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.

Diabetology doi: 10.3390/diabetology7050092

Authors: Andrea J. Glenn Joseph C. Larson Ellie Hsu Hind A. Beydoun Michael J. LaMonte Lisa Warsinger Martin Anna C. Rivara Jean Wactawski-Wende Thomas E. Rohan Phyllis A. Richey Aladdin H. Shadyab Lauren Hale Su Yon Jung Cassandra N. Spracklen Mace Coday Thanh-Huyen T. Vu Eric T. Hyde Simin Liu JoAnn E. Manson Lesley F. Tinker

Objective: To examine the association between Life Essential 8 (LE8) and incident T2D in the Women’s Health Initiative (WHI), and to assess whether associations varied by race and ethnicity. Research Design and Methods: Prospective cohort study of 19,403 postmenopausal women enrolled in the WHI without T2D at baseline. Data were analyzed from 1993 through 2024. The LE8 score (range, 0–100), comprising blood glucose, blood lipids, blood pressure, smoking, physical activity, diet, sleep, and body mass index (BMI), categorized as high (80–100), moderate (50–79), and low (0–49) according to AHA definitions. Incident treated T2D was self-reported during follow-up. Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs for LE8 categories and continuous scores. Results: During a mean follow-up of 16.3 years, 3921 women developed T2D. Compared with the lowest category, women in the highest LE8 category had a 57% lower risk of T2D (HR, 0.43; 95% CI, 0.38–0.49). A 20-point increase in LE8 score was associated with a 43% lower risk (HR, 0.57; 95% CI, 0.54–0.60). Among individual domains, BMI and glucose were most strongly associated with T2D. Subgroup analyses by 20-point increase in LE8 showed greater risk reduction among Hispanic/Latina women (HR, 0.46; 95% CI, 0.41–0.53) compared with non-Hispanic women (HR, 0.58; 95% CI, 0.55–0.62), but no significant association with race was observed. Conclusions: Higher LE8 scores are associated with a reduced risk of T2D in postmenopausal women, supporting LE8 as a useful framework for lifestyle-based diabetes prevention strategies.

Diabetology doi: 10.3390/diabetology7050091

Authors: Tanja Milicic Nebojsa M. Lalic Aleksandra Jotic

This review aims to present an updated, comprehensive analysis of data on the diversity and challenges of current approaches to the screening and monitoring of subjects at risk of T1D, as the earliest interventions during the course of the disease. Previously, screening for T1D was justified only for research purposes. A major turning point occurred when teplizumab, an immunomodulatory drug that delays the onset of overt T1D, was approved. Nowadays, there is a growing number of screening initiatives, and this trend is spreading fast across the world. In this context, novel recommendations emphasize the need for the wider identification of subjects at risk of T1D, suggesting that screening should not include only first-degree relatives of persons with T1D. Furthermore, current experts’ opinions have shifted the detection of T1D risk in the direction of ultimate goal-screening in the general population. Also, subjects at risk should be monitored, undergo metabolic testing, be informed about their risk, and be educated about the disease. Currently, there is a diversity in approaches to the screening and monitoring of subjects at risk of T1D, predominantly in the pediatric population. Several knowledge gaps persist in this area of investigation, especially in recommendations and potential benefits for the adult population. However, the scientific community is focusing on developing and adapting screening and monitoring strategies to suit particular countries, aiming to make them more universal while refining the definition of individual risk for T1D. Nevertheless, the screening and monitoring of subjects at risk should be the earliest interventions focused on delaying T1D.

Diabetology doi: 10.3390/diabetology7050090

Authors: Samir H. Assaad-Khalil Talaat Abdelaaty Mary N. Rizk Magdy Helmy Megallaa Mohamed Elsayed Alaa M. Wafa Azza Ismail Bahaa Sharafeldeen Noha G. Amin

Background/Objectives: Egypt ranks among the top ten countries globally with the highest burden of type 2 diabetes mellitus (T2DM), with prevalence projected to rise significantly by 2050. Despite multiple therapeutic options, glycemic control remains suboptimal due to therapeutic inertia, treatment complexity, and healthcare system limitations. Fixed-ratio combinations (FRCs) of basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer a simplified injectable strategy addressing complementary pathophysiological defects in T2DM. This study aims to develop expert consensus recommendations for the use of FRCs in Egyptian adults with T2DM, integrating international evidence with local practice. Methods: A modified Delphi technique was employed to achieve consensus among 9 diabetes experts across Egypt. Statements were formulated based on a targeted literature review and voted on using a structured Likert scale. Consensus was defined as ≥70% agreement. Results: Twenty-nine statements were endorsed with strong to very strong consensus. Recommendations covered patient selection, initiation after oral therapy or GLP-1 RA, switching from premixed or complex insulin regimens, dosing strategies, safety considerations, and intensification options. FRCs were favored for early injectable use, regimen simplification, and improved adherence, with liraglutide-based FRCs preferred for cardiovascular and renal benefits. Digital health integration was strongly recommended to enhance glycemic control and patient engagement. Conclusions: FRCs offer a simple and effective treatment simplification option for patients with uncontrolled T2DM on premix insulin, complex insulin regimens, or oral therapy. FRCs may improve glycemic control with generally favorable effects on hypoglycemia risk and body weight across many randomized and real-world studies, while reducing injection burden, simplifying the treatment regimen, and supporting patient adherence and satisfaction.

Diabetology doi: 10.3390/diabetology7050089

Authors: Alejandro Fernandez-Montero Alexander Finnemore Anne Gribble María Llavero-Valero Francisco J. Basterra-Gortari Maira Bes-Rastrollo Miguel Ángel Martínez-Gonzalez

Background: Type 2 diabetes (T2D) is a leading chronic disease worldwide. Physical activity, sedentary time and sleep are modifiable risk factors for T2D that share the same 24 h time budget. The 24 h Movement Guidelines propose an integrated approach to these daily movement behaviors. Objective: To evaluate the association between adherence to the 24 h Movement Guidelines and incident T2D in the ‘Seguimiento Universidad de Navarra’ (SUN) cohort. Methods: We included 13,321 university graduates free of diabetes at baseline (1999–2024). A 24 h movement score (0–3) was computed at baseline by awarding one point for meeting each guideline component (physical activity, sedentary behavior and sleep). Incident T2D was identified in biennial questionnaires and confirmed using additional information. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox models using age as the underlying time scale. Results: During follow-up (approximately 192,000 person-years), 141 incident T2D cases were confirmed. In multivariable models, participants meeting all three guidelines had a 53% lower risk of T2D compared with those meeting none (HR 0.47; 95% CI 0.24–0.93). Each additional guideline met was associated with a reduction in risk (HR per 1-point increase 0.81; 95% CI 0.66–0.98). Conclusions: Higher adherence to the integrated 24 h Movement Guidelines was associated with a lower incidence of T2D in this cohort.

Diabetology doi: 10.3390/diabetology7050088

Authors: João Antonio Correa Sofia Torres Velloso Luciene do Nascimento Lima Patricia Paola Cagol Julia Yamanaka Agnelo Gustavo Lolli João Paulo Tardivo Rafael Carvalho de Vilhena Furst Gabriela Tessaro Cremoneis Rodrigo Daminello Raimundo

Introduction: Type 2 diabetes mellitus predisposes patients to neuropathy, peripheral arterial disease, and diabetic foot ulcers, which may become infected and progress to osteomyelitis, increasing the risk of amputation. The growing prevalence of multidrug-resistant organisms complicates management. Photodynamic therapy (PDT), which combines a photosensitizer with light-emitting diode irradiation to generate reactive oxygen species, has emerged as a potential adjunctive antimicrobial strategy without inducing resistance. Objective: To describe clinical outcomes observed in patients with diabetic foot osteomyelitis treated with adjunctive photodynamic therapy (PDT), with emphasis on wound evolution, limb preservation, and healing time. Methods: This prospective case series included patients with osteomyelitis secondary to infected diabetic foot ulcers treated at a university hospital. Demographic and clinical data were collected from medical records. Serial photographic documentation was used to monitor wound progression and tissue response during therapy. Results: Sixteen patients with diabetic foot osteomyelitis were included. Complete healing was achieved in 13 patients (81.25%), while 2 patients (12.5%) remained under treatment with partial healing and 1 (6.25%) underwent major amputation. Among healed patients, healing time ranged from 19 to 546 days, with a median of 118 days. The number of photodynamic therapy sessions ranged from 2 to 12, depending on the clinical course of each case. Healing time varied among patients, and the hallux was the most frequent site of osteomyelitis. During follow-up, only one patient underwent major amputation, whereas the remaining patients either achieved complete healing or were still under treatment at the time of analysis. Healing time was comparable between insulin-dependent and non-insulin-dependent diabetes, although numerically shorter in the latter. Longer healing periods were associated with more treatment sessions. Conclusions: In this prospective uncontrolled case series, adjunctive PDT was associated with favorable clinical evolution in a subset of patients with diabetic foot osteomyelitis. However, because of the small sample size and the absence of a control group, these findings should be considered preliminary and hypothesis-generating.

Diabetology doi: 10.3390/diabetology7050087

Authors: Isaiah Olumeko Sai S. Cheruvu Samuel C. Ofili Susan Abughosh

Background/Objectives: Diabetes is a prevalent chronic condition and a major contributor to morbidity, mortality, and healthcare costs in the U.S., particularly among older adults with comorbidities such as hypertension and dyslipidemia. Complex medication regimens increase the risk of nonadherence, which can worsen glycemic control, cardiovascular outcomes, and healthcare utilization. This study assessed longitudinal adherence patterns to oral antidiabetic medications among high-risk older adults and identified predictors using group-based trajectory modeling (GBTM). Methods: This retrospective cohort study used 2016–2017 Texas Medicare Advantage claims. Participants were older adults with diagnoses of diabetes, hypertension, and hyperlipidemia who had continuous plan coverage throughout the study period and at least one prescription fill for an oral antidiabetic, a statin, and a renin–angiotensin system (RAS) antagonist. Adherence was measured monthly over 12 months using the proportion of days covered (PDC). GBTM identified adherence trajectories, and multinomial logistic regression, based on the Andersen Behavioral Model, evaluated predictors using perfect adherence as the reference. Results: Among 7847 patients, three trajectories were observed: perfect adherence (59.50%), near-perfect adherence (29.21%), and rapid decline (11.29%). Female sex (OR, 1.38; 95% CI, 1.19–1.60) and absence of health plan subsidy (OR, 0.79; 95% CI, 0.68–0.92) were associated with rapid decline. Female sex (OR, 1.13; 95% CI, 1.02–1.25) and age ≥ 75 years (OR, 1.20; 95% CI, 1.00–1.43) were associated with near-perfect adherence. Conclusions: Older adults with diabetes and comorbidities exhibit distinct medication adherence patterns. Trajectory-based methods can identify those at risk for declining adherence and guide interventions to improve outcomes.

Diabetology doi: 10.3390/diabetology7050086

Authors: Yamini Mallisetty Shruti Chaudhary Ashley W. Ellis Rushin Shah Satya Surbhi

Background/Objectives: To examine the association of social determinants of health (SDOHs) with primary and cost-related medication nonadherence among adults with diabetes. Methods: A retrospective cross-sectional analysis was conducted using 2021 data from the Medical Expenditure Panel Survey (MEPS), a nationally representative sample of the United States civilian noninstitutionalized population. Adults aged ≥ 18 years with a diagnosis of diabetes in 2021 were included. The outcomes include primary medication nonadherence (no antidiabetic prescriptions filled) and cost-related medication nonadherence (delaying prescriptions due to cost). The exposure variables include SDOHs such as financial stress, food insecurity, transportation barriers, social support, access to medical care in the neighborhood, and healthcare discrimination. Weighted multivariable logistic regression analyses were conducted to assess the association between SDOHs and medication nonadherence. Results: Among 21.9 million patients with diabetes, 6.5% reported cost-related nonadherence and 17.4% exhibited primary nonadherence. Difficulty paying rent or mortgage (OR 2.32, 95% CI: 1.27–4.23), food insecurity (OR 2.13, 95% CI: 1.27–3.58), and transportation barriers (OR = 2.15; 95% CI: 1.20–3.63) were significantly associated with cost-related nonadherence. In the Medicare subgroup, both difficulty paying rent or mortgage (OR = 2.41, 95% CI: 1.03–5.64) and food insecurity (OR = 2.16, 95% CI: 1.18–3.96) significantly increased cost-related nonadherence. Conclusions: Financial strain, food insecurity, and transportation barriers are associated with cost-related nonadherence. These findings suggest considering social and economic factors in strategies supporting diabetes medication adherence across populations, including Medicare beneficiaries.

Diabetology doi: 10.3390/diabetology7050084

Authors: Gui-Hwa Jeong

Diabetic kidney disease (DKD) remains a primary driver of end-stage kidney disease and cardiovascular morbidity despite the optimized use of renin–angiotensin system (RAS) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Recent evidence identifies the overactivation of the mineralocorticoid receptor (MR) as a critical, independent pathway leading to persistent renal inflammation and fibrosis. In the diabetic milieu, MR overactivation—driven by both aldosterone and ligand-independent factors such as Rac1 GTPase and oxidative stress—triggers pro-inflammatory and pro-fibrotic gene networks. Unlike traditional steroidal mineralocorticoid receptor antagonists (MRAs), the novel non-steroidal MRA finerenone exhibits a distinct binding mode that more effectively blocks the recruitment of transcriptional co-activators, thereby silencing detrimental downstream signaling in podocytes, fibroblasts, and myeloid cells. Preclinical models have demonstrated that MR blockade significantly reduces albuminuria and preserves podocyte integrity independent of systemic blood pressure. These findings translated into landmark clinical trials; the FIDELIO-DKD and FIGARO-DKD trials established that finerenone significantly reduces the risk of kidney disease progression and cardiovascular events across a broad spectrum of chronic kidney disease stages in type 2 diabetes. Furthermore, recent data from the FINEARTS-HF and CONFIDENCE trials suggest a synergetic benefit when combined with SGLT2 inhibitors, offering more robust cardiorenal protection with a manageable risk of hyperkalemia. This review synthesizes the current understanding of MR pathophysiology and clinical evidence, providing a comprehensive framework for the integration of MRAs into the evolving standard of care for patients with diabetic kidney disease.

Diabetology doi: 10.3390/diabetology7050085

Authors: Barbara Gómez-Taylor Jorge Casaña Mohedo Alma María Palau-Ferrè Rocío Práxedes Gómez Aáron Quesada Hernández Ernesto Navarro Escobar Elena Sandri Sara Morales Palomares

Background and aims: The aim of this study was to examine the relationships between muscle function, dietary quality, body composition markers, and metabolic status in ambulatory patients with type 2 diabetes. The study sought to validate low-cost tools, such as handgrip strength and waist circumference, as potential “nursing vital signs” for metabolic risk stratification. Methods: A cross-sectional observational study was conducted with adult patients with type 2 diabetes. Muscle function was assessed through handgrip strength (dynamometry) and metabolic status via the HOMA-IR index. Visceral adiposity was estimated using waist circumference and the Lipid Accumulation Product (LAP); dietary quality was evaluated with the Spanish Healthy Eating Index (IASE), and cellular health through the phase angle (PhA) obtained by electrical bioimpedance. Non-parametric tests and Spearman correlations were applied due to the non-normal distribution of the data. Conclusions: In this ambulatory diabetic population, waist circumference emerged as a practical and potent surrogate for insulin resistance burden. Although metabolic dysfunction was not directly associated with dietary quality or phase angle, a high prevalence of probable sarcopenia (36.1%) and poor dietary quality (77.8%) were detected. The implementation of non-invasive tools like waist circumference and handgrip strength in nursing consultations could optimize early risk stratification and allow for more targeted lifestyle interventions.

Diabetology doi: 10.3390/diabetology7050083

Authors: Alessio Mazzieri Livia Maria Rita Marcon

Sodium glucose-1 cotransporter (SGLT1) is a low-capacity, high-affinity glucose transporter expressed in the proximal renal tubule. It is also expressed in different human tissues and, primarily, in the brush border of the small intestine. At this level, SGLT1 inhibition results in an increase in glucose supply to the distal intestine with a reduction in intestinal pH and a consequent alteration of the intestinal microbiota. Specifically, SGLT1 inhibitors (SGLT1is) lead to an intensification of the production of short-chain fatty acids (SCFAs) and an enhancement of the incretin pathway. Potential mechanisms by which SGLT1is could reduce the occurrence of stroke and myocardial infarction may therefore involve the anti-inflammatory, anti-fibrotic and anti-atherosclerotic effects associated with an increased production of endogenous glucagon-like peptide-1 (GLP-1).

Diabetology doi: 10.3390/diabetology7050082

Authors: Sophia C. Bremer Rodrigo D. Raimundo Andrey A. Porto David M. Garner Luana P. Oliveira Caroline S. Ferrari Edilaine A. Nascimento Sandra Maria Barbalho Vitor E. Valenti

Background: We aimed to study the association between accelerometer-measured physical activity and metabolic markers of diabetes in a nationwide representative sample of U.S. adults. Methods: This cross-sectional analysis included 1259 adults aged ≥18 years from the 2003–2004 National Health and Nutrition Examination Survey (NHANES), the only cycle incorporating objective accelerometry. Physical activity was assessed using hip-worn accelerometers, with moderate-to-vigorous physical activity (MVPA) and sedentary time derived from validated count thresholds. Metabolic outcomes included fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and insulin resistance estimated by the Homeostatic Model Assessment (HOMA-IR). Survey-weighted linear regression models accounting for the complex sampling design were applied, with sequential adjustment for demographic, socioeconomic, anthropometric, and behavioral covariates. Sensitivity analyses tested alternative MVPA thresholds and wear-time criteria. Results: In unadjusted models, higher MVPA was inversely linked with fasting glucose and insulin concentrations; but, these associations were attenuated after full multivariable adjustment. In contrast, MVPA established a constant inverse association with insulin resistance. Higher MVPA was connected with lower HOMA-IR values, and this relationship remained statistically significant in fully adjusted models and across all sensitivity analyses (all p < 0.001). Associations between sedentary time and metabolic markers were non-sustainable after multivariable adjustment. No significant effect modification by sex was detected. Conclusions: Objectively measured moderate-to-vigorous physical activity is independently linked with lower insulin resistance in U.S. adults. These results emphasize the value of accelerometer-based assessments for identifying early metabolic risk and reinforce physical activity promotion as a key strategy for improving insulin sensitivity.

Diabetology doi: 10.3390/diabetology7040081

Authors: Valery M. Dembitsky Alexander O. Terent’ev

Plants of the genus Salacia (Celastraceae) have long been used in traditional medical systems of South and Southeast Asia for the management of diabetes and related metabolic disorders. Modern phytochemical and pharmacological studies have confirmed the antidiabetic potential of several Salacia species, leading to the identification of a distinctive group of sulfur-containing sugars as their principal bioactive constituents. Salacinol, neosalacinol, kotalanol, neokotalanol, and related analogues represent a novel class of thiosugar sulfonium compounds that act as potent and selective α-glucosidase inhibitors, providing a clear mechanistic basis for their glucose-lowering effects. Simpler thiosugars, such as 5-thiomannose, further contribute to the overall metabolic activity of Salacia extracts and may serve as biosynthetic or functional precursors. Beyond Salacia, sulfur-containing natural products are widespread in nature and perform diverse biological roles. In particular, the genus Allium is well known for producing organosulfur compounds, including thioethers and polysulfides, which exhibit antidiabetic, hypolipidemic, antioxidant, and cardioprotective activities. In a different context, sulfur-containing hopanes have been identified in sediments and petroleum as products of early diagenetic sulfurization of bacterial hopanoids. Although these compounds have been studied primarily as geochemical biomarkers, recent QSAR/PASS analyses suggest that sulfur hopanes may also possess biologically relevant activities, particularly related to metabolic and cardiovascular regulation. Recent PASS-based QSAR evaluations of Salacia-derived thiosugars and sulfur hopanes predict significant antidiabetic activity, including potential type 2 diabetes-related pharmacological effects, supported by predicted α-glucosidase inhibitory, hypoglycemic, hepatic, and gastrointestinal activities. Collectively, these findings highlight sulfur-containing natural products from both plant and sedimentary sources as chemically diverse yet functionally convergent scaffolds with promising potential for the development of functional foods and therapeutic agents targeting metabolic disorders.

