A distinct "South Asian phenotype" and unhealthy dietary patterns contribute to the high burden of type 2 diabetes mellitus (T2DM) in India, highlighting the need for context-specific nutritional management. Five regional advisory board meetings were conducted to gather expert perspectives on the unique epidemiology of T2DM and key aspects of nutritional management, including optimal dietary practices and the role of high-protein, high-fiber (HPHF) supplements or meal replacements. A total of 60 experts attended the meetings. During each meeting, an optional multiple-choice poll was administered as part of the discussion. Expert perspectives were derived from optional poll responses and discussions informed by scientific evidence and participants' clinical experience. High carbohydrate and low protein intake, insulin resistance, central obesity, suboptimal muscle mass, and genetic predisposition characterize Indian patients with diabetes. Recognizing this phenotype is essential for providing tailored nutritional interventions. Key assessments to facilitate nutritional interventions include anthropometry (weight, body mass index, and waist circumference), lipid profile, and 24-hour dietary recalls. Experts emphasized that customized nutrition plans should be developed based on individual nutritional status, clinical profile, and dietary preferences. Dietary strategies should emphasize increased consumption of complex carbohydrates, high-fiber foods, and protein. The high burden of "diabesity" underscores the need for nutritional interventions addressing both glycemic control and weight management, including the appropriate use of meal replacement strategies. Protein and fiber are key nutrients in diabetes management. While dietary sources should be prioritized, experts noted that low-glycemic index, HPHF supplements/replacements may be considered for patients with overweight/obesity, poor nutrition intake, weakness or fatigue, or uncontrolled hyperglycemia. However, their limited use in clinical practice highlights the need for further research to evaluate their indications for use, effectiveness, safety, implementation, cost considerations, and long-term outcomes. This expert opinion highlights the unique epidemiology of T2DM in India and provides context-specific, evidence-informed insights to support nutritional management strategies. These perspectives are derived from advisory board discussions and should be interpreted as expert opinion rather than systematic evidence synthesis or formal guideline recommendations.

Glucagon-Like peptide-1 receptor agonists (GLP-1-RAs) are increasingly prescribed for type 2 diabetes mellitus and chronic weight management, especially for the rapidly-growing population of older adults. However, older adults are also at heightened risk for sarcopenia and frailty, raising morbidity concerns about GLP-1-RA-induced lean body mass loss. This narrative review summarizes recent studies estimating skeletal muscle mass and/or volume, strength, composition, performance, and acute physiological responses during GLP-1-RA therapy in humans, with particular attention to implications for older adults. Because direct evidence in older adults is scarce, this review primarily synthesizes data from general adult populations and reasonably extrapolates implications for older adults. Most studies found that GLP-1-RA therapy was associated with a loss of skeletal muscle mass, accounting for up to 8.5% to 24.5% of total weight loss. Studies assessing muscle quality mostly saw improved muscle quality following GLP-1-RA therapy due to higher muscle density and decreased fat content. Studies measuring muscle strength generally found no significant change. However, from 21 included studies, only four studies specifically examined the older adult population, being methodologically heterogeneous and difficult to compare. The limited published literature in older adults provides insufficient evidence to determine age-related vulnerability to skeletal muscle loss while on GLP-1-RA and the potential clinical complications of resultant frailty; additional research in older adult populations is needed. Provisional considerations for preserving muscle mass during GLP-1-RA therapy are discussed, with particular relevance to older adults. This review demonstrates that the degree of skeletal muscle loss is variable but can account for a meaningful fraction of weight lost during therapy. Providers should consider these potential effects when prescribing GLP-1-RAs, especially in older adults at risk for frailty.

Pancreatogenic diabetes mellitus (type 3c diabetes mellitus, T3cDM) is an underrecognized form of secondary diabetes resulting from pancreatic exocrine disease, including chronic pancreatitis and pancreatic resection. It is frequently misclassified as type 2 diabetes mellitus, leading to delayed diagnosis and suboptimal management. We present a case of a 57-year-old female with a history of chronic alcoholic pancreatitis status post partial pancreatectomy who presented with severe uncontrolled hyperglycemia and medication nonadherence. Laboratory evaluation revealed a serum glucose of 668 mg/dL, hemoglobin A1c of 19%, and a low C-peptide level with normal insulin levels while receiving exogenous insulin, consistent with impaired endogenous insulin secretion and pancreatogenic diabetes. Despite repeated counseling and multiple attempts to optimize insulin therapy, the patient persistently refused insulin administration, resulting in refractory hyperglycemia throughout hospitalization. This case highlights the diagnostic challenges of distinguishing pancreatogenic diabetes from type 2 diabetes mellitus in patients with underlying pancreatic disease and emphasizes the importance of recognizing characteristic clinical features, including prior pancreatic injury and reduced endogenous insulin production. Early identification of T3cDM is essential because its pathophysiology and management differ substantially from type 2 diabetes mellitus and often require early insulin-based therapy to improve glycemic control and reduce long-term metabolic complications.

