in support of the development of trustworthy AI. A staged roadmap for hospitals building towards AI-ready insulin management infrastructure is presented along with governance requirements for trustworthy deployment. The value of iCoDE is that it helps define the conditions under which such AI can become clinically meaningful, trustworthy, and scalable.

Diabetology doi: 10.3390/diabetology7050098

Authors: Peter R. van Dijk Marije van Zanten Mireille A. Edens Frank Ardesch Arianne M. J. Elissen Jan Westerink Dirk Ruwaard Henk J. G. Bilo

Background: Obtaining reliable and detailed information about the population of individuals with diabetes mellitus (DM) in The Netherlands remains a persistent challenge. Previous studies used primary care coding and extrapolations to estimate the countrywide population of individuals with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). In this article, we present a design that aims to define and identify the population receiving treatment for DM in secondary care facilities in The Netherlands, encompassing both persons with T1DM and those with T2DM. Methods: We obtain information using reimbursement data accessible through the Vektis database, which contains information on 99.9% of the Dutch population, and combine these data with Statistics Netherlands data. The identification of subjects considered to have either T1DM or T2DM will be based on definitions derived from reimbursement details and the use of DM-associated medication (based on Anatomical Therapeutic Chemical codes) targeting both pediatric and adult populations over the years 2014–2024. Results: This combined approach will enable a more detailed characterization of the populations with DM treated in secondary care in The Netherlands using data on the total population. Ultimately, the data derived supports healthcare planning and policy making. Conclusions: This paper presents the design, search strategy and research questions related to this project.

Diabetology doi: 10.3390/diabetology7050097

Authors: Addisu Tadesse Sahile Mussie Wubshet Teka Azwihangwisi Helen Mavhandu-Mudzusi

Background: Diabetes mellitus (DM) is an emerging public health challenge in Africa, driven by rapid urbanisation, changing lifestyles and socio-economic transitions. As the global prevalence rises, evidence on the burden and determinants of DM across African countries remains fragmented and inconsistent. Objective: We aimed to synthesize evidence from existing systematic reviews and meta-analyses on the prevalence and determinants of diabetes mellitus across African populations, thereby informing targeted interventions and policy actions. Methods: This umbrella review followed the PRISMA guidelines and included systematic reviews and meta-analyses of studies, published up to December 2024, that reported on DM prevalence and/or risk factors for DM in adults across four African countries. The literature was retrieved from PubMed, Scopus, Web of Science and African Journals Online (AJOL). Quality assessment was conducted using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, version 2) tool, and only moderate- to high-quality reviews were retained. Random-effects models were used to estimate the pooled prevalence and odds ratios (ORs), while heterogeneity, publication bias and sensitivity analyses were also conducted. Findings: Seven reviews were included, covering four countries: Ethiopia, South Africa, Nigeria and Ghana. The pooled prevalence of diabetes mellitus was 9.0% (95% CI: 6.0–12.0%), with significant heterogeneity (I2 = 99.8%). Among the determinants, only family history of DM (OR:5.11, 95% CI: 2.96–8.85), hypertension (OR: 2.52; 95% CI: 1.65–3.83), obesity (OR: 3.04; 95% CI: 1.92–4.82), physical inactivity (OR: 3.32; 95% CI: 1.99–5.54), smoking (OR: 2.59; 95% CI: 1.23–5.47), unhealthy diet (OR: 4.77; 95% CI: 1.73–13.18) and urban residence (OR: 5.81; 95%CI: 4.41–7.65), showed a statistically significant association. Sensitivity analysis confirmed the robustness of pooled prevalence, and no significant publication bias was detected. Conclusions: Diabetes mellitus prevalence in Africa is rising and approaching the global averages. The heterogeneity in risk factors underscores the need for localised, context-specific strategies.

Diabetology doi: 10.3390/diabetology7050096

Authors: Aria Rabet Aminreza Khandan Arian Rabet Mohammad Dehghan Rouzi Fabiola Rodriguez Adriana Garibay David G. Armstrong Bijan Najafi

Background: Smart offloading technologies enable the real-time, objective monitoring of adherence in patients with diabetic foot ulcers (DFUs). Although remote tracking may reinforce adherence and improve wound healing, effectiveness depends on sustained device use, particularly as devices are often removed during rest periods. Real-time, behavior-contingent feedback informed by sensor data, including AI-supported messaging capable of detecting nonadherence, may enhance reinforcement. However, the feasibility and behavioral impact of such strategies remain unclear. Methods: We conducted a prospective feasibility case series nested within a larger DFU cohort of 210 participants, enrolling eight adults with active DFUs. Participants used a sensor-integrated offloading device paired with a smartwatch (SmartBoot) and a mobile application (CORA) that delivered notifications to their smartphones. Notifications were either schedule-based or context-aware, using real-time SmartBoot data to generate personalized messages. The primary outcome was a sensor-detected transition from nonadherent to adherent offloading within 60 min. Results: A total of 130 notifications were delivered, with 125 included in the behavioral response analysis. Context-aware notifications demonstrated higher transition rates than schedule-based notifications. Adaptive Reinforcement yielded the highest response rate (77.4%, 24/31), followed by Clinical Course Correction (71.4%, 20/28), whereas Safety and Technical Assurance (40.7%, 11/27) and Motivational Coaching (30.8%, 12/39) showed lower response rates. Conclusions: Real-time, context-aware feedback is feasible and associated with improved short-term adherence, supporting evaluation in larger trials.