Diabetology doi: 10.3390/diabetology7040080

Authors: Madeline Long Dayna A. Johnson Youjeong Kang Stephanie Alisha Griggs

Background/Objectives: Sleep is critical for young adults, particularly those with type 1 diabetes (T1D), who face unique challenges in achieving recommended sleep and diabetes health targets. The purpose of this study guided by the theoretical framework of self-regulation theory is to explore how these individuals navigate self-regulatory processes in their sleep behaviors through mechanisms of self-monitoring, self-judgment, and self-evaluation. Methods: A qualitative descriptive design was implemented using semi-structured interviews with 34 young adults (ages 18–30) living with T1D. Data were collected through focused interviews, sleep diaries, actigraphy, and continuous glucose monitoring, followed by thematic analysis to identify sleep behavior self-regulation patterns. Results: Three primary themes were identified: (1) Sleep Behavior Self-Monitoring—highlighting participants’ awareness of their sleep habits and the diabetes-related impacts on these habits; (2) Sleep Behavior Self-Judgment—reflecting how personal and societal standards inform their evaluation of sleep health; (3) Sleep Behavior Self-Evaluation—showing emotional responses associated with sleep out-comes, where good sleep led to positive feelings and motivation, while poor sleep resulted in frustration. Conclusions: Understanding sleep behavior self-regulation among young adults with T1D is crucial for improving sleep health and diabetes management. Targeted interventions incorporating sleep education and self-regulatory strategies may enhance both perceived sleep quality and overall well-being in this population.

Diabetology doi: 10.3390/diabetology7040079

Authors: Jason McIntire Hope Oyeyemi Michelle L. Harrison Suchit Chidurala Richard K. McCuller Milena Samora Yu Huo Ann-Katrin Grotle Audrey J. Stone Kimber L. Stanhope Peter J. Havel Rhonda D. Prisby

Background: In type 2 diabetes mellitus (T2DM), bone and microvascular complications may be linked. Methods: The University of California Davis (UCD) polygenic T2DM and Sprague Dawley healthy control (CTL) rats (N = 48) were divided equally into diabetic and age-matched groups: (1) pre-diabetes, (2) diabetes onset, (3) early-stage T2DM, and (4) late-stage T2DM. Body mass, HbA1c, fasted blood glucose and femoral and tibial lengths were measured. Bones were scanned (μCT; 15 µm) to assess trabecular microarchitecture and density and mid-shaft cortical thickness (Ct.Th, µm), density and porosity. Ossified vessel volume (OsVV, %) and thickness (OsV.Th, µm) were also analyzed. A GLM determined significance at p < 0.05. Body mass and HbA1c were higher (p < 0.05) in all T2DM groups and blood glucose became elevated (p < 0.05) in early-stage T2DM and late-stage T2DM. Results: Tibiae and femora were longer (p < 0.05) with diabetes. Tibial bone volume was lower (p < 0.05) in pre-diabetes (4 ± 1% vs. CTL, 9 ± 2%) and late-stage T2DM (5 ± 2% vs. CTL, 8 ± 2%), and femoral bone volume was lower (p < 0.05) in pre-diabetes (7 ± 1% vs. 12 ± 4%). Cortical density (tibia) was lower (p < 0.05) in pre-diabetes and early-stage T2DM. Trabecular density in the femur was lower (p < 0.05) in all T2DM groups and cortical density was reduced (p < 0.05) in pre-diabetes, diabetes onset, and late-stage T2DM. OsVV in both bones were lower (p < 0.05) during early-stage T2DM. Tibial OsV.Th was higher (p < 0.05) in pre-diabetes (69 ± 14 µm vs. CTL, 56 ± 13 µm) and late-stage T2DM (80 ± 10 µm vs. CTL, 59 ± 13 µm) and higher (p < 0.05) in the femur at diabetes onset (58 ± 14 µm vs. CTL, 40 ± 10 µm). Conclusions: Trabecular and cortical bone varied as diabetes progressed, and the thicker ossified vessels may represent microangiopathy.

Diabetology doi: 10.3390/diabetology7040078

Authors: Bernard Kordas Wojciech Matuszewski Robert Modzelewski Jarosław Szuszkiewicz Michał Załęcki Joanna Wojtkiewicz Judyta Juranek

Background/Objectives: Diabetic small fiber neuropathy and related sensory and epidermal problems affect up to 70% of all patients with diabetes. Long-term hyperglycemia disrupts cytoskeletal organization and axonal transport; however, molecular changes within human diabetic epidermis remain understudied. Diaph1 and its cytoskeletal ligands, including β-Actin and Profilin, are key regulators of cytoskeletal dynamics and may be associated with diabetes-related alterations in skin structure and innervation. Methods: Sixteen patients with type 2 diabetes, aged 43.3 ± 9.6 years (disease duration 18.9 ± 8.7 years), and twelve non-diabetic controls, aged 43.9 ± 8.9 years, were enrolled in the study. All participants provided informed consent. Skin punch biopsies were obtained under local anesthesia and processed for staining of PGP 9.5, Diaph1, β-Actin, and Profilin. Quantitative image analysis was performed to assess stained area fraction, signal intensity, and intraepidermal nerve fiber density. Statistical comparisons and Spearman’s rank correlation analyses were used to evaluate group differences and associations between staining parameters. Results: Diabetic skin samples exhibited a significant reduction in PGP 9.5-positive intraepidermal nerve fibers, indicating reduced cutaneous innervation. In contrast, Diaph1 and Profilin showed broader and more diffuse epidermal staining, while β-Actin displayed altered staining patterns and intensity. Significant correlations between Diaph1- and β-Actin-related staining measures indicated an association consistent with altered cytoskeletal organization under chronic hyperglycemic conditions. Conclusions: Long-standing type 2 diabetes was associated with reduced PGP 9.5-positive intraepidermal nerve fibers, together with altered epidermal staining patterns of Diaph1, Profilin and β-Actin. These findings indicate coexisting cutaneous denervation and cytoskeletal alterations in diabetic skin.

Diabetology doi: 10.3390/diabetology7040077

Authors: Miriam Hernández-López Rafael Ramírez-Carracedo Mónica Grande-Alonso Alba Sebastián-Martín Rafael Moreno-Gómez-Toledano

Background: The interplay between vitamin D deficiency, obesity, and depressive symptoms in type 2 diabetes remains poorly understood. Potential sex-specific differences in these associations have not been fully explored. Methods: We conducted a cross-sectional analysis of patients with type 2 diabetes (N = 917) from the NHANES 2017–2018 cycle. Restricted cubic spline models were used to assess potential non-linear associations between serum 25-hydroxyvitamin D3 and PHQ-9 depression scores. Regression-based mediation analysis was performed to estimate total, direct, and indirect associations, with body mass index (BMI) considered as a potential mediator. Models were adjusted for relevant demographic and cardiometabolic covariates. Results: In the overall diabetic cohort, higher vitamin D levels were modestly associated with lower depressive symptom scores. Mediation analysis suggested that this association was statistically accounted for by BMI. In sex-stratified analyses, significant total and indirect associations were observed among men, with a remaining direct association after adjustment for BMI, whereas no statistically significant associations were detected among women. Formal interaction testing supported differential association patterns by sex. Conclusions: Among adults with type 2 diabetes, serum vitamin D levels were inversely associated with depressive symptoms, with evidence suggesting sex-specific association patterns. These findings warrant further investigation in prospective studies to clarify potential underlying mechanisms and clinical implications.

Diabetology doi: 10.3390/diabetology7040076

Authors: Shah Tanzen Jahan Durga H. Kutal Anicha Akter Md. Selim Reza Md. Kabirul Islam Md. Monimul Huq

Background: Diabetic foot ulcer (DFU) is a major complication of type 2 diabetes (T2D), frequently resulting in disability, lower-limb amputation, and substantial healthcare burden. Early identification of patients at high risk of progressing to severe DFU is essential for timely intervention, yet evidence on associated risk factors remains limited in Bangladesh. This study aims to identify demographic, clinical, and behavioral predictors of severe DFU to support early management strategies. Methods: A cross-sectional study was conducted among 159 DFU patients attending the Rajshahi Diabetic Association General Hospital, Bangladesh. Data on demographic characteristics, clinical variables, and behavioral factors were obtained through structured questionnaires and standardized examinations. Severe DFU was defined as Wagner grades 3–5, while grades 0–2 were considered non-severe. Firth’s penalized logistic regression was used to identify determinants of severe DFU. Model performance was assessed using ROC analysis, calibration belt analysis, and decision curve analysis (DCA). Results: Among the 159 participants, 101 (63.5%) presented with severe DFU. Patients with severe DFU had significantly higher BMI (26.1 vs. 23.7 kg/m2), treatment costs (50,000 vs. 20,000 BDT), and were older (57 vs. 54 years). Severe DFU was also associated with higher prevalence of peripheral arterial disease (PAD) (29.7% vs. 3.4%), prior amputation (31.7% vs. 3.4%), peripheral neuropathy (PN) (86.1% vs. 58.6%), and poor glycemic control (71.3% vs. 30.7%) (all p < 0.05). Firth’s regression identified older age (aOR 1.08), poor glycemic control (aOR 3.90), PN (aOR 3.41), PAD (aOR 7.54), and previous amputation (aOR 13.67) as independent predictors of severe DFU. Conclusions: Older age, uncontrolled glycemia, PN, PAD, and prior amputation were significantly associated with severe stages of DFU. Early detection and targeted management of these factors are critical to reducing complications and lowering the healthcare burden.

Diabetology doi: 10.3390/diabetology7040075

Authors: Kristen Masada Daniel Nguyen Madhu Varma

Background/Objectives: Patients with poor sleep are at high risk of developing type II diabetes mellitus (T2DM). Since T2DM is linked to increased risk of obstructive sleep apnea (OSA), and Metformin is commonly used to treat T2DM, we examined how Metformin affects sleep stages in patients with concurrent T2DM and OSA-related symptoms of snoring and fatigue. Patients with T2DM on Metformin progressively develop increased insulin resistance associated with sleep disturbances and poor glycemic control. We therefore explored sleep pattern changes in patients with OSA symptoms and T2DM on Metformin, with a special focus on whether Metformin affects sleep architecture. Methods: Polysomnogram (PSG) data from patients with T2DM on Metformin was evaluated along with data on age, body-mass index (BMI), and biological sex. Data analysis included mean ± standard deviation, t-test with p < 0.05 taken as significant, and linear regression. Results: Patients with a BMI of less than 30 (non-obese) and taking Metformin exhibited a significantly shorter rapid eye movement sleep stage (REM) duration than patients on alternative therapies (p = 0.036). No such difference in REM was found for patients with a BMI of 30 or greater (obese) taking Metformin. While there was also no significant difference in slow-wave sleep stage (N3) duration with Metformin use, linear regression identified a moderate negative correlation between N3 and age in patients taking non-Metformin therapies (R2 = 0.4555). No significant correlations between sleep stage duration and patient sex, smoking status, or BMI greater than 30 were identified. Conclusions: Overall, patients with OSA and T2DM on Metformin had lower mean quantities of N3, and REM sleep compared to those not on Metformin. Non-obese patients with T2DM and OSA being treated with Metformin were observed to have less REM sleep, regardless of sex or smoking history. N3 and REM sleep are needed for the timely secretion of growth hormone and memory consolidation. Since Metformin is correlated with differences in N3 and REM sleep, it may contribute to the development of insulin resistance. Future studies are needed to explore potential causes for this relationship and how it may affect the treatment of T2DM.

Diabetology doi: 10.3390/diabetology7040074

Authors: Kohei Ueda Rie Saito Akiko Matsunaga Takayuki Sonoda Misako Kawaguchi Saori Kaeriyama Satsuki Sato Yasuo Zenimaru Masamichi Ikawa Norio Harada

Background/Objectives: Diabetes threatens independent living among elderly individuals. However, the effects of glycemic management on the severity of functional impairment are unclear. This study aimed to elucidate the relationship between glycemic management and functional impairment severity in elderly individuals with type 2 diabetes (T2D). Methods: We used data from the Japanese National Health Insurance Database from 2017 to 2024. The database included 11,411 elderly individuals (≥65 years) with Long-Term Care Insurance evaluations. Functional status was classified into three categories based on independence—Group A (non-mild impairment), Group B (moderate impairment), and Group C (severe impairment). The factors associated with the severity of functional impairment in patients with T2D were elucidated. Results: The severity of functional impairment was significantly greater in patients with T2D than in those without T2D. In participants with T2D, low glycated hemoglobin (HbA1c) levels were associated with the severity of functional impairment (odds ratio [OR]: 0.78; p < 0.001). In contrast, the use of antidiabetic drugs that could induce severe hypoglycemia (high-risk drugs) was positively associated with the severity of functional impairment (Group A vs. B/C: OR: 1.42; p < 0.001; Group C vs. A/B: OR: 1.90; p < 0.001). The frequency of high-risk drug use increased as functional impairment increased. Conclusions: The use of high-risk drugs is associated with the severity of functional impairment in elderly individuals with T2D. Elucidating the factors associated with the severity of functional impairment in elderly individuals with T2D may contribute to maintaining their quality of life and reducing the economic burden on healthcare and long-term care systems.

Diabetology doi: 10.3390/diabetology7040073

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

Background: Adipose tissue grafting is a regenerative medicine approach based on the use of autologous adipose tissue showing significant potential for the treatment of diabetic foot lesions. In subjects with diabetes, impaired wound healing, peripheral neuropathy, and vascular insufficiency contribute to the development of chronic ulcers and osteomyelitis, complicating traditional treatment strategies. Materials and Methods: We conducted a retrospective analysis of our center’s database, including all subjects treated for chronic diabetic foot ulcers who underwent adipose grafting with a follow-up of at least six months. For the control group, we included patients who received artificial dermis grafts rather than adipose grafts. Results: We identified 45 patients in the adipose group and 39 in the control group. Baseline characteristics were similar between the two groups for: mean age, diabetes duration, creatinine level, HbA1c, peripheral neuropathy, peripheral vascular disease and osteomyelitis. Coronary artery disease was prevalent in the control group. Wound location demonstrates a prevalent heel involvement for the adipose group. No patients experienced severe complications due to adipose graft: four patients (9%) developed a hematoma at the adipose tissue harvesting site, which was resolved spontaneously. At a mean follow-up of 12 ± 5 months, 30 (67%) patients achieved healing with a mean healing time of 202 ± 82 days, without requiring further surgical interventions. The control group achieved 51% of healing (p = 0.04), with a mean healing time longer than in the adipose graft group: 275 ± 132 days (p = 0.02). Moreover adipose graft permitted the best performance in rearfoot lesions. Conclusions: Adipose grafting is a safe and minimally invasive procedure with no major adverse events. Our data demonstrate its efficacy in promoting healing, even in chronic lesions with osteomyelitis and those located on the heel. Efficacy was found to be superior to that of the artificial dermis graft group.

Diabetology doi: 10.3390/diabetology7040072

Authors: Albion Luzha Michael Y. Henein Guxim Bytyçi Rina Tafarshiku Gani Bajraktari Venera Berisha-Muharremi

Atherosclerosis, manifesting as acute myocardial infarction, stroke and peripheral artery disease, is the main cause of death worldwide. Conventional risk factors contributing to the development and progression of atherosclerosis are well established, including diabetes mellitus, hypertension, hypercholesterolemia, smoking and obesity. In recent decades, other lipid molecules have been identified as risk factors for atherosclerosis and arterial calcification, including lipoprotein (a) and apolipoproteins. Despite the available evidence for the association between those biomarkers and atherosclerosis in the general population, their impact on diabetic patients is incompletely characterized. This review aims to summarize the current evidence on the relationship between lipoprotein (a), apolipoproteins and atherosclerotic cardiovascular disease in diabetic patients. By integrating genetic, epidemiological, and mechanistic data, this review highlights the dual and context-dependent associations of lipoprotein (a) with incident type 2 diabetes and atherosclerotic cardiovascular risk, supporting more nuanced interpretation of Lp(a) in diabetes-related risk assessment.

Diabetology doi: 10.3390/diabetology7040071

Authors: Victoria Tsvetkova Malvina Todorova Milena Atanasova Irena Gencheva Katya Todorova

Aims/hypothesis: Hypoxia and oxidative stress have been implicated in both metabolic syndrome and COVID-19-associated dysglycaemia, yet it remains unclear whether shared or distinct mechanisms underlie β-cell dysfunction across these conditions. We investigated hypoxia- and oxidative stress-related pathways in relation to β-cell function during acute COVID-19, post-COVID metabolic states, and COVID-negative metabolic syndrome. Methods: In this prospective observational study, 100 adults were stratified into three groups: active COVID-19 (n = 32), post-COVID with newly diagnosed carbohydrate metabolism disorders (n = 35), and COVID-negative individuals with metabolic syndrome (n = 33). Circulating markers of hypoxia (HIF-1α), oxidative stress (8-epi-prostaglandin F2α), and antioxidant response (NFE2L2) were measured alongside α- and β-cell functional markers, including C-peptide, proinsulin, glucagon, and derived indices of β-cell processing and secretory efficiency. Non-parametric statistical analyses were applied. Results: Circulating HIF-1α levels differed significantly across study groups (p < 0.001), with the highest concentrations observed during active COVID-19, intermediate levels in COVID-negative individuals with metabolic syndrome, and the lowest levels in the post-COVID group. In contrast, oxidative stress, assessed by 8-epi-prostaglandin F2α, differed significantly across groups (p < 0.001), increasing from acute COVID-19 to post-COVID and reaching the highest levels in metabolic syndrome; however, the difference between the post-COVID and metabolic syndrome groups did not remain significant after correction for multiple testing. NFE2L2 concentrations did not differ significantly between groups. Marked β-cell dysfunction was observed predominantly in COVID-negative individuals with metabolic syndrome, characterized by reduced C-peptide levels, elevated glucagon concentrations, increased proinsulin/C-peptide ratios, and reduced C-peptide/glucose ratios (all overall group comparisons p < 0.001). In contrast, β-cell secretory indices were relatively preserved during acute and post-COVID states despite pronounced alterations in hypoxia and oxidative stress markers. Conclusions/interpretation: Hypoxia- and oxidative stress-related pathways exhibit distinct, context-dependent patterns across acute COVID-19, post-COVID dysglycaemia, and metabolic syndrome. Acute COVID-19 is characterized by pronounced hypoxia signalling with relative preservation of β-cell function, whereas chronic metabolic syndrome is associated with sustained oxidative stress and impaired β-cell processing and secretory efficiency. These findings suggest that diabetes-related β-cell dysfunction is more closely associated with chronic oxidative and metabolic stress than with transient infection-related hypoxia during SARS-CoV-2 infection.

Diabetology doi: 10.3390/diabetology7040070

Authors: Sicco A. Bus Jaap J. van Netten Diekje R. Schouten Marcel G. W. Dijkgraaf

Background: Custom-made footwear that improves offloading using in-shoe pressure-guided techniques, when worn as recommended, reduces the risk of diabetic foot ulcer recurrence. We aimed to assess the cost-effectiveness of this approach, as it requires extra investments in equipment and personnel, and implementation is not yet widespread. Methods: We conducted an economic evaluation using data from the DIAFOS RCT that randomized 171 participants at high ulcer risk to either pressure-guided-offloading-improved (intervention) or non-pressure-guided (usual care) custom-made footwear. The clinical outcome was the 18-month ulcer recurrence incidence, available from the RCT. Costs were modeled from a partial healthcare perspective using bottom-up unit cost calculation, with ulcer treatment costs obtained from reference data. Univariable regression analyses were executed to obtain incremental cost-effectiveness ratios (ICERs). Bootstrapping techniques accounted for uncertainty. Results: For the intervention, costs for ulcer recurrence were non-significantly lower (€−436; 95% CI: €−1434; €563) than for usual care. The ICER was €−8124 (i.e., costs saved to prevent one extra participant from having an ulcer), and the maximum probability for cost-effectiveness was 0.81. In the subgroup of participants who were adherent to wearing their prescribed footwear, costs for the intervention were non-significantly lower at €−1170 (95% CI: €−2595; €254), with ICER of €−5317, and a maximum probability for cost-effectiveness of 0.94. Conclusions: The use of in-shoe pressure-guided-offloading-improved custom-made footwear to help prevent diabetic foot ulcer recurrence is cost-effective with high probability when ulcer treatment costs are considered. Probability further increases when users adhere to their footwear. Future economic analyses should consider a full healthcare and societal perspective and use prospectively collected data on ulcer treatment costs.

Diabetology doi: 10.3390/diabetology7040069

Authors: Sol Tejeda-Ramírez José Luis Lázaro-Martínez Esther García-Morales Sara García-Oreja Laura Palacios-Abril Aroa Tardáguila-García

Aims: To evaluate the effectiveness of preventive educational interventions in individuals with diabetic foot syndrome (DFS) and to summarise current evidence on knowledge, self-care and health-education strategies related to this complication. Materials and methods: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Risk of bias was evaluated using the Cochrane Handbook recommendations. Analyses were performed with Review Manager v5.4.1. Results: Educational interventions produced a significant improvement in patient knowledge and self-care practices compared with usual care. Despite some heterogeneity across studies, the overall effect favoured structured education as a preventive strategy for DFS-related complications. Conclusions: Preventive educational interventions enhance knowledge and self-care among individuals with DFS. Implementing structured education programs may help reduce complications and improve clinical outcomes.

