Journal of Diabetes and Metabolic Disorders最新文献

Background: Toxoplasma gondii (T. gondii) infection has been associated with type 2 diabetes mellitus (T2DM) through mechanisms involving chronic inflammation and immune dysregulation. However, prior meta-analyses were limited by their inability to distinguish between T2DM and type 1 diabetes, as well as the lack of antibody-based stratification.

Methods: A comprehensive search was conducted on PubMed, Google Scholar, and EBSCOhost up to July 4, 2025, for observational studies reporting T. gondii seropositivity among T2DM patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were also conducted to strengthen the study results further.

Results: Eleven case-control studies comprising 1,956 cases and 1,423 controls were included in the analysis. A significant association was found between T. gondii seropositivity and T2DM (OR: 2.21; 95% CI: 1.47-3.33; I² = 82%). IgG seropositivity demonstrated a consistent significant association (OR: 2.26; 95% CI: 1.45-3.53), whereas IgM seropositivity reached significance only in sensitivity analyses (OR: 5.65; 95% CI: 1.61-19.80). No publication bias was identified.

Conclusion: T. gondii seropositivity is associated with an increased risk of T2DM, which may suggest a potential infectious component in the pathogenesis of diabetes. Further research involving larger, high-quality studies is warranted.

Background and aim: Poor glycemic control leading to hyperglycemia is a major risk factor for diabetes and its complications. Several primary studies have demonstrated that co-supplementation with curcumin plus piperine (Curc + Pipe) can enhance glycemic control. However, findings across studies are inconsistent. This meta-analysis aims to evaluate the efficacy of Curc + Pipe in glycemic indices in adults.

Method: A comprehensive search of major databases was conducted through October 2025 to identify eligible randomized controlled trials (RCTs). Extracted data included fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin (FI), and the homeostatic model assessment for insulin resistance (HOMA-IR). Outcomes were pooled using a random-effects model, with weighted mean differences (WMDs) and 95% confidence intervals (CIs).

Results: This meta-analysis included 15 RCTs comprising 1,020 participants (514 in the intervention group and 506 in the control group). Pooled analyses demonstrated that Curc + Pipe co-supplementation significantly reduced FBG (WMD: -5.89 mg/dL; 95% CI: [- 9.52, - 2.26], p = 0.001). However, no significant effects were observed for HbA1c (WMD: -0.34%; 95% CI: [- 0.80, 0.11], p = 0.135), FI (WMD: -0.19 mIU/L; 95% CI: [- 1.44, 1.83], p = 0.815), or HOMA-IR (WMD: -0.02; 95% CI: [- 0.67, 0.63], p = 0.957). According to the GRADE assessment, the certainty of evidence was rated as low for FBG, HbA1c, and FI, and moderate for HOMA-IR, indicating limited confidence in the overall findings.

Conclusion: Curc + Pipe co-supplementation may modestly improve FBG in adults, particularly in overweight patients with metabolic disorders, but the low-quality evidence, small effect sizes, and non-significant effects on HbA1c, FI, and HOMA-IR limit its clinical relevance. Well-designed, large-scale RCTs are needed to confirm these findings, clarify mechanisms, and determine their potential role in metabolic health management.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-025-01799-y.

Purpose of the review: The aim of this study was to provide a scoping review of the clinically approved tyrosine kinase inhibitors (TKIs) in cancer treatment and focus on the potential effect of these antineoplastic medicines on the metabolic effects of diabetes mellitus (DM), emphasizing how some of these medicines can work as anti-diabetic agents during cancer treatment.

