Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

Background: Metabolic Syndrome (MetS) is a significant public health concern globally, driven by factors like obesity and sedentary lifestyles. In Iran, numerous meta-analyses have estimated its prevalence, but results vary. This umbrella review aims to synthesize these findings to provide a definitive summary of MetS prevalence across both general and high-risk populations in Iran.

Methods: We systematically searched international (PubMed/Medline, Scopus, Web of Science) and Persian databases (SID, Magiran) for meta-analyses published between January 2014 and August 2025 reporting pooled MetS prevalence in Iranian populations. Data extraction covered overall prevalence, subgroup analyses (gender, diagnostic criteria, population risk strata), and study characteristics. Methodological quality was assessed using AMSTAR 2, and evidence quality was evaluated using GRADE framework. Meta-analysis of pooled estimates was performed using random-effects models.

Results: Nineteen meta-analyses comprising 119 prevalence estimates and 1,954,049 participants were included. The overall pooled prevalence of MetS in Iran was 30.4% (95% CI: 28.44-32.33). Prevalence was higher in females (33.05%) than in males (27.57%). The prevalence varied by diagnostic criteria, with the Joint Interim Statement (JIS) criteria yielding the highest estimate (36.47%), followed by the International Diabetes Federation (IDF) criteria (32.03%), and the NCEP-ATP III criteria (26.86%). High heterogeneity (I² > 99%) was observed. The methodological quality of included studies was predominantly moderate, and the GRADE evidence quality for most outcomes was moderate.

Conclusion: Approximately one in three Iranian adults is affected by MetS, with disproportionately higher burden among women and specific high-risk populations. The choice of diagnostic criteria significantly influences prevalence estimates, and considerable heterogeneity across studies highlights the context-dependent nature of these findings. These results underscore the urgent need for targeted public health interventions and systematic screening strategies tailored to different population risk profiles.

Registration information: The study protocol was registered in the Prospero with ID, CRD420251182425.

Background: Hypertension (HTN) and dyslipidemia (DYS) frequently complicate type 2 diabetes mellitus (T2DM), increasing cardiovascular risk. Genetic variation within the DPP4-ABCC8-INSR-IGF1 axis may underlie this clustering.

Methods: A total of 444 T2DM patients were stratified into T2DM (n = 256), T2DM with HTN (T2MH, n = 134), and T2DM with HTN and DYS (T2MH-DYS, n = 54). Six single nucleotide polymorphisms (SNPs) were genotyped, and associations were assessed by logistic regression and haplotype analysis with Bonferroni correction.

Results: Clinical profiling showed higher C-reactive protein (CRP) and adrenocorticotropic hormone (ACTH) in T2MH and more severe metabolic derangements in T2MH-DYS. DPP4 rs3788979 was strongly linked to hypertension: CT (adjusted OR = 0.370, P = 0.001) and CC (adjusted OR = 0.424, P = 0.001) were protective versus TT, while in the T2MH vs T2MH-DYS comparison, the same CT and CC genotypes conferred increased dyslipidemia risk (adjusted OR = 5.418, P = 0.001; OR = 5.620, P = 0.002). In the comparison between T2DM and T2MH-DYS, the same genotypes also increase the susceptibility risk. IGF1 rs972936 TC genotype also reduced T2MH risk (adjusted OR = 0.460, P = 0.006). Haplotype analysis identified GAATGT as protective against hypertension (OR = 0.312, P = 0.0014) and GACCGT as a risk haplotype for dyslipidemia (OR = 4.113, P = 0.0021); both remained significant after Bonferroni correction.

Conclusion: Variants within the DPP4 axis influence susceptibility to HTN and DYS in T2DM, with GAATGT and GACCGT emerging as robust haplotype markers. Notably, the risk conferred by DPP4 rs3788979 genotypes was modulated by lipid status: CT/CC were protective against hypertension alone but became risk factors when dyslipidemia co-occurred.