Diabetology doi: 10.3390/diabetology7040068

Authors: Ramona M. Tecucianu Sorin Tunaru Stefana M. Petrescu

G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and are critical regulators of β-cell physiology. Nearly 300 GPCRs are expressed in human islets, where they integrate metabolic, hormonal, neuronal, and inflammatory cues to control insulin secretion, proliferation, and survival. Altered GPCR signaling contributes to β-cell dysfunction and the pathogenesis of both type 1 and type 2 diabetes. This review provides an overview of GPCR functions in β-cell biology, highlighting receptors that stimulate or inhibit glucose-stimulated insulin secretion, as well as those influencing β-cell fate. We also examine GPCR biosynthesis, trafficking, and subcellular localization—processes that shape receptor availability and signaling specificity. Aberrant folding, retention, or misrouting of GPCRs can disrupt β-cell function and contribute to metabolic disease. Thus, beyond receptor pharmacology, understanding the molecular mechanisms governing GPCR biogenesis and spatial distribution is essential for designing targeted strategies to preserve β-cell function and improve glucose homeostasis.

Diabetology doi: 10.3390/diabetology7040067

Authors: Lenka Nemcová Janka Kubincová Mária Chomová Katarína Orešanská Monika Ďurfinová

Background/Objectives: Altered lipid metabolism is a key feature of type 2 diabetes mellitus (T2DM), yet its impact on early spinal cord involvement remains poorly understood. Distinguishing between pathological lipid accumulation and adaptive metabolic responses is essential for interpreting initial stages of neural alteration in T2DM. This study aimed to characterize spinal cord lipid composition and ATPase activities in a rat model of T2DM. Methods: Zucker diabetic fatty (ZDF) rats were used as a model of T2DM and divided into diabetic and obese groups, with lean Zucker rats as controls. ATPase activities in spinal cord tissue were measured spectrophotometrically, and lipid profiling was performed using gas chromatography with flame-ionization detection. Indices of stearoyl-CoA desaturase-1 (SCD1) and delta-5 desaturase activity (D5D) were calculated from specific fatty acid ratios as estimates of enzyme-related activity. Results: Diabetic rats exhibited significantly higher levels of free monounsaturated fatty acids (MUFAs) compared with controls, while the obese group showed a moderate increase. Elevated SCD1 indices were indicative of increased estimated MUFA synthesis. Levels of free polyunsaturated fatty acids (PUFAs), including those crucial for myelin stability, as well as ATPase activities, remained unchanged, suggesting preserved basal membrane-associated enzyme function. Conclusions: This study identifies lipid alterations in the spinal cord preceding overt neurodegenerative changes in T2DM, characterized by increased free MUFA abundance, without evidence of altered ATPase activities. These findings support the interpretation that lipid changes observed at this stage are more consistent with adaptive metabolic remodeling than with overt structural or functional neural impairment.

Diabetology doi: 10.3390/diabetology7040066

Authors: María Alicia Mejía-Blanquel Ricardo Castrejón-Salgado Miguel Trujillo-Martínez María G. Ortiz-López Gabriela Monserrat Huitzil-Juárez Marco Antonio León-Mazón Edith Araceli Cano-Estrada José Ángel Hernández-Mariano

Background/Objectives: Previous evidence suggests that psychosocial factors may play an important role in shaping medication adherence among individuals with chronic diseases; however, the relationship between adaptive coping and medication adherence in adults with type 2 diabetes (T2D) remains inconsistent, and evidence from low- and middle-income settings, including Mexico, is limited. Given the high burden of T2D and the persistently high prevalence of medication non-adherence in this population, understanding potentially modifiable psychosocial determinants is particularly relevant. Hence, we aimed to evaluate the association between adaptive coping and medication adherence among Mexican adults with T2D. Methods: We conducted an analytical cross-sectional study among 564 adults attending two primary care health centers in Hidalgo, Mexico. Adaptive coping was assessed using the Coping and Adaptation Processing Scale, and medication adherence was measured with the four-item Morisky–Green–Levine Medication Adherence Scale. Associations of interest were evaluated using Poisson regression models to estimate prevalence ratios and 95% confidence intervals, adjusting for confounders. Results: The prevalence of medication non-adherence was 81.4%. Each 20-point increase in adaptive coping was associated with a 4.8% lower prevalence of non-adherence in adjusted models (PR = 0.95; 95% CI: 0.92–0.98), with no significant effect modification by sex or educational level. Conclusions: Lower adaptive coping was associated with a higher prevalence of medication non-adherence in adults with T2D. These findings contribute to the literature describing psychosocial factors in the context of diabetes care and situate coping among the psychosocial characteristics reported in individuals managing type 2 diabetes in primary care settings.

Diabetology doi: 10.3390/diabetology7040065

Authors: Carmen Alba-Linero José Coín Ruiz Marta Mérida Luque Javier Espíldora-Hernández Mario Gutiérrez Bedmar

Objectives: The aim of this study was to analyze the association between cardiovascular risk factors such as glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), hypertension, overweight, and smoking and longitudinal anatomical and functional changes in diabetic macular edema (DME) during intravitreal therapy. Materials and Methods: This is a retrospective, observational, descriptive study conducted on a sample of 318 patients with DME associated with some degree of diabetic retinopathy (DR). They were treated with aflibercept, ranibizumab, and/or dexamethasone, assessing anatomical and functional outcomes through visual acuity, retinal thickness, and macular volume. Simultaneously, serum HbA1c and LDL-C levels, blood pressure, body mass index (BMI) and tobacco use were measured at baseline, 6, and 12 months to determine their association with treatment response using linear mixed models. Results: Of the variables analyzed in this study, HbA1c and degree of retinopathy were significantly associated with greater retinal thickness over time. Likewise, we found that, compared with aflibercept, dexamethasone intravitreal treatment was associated with greater retinal thickness over time. Concerning visual acuity, we found an inverse relationship with age, tobacco use and degree of retinopathy. Associations between outcomes and the initial intravitreal agent were observed; however, these findings should be interpreted cautiously. Conclusions: This study was consistent with previous research suggesting an association between glycemic control and DME response and progression. It also highlighted the importance of degree of retinopathy and intravitreal treatment in diabetic macular edema progression. Treatment-related findings represent exploratory associations and should not be interpreted as evidence of comparative effectiveness.

Diabetology doi: 10.3390/diabetology7040064

Authors: Marina Cetkovic-Cvrlje Hans Addo Mohammad A. Nimer Sunny S. K. Chan Gengyun Le-Chan

Objectives: This study aimed to assess the effects of voluntary exercise on type 1 diabetes mellitus (T1D) development and splenic immunological profiles in non-obese diabetic (NOD) mice, a spontaneous model of human T1D. Methods: Prediabetic female NOD mice were randomly assigned to sedentary or exercise groups, with mice in the exercise group given 10-week wheel access and sedentary mice receiving none. Late-time mice were monitored to diabetes onset or 24 weeks of age; early-time mice were analyzed immediately post-intervention. Blood glucose, food intake, water consumption, and body mass were monitored weekly. At the endpoints, splenocyte counts, T and B cell subsets, and mitogen-stimulated cytokine production were analyzed using flow cytometry. Results: Mice in the exercise group ran an average of 20.76 ± 0.22 km/day. By the late-time endpoint, 75% of mice in the exercise group remained non-diabetic versus 35% of sedentary mice (p = 0.006). Mice in the exercise group demonstrated lower blood glucose (p = 0.015), visceral fat mass (p = 0.035), and water intake (p < 0.001) but higher food intake (p = 0.001), with no difference in body mass (p = 0.389) compared to sedentary mice. No differences were observed in splenocyte counts or Th, Tc, Treg, or B cell populations at either time point (p ≥ 0.185). Early-time point cytokines also did not differ between groups (p ≥ 0.08). Conclusions: Voluntary exercise reduces T1D incidence and mitigates hyperglycemia in NOD mice, suggesting a protective effect against disease progression. Despite the benefits, physical activity did not alter splenic Tcell subsets or inflammatory cytokines, demonstrating systemic immunomodulation may not be the primary driver of benefit. Our results indicate that voluntary exercise protects against T1D through tissue-specific or metabolic mechanisms, which warrant further mechanistic investigation.

Diabetology doi: 10.3390/diabetology7040063

Authors: Andra-Elena Nica Emilia Rusu Carmen Dobjanschi Florin Rusu Claudia Sivu Oana Andreea Parliteanu Ioana Verde Andreea Andrita Gabriela Radulian

Background: Diabetic retinopathy (DR) remains one of the most frequent and severe complications in patients with type 2 diabetes (T2DM), with significant implications for vision and quality of life. While classical screening methods are effective, they are not always accessible or systematically used. Sudoscan, a device that evaluates sweat gland function by measuring electrochemical skin conductance (ESC)—an indicator of chloride ion flow through sweat glands and a marker of peripheral autonomic nerve function—has recently attracted attention as a potential adjunct tool for risk assessment of microvascular complications. Objectives: In this cross-sectional study, we investigated its utility in identifying DR among 271 adults with T2DM. DR was diagnosed in 35.8% of patients, and those affected showed lower Sudoscan scores in the lower limbs and higher scores indicating cardiovascular autonomic neuropathy. Methods: Statistical analyses, including ROC curve evaluation and multiple linear regression, revealed moderate diagnostic accuracy and significant correlations between Sudoscan parameters and DR severity. Results: Our results suggest that Sudoscan could serve as a fast, painless, and informative screening tool, particularly valuable in settings with limited access to ophthalmologic services. Conclusions: Although it does not replace fundus examination, it may offer complementary insights and help stratify patients by risk level, guiding more targeted monitoring and intervention strategies.

Diabetology doi: 10.3390/diabetology7040062

Authors: Taichi Muramatsu Ayaka Sugiura Daisuke Yamamuro Ryosuke Kumazawa Manabu Akazawa Akifumi Kushiyama Takako Kikuchi

Background/Objective: This study investigated the association between tendon reflexes (Achilles and patellar) and the development of diabetic retinopathy (DR) in patients with type 2 diabetes (T2D). Methods: This single-center retrospective cohort study enrolled patients with T2D. The primary outcome was the development of DR. Tendon reflex findings were classified into four groups (normal, decreased, absent, and not examined). A regression analysis using a Cox proportional hazard model was performed to evaluate the association between tendon reflex findings and the outcome. Results: A total of 1172 patients were included in the primary outcome analysis. The median follow-up period was 4.3 years, and 271 experienced DR development. In the multivariate analysis, an absent Achilles tendon reflex (hazard ratio [HR], 1.52; 95% confidence interval [CI]: 1.01–2.27) and an absent patellar tendon reflex (HR: 1.89, 95% CI: 1.18–3.03) were independently associated with DR development. Conclusions: The absence of the Achilles and patellar tendon reflexes may serve as risk markers for DR development. Clinical Practice Implications: Non-invasive assessment of tendon reflexes may serve as an adjunctive tool to identify patients with T2D at high risk for future DR, enabling timely ophthalmologic referral and targeted management.

Diabetology doi: 10.3390/diabetology7030061

Authors: George Theodorakopoulos David G. Armstrong

Background: Preventing diabetic foot ulcer (DFU) recurrence after healing is a major challenge in the remission phase. In this context, remission is not synonymous with healed; it refers to a confirmed post-healing state in which the ulcer is closed, but the individual remains at high risk of recurrence and requires ongoing preventive care. Armstrong, Boulton, and Bus suggested that DFU recurrence is about 40% at 1 year, 60% at 3 years, and 65% at 5 years and argued that limb preservation should follow a long-term “survivorship” model similar to cancer care. However, these estimates combine heterogeneous follow-up intervals and definitions, and there is limited work focusing specifically on the first 12 months after confirmed remission. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Searches of PubMed/MEDLINE, Scopus, ScienceDirect, and the Cochrane Library were performed on 16 December 2025. Eligible studies enrolled adults with diabetes in confirmed remission after a healed DFU and reported an exact 12-month recurrence outcome (n/N or Kaplan–Meier estimate). Risk of bias was assessed using the Critical Appraisal Skills Program and Joanna Briggs Institute tools, and certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Twelve-month recurrence proportions were pooled using a random-effects model on the logit scale, and results were interpreted cautiously due to the limited number of eligible cohorts. Results: Across three cohorts with confirmed remission at baseline (total n = 469) and an exact 12-month outcome, the pooled 12-month recurrence proportion was 29.3% (random-effects; 95% CI 24.9–34.1), i.e., about one in three. Although this estimate is lower than the widely cited ~40% 1-year recurrence benchmark, it reflects a strictly defined remission population and a fixed 12-month timepoint, rather than mixed follow-up intervals or less precise definitions. Conclusions: Approximately one in three adults in remission after a healed DFU develop a recurrent ulcer within 12 months. Because this estimate is based on a small number of cohorts and on strictly confirmed remission, it should be interpreted cautiously and should not be generalized to all individuals with a healed DFU. These findings support prevention-focused surveillance and ongoing risk management during remission. Larger, preregistered multicenter cohorts with standardized remission and recurrence definitions are needed to refine short-term recurrence estimates and inform survivorship-style models of care.

Diabetology doi: 10.3390/diabetology7030060

Authors: Ron T. Varghese Isabella A. Sharifi Ugur D. Ayar Samuele F. Petridis Sneha Akurati Ernesto Bernal-Mizrachi Naresh Punjabi

Background: Cerebrovascular accidents (stroke) remain a leading global cause of death and disability, with its burden increasingly overlapping the rising prevalence of obstructive sleep apnea (OSA) and diabetes mellitus (DM). These highly prevalent cardiometabolic conditions frequently coexist and may jointly amplify cerebrovascular risk through shared and interacting pathophysiologic pathways. This narrative review synthesizes current evidence on the independent and combined contributions of OSA and DM to cerebrovascular complications, with emphasis on mechanisms, stroke outcomes and implications for screening and integrated management. Methods: A narrative review was conducted using PubMed, MEDLINE, and the Cochrane Library to identify English-language articles published between January 2000 and December 2024. Search terms combined OSA or sleep-disordered breathing with stroke or cerebrovascular disease and DM or hyperglycemia. Secondary searches targeted mechanistic domains including intermittent hypoxia, insulin resistance, metabolic syndrome, atrial fibrillation, hypercoagulability, and bariatric surgery. Priority was given to systematic reviews and meta-analyses, randomized controlled trials, and large prospective cohort studies, with smaller studies included when mechanistically informative. Findings were synthesized thematically across OSA-related mechanisms, DM-related mechanisms, bidirectional interactions, combined risk through metabolic syndrome, stroke outcomes, and clinical management considerations. Results: OSA is associated with increased cerebrovascular risk through intermittent hypoxemia-related oxidative stress and inflammation, sympathetic activation with blood pressure surges and sustained hypertension, endothelial dysfunction and atherosclerosis, impaired cerebral autoregulation, arrhythmogenesis, particularly atrial fibrillation and prothrombotic changes. DM increases stroke risk via accelerated atherosclerosis, cerebral small vessel disease, endothelial injury, hypercoagulability, glycemic variability, and cardioembolic mechanisms. Evidence indicates that coexisting OSA and DM are common and associated with greater vascular injury markers, higher rates of cerebrovascular events, and poorer post-stroke recovery. Conclusions: OSA and DM contribute to cerebrovascular complications through convergent mechanisms centered on metabolic syndrome, obesity, inflammation, vascular dysfunction, and thrombosis. These findings support proactive screening and coordinated management strategies to reduce cerebrovascular risk and improve outcomes.

Diabetology doi: 10.3390/diabetology7030059

Authors: Ioan Cristian Crăciun Dan Claudiu Măgureanu Ioana Corina Bocsan Anca Elena Crăciun Anca Dana Buzoianu Maria Adriana Neag

Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder in which gut microbiota dysbiosis contributes to insulin resistance, metabolic inflammation, and impaired glucose homeostasis. Dietary fibers and prebiotics selectively modulate gut microbiota composition and function and may offer metabolic benefits in T2DM. This review examines the mechanistic links between dietary fibers, prebiotics, gut microbiota modulation, and metabolic outcomes in T2DM. Methods: Relevant experimental and clinical studies were reviewed to assess the effects of dietary fibers and prebiotics on microbial diversity, short-chain fatty acid production, intestinal barrier function, bile acid signaling, and glycemic control in T2DM. Results: Evidence indicates that T2DM is associated with reduced abundance of SCFA-producing bacteria, increased intestinal permeability, metabolic endotoxemia, and altered bile acid metabolism. Dietary fibers and prebiotics enhance SCFA production, support gut barrier integrity, and modulate inflammatory and metabolic pathways. Clinical evidence demonstrates modest improvements in glycemic and inflammatory parameters, though outcomes vary according to fiber type, dose, and baseline microbiota composition. Conclusions: Dietary fibers and prebiotics are promising, low-risk strategies for gut microbiota modulation in T2DM. Further standardized, long-term randomized studies integrating microbiome profiling and clinically meaningful endpoints are required to support precision nutrition approaches.

Diabetology doi: 10.3390/diabetology7030058

Authors: Miriam Zambrano-Mármol Gema López Gallardo Ana Piñar-Gutiérrez Costanza Navarro Moreno Ana Lucía Gómez Gila Emilio García-García Pilae Santacruz Sandra Amuedo Noelia Gros Herguido Viginia Bellido Alfonso Soto Moreno

Objectives: To describe a structured transition model for individuals with type 1 diabetes mellitus (T1DM) from pediatric to adult care in a tertiary hospital, and to explore demographic, clinical, and psychosocial factors associated with glycemic outcomes. Research Design and Methods: We conducted an observational, cross-sectional study including all patients with T1DM who transitioned from the Pediatric Endocrinology Clinic to the Adult Endocrinology and Nutrition Unit at Virgen del Rocío University Hospital between 2021 and 2024. Demographic, clinical, biochemical, glucometric, and socioeducational variables were collected at the first adult care visit. Statistical analyses included nonparametric tests and exploratory multivariate logistic regression models. Results: A total of 73 patients (45% female) were included, with a median age of 18 years and median diabetes duration of 9 years. The 46.6% of our cohort had an HbA1c > 7.5%. Overweight and obesity were present in 25% and 8% of patients, respectively, and 11% were active smokers. Eighteen percent were receiving mental health follow-up, mainly for anxiety–depressive disorders. Those using hybrid closed-loop insulin delivery and continuous glucose monitoring achieved significantly better glycemic control (TIR 67% vs. 48%; p < 0.01) and lower glycemic variability. In exploratory multivariable analyses, continuous glucose monitoring use > 90% of the time and higher maternal educational level were associated with a lower likelihood of HbA1c > 7.5%. Conclusions: In this cross-sectional transition cohort, intensive use of diabetes technology and higher maternal educational level were associated with better glycemic control at the time of transfer to adult care. These findings should be interpreted as exploratory and hypothesis-generating, and warrant confirmation in larger, prospective studies.

Diabetology doi: 10.3390/diabetology7030057

Authors: Wojciech Zasada Beata Bobrowska Agata Krawczyk-Ożóg Tomasz Rakowski Stanisław Bartuś Artur Dziewierz Barbara Zdzierak

Background/Objectives: Physiological assessment of borderline coronary lesions is recommended by current guidelines for revascularization decision-making. The aim of our study was to assess the prognostic utility of physiological indices and determine whether their predictive value differs between patients with and without diabetes (DM). Methods: A physiological assessment was conducted in 381 patients with borderline coronary artery disease. The study cohort was divided according to the presence or absence of DM, and all individuals were followed over a four-year period. Results: Of the 381 patients, 154 (40.4%) had DM. Patients with DM had a higher BMI (30.1 kg/m2 vs. 27.8 kg/m2, p < 0.0001) and a lower left ventricular ejection fraction at the time of enrollment (50% vs. 55%, p = 0.0414) compared to the non-diabetic group. Patients diagnosed with DM had significantly more positive FFR results for ischemia, regardless of the assessed vessel, positive non-hyperemic evaluation of LAD and more PCI procedures, including PCI of the LAD. The mortality rate in FU among diabetics was 23.4%, while in patients without diabetes, it was 16.8%; (p = 0.1081). The clinical profile of deceased patients was largely comparable between groups. In patients with diabetes, the non-hyperemic physiological assessment by RFR/iFR (OR 0.68, 95%CI: 0.49–0.96; p = 0.0261) as well as iFR alone (OR 0.55, 95%CI: 0.32–0.97; p = 0.0388) was strongly correlated with the risk of death. In contrast to patients with DM, in the non-DM group, the non-hyperemic assessment using RFR (OR 0.37, 95%CI: 0.18–0.78; p = 0.0085) proved to be a significant prognostic factor. Conclusions: Non-hyperemic physiological indices (RFR/iFR) demonstrated a strong prognostic value in both diabetic and non-diabetic populations. Higher RFR/iFR values were consistently associated with a reduced risk of death. In the group of patients with DM, the iFR value may be considered a significant prognostic factor for long-term mortality. In the group without DM, the RFR assessment is such a factor.