Type 2 diabetes mellitus (T2DM) is characterized by progressive β-cell dysfunction, insulin resistance, and glucotoxicity, some of which may remain reversible early in the disease course. Short-term intensive insulin therapy (SIIT) may rapidly normalize hyperglycemia and facilitate β-cell recovery in newly diagnosed T2DM. This systematic review evaluated the effects of SIIT on glycemic control, drug-free remission, β-cell function, durability, and safety. PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language randomized controlled trials published during the five-year period ending in April 2026. Four trials met the eligibility criteria. Because interventions, remission definitions, maintenance strategies, and follow-up periods differed substantially, study-level effect estimates, 95% confidence intervals, and p values were synthesized without statistical pooling. SIIT consistently improved early glycemic control, β-cell function, and insulin sensitivity. In one 245-participant trial, medication-supported hemoglobin A1c (HbA1c) below 6.5% at three months was achieved by 78.7% of participants receiving SIIT plus metformin-pioglitazone versus 59.0% receiving SIIT alone (adjusted p < 0.05); however, 12-month drug-free remission rates were similar at 50.0% and 50.6%, respectively (p = 0.972). Another trial found that linagliptin-metformin maintenance after SIIT increased the adjusted odds of achieving HbA1c below 7.0% at 48 weeks (odds ratio 2.78, 95% confidence interval 1.37-5.65; p = 0.005), although this represented medication-supported glycemic control rather than remission. In a two-year trial, induction SIIT improved β-cell function and insulin sensitivity (all p ≤ 0.0004), but repeated intermittent SIIT did not improve the Insulin Secretion-Sensitivity Index-2 (adjusted difference -35, 95% confidence interval -66 to -3; p = 0.03). Severe hypoglycemia was not reported in trials providing detailed safety data, and transient weight gain was not consistently demonstrated. SIIT may therefore serve as a selective metabolic induction strategy in early T2DM, but durable remission remains uncertain and may depend on effective sequential treatment. Standardized remission definitions, validated response predictors, and longer comparative trials are required before routine implementation.

A green, stability-indicating UV-spectrophotometric methods were designed and optimized for the quantitative determination of gliclazide (GLI), a second-generation sulfonylurea widely used in the management of type 2 diabetes mellitus (T2DM). The methods integrate first-derivative spectrophotometry (D[1]) and Fourier Self-Deconvolution (FSD) to resolve the extensive spectral overlap between GLI and its alkaline degradation product (Gliclazide Impurity A) without prior separation. The assay demonstrated excellent linearity within 2.5-25 µg/mL for GLI and 2.5-15 µg/mL for its degradation product. LOD ranged from 0.31 to 0.43 µg/mL and LOQ from 0.94 to 1.31 µg/mL for both analytes. Using ethanol as a green, non-toxic solvent further enhanced the method's environmental sustainability. Method validation, performed according to ICH Q2(R1) guidelines, confirmed its selectivity, reproducibility, robustness, and accuracy with mean recoveries of 99.48 ± 0.83 and 100.87 ± 1.52 for GLI in the D[1] and FSD methods, respectively. Comprehensive forced degradation studies under alkaline stress verified the procedure's stability-indicating capability, enabling reliable quantification of GLI in the presence of its degradation products. The greenness evaluation using Analytical Eco-Scale, GAPI, AGREE, NEMI tools, EPPI tool, AGSA tool, and MOGAPI method collectively affirmed the method's eco-friendly and sustainable nature. Furthermore, the analytical strategy was comprehensively assessed using multi-dimensional tools, including RAPI and AMRI for analytical performance and reliability, CaFRI for carbon-footprint reduction, CACI for analytical practicality, and the RGB 12 model for an integrated multi-colored analytical profile. In summary, the developed methods provide a highly efficient, environmentally friendly, and analytical alternative to conventional chromatographic techniques for the routine quality control and green pharmaceutical analysis of gliclazide in bulk and dosage forms.