Diabetology doi: 10.3390/diabetology7050095

Authors: Afonso Nobre João Silva Sequeira

Background: Diabetic Foot Ulcers (DFU) are a common complication of diabetes, often leading to infections, amputations and even death if left untreated. Effective management of the Diabetic Foot (DF) requires timely detection and frequent monitoring. Current DF assessment methods, by healthcare professionals, are largely based on visual inspection of feet, together with touch, temperature, and vibration sensitivity, and pedal pulse. Methods: The paper describes a machine-learning approach for the assessment of DF from feet images, combining pre-trained convolutional neural networks (CNN) with Generative AI for dataset annotation. Specifically, the GPT-4o-mini model was used to assign risk labels (Low, Medium or High Risk) to individual foot images, following a structured designed prompt for this task. The labeled dataset was used to train and evaluate two pre-trained CNN architectures, namely, ResNet50 and VGG16. Output predictions are obtained by aggregating the prediction for each of the images of a patient. Results: The results obtained show that both ResNet50 and VGG16 achieved good overall performance, with ResNet50 showing superior results. The High Risk class achieved the highest performance. The Low and Medium Risk classes also showed good performance but were prone to confusion due to the similar features of the images belonging to those classes. Conclusions: The technical contribution of the paper is a Streamlit App, available online for public use, showcases the work. The primary scientific contribution is the demonstration of how Generative AI can be used to train common CNN and automate a highly relevant healthcare process.

Diabetology doi: 10.3390/diabetology7050094

Authors: Ngai Wah Cheung Amanda Hor Simone Marschner Christopher Chan Haeri Min Lauren Lee Tien-Ming Hng Yoon Ji Jina Rhou Yu-Fang Wu Mawson Wang David R. Chipps

Background: Glucocorticoid-induced hyperglycemia is common amongst hospitalized patients. Isophane insulin has been proposed as part of the optimal insulin regimen for managing this, but there are few randomized controlled trials to support this. Our aim was to determine if the addition of a morning dose of isophane insulin would improve glycemic control amongst patients with COVID-19 who had dexamethasone-induced hyperglycemia (DIH) in hospital. Methods: Patients with diabetes admitted to hospital with COVID-19 respiratory infection and treated with dexamethasone were cluster-randomized by ward to receive either basal bolus insulin (BBI) or isophane-augmented BBI (IaBBI) in equipotent doses. Insulin commencement and titration were guided by standardized protocols. The primary outcome was overall finger-prick blood glucose (BG) levels, with predefined secondary outcomes of BGs on day 3 and the final day of admission. Results: A total of 40 patients were included, 25 in the IaBBI group and 15 in the BBI only group, for a duration of 5.4 ± 2.2 days. Both recruitment and the trial were terminated early because of a rapid decline in COVID-19 admissions. There were no differences in overall mean BG levels (IaBBI 11.9 ± 2.5 mmol/L vs. BBI 12.6 ± 2.4 mmol/L, p = 0.193) between the groups. Mean day 3 BGs were lower in the IaBBI group than in the BBI group (11.1 ± 3.5 mmol/L vs. 12.7 ± 3.5 mmol/L, p = 0.029) and on the final day (9.6 ± 2.8 mmol/L vs. 10.7 ± 2.5 mmol/L, respectively, p = 0.011). Conclusions: The restricted sample size in this study limits any conclusions that can be made regarding the effectiveness of the addition of isophane insulin to a BBI insulin regimen for diabetes patients with COVID-19 infection and DIH. However, some improvements in glycemic control were observed, suggesting that this is a glucose management strategy that warrants further evaluation.

Diabetology doi: 10.3390/diabetology7050093

Authors: Gaetano Leto Pietro Crispino Antonello Viceconti Valentina Camardo

Diabetic gastroparesis (DGp) is a chronic complication of diabetes characterized by delayed gastric emptying with nausea, vomiting, early satiety, bloating, and poor glycemic control. Diagnosis requires objective testing, preferably a 4-h gastric emptying scan, along with assessment of symptom severity and quality of life for affected patients. Diabetic gastroparesis is the result of complex and overlapping mechanisms: autonomic (vagal) neuropathy, loss/dysfunction of interstitial cells of Cajal (ICC), enteric neuropathy, pyloric dysfunction (increased pyloric tone), and altered gut–brain signaling. Chronic hyperglycemia precipitates and worsens gastric dysmotility. Management remains multimodal: optimize glycemic control and nutrition, use evidence-based prokinetics and antiemetics, and consider targeted procedural/device therapies (G-POEM, gastric electrical stimulation) for refractory cases. The present is characterized by renewed drug development (ghrelin agonists such as relamorelin, with promising efficacy but a not-yet-well-established commercial pathway) and growing evidence for selective prokinetics already in use for other indications (prucalopride). Neuromodulation (Enterra GES) remains an option for selected refractory patients. Recent guidelines and studies define when and how to use these options, but no randomized head-to-head comparisons of the various therapeutic options are yet available, nor are long-term, real-world safety/efficacy registries for drugs and minimally invasive surgical procedures. There is still unsatisfactory evidence on how to safely manage GLP-1 receptor agonist therapy in diabetic patients predisposed to gastroparesis (balancing cardiorenal glycemic benefits versus gastrointestinal adverse effects), considering that these drugs can worsen gastric emptying and symptoms, requiring careful clinical judgment. This review aims to analyze and update clinicians on new evidence in the diagnosis and treatment of these conditions, starting from earlier recognition to achieving more rational treatment that balances the need for good glycemic control, control of gastrointestinal symptoms related to these complications, and an acceptable quality of life for the diabetic patient.