Diabetology doi: 10.3390/diabetology7030056

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

Background: Despite major advances in insulin formulations and delivery systems since 1921, many people with diabetes (PwDs) still fail to achieve recommended glycemic targets. Common reasons include inadequate education, injection errors, and poor adherence due to factors such as needle phobia and pain. Recognition of these barriers has driven the development of improved injection systems, particularly thinner and shorter needles. An experimental study previously identified the Pic Insupen 34 G 3.5 mm needle as high performing. We therefore conducted an observational study to assess its acceptability directly among PwDs. Methods: This multicentre, open-label, real-world study enrolled 300 insulin-treated PwDs who compared their usual pen needle (30–33 G) with the new 34 G × 3.5 mm needle over two two-week periods. The primary outcome was perceived puncture pain. Results: Participants overwhelmingly preferred the 34 G needle, based on the following findings: Pain perception: 62% of 34 G users reported minimal or no pain, compared with only 8% using their previous needle. Conversely, 22% of participants reported the highest pain score with their old needle, compared with just 5% using the 34 G. Ease of use: 77% rated the 34 G needle at the highest level of ease of use, compared with 20% for their previous needle. Complications: The 34 G needle was linked to significantly fewer hypo-/hyperglycemic episodes and local skin complications such as bruising or irritation. Eighty per cent reported no glycemic fluctuations while using the 34 G needle. Robustness: Ninety-four per cent of PwDs never observed the 34 G needle bending during use, compared with 64% using their previous needle, confirming greater robustness despite its thinner profile. Conclusions: The Insupen® 34 G × 3.5 mm needle substantially reduces puncture pain and improves the overall manageability of insulin injections. Its innovative design—combining reduced thickness with optimised tip geometry—is associated with fewer complications and enhanced injection performance. Because reduced pain and ease of use are critical for improving adherence to insulin therapy, the features of the 34 G needle should inform future prescribing decisions.

Diabetology doi: 10.3390/diabetology7030055

Authors: Alessia Scatena Sara Sandroni Matteo Apicella Michele Mantuano Anna Ranchelli Emanuele Bartolini Rosa Nigro Sofia Butini Teresa Scognamiglio Tommaso Anichini Marco Meloni

Background: Postoperative wounds may arise from several etiologies, including open partial pedal amputation, postoperative infection, and dehiscence of surgical sites from wound failure or patient compliance issues. If negative pressure wound therapy is the gold standard, its application in the toes area could be challenging, and as a consequence, standard care is most likely used. The control of the wound microenvironment, both in terms of pH levels and presence of reactive oxygen species, is a key part of the normal wound-healing process. This study evaluated the effectiveness of an oxygen-enriched oil-based device (OEOd) in post-surgical diabetic foot ulcers (DFUs). Methods: This prospective controlled comparative pilot study enrolled 40 patients with diabetes mellitus and post-surgical foot wounds (narrow and deep lesions, including tunneling ulcers) treated at the Diabetic Foot Unit of San Donato Hospital, Arezzo (March 2024–April 2025). Patients were allocated into two groups: those treated by the standard wound care (n = 20) and those treated by OEOd (n = 20). The primary outcome was complete wound healing at 16 weeks; other exploratory endpoints were wound area reduction at 4 and 16 weeks, onset of infection, need for re-intervention, and adverse events. Results: Complete wound healing was achieved in 85.0% of OEOd patients versus 45.0% in the control group (p = 0.020). At 16 weeks, wound area reduction was significantly greater in the OEOd group compared with standard therapy (89.8% vs. 64.0%, p = 0.013). Although infection rates (10.0% vs. 35.0%, p = 0.130) and need for re-intervention (0% vs. 25.0%, p = 0.056) did not reach statistical significance, both favored the OEOd group. No adverse events were reported. Conclusions: OEOd significantly improved the chance of healing post-surgery and showed favorable trends in reducing complications, with an excellent safety profile. Larger randomized controlled trials are warranted to confirm these findings and assess long-term outcomes.

Diabetology doi: 10.3390/diabetology7030054

Authors: Kaitlyn Leslie Hurka Arun Kiran Movva Anoop Sunkara Siddhartha Kalala Michael O’Connor Sohn Kishen Mitra Albert Thomas Anastasio

Diabetes mellitus (DM) is highly prevalent among patients undergoing foot and ankle surgery and is associated with substantially increased perioperative and postoperative risk. This narrative review synthesizes the current literature on optimization of DM patients undergoing foot and ankle surgery. Complications of chronic hyperglycemia, including neuropathy and peripheral vascular disease, make the foot and ankle particularly vulnerable to ulceration, infection, and deformity, contributing to high rates of both operations and postoperative complications such as surgical site infection and readmission. Glycemic control and obesity are modifiable predictors of surgical outcomes and represent key targets for preoperative optimization. Lifestyle modification and pharmacologic therapy play central roles in DM optimization. Traditional agents such as metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors remain foundational therapies, while newer therapies such as sodium–glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 (GLP-1) agonists offer meaningful improvements to glycemic control and weight loss. Pharmacologic regimens must be individualized, and many agents require careful perioperative management. Despite advances in medical therapy, high-quality evidence specific to foot and ankle surgery remains limited. Future research should focus on developing procedure- and agent-specific guidelines to reduce the substantial clinical and economic burden of DM in foot and ankle surgical patients.

Diabetology doi: 10.3390/diabetology7030053

Authors: Hossein Mirmiranpour Catherine Arden

Reactive oxygen species (ROS) are an essential component for the maintenance of cellular function. However, if produced in excess, ROS can drive cellular dysfunction and compromise cell viability. Indeed, uncontrolled ROS production plays a pivotal role in the pathogenesis of type 2 diabetes (T2D), contributing to the loss of β-cell function and the impairment in insulin signalling, as well as driving the development of diabetic complications, which can severely compromise quality of life. T2D is characterised by persistent hyperglycaemia, which is a leading contributor to ROS overproduction in this disease state. This enhanced, almost uncontrolled, increase in glucose metabolism upregulates several ROS-producing pathways, including the hexosamine pathway, protein kinase C, NADPH oxidase and the mitochondrial electron transport chain. There is accumulating evidence to suggest that in a bid to preserve redox homeostasis, ROS acts to suppress glucose metabolism by inactivating several enzymes involved in the regulation of glycolytic flux, including glucokinase, glyceraldehyde 3-phosphate dehydrogenase, phosphofructokinase-1 and pyruvate kinase. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a multi-faceted transcription factor, with a central role in ROS signalling and redox homeostasis. Whilst NF-κB mediates the transcriptional regulation of many pro-oxidants, NF-κB activity is also regulated by the oxidative status, with ROS having both inhibitory and stimulatory roles in these signalling pathways. Interestingly, NF-κB is also involved in controlling the delicate balance between glycolytic flux and mitochondrial respiration. This review will summarise the interplay linking hyperglycaemia with ROS formation, emphasising the role of glucose metabolism in the process, and the crosstalk of these pathways with NF-κB.

Diabetology doi: 10.3390/diabetology7030052

Authors: Carrie Tackett Kevin Sun Chia-Ding Shih Laura Shin Elizabeth Miranda David G. Armstrong Tze-Woei Tan

Background: Diabetic foot infections (DFIs) are a major cause of hospitalization, limb loss, and mortality among patients with diabetic foot ulcers (DFUs). This study evaluated the risk of developing DFIs among patients with newly diagnosed DFUs across insurance categories. Methods: Adults ≥18 years with a new DFU diagnosis were identified in the PearlDiver insurance claims database (2010–2020) using validated ICD-9/10 codes. Insurance status at the index DFU was categorized as Medicaid, Medicare, commercial, or self-pay. Propensity score matching (1:3) based on age, sex, Charlson Comorbidity Index, and major comorbidities was used to compare Medicaid vs. non-Medicaid patients. Results: Among 258,122 patients with new DFUs, 20,638 (8.0%) were Medicaid beneficiaries. Medicaid patients were younger (50.1 ± 10.2 vs. 60.6 ± 12.1 years, p < 0.001) but had similar comorbidity burden compared with commercially insured and Medicare patients. In matched analysis post-matching, Medicaid insurance was independently associated with higher odds of DFI-related hospitalization within 12 months (aOR 1.18, 95% CI 1.14–1.24) and major amputation at 3 years (aOR 1.72, 95% CI 1.39–2.13). Higher CCI, chronic kidney disease, congestive heart failure, COPD, and peripheral vascular disease also predicted adverse outcomes. Conclusions: Medicaid insurance was independently associated with increased risks of DFI and major amputation among patients with newly diagnosed DFUs. These findings highlight infection as a potentially modifiable pathway driving limb loss and emphasize the need to improve early ulcer evaluation and infection management for Medicaid beneficiaries.

Diabetology doi: 10.3390/diabetology7030051

Authors: Jelena Stanarcic Gajovic Dusica Lecic Tosevski Katarina Lalic Tanja Milicic Ljiljana Lukic Marija Macesic Milica Stoiljkovic Mina Bozic Djurdja Rafailovic Nikola Jovanovic Olivera Vukovic Sanja Stankovic Ognjen Milicevic Stefan Maric Nina Krako Jakovljevic Kasja Pavlovic Nebojsa M. Lalic Aleksandra Jotic

Background: Depression is approximately twice as prevalent in type 2 diabetes (T2D) compared to non-diabetic individuals, but its underlying mechanisms remain unclear. Insulin resistance (IR) and low-grade inflammation have been proposed as potential contributors. This study investigated whether IR and inflammatory markers are associated with depression in people with T2D. Methods: This cross-sectional study included 189 participants divided into four groups: T2D with depression (A, n = 38), T2D without depression (B, n = 60), depression without T2D (C, n = 44), and healthy controls (D, n = 47). Depression was diagnosed using the MINI-6 and HAMD scale. IR was assessed using the Matsuda index and HOMA-IR, while low-grade inflammation was evaluated by high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Results: The Matsuda index was significantly lower in group A compared with B, C and D groups (p < 0.001). HOMA-IR was higher in A than in C and D groups, though not significantly different from group B. Hs-CRP was highest in group A (p < 0.001), with no differences among B, C and D. IL-6 was significantly higher in A than B and D (p < 0.001), and similar between A and C. In multivariable analysis younger age, lower Matsuda index, and higher IL-6 independently predicted depression in people with T2D. ROC analysis detected an AUC of 0.75 (p < 0.001) for IL-6, with a sensitivity of 57% and specificity of 82% at the cutoff of 5.29 pg/mL. Conclusions: Our findings suggest that people with T2D and depression exhibit higher IR and elevated IL-6 and hs-CRP levels as parameters of low-grade inflammation. Depression in T2D was associated with younger age, lower Matsuda ISI, and higher IL-6, highlighting the potential relevance of those metabolic and inflammatory biomarkers in this co-occurrence. Further longitudinal studies are needed to clarify causal relationships.

Diabetology doi: 10.3390/diabetology7030050

Authors: Grazia Piras Sara Brasili Davide Demontis Leonardo Della Sala Francesco Cocchiara Davide Carlo Maggi Anna Arecco

Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are essential regulators of glucose homeostasis, energy balance, and metabolic communication between organs. While therapies based on incretins are well established for type 2 diabetes (T2DM), their physiological significance and therapeutic potential in type 1 diabetes (T1DM) are less understood. In T1DM, the autoimmune destruction of pancreatic β-cells greatly reduces but does not abolish insulin production. However, various extrapancreatic actions of incretins continue, including effects on gastric emptying, glucagon secretion, appetite, inflammation, and cardiovascular function. The increasing prevalence of overweight, obesity, and insulin resistance among individuals with T1DM has heightened interest in exploring incretin-based treatments as adjuncts to insulin therapy. Data from randomized controlled trials, retrospective cohorts, and mechanistic studies were analyzed. This narrative review synthesizes available experimental, clinical trial, and real-world evidence on the physiology of incretins, their altered actions in T1DM compared with T2DM, and the effects of GLP-1 receptor agonists (GLP-1RAs) and tirzepatide, a dual GIP/GLP-1 agonist, on glycemic control, body weight, and cardiovascular outcomes in patients with T1DM. The use of GLP-1RAs in T1DM showed a weight reduction between 3.6 kg and 8.8 kg and improved glycated hemoglobin (HbA1c) by 0.2–0.8%, while treatment with tirzepatide for 6 months resulted in a body weight change of −10.3 to −10.6 kg. Growing evidence suggests a significant role of incretins in certain patients with T1DM, although large-scale, adequately powered randomized controlled trials are necessary to confirm their long-term efficacy and safety.

Diabetology doi: 10.3390/diabetology7030049

Authors: Natalia P. Sanchez Santiago De Loredo Maria F. Recanatesi Silvia Gorban de Lapertosa Daniel O. Croatto Lucia Marchese Mercedes Loza Aintzane Zubimendi Francisco Rivera Maria F. Gonzalez Bagnes Luis De Loredo Claudio D. Gonzalez

Background and Objectives: The objectives of this study were to determine the prevalence of diabetes mellitus (DM) and major cardiometabolic comorbidities in adults living in El Trébol, Argentina, and to evaluate their associations using laboratory-confirmed, community-based data. Methods: A cross-sectional, probabilistic, two-phase design was implemented, combining a household survey with clinical and biochemical assessments. Of 1112 surveyed adults aged 20–79 years, 860 completed the clinical phase and formed the effective sample. Cardiometabolic risk factors, including obesity, hypertension, dyslipidemia, and physical inactivity, were assessed through standardized measurements and questionnaires. Multivariate logistic regression explored independent associations with DM. Results: Crude DM prevalence was 10.47%, higher in men and increasing markedly with age; the age-standardized prevalence for the Argentine population was 9.87%. Of all diabetes cases, 23% were previously undiagnosed. Obesity (35.62%), hypertension (38.83%), dyslipidemia, and physical inactivity (83.84%) were highly prevalent. DM was independently associated with older age, higher BMI, elevated triglycerides, lower HDL cholesterol, and insufficient physical activity. Conclusions: This study reveals a substantial cardiometabolic burden in a small urban Argentine population and suggests that self-report-based national surveys may misestimate true DM prevalence. Laboratory-confirmed, community-based surveillance is essential to strengthen early detection, guide targeted interventions, and inform equitable public health strategies.

Diabetology doi: 10.3390/diabetology7030048

Authors: Christian Göbl Agnese Piersanti Florian Heinzl Tina Linder Micaela Morettini Andrea Tura

Background/Objectives: In pregnancy, beta-cell function is of interest since not only insulin resistance but also beta-cell dysfunction is common, especially when gestational diabetes mellitus (GDM) occurs. Typically, model-based beta-cell function is assessed with (at least) five-sample oral glucose tolerance test (OGTT). The aim of this study was to investigate whether the clinically common three-sample OGTT is sufficient for model-based beta-cell function assessment in pregnancy. Methods: We studied a group of pregnant women undergoing a 2 h five-sample OGTT with glucose, insulin, and C-peptide measurement at early and/or mid-pregnancy, for a total of 152 OGTTs. The five-sample OGTT was used for model-based beta-cell function assessment, yielding three beta-cell function parameters, i.e., glucose sensitivity (GSENS), potentiation factor ratio (PFR), and rate sensitivity (RSENS). GSENS, PFR, and RSENS assessment was repeated with the three-sample OGTT (at 0, 60, 120 min) and related values were compared to those from the five-sample OGTT (reference). Results: We found that, for GSENS, regression and Bland–Altman analyses showed satisfactory results (conditional and marginal R2 values: 0.56 and 0.75, p < 0.0001, and limits of agreement containing 94.2% of samples). Moreover, five-sample and three-sample OGTT GSENS versions were fully consistent in patient subgroup analyses. Results for PFR were less satisfactory but acceptable, whereas those for RSENS were not reliable. Conclusions: The three-sample OGTT is acceptable for model-based beta-cell function assessment in pregnancy, although not for all parameters. Our methodology may be used to explore the effect of time sample reduction in other in-silico models.

Diabetology doi: 10.3390/diabetology7030047

Authors: Thelma I. Morales-Ramírez Daniel Román-Rojas Aurora Espinoza-Valdez

One of the most common and severe complications of diabetes mellitus is diabetic foot, making early detection a public health priority. Infrared thermography is a promising noninvasive technique for identifying abnormal thermal patterns associated with inflammation, neuropathy, angiopathy, and tissue damage. This technique involves acquiring infrared radiation emitted by the skin and processing it to generate thermal maps that reflect underlying physiological changes. However, the reliability of thermographic assessments depends on strict technical conditions, including sensor performance, environmental control, and reproducible measurements. Despite its advantages, the clinical adoption of thermography is limited by the absence of standardized acquisition protocols and the influence of external and physiological factors on temperature measurements. Addressing these challenges is essential to ensure the accurate interpretation and validation of results. Recent advances, such as the incorporation of artificial intelligence algorithms and the development of portable, low-cost devices, offer new opportunities to enhance thermography’s applicability in clinical settings and home monitoring.

Diabetology doi: 10.3390/diabetology7030046

Authors: Dhruba Podder Olivia Stala Atikul Miah Abigail Agyapong Madeline Elizabeth Moore Rahim Hirani Danielle Diegisser Victor Garcia Mill Etienne

Type 2 diabetes mellitus (T2DM) and obesity affect hundreds of millions of adults worldwide and represent leading drivers of cardiovascular disease, chronic kidney disease, and escalating healthcare expenditures. Incretin-based therapies have fundamentally reshaped cardiometabolic disease management, with dual- and triple-receptor agonists extending the benefits of traditional glucagon-like peptide-1 (GLP-1) receptor agonism. By synthesizing clinical, mechanistic, and real-world data, this review examines the evolving therapeutic landscape of GLP-1-based multi-agonists. Dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists demonstrate superior metabolic efficacy compared with GLP-1 receptor agonists alone, achieving greater reductions in body weight and glycemic indices across diverse patient populations. Emerging triple agonists targeting GLP-1, GIP, and glucagon receptors further enhance metabolic outcomes, with weight loss approaching that observed following bariatric surgery in late-phase clinical trials. Mechanistically, multi-receptor co- agonism produces synergistic effects through complementary pathways, including appetite suppression, glucose-dependent insulin secretion, improved adipose tissue metabolism, increased energy expenditure, enhanced hepatic lipid oxidation, and reductions in hepatic steatosis. Beyond glycemic and weight endpoints, GLP-1-based therapies confer clinically meaningful cardiovascular and renal protection. Trials consistently demonstrate reductions in major adverse cardiovascular events across populations with and without T2DM, while kidney-specific trials show significant slowing of disease progression. However, gastrointestinal adverse events remain common and contribute to substantial treatment discontinuation, particularly in real-world settings. Despite their transformative efficacy, the population-level impact of these therapies is constrained by significant implementation barriers, including high drug costs, limited insurance coverage, restrictive utilization management policies, and pronounced racial and socioeconomic disparities in access. Emerging innovations including oral formulations, longer-acting injectables, and novel peptide combinations look to improve tolerability, adherence, and scalability, while therapeutic indications continue to expand to conditions such as metabolic dysfunction-associated steatohepatitis, chronic kidney disease, obstructive sleep apnea, and neurodegenerative disease. This review provides a comprehensive framework for understanding the clinical potential, mechanistic basis, and real-world challenges of GLP-1-based multi-agonists and outlines key priorities for optimizing implementation and maximizing their impact on global cardiometabolic health.