Purpose: The ratio of gamma-glutamyl transferase (GGT) to high-density lipoprotein cholesterol (HDL-C) (GHR) represents a novel non-insulin-based biomarker for evaluating the risk of NAFLD and T2DM. However, its correlation with diabetic kidney disease (DKD) remains unexplored. This study aims to explore the association between GHR and DKD in patients with T2DM.

Patients and methods: In this cross-sectional study, 2798 patients diagnosed as T2DM admitted to the hospital from 2018 to 2023 were assessed. The analysis was conducted through restricted cubic spline (RCS) and logistic regression methodologies, complemented by additional stratified and interaction analyses.

Results: As the quartiles of GHR increase, there is a notable increase in the prevalence of DKD, with the rates of 43.2%, 47.2%, 52.1%, and 57.4%, respectively. Logistic regression analysis showed a positive association between GHR and DKD (OR=1.17, 95% CI: 1.05-1.30), which was consistently observed across all subgroups through stratified analysis. RCS analysis identified an inverted L-shaped association, with an inflection point at 84.5. Additionally, AUC for GHR (AUC = 0.637, 95% CI: 0.616-0.657) was significantly higher compared to those of GGT and HDL alone.

Conclusion: GHR exhibits a positive association with the risk of DKD, underscoring its potential utility as a cost-effective biomarker for stratifying the risk of DKD.

Introduction: Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease (ESKD), with renal fibrosis as a key pathological hallmark. However, the cellular and molecular drivers of fibrosis remain incompletely defined. Here, we employed single-cell RNA sequencing (scRNA-seq) to delineate pro-fibrotic cell subsets and their key regulatory factors in human DN kidneys, providing a higher-resolution view compared to previous fibrosis-related scRNA-seq studies.

Methods: Publicly available scRNA-seq datasets from human DN and control kidneys were analyzed to identify fibrosis-associated fibroblast subsets. A Tmsb10-high fibroblast population was prioritized. Functional validation was performed through Tmsb10 knockdown in NIH-3T3 fibroblasts and in a diabetic mouse model, followed by assessment of fibrosis markers, extracellular matrix (ECM) deposition, and TGF-β/SMAD signaling.

Results: scRNA-seq revealed a significant expansion of Tmsb10-high fibroblasts in DN kidneys, exhibiting strong enrichment of ECM-related and TGF-β/SMAD-responsive genes. Tmsb10 knockdown reduced Fn1, Col1a1, and α-Sma expression by approximately 50-70% and markedly attenuated ECM accumulation in vivo. Mechanistically, TMSB10 deficiency suppressed phosphorylation of SMAD2/3, mitigating fibroblast activation and matrix deposition.

Discussion: This study identifies TMSB10 as a novel fibroblast-specific regulator of renal fibrosis in DN, acting through the TGF-β/SMAD pathway. These findings expand current understanding of fibroblast heterogeneity and highlight TMSB10 as a potential therapeutic target for DN and other fibrotic diseases. Limitations include validation in a limited sample size and the use of murine fibroblast models, warranting further confirmation in human primary cells.

Background: The developmental origins of health and disease (DOHaD) framework highlights the importance of the intrauterine environment in shaping lifelong health outcomes. Maternal nutrition, toxic exposures, and epigenetic reprogramming are key factors influencing offspring susceptibility to obesity and cardiometabolic disorders. However, prior reviews have typically addressed nutrition and toxicants separately, limiting insights into their combined effects on the fetal epigenome. This review integrates current evidence on how maternal nutrition and toxicant exposures converge through epigenetic mechanisms to influence obesity risk, while outlining translational opportunities for mitigating intergenerational metabolic disease.

Methods: A narrative review was conducted of studies published from 2000 to 2025, sourced from PubMed, Scopus, and Web of Science, supplemented by manual screening. Search terms included maternal nutrition, environmental toxicants, epigenetic mechanisms, and offspring obesity outcomes. Studies on animal models, human cohorts, and intervention trials were included, focusing on links between maternal exposures, epigenetic changes, and metabolic disease.