Recent findings: TKIs are potential cancer therapeutic targets that have made significant strides in revolutionizing the field of cancer treatment. Notwithstanding their enormous promise, the development of TKIs continues to exhibit multiple endocrine effects, particularly on glycemic control. Given that β-cells are essential for maintaining glucose homeostasis and that the pathophysiology of DM involves a loss of β-cell function and survival, β-cell protection effect may be a significant response for the antidiabetic effects of TKIs. Treatment with TKIs in cancer patients with diagnosis of DM have significant potential to clinically affect glycemic control and produce anti-diabetic effects by maintaining functional β-cell mass, boosting insulin secretion and insulin sensitivity. These functions of TKIs are produced on several targets, including cellular Abelson non‑receptor tyrosine kinase (c‑Abl) inhibition, decreased Platelet-Derived Growth Factor Receptor (PDGFR) signaling, suppression of Vascular Endothelial Growth Factor Receptor (VEGFR), inhibition of Epidermal Growth Factor Receptor (EGFR), and obstruction of c-Kit signalling. These metabolic effects on blood glucose level were detected by many clinical reports in patients with type 1 DM (T1DM) and type 2 DM (T2DM) through multiple clinical effects, including, lower blood glucose level and HbA1c, increasing C-peptide levels which were associated with reducing the dose or stopping the treatment with antidiabetic medications. Most of these hypoglycemic effects were observed during the clinical use of imatinib, dasatinib, erlotinib, and sunitinib in cancer patients with diagnosis of DM.

Summary: TKIs are considered important approaches for the treatment of many cancer types. The use of these antineoplastic agents in patients with DM and a diagnosis of cancer shows that these agents have the ability to lower blood glucose, which can be associated with tapering down or discontinuing the use of anti-diabetic treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-025-01811-5.

Background: Diabetes mellitus (DM) type 2, the most prevalent form of diabetes, is affecting a population of 460 million worldwide. Individuals with diabetes are at a higher risk of developing sepsis which can be lethal if not managed properly. This study aims to analyse the trends in mortality due to diabetes mellitus type 2 and sepsis in the United States between 1999 and 2020.

Methods: Death certificate data from the CDC WONDER database was retrospectively analysed from 1999 to 2020 for mortality due to DM type 2 and sepsis in the adult population using ICD-10 codes. Age-adjusted mortality rates (AAMRs) obtained were stratified by year, sex, race/ethnicity, age, location of death, urbanization and census region. The Joinpoint regression programme was then used to calculate Annual Percentage Change (APC).

Results: 109,094 DM type 2 and sepsis-related deaths were reported among adults of United States from 1999 to 2020 with an overall AAMR of 2.29 (95% CI: 2.28-2.31). The overall AAMR was higher in males (2.61; 95% CI: 2.58-2.63) than in females (2.05; 95% CI: 2.03-2.07). Geographically, the mortality rates were higher in the Western region (3.05; 95% CI: 3.02-3.09). Similarly, the AAMRs for non-metropolitan areas were consistently higher than those of metropolitan areas. Stratification by race/ethnicities showed that NH American Indians/Alaska Natives had the highest AAMR (5.09, 95% CI: 4.80-5.37) while the lowest was observed in NH Whites (1.88, 95% CI: 1.87-1.90). Most deaths occurred at medical facilities (77.45%).

Conclusion: Males, older adults, NH American Indians, non-metropolitan areas and Western region were associated with higher DM type 2 and sepsis-related mortality, which is concerning. This study has brought light on the need for strategies and interventions to reduce the impact of sepsis on the population having DM type 2. Further research is necessary to identify effective strategies for prevention, early detection, and management of sepsis in this high-risk population.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-025-01781-8.

Purpose: This study aimed to investigate the effects of cemtirestat, a promising drug candidate with both aldose reductase (AR) inhibitor (ARI) and antioxidant (AO) properties, on hepatic and pancreatic stress responses in rats, by comparing it with the ARI drug epalrestat and the antioxidant compound stobadine.

Methods: Two metabolic disorder models characterized by glycolipotoxicity were induced in rats by administering fructose alone (CF) or together with streptozotocin (DF). The rats were subsequently treated once daily for 14 weeks with either cemtirestat at two different doses (2.5, 7.5 mg/kg), the ARI drug epalrestat (25, 50 mg/kg), or antioxidant compound stobadine (25, 50 mg/kg).