Diabetology doi: 10.3390/diabetology7030045

Authors: María de la Concepción Martín Trujillo Andrés Gaspar Castillo Sanz Jaime Barrio-Cortes

Background/Objectives: An increasing proportion of patients with Type 2 diabetes mellitus (T2DM) are classified as high risk, often presenting with multimorbidity, functional vulnerability, and complex treatments. This study compared the sociodemographic, functional, clinical, therapeutic, and healthcare utilization profiles of high-risk chronic patients with and without T2DM in primary health care. Methods: A cross-sectional study included adults classified as high-risk chronic patients in primary health care electronic health records in the Madrid Region (30 April 2021). Sociodemographic, functional, clinical, lifestyle, pharmacological variables, and primary health care services utilization were analyzed. Multivariate logistic regression identified factors independently associated with T2DM. Results: Among 163,188 high-risk chronic patients, 41.5% had T2DM. Patients with T2DM were older, more often male, and had a comparable deprivation index values to non-diabetic patients. They showed higher functional dependency and greater need for informal caregiving. Clinically, patients with T2DM had a higher burden of chronic conditions and a predominance of cardiometabolic, hematological and renal comorbidities, whereas non-diabetic patients exhibited more neuropsychiatric, chronic infectious, oncological and respiratory profiles. Polypharmacy was more frequent in T2DM patients, who also showed lower medication adherence. In the explanatory model, older age (OR 1.02/year), cardiometabolic comorbidities (ORs ~1.2–1.6), highest quartile of morbidity complexity (OR 1.27), polypharmacy (OR 1.34), and concern about medications (OR 1.08) were associated with T2DM, while female sex (OR 0.660), depression (OR 0.888), COPD (0.704), neoplasms (0.688), and higher medication adherence (OR 0.53) were associated with not having T2DM. Conclusions: High-risk chronic patients with T2DM exhibit distinct sociodemographic, functional, and clinical profiles compared with those without T2DM, characterized by greater complexity, cardiometabolic burden, therapeutic intensity and use of healthcare services, supporting the need for tailored, integrated primary health care strategies.

Diabetology doi: 10.3390/diabetology7030044

Authors: David G. Armstrong Bijan Najafi Shervanthi Homer-Vanniasinkam

Offloading remains the cornerstone of diabetic foot ulcer (DFU) management. This review traces the evolution of mechanical offloading from early plaster casting in South Asian leprosy clinics to modern removable walkers and emerging “SmartBoot” technologies. We examine the historical progression from total contact casting (TCC) through the era of randomized trials and instant TCC (iTCC), up to the current integration of wearable sensors and digital adherence tools. Contemporary evidence—including meta-analyses—is discussed to compare the effectiveness of offloading modalities (non-removable vs. removable devices, knee-high vs. ankle-high boots, therapeutic footwear, and adjunctive surgeries). Current challenges, such as patient adherence, frailty, and balance, are linked to technological responses like smart insoles, remote monitoring, and gamification strategies. Through this historical and evidence-based lens, we highlight how decades-old biomechanical principles are being reimagined with 21st-century innovations, aiming to improve healing rates and patient engagement in DFU care.

Diabetology doi: 10.3390/diabetology7030042

Authors: Vineeta Kaushik Saurav Karmakar Humberto Fernandes

Aldose Reductase (AR; AKR1B1) is an enzyme that plays a key role in the metabolism of glucose and other carbonyl compounds, and whose hyperactivity contributes to oxidative stress and vascular dysfunction. Despite decades of investigation into this enzyme, inhibitors have failed to translate into clinical application for Diabetic Retinopathy (DR). We argue that these failures might arise from non-selective inhibition, considering the dual roles of AR, which contribute not only to DR pathology but also support retinal health, as AR is an important detoxifying enzyme for aldehydes produced during oxidative stress. Here, we discuss missing structural information, despite more than one hundred crystal structures of AR in complex with inhibitors. Our review bridges this gap by discussing how recent advances in structural biology, e.g., fragment-based drug discovery and MicroED, provide novel ways to selectively modulate AR functions, offering advantages for the detection of weak, allosteric, or conformation-dependent binding events. Despite past challenges, we suggest that therapeutic targeting of AR to find new-generation inhibitors will become more effective once we have a clearer understanding of the requirements for selective inhibition of AR, blocking its pathological impact while preserving its physiological functions. By integrating fragment screening and structural biology, we outline a strategy to reinvigorate AR modulation as a viable retina-specific approach for managing DR, with potentially broader relevance toward multiple diabetic microvascular complications.

Diabetology doi: 10.3390/diabetology7030043

Authors: Parul Naib Giang Vu Akhil Nair Christian King

Background: Diabetes is associated with an increased risk of oral health complications, yet adults with diabetes remain less likely to obtain dental care in the United States. Objective: To examine socioeconomic, demographic, and insurance-related determinants of dental spending among adults with and without diabetes using nationally representative 2023 Medical Expenditure Panel Survey (MEPS) data. Materials and Methods: A two-part model was estimated: (1) a logistic regression predicting the likelihood of any dental spending, and (2) a generalized linear model (GLM) with a Gamma distribution and log link for positive spending. Covariates included age, sex, race/ethnicity, education, income, region, and insurance coverage. Results: The MEPS dataset included 15,071 adults (diabetes n = 2104; no diabetes n = 12,967), Adults with diabetes were less likely to have any dental spending than adults without diabetes (38.6% vs. 43.8%). Mean expenditures among users were higher for adults with diabetes but diabetes was not a statistically significant predictor of conditional spending after adjustment. Insurance coverage and preventive care were strong positive predictors of dental spending. Conclusions: Insurance coverage and preventive dental care are major drivers of dental spending and utilization among U.S. adults. Disparities observed among adults with diabetes appear to be driven primarily by reduced access to dental care rather than differences in spending intensity once care is obtained.

Diabetology doi: 10.3390/diabetology7030041

Authors: Evelina Maines Stefania Fanti Vittoria Cauvin Massimo Soffiati Silvana Anna Maria Urru Roberto Franceschi

Introduction: Recurrent hypoglycemia occurring prior to the initiation of insulin therapy is an uncommon finding at the onset of pediatric type 1 diabetes mellitus (T1D). Aim: The aim of this study was to describe an unusual presentation of T1D onset characterized by recurrent hypoglycemia in a pediatric patient and to provide an updated review of the literature on hypoglycemic episodes occurring before insulin initiation in children with new-onset T1D. Case report: We present the case of a child who exhibited recurrent fasting hypoglycemia and postprandial hyperglycemia at the onset of T1D. Clinical findings also included persistently elevated glucagon levels (66–93 pmol/L; normal values [n.v.] 3–60); markedly elevated glycated hemoglobin (98 mmol/moL); low C-peptide levels (0.05 nmol/L); and a slight positivity for antibodies to glutamic acid decarboxylase (38.3 KUI/L; n.v. < 10). Review of the literature: A narrative review of the literature was conducted using the PubMed (MEDLINE) database to identify studies reporting hypoglycemia at the onset of T1D in pediatric patients prior to insulin initiation. The search included combinations of the terms hypoglycemia, new-onset, type 1 diabetes, child, and adolescent, with an exclusion of insulin-treated cases. We also explore potential pathogenetic mechanisms underlying this unusual presentation, including alpha-cell acute damage or dysregulation and loss of intra-islet paracrine signaling. Conclusions: Among individuals with T1D onset, episodes of recurrent hypoglycemia before the initiation of insulin therapy have been reported in a few studies. The presented case expands the clinical spectrum of early T1D and suggests that early alpha-cell dysfunction may contribute to atypical glycemic patterns during disease onset.

Diabetology doi: 10.3390/diabetology7020040

Authors: Keiichi Hiramoto Eisuke F. Sato

Background/Objectives: Diabetes is classified into type 1 and type 2 diabetes. Type 1 diabetes is an autoimmune disease that develops in young people. While several factors are known to worsen type 1 diabetes, the effects of blue light remain unclear. This study aimed to explore this literature gap. Methods: In this study, we examined the effects of blue light exposure on diabetes using streptozotocin-induced type 1 diabetic mice. Furthermore, we used go91phox-/- mice to investigate the cause of blue light-induced diabetes exacerbation. Results: Blue light exposure exacerbated type 1 diabetes and activated the gp91phox/reactive oxygen species (ROS)/complement component 1/wingless-type MMTV integration site family, member 5A (Wnt5a)/α-catenin or peroxisome proliferator-activated receptor γ pathway in the liver and the gp91phox/ROS/DKK1/Wnt3a/α-catenin pathway in the pancreas, resulting in decreased β-catenin expression. These results indicated that blue light exacerbates type 1 diabetes by activating Wnt5a in the liver and decreasing Wnt3a in the pancreas. The use of gp91phox-/- was shown to cancel the worsening of diabetic symptoms caused by blue light. Conclusions: These results suggest that type 1 diabetes worsens with blue light and that this is due to the activation of gp91phox by blue light.

Diabetology doi: 10.3390/diabetology7020039

Authors: Federico Rolando Bonanni Marco Meloni Martina Salvi Ermanno Bellizzi Luigi Uccioli Valeria Ruotolo Aikaterini Andreadi Alfonso Bellia Davide Lauro

Objectives: To assess the impact of peripheral artery disease (PAD) on the outcomes of patients admitted for infected diabetic foot attack (DFA). Methods: Retrospective observational study of consecutive patients admitted to a third-level multidisciplinary diabetic foot service in 2024 for diabetic foot ulcers (DFUs) complicated by moderate or severe infection. Based on the presence of PAD, patients were divided into two groups: those with neuro-ischemic DFA (PAD+), treated with prompt revascularization, and those with neuropathic DFA (PAD-). The following in-hospital outcomes were evaluated: minor and major amputations; length of stay (LOS); mortality. Once discharged, patients were regularly followed as outpatients, and their six-month outcomes (healing, major amputation, and mortality) were analyzed. Results: Overall, 119 patients were included (70% PAD+ vs. 30% PAD-). The mean age was 67 ± 13 years, most patients were male (75%) and had type 2 diabetes (92%) with a mean duration of 20 ± 12 years. In-hospital outcomes for the two groups (PAD+ vs. PAD-) were as follows: minor amputation (41.7 vs. 25.7%, p = 0.09); major amputation (2.4 vs. 2.9%, p = 0.8); LOS (21 ± 11 vs. 14 ± 11 days, p = 0.004); mortality (3.6 vs. 0%, p = 0.1). The six-month follow-up outcomes (PAD+ vs. PAD-) were as follows: healing (40.5 vs. 90.6%, p < 0.0001); major amputation (8.1 vs. 3.1%, p = 0.1); mortality (8.1 vs. 0%, p = 0.01). Additionally, PAD (OR 3.6, CI: 1.4–12.1, p = 0.001) was independently related to non-healing. Conclusions: In the context of infected DFA, PAD appeared to play a significant role only in hospitalization length, while having greater influence on mid-term outcomes at the six-month follow-up, particularly in reducing healing chances.

Diabetology doi: 10.3390/diabetology7020038

Authors: Hung Quoc Ha Vu Ton Ngoc Phan Duyen Thi Hanh Bui Dai Quang Huynh Khoi Minh Le

Purpose: Hyperglycemia frequently occurs in critically ill patients with COVID-19 and may worsen outcomes. This study evaluated the prevalence, predictors, and clinical impact of poor glycemic control in severe and critical cases. Methods: We conducted a retrospective observational study of 338 ICU patients with COVID-19 and hyperglycemia at a tertiary center in Vietnam (August 2021–February 2022). Nearly 15,000 bedside glucose measurements were analyzed. Patients were classified into well-controlled or poorly controlled groups based on mean glucose levels (140–180 mg.dL−1 target). Logistic regression identified predictors of poor control. The primary outcome was in-hospital mortality. Propensity score matching (PSM) and multivariable Cox regression were performed to adjust for confounders. Results: Poor glycemic control occurred in 79% of patients. Independent predictors included invasive mechanical ventilation, elevated admission glucose, pre-existing diabetes, HbA1c > 7.0%, and prolonged corticosteroid exposure. After PSM, mortality was higher in the poorly controlled group compared to the well-controlled group (54.8% vs. 35.5%, p = 0.047). Cox regression confirmed poor glycemic control as an independent predictor of death (adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.01–2.55, p = 0.045). Conclusions: Poor glycemic control is common and strongly associated with excess mortality in critically ill COVID-19 patients. Prolonged corticosteroid use emerged as a modifiable risk factor. Careful glucose monitoring and tailored steroid management are warranted to improve outcomes.

Diabetology doi: 10.3390/diabetology7020037

Authors: Lewis J. Frey Mulugeta Gebregziabher Kinfe G. Bishu Brianna Youngblood Jihad S. Obeid Jianlin Shi Patrick R. Alba Chanita Hughes Halbert

Background: Type 2 diabetes mellitus (T2DM) is a chronic condition that has been attributed to social factors; however, the cumulative effect of social determinants of health (SDOH) on T2DM incidence is not known. Objective: The aim of the present study was to examine the association between T2DM and the cumulative burden of multiple SDOH. Design: The study is a retrospective cohort study with a baseline between 2008 and 2009 and a ten-year follow-up between 2010 and 2019. Setting: The study was conducted using data from the United States Veterans Health Administration (VHA). Participants: Out of 10,537,027 patients treated in the VHA between 2010 and 2019, 6,518,102 patients were selected who had no evidence of T2DM or Elixhauser comorbidities at baseline (2008–2009). Measurements: Over 10 years following baseline, the exposure consisted of seven types of SDOH occurring in structured data: social isolation, financial stress, employment issues, food insecurity, transportation insecurity, unstably housed, and psychosocial need. Incidence of T2DM in the ten-year follow-up window was the primary outcome. Results: Veterans with ≥3 SDOH doubled their adjusted odds of T2DM (2.07; CI: 2.05–2.09). There were significant racial differences in cumulative SDOH, with 8.8% of Black individuals having the highest burden of ≥3 SDOH compared with 3.8% of White individuals. Transportation insecurity, psychosocial need, and financial stress significantly increased the odds of T2DM across all racial and ethnic groups. Black individuals had the highest T2DM odds ratio for psychosocial need (OR = 1.58; CI: 1.56, 1.60). Limitations: The Veteran population is predominantly male, limiting generalization to the wider population. Conclusions: With each additional SDOH burden, the odds of T2DM increased, and ≥3 SDOH doubled the odds. The cumulative SDOH burden and associated disparities warrant investigation to reduce T2DM incidence.

Diabetology doi: 10.3390/diabetology7020036

Authors: Jung Eun Hong Soo-Young Yu Jeonghee Ahn Hye Ok Park Seungmi Park

Background/Objectives: Gestational diabetes mellitus (GDM) affects approximately 12.7% of pregnant women in South Korea. While breastfeeding provides critical health benefits for mothers with GDM and their infants, including improved insulin resistance and reduced Type 2 diabetes risk, no validated GDM-specific breastfeeding knowledge instrument exists. This study aimed to develop and validate a breastfeeding knowledge instrument for women with GDM. Methods: This methodological study employed systematic procedures for the development and validation of knowledge test. Initial item generation yielded 30 items across three domains: postpartum physical characteristics, breastfeeding barriers, and breastfeeding benefits. Content validity was evaluated by six clinical experts and ten experiential experts (women with GDM). An online survey was conducted in October 2022 with 220 women diagnosed with GDM who were either pregnant or within six months postpartum. Item analysis, exploratory factor analysis, and reliability testing were performed. Convergent validity was assessed by calculating the Pearson correlation coefficient with an established breastfeeding knowledge scale. Results: Following expert review and psychometric analysis, the final instrument comprised 14 items across three factors: postpartum physical characteristics (3 items), breastfeeding barriers (2 items), and breastfeeding benefits (9 items). The Kaiser–Meyer–Olkin measure was 0.884, Bartlett’s test was significant (χ2 = 838.835, p < 0.001), and factor loadings were satisfactory. The KR-20 reliability coefficient was 0.826, and criterion validity was confirmed. Conclusions: This first validated GDM-specific breastfeeding knowledge instrument enables the identification of knowledge gaps and the development of targeted educational interventions to improve maternal-child health outcomes.

Diabetology doi: 10.3390/diabetology7020035

Authors: Diego Castro Musial Talita Ferreira Marques Aguiar Guilherme H. Souza Bomfim

Diabetic foot ulcers (DFUs) are among the most severe and costly complications of diabetes, affecting millions of individuals worldwide. This narrative review summarizes major advances in regenerative medicine relevant to the management of DFUs and discusses how these approaches contribute to faster and more effective wound healing. Stem cell-based therapies, particularly those using adipose-derived mesenchymal stem cells (AD-MSCs), have demonstrated promising clinical outcomes through their ability to modulate inflammation, promote angiogenesis, and support skin and soft tissue regeneration. Platelet-rich plasma (PRP), an accessible autologous therapy, delivers concentrated growth factors that accelerate wound closure, enhance neovascularization, and shorten healing time compared with standard care. In addition, decellularized extracellular matrix (dECM) scaffolds provide a biologically active structural framework that supports cell adhesion, tissue remodeling, and granulation tissue formation. Collectively, these regenerative strategies offer new perspectives for improving functional recovery and quality of life in patients with DFUs, transforming chronic non-healing wounds into opportunities for effective tissue repair.

Diabetology doi: 10.3390/diabetology7020034

Authors: Angelina P. Nguyen Tu-Mai Tran Quynh Vuong Tu Timothea Vo Cherry Tran Ylan M. Liu Tam H. Nguyen

Background/Objectives: There is an invisibility of the diabetes epidemic among Vietnamese Americans. Not only is there limited availability of culturally and linguistically tailored national Diabetes Prevention Program (DPP) and Diabetes Self-Management Education and Support (DSMES) programs, but there are enrollment and retention challenges that hinder these programs’ sustainability and expansion. The purpose of this study was to explore the cultural beliefs, perceived barriers, and motivating factors that influence Vietnamese Americans’ willingness to engage in existing diabetes prevention and self-management programs. Methods: A qualitative descriptive study design was used. A total of 26 participants were recruited through snowball sampling. Bilingual Vietnamese American researchers conducted semi-structured interviews. Content analysis was used to analyze data. Results: Most participants were in the earlier stages of readiness for engagement in a national diabetes program. Major barriers to engagement were related to financial and time constraints, notable among middle-aged participants. Key motivators for engagement included increasing health awareness and family and other social support. Despite their hesitation regarding diabetes program engagement, most participants were further along in the stages of readiness for self-directed lifestyle management. Conclusions: These results will guide the development of a linguistically and culturally adapted diabetes prevention and management program that will support individuals at various stages of their behavior change journey. The program should align with cultural values, address structural barriers, and emphasize the integration of social and familial motivators.

Diabetology doi: 10.3390/diabetology7020033

Authors: Yıldız Öner-İyidoğan Hikmet Koçak

Metabolic inflammation, a state of chronic low-grade inflammation linked to insulin resistance, plays a central role in the development of obesity-related conditions such as type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders. In recent years, two molecules have gained significant prominence in this field, owing to their mechanistic involvement in metabolic inflammation and insulin resistance: fetuin-A (FetA), aliver-derived hepatokine, and chymase, a serine protease released from mast cells. Although they arise from distinct biological sources, they converge on overlapping inflammatory and metabolic pathways. FetA acts as an endogenous ligand for Toll-like receptor 4 (TLR4), activating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, driving proinflammatory cytokine release, and impairing insulin signaling. Chymase, on the other hand, generates angiotensin II and activates transforming growth factor-β (TGF-β), thereby promoting oxidative stress, fibrosis, and secondary metabolic dysfunction. This review proposes a conceptual dual-target framework in which FetA and chymase are considered complementary, rather than independent, mediators of metabolic inflammation. Importantly, this framework is not intended to supersede other established pathways implicated in metabolic inflammation, but rather to provide an integrative perspective that complements existing hepatokine and immune-centered models. Their convergence on NF-κB and TGF-β signaling pathways highlights shared mechanistic nodes within metabolic inflammation. Accordingly, the emphasis of this review is on mechanistic integration within metabolic inflammation, rather than on immediate therapeutic innovation or clinical translation.

Diabetology doi: 10.3390/diabetology7020032

Authors: Pranav Ramesh Loai K. Althagafi Kelly Parke Melanie J. Davies Gaurav S. Gulsin Gerry P. McCann Emer M. Brady

Background: Type 2 diabetes (T2D) increases cardiovascular disease (CVD) risk and predisposes individuals to heart failure with preserved ejection fraction. Metabolic dysfunction-associated steatotic liver disease (MASLD), prevalent in T2D, may worsen cardiac remodelling and haemodynamics. This secondary analysis of the DIASTOLIC trial examined the relationship of liver fat to cardiac remodelling in T2D at baseline and after a 12-week intervention or standard care. Methods: Adults with obesity and T2D and matched controls underwent hepatic MRI, cardiac MRI, echocardiography, and adipokine profiling as part of the DIASTOLIC study (NCT02590822). Participants with T2D were randomised to supervised exercise, a low-calorie meal-replacement plan (MRP), or routine care for 12 weeks. A baseline case–control and then pre- and post-analyses in those with T2D were performed. Associations between changes in liver fat and cardiovascular measures were assessed using correlation and adjusted generalised linear models. Results: At baseline, 81 T2D and 35 healthy controls were compared, and 76 subjects with T2D completed the trial. Participants with T2D had ~4× higher hepatic fat and adverse haemodynamics. The MRP arm achieved the greatest reductions in BMI, blood pressure, dysglycaemia, insulin resistance, and hepatic fat (−8.9%), with favourable adipokine changes. Overall, hepatic fat loss was associated with reductions in cardiac index and stroke volume and with additional reductions in end-diastolic volume in the MRP arm, independent of BMI. Conclusions: In T2D, hepatic fat is strongly linked to pathological haemodynamic profiles. Intensive caloric restriction achieves substantial hepatic fat loss and normalisation of hyperdynamic cardiovascular physiology independent of weight loss, identifying hepatic steatosis as a potential therapeutic target for early cardiovascular risk reduction.