Higher exposure to organophosphate flame retardants (OPFRs) may contribute to type 2 diabetes mellitus (T2DM), but prospective evidence, lifestyle modification, and biological plausibility remain insufficiently characterized. We conducted a nested case-control study within the Henan Rural Cohort to evaluate associations between OPFRs exposure and incident T2DM. Cox models, WQS, QGC, BKMR, and an adaptive elastic-net-based environmental risk score were used to assess single and mixed OPFRs exposure. Baseline and trajectory-based healthy lifestyle scores were applied to evaluate joint effects, and signed Wald χ[2] decomposition quantified contributions of OPFRs and lifestyle domains. Mechanistic evidence was integrated from in vitro experiments and toxicogenomic analyses, including RNA-sequencing, network toxicology, molecular docking, and GEO re-analysis, to evaluate EGFR-related signaling and build an integrative adverse outcome pathway. Higher urinary OPFRs, particularly TPHP, were associated with increased T2DM risk, and OPFRs mixtures showed a linear dose-response relationship with T2DM risk. High OPFRs exposure combined with unhealthy or deteriorating lifestyle trajectories conferred the greatest risk, with OPFRs plus lifestyle explaining 55.36% of total model χ[2]. In HepG2 cells, TPHP impaired glucose consumption and downregulated EGFR, whereas EGFR overexpression alleviated the TPHP-associated abnormal glucose consumption. EGFR overexpression was confirmed at both mRNA and protein levels. The p-AKT/total AKT results provided supportive evidence of AKT-related signaling changes, whereas total GLUT2 protein abundance was not significantly altered. Molecular docking supported potential TPHP-EGFR binding affinity of -8.5 kcal/mol, and GEO analyses provided external supportive evidence that EGFR expression tended to be higher in healthier lifestyle-related conditions. These findings suggest that mixed OPFRs exposure, dominated by TPHP, was associated with higher incident T2DM risk, partly attenuated by healthier lifestyle trajectories, supporting combined exposure-reduction and lifestyle-based prevention strategies.

TXNIP and DYRK1A are two novel drug targets for the treatment of type 2 diabetes (T2DM), and their respective inhibitors have been shown to suppress islet β-cell apoptosis and promote islet β-cell proliferation. The quinazoline scaffold constitutes the core pharmacophore of TXNIP inhibitors. Harmine, a prototypical DYRK1A inhibitor bearing a β-carboline scaffold, has demonstrated robust β-cell proliferative activity. Carbazole serves as a structurally simplified bioisostere of β-carboline. Guided by the principles of multi-target drug design and combinatorial chemistry, we designed and synthesized a series of quinazoline-carbazole hybrids as dual TXNIP/DYRK1A inhibitors. Compounds PF-5 and PF-6 markedly attenuated palmitic acid (PA)-induced β‑cell injury by suppressing the TXNIP-NLRP3-IL-1β signaling axis. Meanwhile, compounds PF-6 and PF-8 enhanced β-cell proliferation via DYRK1A inhibition. Molecular docking confirmed PF-6 bound with high affinity to both targets, and ADMET predictions supported its drug-like properties. Thus, PF-6 emerges as a potential dual-target therapeutics for T2DM. In conclusion, PF-6 can be used as a potential new chemical entity against T2DM.

Neutrophil extracellular traps (NETs) -associated inflammatory traits play a significant role in type 2 diabetes mellitus (T2DM) and its complications. Notably, IL-6, a key inflammatory cytokine, is intricately linked to the formation of NETs and the pathogenesis of T2DM and its complications. This study aimed to explore the causal association between NETs-associated inflammatory traits and T2DM, as well as its complications, using a Mendelian Randomization (MR) approach. This study utilized a two-sample MR design with data from Genome-Wide Association Studies (GWAS), comprising a large European population-based meta-analysis for T2DM and its complications. The primary method of analysis was the inverse variance weighted (IVW) approach, complemented by MR-Egger regression, weighted median, and weighted mode methods. Sensitivity analyses included MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out methods to assess the robustness of the findings. The study indicated that genetically predicted levels of interleukin-6 (IL-6) were inversely associated with diabetic coronary artery disease (CAD) (OR = 0.8997, 95% CI: 0.8257-0.9803, P = 0.0158). Additionally, NETs showed significant associations with T2DM with renal complications (OR=0.97, 95% CI 0.9428-0.998, P = 0.0358) and T2DM with peripheral circulatory complications(OR = 1.0342, 95% CI 1.002-1.0673, P = 0.037). The significant IVW associations showed no evidence of heterogeneity or horizontal pleiotropy. This study suggests that genetically predicted NETs-associated inflammatory traits are associated with specific T2DM complications. Genetically predicted IL-6 was inversely associated with diabetic CAD, whereas NETs were associated with renal and peripheral circulatory complications in T2DM.