Results: Maternal dietary imbalances, such as deficiencies in one-carbon donors or excess caloric intake, cause persistent epigenetic changes on genes regulating adipogenesis and energy homeostasis, increasing offspring obesity risk. Prenatal exposure to environmental toxicants, including endocrine disruptors and heavy metals, amplifies these vulnerabilities by altering DNA methylation, histone modifications, and noncoding RNA networks. Combined nutritional deficits and toxicant exposures, particularly in low- and middle-income countries (LMICs), create a "dual burden" that intensifies epigenetic instability. Nutrients like methyl donors and antioxidants may mitigate toxicant-induced epimutations, offering potential for precision maternal nutrition interventions.

Conclusion: Maternal nutrition and toxicant exposures interact through epigenetic mechanisms to program obesity and related diseases. Addressing these factors through precision nutrition, stricter environmental regulations, and early-life epigenetic biomarkers offers promising prevention strategies. Large, diverse, multi-generational cohorts and multi-omics approaches are needed to strengthen causal inference and inform equitable policies to break the intergenerational cycle of metabolic disease.

Background: Insulin resistance (IR) is a pivotal pathological feature in the development of type 2 diabetes mellitus (T2DM). MicroRNA-199a (miR-199a) has been implicated in various metabolic disorders, but its precise role and mechanism in hepatic IR remain largely unexplored. This study aimed to investigate the role of miR-199a in IR and inflammation and to determine whether its effects are mediated through DDIT4 and the PI3K/AKT pathway.

Methods: An in vitro IR model was established in HepG2 cells using palmitic acid, and an in vivo T2DM model was induced in mice using a high-fat diet combined with streptozotocin injection. Functional assays, including glucose uptake and ELISA, were employed to assess metabolic and inflammatory responses. The interaction between miR-199a and its putative target, DDIT4, was validated by luciferase reporter and RNA immunoprecipitation assays. Key proteins in the PI3K/AKT signaling pathway were analyzed by Western blotting.

Results: We found that miR-199a was significantly upregulated, while DDIT4 was downregulated in both IR HepG2 cells and diabetic mice. Mechanistically, we identified DDIT4 as a direct target of miR-199a. Knockdown of miR-199a ameliorated insulin resistance and suppressed inflammation, whereas concomitant depletion of DDIT4 abolished these protective effects. Furthermore, miR-199a inhibition activated the PI3K/AKT pathway, as evidenced by increased phosphorylation of PI3K, AKT, and AS160, and decreased phosphorylation of FOXO1. These signaling changes were also dependent on DDIT4. In vivo, inhibition of miR-199a improved glucose homeostasis, attenuated systemic inflammation, and activated pancreatic PI3K/AKT signaling in T2DM mice.

Conclusion: Our findings reveal a novel miR-199a/DDIT4 axis that regulates insulin sensitivity and inflammation via the PI3K/AKT pathway, suggesting miR-199a as a potential therapeutic target for T2DM.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder indicated by hyperglycemia. The potential for adverse effects occurring in conventional therapies necessitates the exploration of natural alternatives.

Aim: This study aimed to evaluate the protective effect of mermelosin in a high-fat diet and streptozotocin (STZ) induced rat model of T2DM.

Methods: Twenty-four rats were randomly allocated to four experimental groups (n=6) for a 28-day study. Group 1 served as the control, receiving 0.5 mL of normal saline. Group 2 (T2DM control) received 35 mg/kg STZ and HFD to induce diabetes. Groups 3 and 4 received 10 mg and 20 mg of marmelosin orally, respectively. After 28 days, biochemical analyses were performed to assess pancreatic oxidative stress, insulin levels, and essential biochemical markers, including a lipid profile, liver function, inflammatory responses, oxidative stress levels, and apoptotic activity.