Diabetology doi: 10.3390/diabetology7020031

Authors: Espiridión Ramos-Martínez Ramcés Falfán-Valencia Gloria Pérez-Rubio Francisco Javier García-Vázquez Jorge Rojas-Serrano Anayántzin Paulina Heredia-Antúnez Gerardo Aristi-Urista Anahí Chavarria-Krauser

Background: This work aimed to determine whether curcumin influences the development of type 1 diabetes mellitus (DM) in a murine model. Methodology: Four groups of six non-obese diabetic (NOD) mice (A, B, C, and D) and one CD1 control group (E) were included. Groups A, B, and C received different doses of turmeric curcumin (50 mg/kg body weight (bw), 100 mg/kg bw, and 200 mg/kg bw, respectively) for six weeks, while groups D and E received only the vehicle simultaneously. Glycemia, body weight, and inflammatory infiltrate in the pancreatic islets were determined in all cases. Also, insulin and vitamin D receptor (VDR) expression in pancreatic cells was evaluated relative to the basal expression in the control (group E). Results: Glycemia in all the animals treated with curcumin remained stable from weeks 1 to 6, while the control group showed hyperglycemia (≥500 mg/dL) and weight loss (16.7 g ± 1 g). Treated animals had less inflammatory infiltrate, while maintaining insulin and VDR expression in the pancreas, compared with the control group. Finally, the serum concentrations of proinflammatory cytokines in treated animals were statistically lower than in the control group without curcumin. Conclusions: Curcumin delays the onset of T1DM and reduces pancreatic inflammatory infiltrate.

Diabetology doi: 10.3390/diabetology7020030

Authors: Gareth J. Dunseath David R. Owens Stephen D. Luzio

Background: The pancreatic beta-cell hormone insulin regulates the metabolism of carbohydrates, as well as fats and protein. While the insulin response to a carbohydrate challenge is well defined in normoglycaemic as well as dysglycaemic (prediabetes and type 2 diabetes (T2DM)) individuals, the response of co-secreted beta-cell products (C-peptide, proinsulin and proinsulin intermediates) is less well defined. This analysis aimed to establish the expected glycaemic and pancreatic beta-cell responses to a standardised mixed meal in individuals with impaired glucose tolerance (IGT) and T2DM alongside reference ranges established in normoglycaemic individuals (NGT). Methods: A total of 743 adults (104 NGT, 85 IGT and 554 T2DM) were included, none of whom were on any anti-diabetic medication at the time of initial testing. All attended following a 10 h fast, before consuming a 500 kcal solid mixed meal (calorie contribution: 58% carbohydrates, 22% fat and 20% protein). Blood samples were collected every 30 min for the 4.5 h duration of the test for the determination of plasma glucose, insulin, C-peptide and intact and total proinsulin. Median profiles with corresponding 2.5th and 97.5th percentile lines to display the expected range were calculated and plotted for the three participant groups. Results: Median profiles with ranges over a 4.5 h meal period have been created for glucose, insulin, C-peptide and intact and total proinsulin, along with respective fasting and post-meal intervals in the three participant groups with differing glycaemic status. Conclusions: The resulting profiles and ranges allow for comparison in responses to a carbohydrate challenge in individuals across the glycaemic spectrum.

Diabetology doi: 10.3390/diabetology7020029

Authors: Viktor Husak Volodymyr Shvadchak Olena Bobrova Milos Faltus Yaroslava Hryhoriv Uliana Karbivska Myroslava Vatashchuk Viktoria Hurza Vitaliy Mel’nyk

Diabetes mellitus remains a major global health burden, and many patients do not achieve durable glycemic control despite modern pharmacotherapy. This narrative review synthesizes evidence on plant-derived strategies that may complement standard care, focusing on two clinically aligned domains: glucose-lowering medicinal plants and plant-based sugar substitutes that reduce dietary glycemic load. We summarize key mechanistic pathways, including inhibition of α-amylase/α-glucosidase, reduced intestinal glucose entry and absorption kinetics, glucose-dependent insulinotropic effects, improved insulin signaling, suppression of hepatic gluconeogenesis, and microbiota-linked effects. We critically appraise human evidence for selected botanicals (cinnamon, fenugreek, mulberry, gymnema, gynura, rosehip, and Jerusalem artichoke) and plant sweeteners (stevia and monk fruit). Overall, clinical effects are modest and heterogeneous; the most reproducible signals are observed for mulberry leaf in blunting postprandial glucose excursions, and for cinnamon, fenugreek, and gymnema, where meta-analyses suggest modest improvements in glycemic markers. Stevia and monk fruit are best supported as glycemically neutral sucrose substitutes, while inulin-type fructans show small-to-moderate benefits with sustained intake, limited by gastrointestinal tolerability at higher doses. Key gaps include a shortage of long-term randomized trials using standardized preparations and durable endpoints such as glycated hemoglobin. Plant-derived interventions are therefore best positioned as adjuncts within individualized, evidence-based glycemic management.

Diabetology doi: 10.3390/diabetology7020028

Authors: Mahesh Ramanan Aashish Kumar

Diabetic ketoacidosis (DKA) remains a life-threatening complication of diabetes mellitus with suboptimal outcomes despite standard management. Emerging evidence suggests that thiamine (vitamin B1) deficiency may play an under-recognized role in DKA pathophysiology and clinical course. This narrative review synthesizes current evidence regarding thiamine deficiency in diabetes and DKA, examining molecular mechanisms, clinical implications, and the rationale for thiamine supplementation as adjunctive therapy. Thiamine deficiency is highly prevalent in diabetes, with plasma concentrations reduced by approximately 75% compared to healthy controls. In DKA specifically, 25–35% of patients present with thiamine deficiency, which often worsens during insulin therapy. The primary mechanism involves hyperglycemia-induced downregulation of renal thiamine transporters (THTR-1 and THTR-2), resulting in 16–24-fold increased renal clearance and massive urinary losses. Thiamine pyrophosphate serves as an essential cofactor for three critical enzymes in glucose metabolism: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Deficiency impairs these pathways, causing pyruvate accumulation with conversion to lactate (resulting in lactic acidosis), compromised TCA cycle function (reducing ATP production by 40–48%), and decreased NADPH generation (increasing oxidative stress). Clinical manifestations include persistent metabolic acidosis despite standard therapy, myocardial dysfunction with elevated cardiac biomarkers, neurological impairment, and prolonged recovery times. Cellular studies demonstrate that thiamine supplementation significantly improves mitochondrial oxygen consumption in DKA patients. The high prevalence of thiamine deficiency in DKA, compelling biochemical rationale, excellent safety profile, and preliminary mechanistic evidence support the urgent need for large-scale randomized controlled trials examining thiamine supplementation to definitively establish efficacy, optimal dosing, and patient selection criteria.

Diabetology doi: 10.3390/diabetology7020027

Authors: Shinichi Watanabe Kota Yamauchi Yuji Naito Ayato Shinohara Yasunari Morita Yuki Iida from the RELIFE Network from the RELIFE Network

Background: Diabetes mellitus is known to affect the prognosis of critically ill patients; however, its impact on independence in activities of daily living (ADL) at hospital dis-charge remains unclear. This study aimed to investigate whether preexisting diabetes is associated with reduced ADL independence at hospital discharge among critically ill patients. Methods: In this prospective cohort study, 423 adult intensive care unit (ICU) patients who were admit-ted for ≥48 h were enrolled and categorized by the presence or absence of diabetes. Primary outcomes included time to achieve walking independence (unassisted walking over 50 m) and the Barthel Index at discharge. Secondary outcomes were handgrip strength, ICU length of stay, and highest ICU Mobility Scale (IMS) scores. Multivariable analyses adjusted for age, illness severity, and other confounders. Results: Among the 101 patients with diabetes, time to achieve walking independence at discharge was significantly longer compared to those without diabetes (p = 0.013). The diabetes group also had a lower Barthel Index (p = 0.020), longer ICU stays (p = 0.003), weaker handgrip strength (p = 0.041), and lower maximum IMS scores (p = 0.002). Multivariable analysis confirmed that diabetes was independently associated with reduced ADL independence and poorer physical function at discharge. Conclusions: Preexisting diabetes is an independent predictor of impaired ADL independence in critically ill patients. These findings highlight the importance of early and individualized rehabilitation strategies for patients with diabetes in the ICU.

Diabetology doi: 10.3390/diabetology7020026

Authors: Ryota Kobayashi Hideyuki Negoro

Background/Objectives: Postprandial hyperglycemia and sleep quality can influence arterial stiffness; however, the interaction between sleep quality and postprandial hyperglycemia-induced changes in arterial stiffness remains poorly elucidated. Therefore, the purpose of this study was to investigate whether sleep quality modifies postprandial changes in blood glucose levels and arterial stiffness following a 75 g oral glucose tolerance test in healthy middle-aged and older adults. Methods: In this study on 104 healthy middle-aged and older adults (50–83 years old), arterial stiffness was assessed using carotid–femoral pulse wave velocity (cfPWV) and brachial–ankle pulse wave velocity (baPWV) before and 60 min after a 75 g oral glucose tolerance test (OGTT). Poor sleep quality was defined as a Pittsburgh Sleep Quality Index score > 5.5. Results: In the 51 participants with poor sleep quality, baPWV increased significantly from baseline to 60 min after the 75 g OGTT (p < 0.01), whereas no such change was observed in the 53 subjects with good sleep quality. baPWV was significantly higher in the poor-sleep-quality group than in the good-sleep-quality group 60 min after the 75 g OGTT (p < 0.01). Moreover, baPWV and blood glucose levels 60 min after the 75 g OGTT had a positive correlation (p < 0.01, r = 0.64). Conclusions: These findings suggest that a poor sleep quality may enhance postprandial hyperglycemia-induced arterial stiffness, whereas a good sleep quality may help protect vascular function.

Diabetology doi: 10.3390/diabetology7020025

Authors: Sanne Janssen Eva C. I. Woelders Denise A. M. Peeters Patty J. C. Winkler Peter Damman Wouter S. Remkes Jasper J. P. Luijkx Audrey H. H. Merry Saman Rasoul Robert Jan M. van Geuns Arnoud W. J. van ’t Hof

Background: Diabetes is a known risk factor of acute coronary syndrome (ACS). However, diabetes de novo and prediabetes are also common in ACS patients. This study explored the prevalence of prediabetes and diabetes de novo in ACS patients, glucose-mediating therapy at discharge, and compared the prevalence of 30-day major adverse cardiac and cerebrovascular events (MACCE) in patients with prediabetes and diabetes de novo with known diabetes. Methods: ACS patients with measured haemoglobin A1c (HbA1c) from the South-East Netherlands Heart Registry, a prospective, multicentre registry of patients undergoing percutaneous coronary intervention (PCI), were analysed. Patients were stratified into two groups: known diabetes, and prediabetes (HbA1c 39–47 mmol/mol) or diabetes de novo (HbA1c ≥ 48 mmol/mol). Outcomes were analysed at 30 days post-PCI. Results: HbA1c was available in 34.1% of ACS patients (n = 1836), of whom 526 (28.7%) had known diabetes, 619 (33.7%) prediabetes, and 180 (9.8%) diabetes de novo. Compared with patients with known diabetes, patients with prediabetes and diabetes de novo had a significantly higher risk of MACCE (HR = 1.81, 95% CI 1.12–2.93, p = 0.016) after multivariable adjustment. At discharge, 59% of patients with diabetes de novo received no insulin, metformin, nor sodium-glucose co-transporter-2 inhibitor, compared with 16% of patients with known diabetes (p < 0.001). Conclusions: Impaired glucose metabolism without known diabetes was observed in nearly 45% of ACS patients and they demonstrated a significantly higher risk of 30-day MACCE compared with patients with known diabetes. Despite clear guideline recommendations, routine screening for hyperglycaemia and the appropriate initiation of glucose-mediating therapy remain underutilised in clinical practice.

Diabetology doi: 10.3390/diabetology7020024

Authors: Shanshan Lin Gary Deed Chee Khoo Giuliana Murfet Alan Winston Barclay Glen Maberly Anna Blackie Wenbo Peng Sofianos Andrikopoulos

Background/Objectives: Achieving a balanced wholefood diet while stabilising glycaemic management is challenging for many people with type 2 diabetes (T2D) due to barriers such as food preparation skills, time, and medication effects. Diabetes-specific nutritional formulas (DSNFs) are nutritionally complete products designed to support glycaemic management and overall nutritional adequacy and may complement wholefood dietary approaches when these are not feasible or are insufficient. Despite growing clinical evidence of efficacy, practical guidance for routine use is limited. Methods: A multidisciplinary expert working group developed a Clinical Practice Guide (CPG) for integrating DSNFs into diabetes care. Development was informed by a literature review and iterative consensus among experts, including representatives of the Australian Diabetes Society, Australian Diabetes Educators Association, and the Royal Australian College of General Practitioners. Results: The CPG outlines a three-step pathway: (1) assess suitability (clinical indications, contraindications, preferences, cultural context); (2) tailor the approach (individual goals, dose/timing relative to weight and body composition goals and observed glycaemic patterns, integration with lifestyle care); and (3) monitor progress (baseline, 2–4 weeks to assess initial response, then 3, 6, and 12 months for glycaemic indices, weight/body composition where available, and medication review). Conclusions: This CPG provides practical, multidisciplinary guidance for the person-centred use of DSNFs as an adjunct to standard care, supporting translation of current evidence into clinical practice and promoting consistent, multidisciplinary implementation.

Diabetology doi: 10.3390/diabetology7020023

Authors: Veronica Cumpata Ana-Maria Gheorghe Luminita Suveica Oana-Claudia Sima Natalia Loghin-Oprea Mihai Costachescu Eugenia Petrova Alexandra-Ioana Trandafir Ana Popescu Dana Manda Sorina Violeta Schipor Mara Carsote

Background: Irisin, a recently discovered muscle-originating hormone, has been found to act as a biomarker of several ailments, while no guideline clearly indicates its testing so far in any particular population category or pathological condition. Objective: We analyzed blood (circulating) irisin in relation to the potential correlations with the evaluation of glucose and bone profile. Methods: This was a prospective, pilot, exploratory study (between December 2024 and August 2025). The enrolled patients were menopausal women aged ≥50. Exclusion criteria: Endocrine tumors, thyroid dysfunction, malignancies, or chronic kidney disease. Baseline (fasting) testing was followed by 75 g oral glucose tolerance test (OGTT). Enzyme-linked immunosorbent assay (ELISA)-based irisin assay (MyBioSource) was performed. The subjects underwent central Dual-Energy X-Ray Absorptiometry (DXA), which provided lumbar, femoral neck and total hip bone mineral density (BMD)/T-score (GE Lunar Prodigy), and lumbar DXA-based trabecular bone score (TBS iNsight). Results: We enrolled 89 females [mean age of 62.84 ± 9.33 years, average years since menopause (YSM) of 15.94 ± 9.23]. Irisin (102.69 ± 98.14 ng/mL) did not correlate with age, YSM, but with body mass index (r = 0.36, p < 0.001). Bone formation marker osteocalcin (r = −0.25, p = 0.018) was negatively associated with irisin, amidst multiple other mineral metabolism assays (including PTH and 25-hydroxyvitamin D). Irisin positively correlated with insulin (r = 0.385, p = 0.0008), HbA1c (r = 0.243, p = 0.022), and HOMA-IR (r = 0.313, p = 0.007). Additional endocrine assays pointed a statistically significant association between irisin and TSH, respectively, ACTH (r = 0.267, p = 0.01, and r = 0.309, p = 0.041, respectively). No correlation irisin-BMD/T-score/TBS was confirmed. Conclusions: Irisin correlates with markers of glucose status (insulin, HOMA-IR, and HbA1c), as well as body mass index and, to a lesser extent, bone metabolism markers. Interestingly, TSH and ACTH correlations open a new (hypothesis-generating) perspective in the endocrine frame of approaching this exerkine. To the best of our knowledge, no distinct study has so far addressed the TBS–irisin relationship or pinpointed the glucose effects on TBS, particularly in menopausal women.

Diabetology doi: 10.3390/diabetology7020022

Authors: Ying Meng Loralei L. Thornburg Susan W. Groth Emily S. Barrett Richard K. Miller Thomas G. O’Connor

Background/Objectives: Inflammation may play a critical role in the pathogenesis of gestational diabetes mellitus (GDM). However, evidence linking early-pregnancy cytokines to subsequent GDM risk remains inconsistent, with most prior research focusing only on CRP, IL6, and TNFα. In this study, we expand on prior work by evaluating a broader range of immune markers and assessing sociodemographic factors as potential moderators. Methods: Data from a prospective U.S. pregnancy cohort (n = 308) were analyzed. Twenty cytokines were quantified in maternal first-trimester plasma using the MILLIPLEX High-Sensitivity Human Cytokine Magnetic Bead Panel. One-hour oral glucose (50 g) tolerance test (OGTT) values assessed at an average gestational age of 27.7 weeks (SD = 2.9) and GDM diagnosis were abstracted from medical records. Multivariable linear and logistic regression models were used to examine associations between cytokines and 1 h 50 g OGTT levels or GDM diagnosis, adjusting for key sociodemographic factors. Interactions terms were included to evaluate whether sociodemographic factors moderated cytokine–GDM relationships. Results: Sixteen women (5.1%) were diagnosed with GDM. Higher first-trimester high-sensitivity-IL6 levels were significantly associated with increased 1 h 50 g OGTT values (b = 3.76; 95% CI: 0.21, 7.32; p = 0.04) and greater odds of GDM (OR = 2.36; 95% CI: 1.17, 4.77; p = 0.02). These associations were more pronounced among Non-Hispanic White women compared to Non-Hispanic Black women (p for interaction = 0.03) and potentially those with normal weight or underweight during early pregnancy compared to overweight or obese women (p for interaction = 0.08). Conclusions: Elevated inflammatory markers, particularly high-sensitivity IL6, in early pregnancy are linked to impaired glucose metabolism and increased GDM risk later in pregnancy. These relationships appeared stronger in Non-Hispanic White women and women with normal weight or underweight during early pregnancy, underscoring the potential to develop serology-based early identification and prevention strategies.

Diabetology doi: 10.3390/diabetology7010021

Authors: Megan Beardmore Michelle M. Perfect

Background/Objectives: Youth with type 1 diabetes (T1DM) face unique challenges in balancing dietary choices, physical health outcomes, and social–emotional well-being in school settings. This cross-sectional exploratory pilot study examined the associations of diet with physical health and teacher-reported social–emotional functioning in students with T1DM. Methods: Students with T1DM (mean age = 13.42; 47 female, 50 male; 50% White, Non-Hispanic, 50% minority) self-reported their nutritional habits using the KBlock Dietary Screener for Children when school was in session. Teacher-rated school-related behaviors were assessed through the Behavior Assessment Scale for Children-2nd Edition (BASC-2). Canonical correlation analysis was conducted to determine whether the variable sets (diet with physical health and school-related behavioral health) shared a significant multivariate relationship. Results: Youth with lower glycemic loads and consuming more sugar, dairy, and meat/poultry/fish but fewer legumes, fruit, and less saturated fat exhibited fewer externalizing symptoms and higher BMI. Diet uniquely accounted for modest variance in combined social–emotional and physical health, controlling for demographics and T1DM duration. Findings support increasing the availability of whole, nutrient-rich foods, integrating comprehensive nutrition education into curricula, and ensuring access for all students, regardless of socioeconomic status. Conclusions: Comprehensive dietary assessments and school-based randomized control trials are needed to enact more evidence-based dietary recommendations or interventions for youth, aiming for a balanced approach that addresses both mental and physical health outcomes.

