Type 2 diabetes mellitus (T2DM) remission is increasingly recognized as an achievable clinical state. However, its long-term associations with mortality and vascular complications remain uncertain. We conducted a systematic review and meta-analysis of longitudinal studies to evaluate the associations of T2DM remission with all-cause mortality, cardiovascular events, microvascular complications, and macrovascular complications. PubMed, Embase, Web of Science, and Scopus were searched from inception to July 20, 2026, without language restrictions. Longitudinal studies were eligible if they included adults with T2DM, assessed remission before outcome ascertainment, compared participants who achieved remission with those who did not achieve or maintain remission, and reported an adjusted effect estimate after at least 12 months of follow-up. Methodological quality was assessed using the Newcastle–Ottawa Scale. Adjusted hazard ratios (HRs) and 95
Diabetic foot ulcers (DFUs) is strongly correlated with aging, yet the effects of anti-senescent treatments on DFU wound repair are poorly characterized. We aimed to investigate whether glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of geroprotective agents, promote wound healing in patients with DFUs. In this prospective, randomized placebo-controlled clinical trial, we enrolled 105 eligible participants, who were randomly assigned in a 1:1 ratio to receive either GLP-1RA (liraglutide) or placebo. The primary outcome was wound healing time, and the key secondary outcome encompassed the circulating levels of senescence-associated secretory phenotype (SASP) factors. The mean age of the overall cohort was 73.7 ± 7.9 years, and males accounted for 55.2
Metabolically unhealthy obesity (MUO) is characterized by adipose tissue dysfunction and insulin resistance (IR), though the causal genetic drivers remain elusive. We applied multi-omics Mendelian randomization (MR) to identify suggestive genetically associated glycolysis-related candidates and molecular signals linked to IR in MUO. We integrated transcriptomic data from MUO/MHO subcutaneous adipose tissue (GSE156906) to screen the MUO-related glycolysis genes. By integrating IR GWAS data with DNA methylation quantitative trait loci (mQTLs), expression QTLs (eQTLs), and protein QTLs (pQTLs) information, we performed Summary-data-based MR (SMR) analysis to investigate the genetic association between MUO-related glycolysis genes and the IR. Colocalization analysis was performed to determine if identified signals share a causal genetic variant. Additionally, tissue-specific validations were performed using GTEx v8 eQTL data. In MUO adipose tissue, 205 glycolysis genes were downregulated and 89 upregulated (p < 0.05). Founded on the MUO-related glycolysis genes, our analysis identified 64 mQTLs, 11 eQTLs and 7 pQTL associated with IR risk in the discovery dataset. Colocalization analysis provides suggestive evidence in support of these associations. Based on the mQTL-eQTL analysis, HKDC1 (cg05532178, cg11762346) showed convergent SMR and colocalization evidence suggestive of an association with IR in the discovery cohort. Tissue-specific SMR analyses showed directionally consistent negative associations between HKDC1 expression and IR across metabolically relevant tissues. Furthermore, based on the eQTL-pQTL analysis, we identified that ITGAM showed directionally consistent associations at both transcriptomic and proteomic levels with IR risk, though these associations reached only nominal significance and colocalization support was modest. These findings provide exploratory multi-omics evidence for candidate genes potentially linking glycolytic dysregulation to insulin resistance in obesity. Further validation in independent cohorts and experimental systems is warranted.
To identify circulating microRNA (miRNA) signatures associated with metabolic health status independent of body mass index (BMI) and to characterize their underlying regulatory pathways. Plasma samples from 240 Qatari adults were classified as metabolically healthy people with obesity (MHO), metabolically unhealthy people with obesity (MUHO), metabolically healthy normal-weight (MHNW), or metabolically unhealthy normal-weight (MUHNW) (n = 60/group). Differential miRNA expression was assessed using chemometric analyses, followed by target-gene and pathway enrichment analyses. Distinct circulating miRNA profiles differentiated metabolic phenotypes. Key miRNAs distinguishing MHO from MUHO included hsa-miR-122-5p, hsa-miR-195-5p, among others, differentiated MHNW from MUHNW. Predicted targets of MUHO-associated miRNAs were enriched in pathways related to lipid metabolism, insulin signaling, inflammation, oxidative stress, and apoptosis. In contrast, MUHNW-associated miRNAs were linked to immune regulation, inflammatory signaling, leukocyte migration, and lipid transport. Several miRNAs and miRNA ratios showed strong discriminatory performance across metabolic phenotypes. Circulating miRNA signatures distinguish metabolic health phenotypes independent of BMI and highlight distinct molecular pathways associated with metabolic dysfunction in people with obesity and normal weight.
Endometrial cancer (EC) is strongly associated with obesity, and tirzepatide produces substantial weight loss with preclinical evidence of direct antitumor activity. We aimed to evaluate the association between tirzepatide use and incident EC risk in women with overweight or obesity. Using the TriNetX US Collaborative Network, we identified women with overweight or obesity who initiated tirzepatide (study group) or lifestyle modification interventions (control group) between January 1, 2022, and December 31, 2025. After 1:1 propensity score matching (PSM), the risk of incident EC over two years was compared using Cox proportional hazards regression. After matching, 176,981 patients were included in each group. The mean age was 49.3 ± 13.8 years in the study group and 49.1 ± 16.1 years in the control group. The estimated cumulative follow-up was approximately 202,632 person-years in the tirzepatide group and 194,447 person-years in the lifestyle modification group. During a maximum follow-up window of two years, tirzepatide use was associated with a lower hazard of newly recorded EC diagnoses compared with the comparator cohort (HR, 0.717; 95
