Diabetology, Volume 7, Issue 9 (September 2026) – 26 articles

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article