Diabetology doi: 10.3390/diabetology7010020

Authors: Ualikhan Zhumabayev Nursultan Nurdinov Ibragim Ishigov Rakhat Pernebekova Yerbolat Saruarov Bakhyt Baizakova Akbota Skenderova Bagdat Ashimbekova Perizat Tasenova Arailym Tastemirova Kozakhmet Baimyrza Elmira Kozhambekova

Background/Objectives: This study examined the metabolic, oxidative, immunological, and histomorphological effects of the multicomponent fermented biological product derived from camel milk, Inullact-Fito, in comparison to metformin in a rat model of alloxan-induced diabetes resulting from insulin insufficiency. The model was chosen as an experimental system that replicates pancreatic β-cell damage induced by oxidative stress rather than insulin resistance. Methods: Alloxan-induced diabetes was used to evaluate metabolic, oxidative, immunological, and histomorphological alterations. Metformin was utilized as a pharmacological comparator. Blood glucose levels, circulating insulin concentrations, markers of oxidative stress and lipid peroxidation, immunoglobulin levels, CD4+/CD8+ T cell balance, and pancreatic histostructure were assessed. Results: Alloxan administration led to substantial hyperglycemia, oxidative stress, immunological imbalance, and structural damage to pancreatic tissue. Following therapy with Inullact-Fito, blood glucose levels reduced dramatically (from 21.9 ± 0.22 to 9.85 ± 0.10 mmol/L, p < 0.05), circulating insulin concentrations were largely corrected, oxidative stress and lipid peroxidation markers decreased. Immunological evaluation revealed decreased serum immunoglobulin M and IgG levels (p < 0.05) and partial normalization of the CD4+/CD8+ T cell balance. Metformin showed comparative effects; however, its activity in this model is limited by its primary mechanism related to insulin resistance. Conclusions: Overall, the data reveal that Inullact-Fito combines metabolic, antioxidant, and immunomodulatory actions under experimental oxidative and metabolic stress conditions. Further research using models of insulin resistance and type 2 diabetes, as well as long-term clinical trials, is needed to fully evaluate the therapeutic potential, safety profile, and translational importance of this fermented dairy product as a functional nutritional intervention.

Diabetology doi: 10.3390/diabetology7010019

Authors: Eileen R. Faulds Melanie Natasha Rayan Matthew Mlachak Kathleen M. Dungan Ted Allen Emily Patterson

Background: Dysglycemia remains a persistent challenge in hospital care. Despite advances in outpatient diabetes technology, inpatient insulin management largely depends on intermittent point-of-care glucose testing, static insulin dosing protocols and rule-based decision support systems. Artificial intelligence (AI) offers potential to transform this care through predictive modeling and adaptive insulin control. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, a scoping review was conducted to characterize AI algorithms for insulin dosing and glycemic management in hospitalized patients. An interdisciplinary team of clinicians and engineers reached consensus on AI definitions to ensure inclusion of machine learning, deep learning, and reinforcement learning approaches. A librarian-assisted search of five databases identified 13,768 citations. After screening and consensus review, 26 studies (2006–2025) met the inclusion criteria. Data were extracted on study design, population, AI methods, data inputs, outcomes, and implementation findings. Results: Studies included ICU (N = 13) and general ward (N = 9) patients, including patients with diabetes and stress hyperglycemia. Early randomized trials of model predictive control demonstrated improved mean glucose (5.7–6.2 mmol/L) and time in target range compared with standard care. Later machine learning models achieved strong predictive accuracy (AUROC 0.80–0.96) for glucose forecasting or hypoglycemia risk. Most algorithms used data from Medical Information Mart for Intensive Care (MIMIC) databases; few incorporated continuous glucose monitoring (CGM). Implementation and usability outcomes were seldom reported. Conclusions: Hospital AI-driven models showed strong algorithmic performance but limited clinical validation. Future co-designed, interpretable systems integrating CGM and real-time workflow testing are essential to advance safe, adaptive insulin management in hospital settings.

Diabetology doi: 10.3390/diabetology7010018

Authors: Luis Alberto Sánchez-Briones Sarai Sánchez-Duarte Sergio Márquez-Gamiño Karla Susana Vera-Delgado Montserrat Guadalupe Vera-Delgado Rocío Montoya-Pérez Cipriana Caudillo-Cisneros Elizabeth Sánchez-Duarte

Background/Objectives: In all types of diabetes, elevated blood glucose levels cause pathological changes in skeletal muscle, primarily due to oxidative stress, mitochondrial dysfunction, and excessive production of reactive oxygen species (ROS). Regular exercise can help mitigate these effects; however, the underlying mechanisms, particularly those involving the mitochondrial permeability transition pore (mPTP), remain incompletely understood. This study aimed to explore the effects of aerobic exercise training (AET) on oxidative stress and the expression of mPTP components in the skeletal muscle of streptozotocin-induced diabetic rats. Methods: Male Wistar rats were randomly divided into three groups: Healthy Sedentary (H-SED), Diabetic Sedentary (D-SED), and Diabetic Exercise-trained (D-EXER); n = 6 per group. The D-EXER group performed AET (0° slope) 5 days/week for 8 weeks. After the intervention period, body weight and fasting blood glucose (FBG) levels were measured, and soleus muscles were collected and analyzed for oxidative stress biomarkers, Western blotting, and gene expression using qRT-PCR. Results: Following an 8-week intervention, AET reduced FBG concentrations. Accordingly, in the soleus muscles of the D-EXER group, ROS levels decreased, and redox balance was improved compared to the D-SED group. Exercise training reduced CypD and Casp9 mRNA expression and increased Bcl-2 mRNA expression, whereas Ant1 mRNA expression was only slightly altered. CypD protein expression was decreased in exercised diabetic rats, while VDAC1 protein and mRNA levels remained unchanged. In the D-EXER group, there were significant inverse correlations between CypD and Casp9 mRNA expression levels and glutathione redox state. Conclusions: The current study suggests that 8 weeks of AET, in addition to reducing hyperglycemia, may favorably influence oxidative balance and the expression of mPTP-related molecular components in diabetic skeletal muscle.

Diabetology doi: 10.3390/diabetology7010017

Authors: Elena Gervilla-García Patricia García-Pazo Mireia Guillén-Solà Federico Leguizamo Ignacio Ricci-Cabello María Jesús Serrano-Ripoll Miquel Bennasar-Veny Maria Antònia Fiol-deRoque Escarlata Angullo-Martínez Rocío Zamanillo-Campos

Background/Objectives: Mobile health (mHealth) interventions can enhance chronic disease management, but their integration into public healthcare systems remains complex. DiabeText is the first SMS-based intervention in Spain delivering personalized diabetes self-management support using electronic health record data. This study explored perceived barriers and facilitators to the implementation of DiabeText in the Spanish public health context from the perspective of key stakeholders. Methods: A qualitative study was conducted using semi-structured interviews with 14 purposively selected stakeholders involved in digital health, diabetes care, data protection, and healthcare management across several Spanish regions. Interviews were thematically analyzed using Braun and Clarke’s approach and guided by the Implementation Research Logic Model. Results: Participants reported several barriers, including concerns regarding data protection, uncertainty about long-term sustainability, insufficient training and engagement of healthcare professionals and low digital literacy among certain patient groups. Facilitators included favorable institutional momentum for digital innovation, funding availability, perceived clinical utility and scalability of DiabeText, and growing patient familiarity with digital tools. Recommended strategies included integration into existing healthcare systems and workflows, professional training and use of familiar communication platforms. Conclusions: Effective implementation of DiabeText requires addressing regulatory, organizational, and equity-related barriers while leveraging institutional support and readiness for innovation. Early involvement of healthcare professionals, robust data governance, and investment in digital literacy are essential to ensure sustainable and equitable adoption. These findings provide actionable insights to support the integration of mHealth tools into chronic disease care in Spain and similar settings.

Diabetology doi: 10.3390/diabetology7010016

Authors: Pilar García Pertegaz Pedro Juan Tárraga López Irene Coll Campayo Carla Busquets-Cortés Ángel Arturo López-González José Ignacio Ramírez-Manent

Background: Insulin resistance (IR) is a key metabolic abnormality underlying type 2 diabetes and cardiometabolic diseases. Although lifestyle and sociodemographic determinants are well described, the role of psychosocial constructs—such as purpose in life—remains insufficiently characterized. No prior study in large occupational samples has examined the associations between purpose in life and IR when evaluated through three complementary indices: the triglyceride–glucose index (TyG), the Single-Point Insulin Sensitivity Estimator for Insulin Resistance (SPISE-IR), and the metabolic score for insulin resistance (METS-IR). Objectives: To analyze the cross-sectional associations between purpose in life and IR indicators in a large working population and determine whether these associations persist after accounting for sociodemographic and lifestyle factors. Methods: A cross-sectional study was conducted among 93,077 Spanish workers aged 20–69 years undergoing routine occupational health examinations. IR was estimated using TyG, SPISE-IR, and METS-IR indices. Purpose in life was assessed using the 10-item Purpose in Life Test and categorized into three groups based on the empirical distribution of scores. Multinomial logistic regression models adjusted for age, sex, social class, smoking, Mediterranean diet adherence, physical activity, and BMI were used to examine associations. Results: Lower purpose in life was consistently associated with higher IR categories across all indices. Compared with individuals reporting high purpose, those with low purpose had higher odds of belonging to the high IR category (TyG ORa 1.59; 95% CI 1.45–1.74; SPISE-IR ORa 1.94; 95% CI 1.76–2.13; METS-IR ORa 2.21; 95% CI 1.98–2.47). Adding purpose in life to sociodemographic and lifestyle models modestly improved discrimination for identifying high IR categories. Conclusions: In this large occupational cohort, purpose in life was independently associated with insulin resistance as measured by three metabolic indices. These findings highlight the relevance of psychosocial factors in metabolic health. Longitudinal studies are needed to clarify temporal pathways and assess whether purpose-oriented approaches may contribute to improved metabolic profiles.

Diabetology doi: 10.3390/diabetology7010015

Authors: Jaeyi Hahn Morgan P. Stewart Samuel D. C. Towne YunYing Zhong Nicholas Sherwin Boon Peng Ng

Background/Objectives: The increasing availability of online health information underscores the importance of digital resources and internet use, especially for older adults. Despite the benefits, utilization of Welcome to Medicare (WTM) and Annual Wellness Visits (AWV) remains suboptimal, particularly for those with diabetes. This study examined the relationship between internet use and WTM/AWV utilization among Medicare beneficiaries with diabetes. Methods: The 2021 Medicare Current Beneficiary Survey was analyzed, which is a nationally representative survey of Medicare beneficiaries aged ≥65 years with self-reported type 2 diabetes (n = 1444). The binary dependent variable was self-reported WTM/AWV utilization. The 3 binary independent variables were whether beneficiaries used the internet to (1) look up health information; (2) schedule an appointment with healthcare provider; and (3) communicate with healthcare provider. A survey-weighted logistic regression model was used to examine their associations, adjusted for socio-demographics and comorbidities. Results: Of study beneficiaries, 57.5% reported WTM/AWV utilization. Among WTM/AWV users and non-users, 56.1% and 42.5%, respectively, looked up health information online. Additionally, among WTM/AWV users and non-users, 31.6% and 26.1%, respectively, scheduled appointments online, and 39.8% and 34.3%, respectively, communicated with providers online. Adjusted analysis found that looking up health information online was associated with higher odds of WTM/AWV utilization (OR: 1.76, 95% CI: 1.36–2.28), while the other internet use behaviors were not statistically significant. Conclusions: Approximately 40% of study beneficiaries did not report using WTM/AWV. Improving internet use for health information and digital literacy among at-risk Medicare beneficiaries with diabetes may have a positive influence on WTM/AWV utilization and may support broader use of digital tools in diabetes care.

Diabetology doi: 10.3390/diabetology7010014

Authors: Patcharin Phuwilert Supatra Noo-In Chitkamon Srichomphoo Jirarat Ruetrakul Ruchakron Kongmant Santisith Khiewkhern

Background: Type 2 diabetes mellitus (T2DM) is a major public health problem in Thailand, particularly in rural areas where individuals have limited access to structured diabetes care and education. Poor self-management contributes to uncontrolled glycemic levels and long-term complications. Objectives: This study evaluated the effectiveness of a community-based health care program on glycemic control and self-care behaviors among adults with uncontrolled T2DM. Methods: A quasi-experimental study was conducted among 80 patients with uncontrolled T2DM in Kalasin Province. Participants were assigned to either an intervention group (n = 40) or a comparison group (n = 40). The 12-week intervention consisted of diabetes self-management education, individualized lifestyle support, and community/family engagement. Diabetes self-care behavior and glycated hemoglobin (HbA1c) were assessed at baseline and Week 12. Statistical analyses included paired t-test, independent t-test, and 95% confidence intervals. Results: The intervention group demonstrated a significant improvement in self-care behavior (MD = 14.83; p < 0.0001), compared with a minimal change in the comparison group (0.80; p = 0.756). HbA1c levels significantly decreased in the intervention group (−0.47%; 95% CI: −0.61 to −0.33; p < 0.0001), while a slight nonsignificant increase was observed in the comparison group (0.11%; p = 0.210). The between-group analysis showed a significant reduction in HbA1c favoring the intervention (−0.92%; p < 0.0001), supported by a large effect size (Hedges’ g = 0.87). Conclusions: This community-based health care program effectively enhanced diabetes self-management behaviors and improved glycemic control. Integrating such behavioral support into primary health care services may strengthen long-term diabetes management and reduce complications among patients with uncontrolled T2DM.

Diabetology doi: 10.3390/diabetology7010013

Authors: Christy Foster Nekayla Anderson Ivree Datcher Ambika Ashraf Bertha Hidalgo

Background/Objectives: Type 2 diabetes (T2D), a chronic metabolic disorder characterized by systemic inflammation, disproportionately affects African American adolescents. Metformin may reduce inflammation beyond glycemic control; however, its impact on inflammatory markers in adolescents remains unclear. We hypothesized that inflammatory markers would differ across groups defined by diabetes, obesity, and metformin use. Methods: In this cross-sectional analysis, inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]), metabolic panels, and metformin exposure were assessed in African American adolescents from Children’s of Alabama. Simple and multivariate linear regression models were used to test associations between metformin use and inflammatory markers, adjusting for age, sex, and BMI z-score. Results: Among 78 adolescents, metformin use was reported in 73.6% of those with T2D + obesity and 27.3% of those with obesity-only. In the T2D + obesity group, metformin use was associated with TNF-α (β = 0.34, p = 0.02). Conclusions: Metformin use was associated with higher levels of specific inflammatory markers, potentially reflecting that metformin was more likely utilized in more severe diseases. Longitudinal studies are needed to disentangle treatment effects from underlying disease progression.

Diabetology doi: 10.3390/diabetology7010011

Authors: José Carlos Arévalo-Lorido Juana Carretero-Gómez Alberto Muela Molinero Esther Montero-Hernández Juan Bosco López-Sáez Maria Isabel González-Anglada Miguel Angel Vazquez-Ronda Jesús Castiella-Herrero José Pablo Miramontes-González Rocío García-Alonso on behalf of Sumamos-FA-SEMI Registry on behalf of Sumamos-FA-SEMI Registry

Aim: To analyse the importance of inflammation in the disease burden and prognosis of patients with type 2 diabetes (T2DM) and atrial fibrillation (AF). We assessed these patients according to their neutrophil-to-lymphocyte ratio (NLR) values, examining their baseline characteristics and their prognosis at one year of follow-up based on a prospective AF registry in Spain (Sumamos-FA-SEMI). Methods: A prospective, multicentre, observational study of patients with AF (Sumamos-FA-SEMI) was conducted. We categorised the patients into four groups according to the presence of T2DM and NLR levels with a reference cut-off point of three. We compared the characteristics of the four groups and evaluated the prognosis using the mean values of all-cause mortality and all-cause mortality plus readmissions during a year of follow-up. Results: We analysed 1071 patients, 482 of whom had T2DM. This group had significantly higher rates of obesity and comorbidities. Groups with an NLR greater than three points had a higher prevalence of cancer, lower HDL cholesterol levels, and more albuminuria. Other inflammatory markers, such as C-reactive protein, were also higher in these groups. Regarding prognosis, groups (both with and without T2DM) with an NLR greater than three had significantly higher mortality, with a higher probability in those without T2DM (HR 3.58, 95% CI: 1.99–6.43, p < 0.00). In terms of mortality and readmissions, only the group without T2DM and with an NLR greater than three had significantly higher mortality (HR 2.19, 95% CI: 1.51–3.19, p < 0.00). Conclusions: Among atrial fibrillation patients, the combination of T2DM and high inflammation (NLR) was linked to higher comorbidity, worse metabolic and kidney disease, and the poorest prognosis. Surprisingly, the highest risk of readmission or death was in non-T2DM patients with higher NLR levels, suggesting that T2DM treatments may mitigate risk.

Diabetology doi: 10.3390/diabetology7010012

Authors: Sara Mustafa Mark Rodrigues Le Tuan Anh Nguyen Tim Kenealy Rawiri Keenan Barbara de Graaff Ryan Paul Lynne Chepulis

Background/Objectives: Ethnic disparities in type 2 diabetes (T2D) outcomes remain a significant public health challenge in Aotearoa New Zealand (NZ), but are not accurately reported in large datasets. This cross-sectional study used linked regional health records to examine ethnic inequities in glycaemic control and achievement of clinical targets among adults with T2D in the Waikato and Auckland regions. Methods: A cross-sectional analysis was conducted on 57,734 adults aged 18–75 years with confirmed T2D enrolled in four Primary Healthcare Organisations. Clinical and sociodemographic data from February 2021 to December 2023 were linked via National Health Index numbers. Key outcomes included the percentage of patients at target for HbA1c, blood pressure, lipid profiles, renal and liver function tests. Logistic regression assessed associations between ethnicity, socioeconomic deprivation, and clinical target attainment. Results: The mean age was 56.5 ± 12.4 years, and 86.8% of the cohort were overweight or obese. Overall, only 46.3% achieved the HbA1c target (<53 mmol/mol) in their most recent test, with Māori (OR 1.35) and Pacific (OR 1.84) ethnicities, higher deprivation, obesity, and younger age independently associated with elevated HbA1c. Hypertension affected two-thirds of participants (71.9% above target), notably Asians and Pacific peoples. Māori and Pacific peoples had over twice the odds of renal impairment and were 2.5 times more likely to have elevated albumin-to-creatinine ratios. Abnormal liver function test decreased with age (OR ≤ 0.65), though Asians had over twice the odds of elevated ALT and AST compared to Europeans. Conclusions: Significant ethnic inequities exist in glycaemic and clinical target attainment among people with T2D in NZ. These findings highlight critical gaps in diabetes management and underscore the urgent need for targeted, equity-focused interventions addressing both socioeconomic and ethnic disparities to improve outcomes and reduce health inequities.

Diabetology doi: 10.3390/diabetology7010010

Authors: Regina Castaneda Diego Sepulveda Rene Rivera Gutierrez Jose Villamarin Dima Bechenati Maria A. Espinosa Alfredo Verastegui Elif Tama Allyson W. McNally Pamela K. Bennett Andres Acosta Maria D. Hurtado Andrade

Background/Objectives: Individuals with type 2 diabetes (T2D) achieve less total body weight loss (TBWL) with obesity medications compared to those without T2D. The individualized metabolic surgery (IMS) score, originally developed to predict T2D remission after bariatric surgery, inversely correlates with TBWL response to semaglutide. IMS reflects T2D severity, incorporating HbA1c and T2D duration and medication use. This study aims to evaluate TBWL with tirzepatide across IMS severity categories and identify predictors of response in a real-world cohort. Methods: This retrospective analysis included 717 adults with T2D using tirzepatide for overweight or obesity within the Mayo Clinic Health System. Patients were stratified by IMS severity (mild, moderate, severe) and quartiles. Primary endpoint: TBWL% at 15 months. Secondary endpoints: categorical thresholds (≥5%, ≥10%, ≥15%, ≥20%) and predictors of TBWL%. Linear mixed-effects models and regression models were employed. Results: At 15 months, TBWL was greater in mild versus severe IMS groups (14.8% vs. 11.0%, p = 0.015), with similar trends across quartiles. The proportion achieving ≥ 20% TBWL was nearly two-fold higher in mild versus severe IMS (27% vs. 14%, p = 0.03). Female sex independently predicted greater TBWL, whereas insulin use, higher T2D medication burden (particularly weight-promoting agents), and HbA1c > 7% were associated with less TBWL. Conclusions: Tirzepatide produced clinically meaningful TBWL across all IMS categories, although TBWL declined with increasing IMS severity. Glycemic control and T2D medication use emerged as strong predictors of TBWL. The IMS score may serve as a practical tool to anticipate weight-loss trajectories, guide personalized treatment decisions, and inform patient counseling.