Results: Marmelosin significantly improved fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in rats with T2DM. It also enhanced insulin sensitivity, as evidenced by increased plasma insulin levels and decreased HOMA-IR values. Marmelosin effectively mitigated dyslipidemia by lowering total cholesterol and serum triglycerides while elevated HDL cholesterol. Furthermore, it acted as a potent antioxidant, as indicated by the elevation of SOD, GSH, CAT, and reduced cytokines (TNF-α, IL-1β, IL-6). Marmelosin also reduced apoptosis by downregulating caspase-3 expression.

Conclusion: These findings collectively suggest that marmelosin acts as a multifaceted protective effect, including metabolic regulation, anti-inflammatory, antioxidant, and anti-apoptotic activities, highlighting its potential as a promising therapeutic agent for the management of T2DM.

Purpose: Dumping syndrome (DS) is a postsurgical complication of bariatric procedures. It is classified into early and late dumping based on occurrence within different postprandial timeframes. This study measures the prevalence of DS among adult patients and its association with social determinants and nutrition knowledge.

Patients and methods: This cross-sectional study used a convenience sampling method via distributing an online validated questionnaires to patients who underwent sleeve gastrectomy or gastric bypass surgery in ≥3 months.

Results: Out of 352 participants, 237 (67.3%) had a modified Sigstad weighted DS score of ≥3.26, indicating the presence of DS; 182 (76.8%) had early DS (symptoms within 1 hour postprandially) and 55 (23.2%) had late DS (symptoms 1-3 hours postprandially). Only gender and monthly income showed statistically significant differences between early and late DS patients. No statistically significant associations were found between the DS subtypes and sociodemographic characteristics, although participants' age approached significance (p = 0.052). Type 1 diabetes was significantly associated with DS and affected patients were 6.7 times more likely to experience symptoms. The mean nutrition knowledge score among all the participants was 60.88 (SD = 14.76) suggesting moderate nutrition knowledge.

Conclusion: There is a high prevalence of DS (67.3%) among post-bariatric surgery patients in Saudi Arabia, and early DS is more common than late DS. The findings suggest a strong correlation between type 1 diabetes and DS. Nutrition knowledge was moderate but insufficient in key areas that affect postoperative outcomes. The study is novel in reporting a high prevalence of DS among post-bariatric patients in Saudi Arabia and uniquely explores the association of DS with social determinants, nutrition knowledge, and type 1 diabetes-areas less examined in previous research. It emphasizes the imperative need for comprehensive patient education and continuous dietary counseling to improve long-term management and outcomes for bariatric surgery patients.

Objective: To search, evaluate and summarize the evidences of health management in middle-aged and elderly patients with type 2 diabetes with traditional Chinese medicine (TCM) characteristics, so as to provide evidence-based basis for improving patients' participation initiative and implementing personalized health management practice for community medical staff.

Methods: Based on evidence-based nursing methods, The domestic and foreign evidence-based resource databases including UpToDate, Elsevier, Web of Science and Cochrane were searched Library, RNAO, PubMed, Medline, CINAHL, Embase, BMJ British Medical Journal, Medical Pulse Guide Network, Chinese Medical Association, Diabetes Society, CMA Chinese Medical Association, OVID database, JBI evidence-based Health Care Center database, Chinese Traditional Medicine Database, Chinese Biomedical Literature Xian database, Wanfang database, VIP database and China National Knowledge Infrastructure. Two researchers based on the critical appraisal for summaries of evidence, CASE) appraisal of guidelines for research and evaluationII (AGREEII) independently assessed the quality of the included literature, and extracted and summarized the literature evidence that met thecriteria.

Results: A total of 10 guidelines, 6 expert consensus, 3 evidence summaries, and 2 Meta-analysis summarized four dimensions, namely nutrition management, exercise management, TCM diet management, and TCM emotional management, with a total of 35 pieces of evidence.