Results: Liver enzymes (ALP, AST, ALT, and GGT) and oxidative stress markers (malondialdehyde, carbonyl, glutathione S-transferase, catalase) were elevated in both CF and DF compared to control rats (C). Cemtirestat, especially at the low dose, significantly prevented the noted abnormalities (except for ALT) and the increase in cholesterol in DF and the increase in triglycerides in CF. While epalrestat only partially prevented the decrease in the GSH to GSSG ratio, but cemtirestat and stobadine almost completely restored the ratio in both CF and DF models. However, histochemical and immunohistochemical analyses revealed that unlike epalrestat and stobadine, cemtirestat did not improve liver histopathology (PAS, Masson trichrome, TUNEL, PCNA and caspase-3 staining) and pancreatic histopathology (TUNEL, PCNA and caspase-3 staining), nor did it alleviate damage to insulin-, glucagon-, and somatostatin-secreting cells in the islets.

Conclusion: The findings may offer valuable insights that could facilitate the development of novel ARI/AO compounds and CMTI derivatives.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-025-01723-4.

Background: This study aimed to resolve conflicting findings on the association between polymorphisms in the glutathione S-transferase (GST) genes and gestational diabetes mellitus (GDM) by conducting a meta-analysis.

Methods: A meta-analysis of case-control studies was conducted in accordance with the PRISMA 2020 guidelines. Comprehensive literature searches were performed in PubMed, Web of Science, and Google Scholar (title search only) up to January 31, 2025. Genotypic distribution between pregnant women with and without GDM was collated. Data were independently extracted by two reviewers into a standardized spreadsheet, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model.

Results: The meta-analysis included 1,933 pregnant women (932 with GDM and 1,001 controls). Of the three GST polymorphisms analyzed (GSTM1, GSTT1, and GSTP1), only the GSTM1 deletion polymorphism was significantly associated with GDM with moderate heterogeneity.

Conclusion: This meta-analysis supports a significant association between the GSTM1 deletion polymorphism and the development of GDM. Further studies are needed to validate this association and elucidate underlying mechanisms.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-025-01808-0.

The World Health Organisation (WHO) periodically updates its Model List of Essential Medicines (EML) and Essential Medicines for Children (EMLc) to address evolving global health priorities. The 24th EML and 10th EMLc, released on 5th September 2025, mark a major milestone by expanding access to twenty new medicines for diabetes, cancer, cystic fibrosis, haemophilia, psoriasis, and blood disorders. Notably, the inclusion of glucagon-like peptide-1 (GLP-1) receptor agonists-semaglutide, liraglutide, dulaglutide-and the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, represents a paradigm shift in the management of type 2 diabetes mellitus (T2DM) and obesity. These agents have demonstrated significant benefits in lowering blood glucose levels, reducing cardiovascular and renal complications, and promoting weight loss in T2DM patients with established cardiovascular disease (CVD), chronic kidney disease (CKD), or obesity. This move aims to bridge the longstanding treatment gap in low- and middle-income countries (LMICs), where high drug costs have limited access to such therapies. Their recognition as essential medicines enables prioritisation of limited resources, facilitates equitable pricing, and supports the development of generics and biosimilars post-patent expiry. This inclusion aligns with Sustainable Development Goal 3.4, which aims to reduce premature mortality from non-communicable diseases (NCDs) by 1/3 by 2030. However, challenges persist, including financial constraints, limited healthcare infrastructure, and risks of irrational use, particularly for obesity alone. Effective implementation through national policies, training, and rational prescribing frameworks is essential to translating this global milestone into tangible public health benefits and to reducing the growing burden of diabetes and obesity worldwide.

Background: Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a common chronic liver condition with significant metabolic and cardiovascular implications. Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated hepatic benefits in diabetic populations, their role in non-diabetic individuals with NAFLD remains unclear.

Objective: This meta-analysis aimed to evaluate the effects of SGLT2 inhibitors in non-diabetic NAFLD/MASLD patients.

Methods: PubMed, Embase, and CENTRAL were searched up to May 2025 for randomized controlled trials (RCTs) comparing SGLT2i with placebo or other pharmacologic agents in non-diabetic adults with NAFLD. Primary outcomes included changes in hepatic function; secondary outcomes assessed anthropometric, metabolic, and imaging-based markers of hepatic steatosis and fibrosis. A random-effects model was applied to estimate pooled mean differences (MDs) and 95% confidence intervals (CIs).