Diabetology doi: 10.3390/diabetology7010009

Authors: Morwenna Kirwan Connie Henson Blade Bancroft-Duroux David Meharg Vita Christie Amanda Capes-Davis Sara Boney Belinda Tully Debbie McCowen Katrina Ward Neale Cohen Kylie Gwynne

Chronic diseases disproportionately impact Indigenous peoples in Australia, with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) representing leading causes of morbidity and mortality. Despite evidence supporting community-based exercise interventions for T2DM management, no culturally adapted programs utilizing wearable technology have been co-designed specifically with Indigenous Australian communities. This study protocol aims to determine if wearable-based exercise interventions can effectively prevent CVD development and manage T2DM progression in Indigenous Australians through culturally safe, community-led approaches. The PrIDE study protocol describes a mixed-methods translational research design incorporating Indigenous and Western methodologies across three phases: (1) co-designing culturally adapted exercise programs and assessment tools, (2) implementing interventions with wearable monitoring, and (3) conducting evaluation and scale-up assessment. Sixty-four Indigenous Australian adults with T2DM will be recruited across remote, rural/regional sites to self-select into either individual or group exercise programs using the Withings ScanWatch 2. Primary outcomes include cardiovascular risk factors, physical fitness, and health self-efficacy measured using culturally adapted tools. Indigenous governance structures will ensure cultural safety and community ownership throughout. The PrIDE protocol presents a novel approach to improving health equity while advancing understanding of wearable technology integration in Indigenous healthcare, informing future larger-scale trials and policy development.

Diabetology doi: 10.3390/diabetology7010008

Authors: Siphesihle Mkhwanazi Tumelo Jessica Mapheto Honey Bridget Mkhondo Olebogeng Harold Majane Sechene Stanley Gololo Mashudu Nemukula

Background: ApoE is a major regulator of lipid metabolism and glycaemic control. The aim of the current study is to investigate the ApoE gene polymorphisms among Black South Africans with and without type 2 diabetes mellitus (T2DM) and associate them with their lipid profile. Methods: A cross-sectional case–control study was conducted among 107 participants, divided into two groups: patients with T2DM (n = 65) and non-diabetic controls (n = 42). Blood samples were collected for analysis of glycated haemoglobin, lipid profile, nitric oxide, high-sensitivity C-reactive protein and DNA genotyping using the MALDI-TOF. Continuous variables were analysed using Student’s t-test or one-way analysis of variance (ANOVA). Genotype and allele frequencies were compared using Fisher’s exact tests. Results: The ApoE3 allele was the most prevalent among both groups, observed in 55.47% in T2DM patients and 52.38% in the non-diabetic group, followed by E4 and E2. HWE analysis revealed a deviation from equilibrium [χ2 (3) = 9.137, p = 0.0275]. TG levels differed significantly across ApoE alleles (F = 3.68, p = 0.03), with higher TG concentrations observed among E3 allele carriers and E4 allele carriers. Poor glycaemic control (HbA1c ≥ 7.0%) predominated across all ApoE alleles. Among E3 allele carriers, 75.0% of participants exhibited poor glycaemic control, whereas only 25.0% achieved good glycaemic control (p = 0.002). Conclusions: ApoE polymorphisms are associated with allele-specific heterogeneity in lipid metabolism and glycaemic control among individuals with T2DM, underscoring the complex, context-dependent role of genetic variation in metabolic dysregulation within African populations.

Diabetology doi: 10.3390/diabetology7010007

Authors: Xu Zhang Hafiza Mahreen Mehwish Pulin Che

Type 2 diabetes mellitus (T2D) affects hundreds of millions worldwide, with recent estimates indicating approximately 589 million adults living with diabetes, most with type 2 disease. Beyond classical insulin signaling pathways, increasing evidence implicates altered protein glycosylation in metabolic dysfunction. The solute carrier 35 (SLC35) family of nucleotide sugar transporters mediates the import of activated sugars into the endoplasmic reticulum and Golgi lumen, thereby influencing global glycosylation patterns. Dysregulation of these transporters can perturb glucose homeostasis, insulin responsiveness, and nutrient-sensing pathways through changes in glycosylation flux. In this review, we dissect the molecular mechanisms by which these transporters modulate glucose homeostasis, insulin signaling pathways, protein O-GlcN acylation, and broader glycosylation processes. We integrate findings from human genetic studies, rodent models, and in vitro functional analyses to characterize how altered SLC35 activity is associated with T2D and metabolic syndrome. Four members demonstrate particularly compelling evidence: SLC35B4 modulates hepatic glucose metabolism, SLC35D3 mutations impair dopaminergic signaling and energy balance, and SLC35F3 variants interact with high-carbohydrate intake to increase metabolic-syndrome risk. SLC35A3, though less studied, may influence glycosylation-dependent insulin signaling through its role in N-glycan biosynthesis. Beyond these characterized transporters, this review identifies potential metabolic roles for understudied family members, suggesting broader implications across the entire SLC35 family. We also discuss how such alterations can lead to disrupted hexosamine flux, impaired glycoprotein processing, aberrant cellular signaling, and micronutrient imbalances. Finally, we evaluate the therapeutic potential of targeting SLC35 transporters, outlining both opportunities and challenges in translating these insights into novel T2D treatments.

Diabetology doi: 10.3390/diabetology7010006

Authors: Špela Volčanšek Andrej Janež Matevž Srpčič

Background: The use of continuous glucose monitoring (CGM) offers several benefits. Compared to point-of-care (POC) capillary glucose tests, user acceptability is greater, and time in the target glucose range is improved. If these advantages can be transferred from outpatient to in-patient settings, CGM could assist clinicians in making timely, proactive treatment decisions. Scope of the review: This scoping review focuses on clinical studies of CGM use in hospital settings among non-pregnant adults, with a particular focus on studies from 2023 to 2025. It examines the latest evidence and guidelines and sets out the clinical and analytical considerations involved in implementing in-patient CGM. Main findings: In-hospital CGM facilitates hypoglycemia detection, especially asymptomatic and nocturnal episodes. Data on the impact of CGM use on clinical outcomes are scarce, and most studies focus on the reliability of CGM technology rather than clinical outcomes. Several factors affect CGM accuracy in hospitals, such as medications, fluid management, and hemodynamic disturbances. Despite between-device and settings-related variability, CGM devices generally show reasonable accuracy, with Mean Absolute Relative Differences (MARDs) ranging from 10% to 23%. In-hospital CGM has also improved workflows and reduced personnel exposure in infectious disease settings. Key implementation challenges: The MARD thresholds for safe in-hospital CGM use without confirmatory POC testing and evidence-based protocols for CGM application in ICU and non-ICU settings are not yet established. Despite challenges related to implementation, including personnel training, integrating diabetes technology with electronic health records, and costs, the benefits of improved monitoring and in-patient safety make CGM use worthwhile to pursue.

Diabetology doi: 10.3390/diabetology7010005

Authors: Xu Bai Hui Chen Jon Odorico Connie Chamberlain Kfir Molakandov Tim R. Dargaville Michel Revel Bernard E. Tuch

Background/Objectives: A stem cell therapy for type 1 diabetes (T1D) is experimentally available but only to those few humans in whom the use of systemic immunosuppression can be justified. For others with T1D, a means to deliver the islets needs to be perfected. We have previously bioengineered a removable device for this purpose and now wish to test the effect of adding extracellular matrix (ECM) derived from decellularised human pancreas to it. Methods: The complete device consists of encapsulated pluripotent stem cell differentiated islets seeded into tubular scaffolds of polycaprolactone made by melt electrospin writing and to which ECM was added. The seeded device was implanted either subcutaneously (SC) or intraperitoneally (IP) into streptozotocin diabetic immunodeficient mice. The outcome over the next few months was compared with that achieved in diabetic mice implanted IP with encapsulated islets alone. Results: The device seeded with encapsulated islets but not containing ECM functioned less well than encapsulated islets implanted alone, with lower human C-peptide production. However, when ECM was added to the seeded device and whether implanted SC or IP, islets functioned as efficiently as those implanted without use of a scaffold. Conclusions: These data provide optimism for the use of seeded scaffolds in diabetic humans in whom a single scaffold seeded with multiple encapsulated islets can more readily be removed if needed for safety reasons than can multiple encapsulated islets not seeded into a scaffold.

Diabetology doi: 10.3390/diabetology7010004

Authors: Stefanie Marie Agius Jessica Mangion Stephen Fava

Background and Hypothesis: Diabetic kidney disease (DKD) is one of the major risk factors for all-cause mortality and cardiovascular disease in patients with diabetes mellitus. Different phenotypes have been described. In view of their different pathophysiology, these subtypes may behave differently. Methods: In this retrospective study, patients with type 2 diabetes mellitus (T2DM) were followed up for a maximum of 10 years or until death, whichever came first. Subjects were categorized into four DKD phenotypes: no DKD (no albuminuria or decreased estimated glomerular filtration rate (eGFR)), albuminuria without decreased eGFR (DKD 1), decreased eGFR without albuminuria (DKD 2 or non-albuminuric DKD), and decreased eGFR with albuminuria (DKD 3). Data on laboratory results, hospitalization, and mortality were obtained through electronic patient records. Univariate analyses were performed and the variables that were significant were entered as covariates in multivariate logistic regression models to estimate the risks of death, hospitalization for CAD, HF, and CrVD, and CKD progression. Results: Among 778 patients, 53.3% had no DKD, 31.2% had DKD 1, 5.4% had DKD 2, and 10% had DKD 3. Patients with DKD 2 exhibited the highest odds of mortality compared to those with no DKD (odds ratio (OR) of 6.7 [95% CI 2.8–16.0], p < 0.001). Pairwise comparisons using the log-rank test showed a significant difference in mortality between DKD 1 and DKD 2 (p < 0.001) and DKD 1 and DKD 3 (p < 0.001). However, no statistically significant difference in mortality was found between DKD 2 and DKD 3. Additionally, the greater variability in HbA1c and higher neutrophil–lymphocyte ratio (NLR) independently predicted all-cause mortality as well as hospitalization for heart failure. Conclusions: This contemporary T2DM cohort demonstrated that the DKD phenotype, HbA1c variability, and elevated NLR are linked to increased mortality. These factors may improve existing risk stratification models by enabling better identification of high-risk DKD patients and guide more personalized management.

Diabetology doi: 10.3390/diabetology7010003

Authors: Julia Grzybowska-Adamowicz Agnieszka Zmysłowska

Microvascular complications of diabetes include retinopathy (DR), diabetic kidney disease (DKD), and neuropathy (DN), which play a crucial role in diabetes management, as they significantly impair the functionality of the patient and remain major causes of morbidity despite advances in glycaemic control. The aim of this review was to summarize multi-omics findings in DR, DKD, and DN. Multi-omics studies consist of genomic, epigenomic, transcriptomic, proteomic, and metabolomic research. These studies provided comprehensive insights into the complex mechanisms underlying microvascular complications of diabetes, such as inflammation, angiogenesis, and apoptosis in the retina, kidneys, and nervous system. They also enabled the search for emerging diagnostic, prognostic, and therapeutic biomarkers. Moreover, changes in microRNA levels were found to differentiate patients with non-proliferative and proliferative DR. In addition, different proteins and metabolites concentrations were noticed in diabetes macular oedema and tractional retinal detachment—serious complications of DR. Specific molecular signatures, such as miR-146a and miR-27 dysregulation, changes in levels of HLA-DRA, AGER, and HSPA1A proteins, and alterations in tyrosine, alanine, 2,4-dihydroxybutanoic acid, ribonic acid, myoinositol, ribitol, 3,4-dihydroxybutanoic acid, valine, glycine, and 2-hydroxyisovaleric acid, were found to be characteristic for all microvascular complications of diabetes. In the future, more studies in multi-omics are expected to help improve precision medicine approaches to treating diabetes, allowing for personalized prediction, prevention, and treatment of microvascular complications.

Diabetology doi: 10.3390/diabetology7010002

Authors: Pasa Sukson Watcharaporn Cholamjiak Nontawat Eiamniran Mallika Khwanmuang

Background/Objectives: Early-stage diabetes often presents with subtle symptoms, making timely screening challenging. This study aimed to develop an interpretable and robust machine learning framework for early-stage diabetes risk prediction using integrated statistical and machine learning–based feature selection, and to evaluate its generalizability using real-world hospital data. Methods: A Union Feature Selection approach was constructed by combining logistic regression significance testing with ReliefF and MRMR feature importance scores. Five machine learning models—Decision Tree, Naïve Bayes, SVM, KNN, and Neural Network—were trained on the UCI Early Stage Diabetes dataset (N = 520) under multiple feature-selection scenarios. External validation was performed using retrospective hospital records from the University of Phayao (N = 60). Model performance was assessed using accuracy, precision, recall, and F1-score. Results: The union feature-selection approach identified four core predictors—polyuria, polydipsia, gender, and irritability—with additional secondary features providing only marginal improvements. Among the evaluated models, Naïve Bayes demonstrated the most stable external performance, achieving 85% test accuracy, balanced precision, recall, and F1-score, along with a moderate AUC of 0.838, indicating reliable discriminative ability in real-world hospital data. In contrast, SVM, KNN, and Neural Network models, despite exhibiting very high internal validation performance (>96%) under optimally selected ML features, showed marked performance decline during external validation, highlighting their sensitivity to distributional shifts between public and clinical datasets. Conclusions: The combined statistical–ML feature selection method improved interpretability and stability in early-stage diabetes prediction. Naïve Bayes demonstrated the strongest generalizability and is well suited for real-world screening applications. The findings support the use of integrated feature selection to develop efficient and clinically relevant risk assessment tools.

Diabetology doi: 10.3390/diabetology7010001

Authors: Hussein Zaitoon Maria S. Rayas Jane L. Lynch

Background/Objectives: Type 1 diabetes (T1D) is a common childhood condition with rising global incidence. Because early-onset T1D coincides with key periods of brain maturation, affected children may face neurocognitive risks. This review summarizes current evidence on the neurocognitive impact of pediatric T1D and related clinical implications. Methods: A structured search of PubMed, Scopus, and Web of Science (inception–October 2025) used combinations of terms related to T1D, cognitive outcomes, and brain imaging. Studies involving participants under 18 years that reported cognitive or neuroimaging findings were included. Results: Diabetic ketoacidosis (DKA) at diagnosis is consistently linked with acute and longer-term neurological injury, including reduced brain volume and potential persistent deficits in memory and executive functioning. Severe or recurrent hypoglycemia disproportionately affects the hippocampus, contributing to lasting learning and memory impairments. Chronic hyperglycemia is a major driver of progressive neurocognitive decline; higher HbA1c is associated with smaller brain volumes and poorer executive function, attention, and processing speed. Early-onset disease and longer duration further increase vulnerability. These neurocognitive effects translate into modest reductions in academic performance and quality of life, especially with poor glycemic control. Emerging evidence suggests that continuous glucose monitoring, insulin pumps, and hybrid closed-loop systems improve metabolic stability and may support healthier brain development. Conclusions: T1D children experience subtle but meaningful neurocognitive risks shaped by glycemic extremes and early disease onset. Routine neuropsychological monitoring, strengthened academic support, and wider use of advanced diabetes technologies may help preserve cognitive development. Larger, longitudinal neuroimaging studies are needed to guide targeted neuroprotective strategies.

Diabetology doi: 10.3390/diabetology6120161

Authors: Scott Reule Sean Pickthorn Stefanie Worwa Areef Ishani Robert Foley

Background/Objectives: In populations with type 2 diabetes mellitus (T2DM), it is unknown whether the survival benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RA) differ by estimated glomerular filtration rate (eGFR). To address this question and in the absence of definitive randomized controlled trials, we performed a retrospective observational study of US Veterans with T2DM to evaluate mortality hazard ratios associated with GLP-1 RA use at different eGFR levels. Methods: This administrative claims-based cohort included 1,188,052 U.S. Veterans with T2DM as of 1 January 2020. Initiation of GLP-1 RA was treated as a time-dependent variable and vital status of Veterans was followed until 31 December 2023. Results: A total of 31,676 Veterans met inclusion criteria. Over the study timeframe, 6.1% initiated treatment with GLP-1 RA and 57.7% died. Older age and eGFR < 15 mL/min/1.73 m2 were associated with a decreased likelihood of GLP-1 RA initiation. In contrast, younger age and lower comorbidity burden were associated with decreased mortality, a finding that persisted even after adjustment for several baseline covariates. Conclusions: Among those with T2DM and eGFR < 25 mL/min/1.73 m2, initiation of GLP-1 RA was associated with improved survival. This association remained significant with decreasing levels of kidney function, as well as among those receiving kidney replacement therapy (KRT). In conclusion, longer survival was observed both in participants on KRT and in those with eGFR 15–24 mL/min/1.73 m2 not on KRT, but these findings were not observed among those with eGFR ≤ 15 mL/min/1.73 m2.

Diabetology doi: 10.3390/diabetology6120160

Authors: Brieba del Río Pascual Antolí Jover Ana María Vázquez Lara Juana María Ruger Navarrete Azahara Vázquez Lara María Dolores Palomo Gómez Rocio Artero García Alejandro Rodríguez Díaz Luciano Fernández Carrasco Francisco Javier

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Diabetology doi: 10.3390/diabetology6120159

Authors: Ailsa Marshall Nghi H. Bui Ann Nillsen Lena Lim Gillian Burke Amelia Christie Sandeep Kaur Karina Pearce Jack Ho Sharon Youde Kim A. Ramjan Amy Wanaguru Ohn Nyunt Louise Baczkowski Debra Waite Sally Duke Darshika Christie David Shihab Hameed

Aim: Assess transition readiness of adolescents with Type 1 Diabetes (T1D) from adolescent, parental, and clinician perspectives. Methods: Cross-sectional study (n = 36, 20 Male/16 Female, 16–18 years, June 2023–June 2024, metropolitan paediatric centre). Adolescents had diabetes knowledge, self-efficacy, and diabetes distress measured. Parents had an assessment of knowledge, diabetes-related distress, and estimated the adolescent’s self-efficacy. Clinicians estimated adolescent self-efficacy. Results: Median HbA1c was 7.4% (IQR 6.6–8.4). One adolescent met the guidelines for multidisciplinary team (MDT) appointments. Paired sample t-tests showed that adolescents’ knowledge was comparable to parent levels (t(24) = −1.69, p = 0.10). Adolescents’ knowledge was strongly associated with higher self-efficacy (r = 0.80 p < 0.001). Higher adolescent self-efficacy was associated with lower adolescent distress (r = −0.368, p = 0.03). Adolescent distress was lower than parent distress (t(24) = −3.13, p = 0.005). Although adolescent self-efficacy was strongly correlated with parent and clinician evaluation (r = 0.76, p < 0.001; r = 0.80, p < 0.001), adolescents reported higher self-efficacy than estimates by parents (t(24) = 4.76, p < 0.001) or clinicians (t(24) = 8.39, p < 0.001). Parent knowledge was moderately correlated with adolescent self-efficacy (r = 0.62, p = 0.001). Conclusions: Diabetes knowledge may confer greater self-efficacy and reduce diabetes distress in adolescents. Distress levels are higher in parents than in adolescents. Engagement with MDT is poor. Transition efforts should focus on parents and adolescents while increasing engagement with MDT.

Diabetology doi: 10.3390/diabetology6120158

Authors: Ricardo E. T. Navarrete Joana C. Freitas Isabel Fonseca Ana Cunha Joao Roberto Sa La Salete Martins

Objective: The aim was to characterize the real-world use of GLP-1 receptor agonists (GLP-1 RAs) and/or SGLT2 inhibitors in kidney transplant recipients (KTRs) with diabetes and to compare the clinical management, safety, and effectiveness between patients with type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM). Methods: This retrospective longitudinal cohort study included 141 adult KTRs (T2DM: 52; PTDM: 89) who initiated GLP-1 RA and/or SGLT2 inhibitor (SGLT2i) therapy between August 2013 and April 2024. Metabolic control, medication use, and safety outcomes were assessed from baseline to end follow-up, with a mean treatment exposure of 2.4 years. Results: Overall, 69% were treated with an SGLT2i and 59% with a GLP-1 RA; because the groups were not mutually exclusive, 28% received both agents. Treatment was associated with significant reductions in body weight (−3.38 kg; p < 0.001) and BMI (−1.28 kg/m2; p < 0.001) in both subgroups. HbA1c showed a non-significant overall decline (−0.31%; p = 0.21), with a greater reduction in the T2DM subgroup (−0.50%; p < 0.01). Significant improvements were also observed in lipid profile and blood pressure. Renal allograft function remained stable in both groups. The overall safety profile of the therapies was favorable, with mild urinary tract infections (18%) and manageable nausea (6%) reported in the entire cohort. No episodes of acute rejection or severe hypoglycemia occurred during the study period. Conclusions: In real-world practice, GLP-1 RAs and SGLT2is were associated with improved cardiometabolic parameters and stable renal function in KTRs, with a manageable safety profile. Similar effectiveness and safety across T2DM and PTDM support the use of these agents throughout the spectrum of diabetes in transplant recipients.