Diabetology, Volume 7, Issue 8 (August 2026) – 19 articles

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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