Results: Five RCTs comprising 273 non-diabetic patients (142 in the SGLT2i group) were included. SGLT2i significantly improved liver enzymes: AST (MD = -2.03; 95% CI: -3.24 to -0.82; p < 0.01), ALT (MD = -4.50; 95% CI: -6.89 to -2.10; p < 0.01), and GGT (MD = -4.12; 95% CI: -6.87 to -1.37; p < 0.01). Modest but significant reductions were also observed in body weight (MD = -3.24 kg), BMI (MD = -1.02 kg/m²), and waist circumference (MD = -3.12 cm). However, SGLT2i did not significantly affect triglycerides, HbA1c, fasting glucose, liver stiffness, CAP scores, or FIB-4 index.

Conclusion: SGLT2i significantly improves liver enzyme levels and anthropometric markers in non-diabetic individuals with NAFLD/MASLD, suggesting potential therapeutic benefits. However, their effects on hepatic steatosis resolution and fibrosis progression remain inconclusive.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-025-01797-0.

Obesity and type 2 diabetes (T2D) are interconnected metabolic disorders driving the global increase in cardiovascular diseases. Obesity contributes to insulin resistance, systemic inflammation, and metabolic imbalances, which hasten the progression of T2D and impair heart function. Persistent low-grade inflammation, disrupted adipokine signaling, and oxidative stress result in endothelial dysfunction, myocardial fibrosis, and cardiac remodeling. In type 2 diabetes, hyperglycemia worsens these conditions by facilitating the formation of advanced glycation end products (AGEs), mitochondrial dysfunction, and lipid buildup, further disrupting cardiac metabolism and elevating the risk of heart failure. Coronary microvascular dysfunction plays a significant role in myocardial ischemia among individuals with obesity and diabetes. This review explore the complex mechanisms that connect obesity, diabetes, and myocardial dysfunction while emphasizing innovative therapeutic strategies to reduce cardiovascular disease (CVD) risk. Pharmacological treatments, such as SGLT2 inhibitors, GLP-1 receptor agonists, and anti-inflammatory agents, demonstrate potential in enhancing metabolic and cardiovascular health by addressing oxidative stress, inflammation, and glucotoxicity. Meanwhile, lifestyle changes, including weight management and regular physical activity, remain fundamental to both prevention and treatment. Tackling these interconnected pathways is crucial for developing effective solutions to lessen the CVD burden in obese and diabetic populations.

Background: High body mass index (BMI) remains a critical public health issue, significantly burdening healthcare systems. This study aimed to evaluate the burden of high BMI and its related causes in Iran from 1990 to 2021.

Methods: Data from the Global Burden of Disease (GBD) 2021 project were used to assess the burden attributable to high BMI in Iran. Measures included years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and deaths, presented by cause, age, sex, province, and sociodemographic index (SDI). Summary exposure values (SEVs) were also analyzed to indicate exposure levels. All estimates were reported with 95% uncertainty intervals (UIs).

Results: The age-standardized DALYs per 100,000 population attributable to high BMI increased by 39.3% (17.4 to 55.9), from 1570.8 (95% UI: 801.5 to 2356.3) in 1990 to 2188.4 (1020.5 to 3231.0) in 2021. Similarly, the age-standardized death rate rose by 28.2% (6.55 to 46.07), from 55.9 (32.4 to 81.7) in 1990 to 71.6 (39.2 to 106.8) in 2021. For both sexes, the premature death rate (under 70 years) rose from 14.05 (7.66-20.36) in 1990 to 26.42 (13.78-37.97) in 2021. Cardiovascular diseases (CVDs) and diabetes and kidney disorders remained the leading causes of high BMI-related deaths. From 2010 to 2021, low SDI provinces saw greater increases in BMI-attributed death rates compared to 1990-2010. SEV values rose across all age groups from 1990 to 2021, particularly among females aged 60-69. Between 2019 and 2021, SEV changes accelerated compared to 2010-2019.

Conclusion: The burden of high BMI and related diseases in Iran has increased substantially over the past three decades. This trend highlights the urgent need for targeted public health initiatives to mitigate the health and economic impacts of obesity, particularly addressing disparities related to sex, age, and provincial SDI levels, while focusing on CVDs and diabetes prevention.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-025-01803-5.