Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including dulaglutide, have been associated with elevations in pancreatic enzymes, yet the magnitude and clinical significance of these changes in overweight and obese patients with type 2 diabetes mellitus (T2DM) remain unclear. This systematic review and meta-analysis quantified the effects of subcutaneous dulaglutide on serum amylase and lipase concentrations in this population. PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to May 2026. Randomized controlled trials comparing dulaglutide with placebo in overweight or obese adults with T2DM and reporting amylase or lipase outcomes were included. Pooled weighted mean differences (WMDs) with 95
Abstract Background Prior studies found that glycolysis-related metabolic markers—particularly lactate and glucose—are associated with short-term mortality after myocardial infarction (MI). However, information on glycolysis-wide metabolite alterations and short-term post-MI mortality remains insufficient. Therefore, this study investigated the associations of glucose, lactate, pyruvate, and citrate with short-term mortality after ST-elevation myocardial infarction (STEMI). Methods This study was based on data from 724 STEMI patients enrolled in the population-based Augsburg Myocardial Infarction Registry. Arterial EDTA blood samples were drawn at the start of the catheterization procedure and plasma concentrations of the metabolites were quantified using a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform developed by Nightingale Health (Finland). Multivariable logistic regression models were used to assess the associations between glycolysis-related metabolites and 28-day mortality. P values were adjusted for multiple testing using the false discovery rate (FDR) method. Results Overall, 677 patients survived the first 28 days after hospitalization, whereas 47 died within this period. Elevated plasma levels of glucose, lactate, pyruvate, and citrate were each significantly associated with an increased risk of short-term mortality. In the multivariable logistic regression models, the strongest association was observed for glucose (OR 2.10, 95% CI 1.53–2.88, p adj ≤ 0.001) and the weakest association for pyruvate (OR 1.60, 95% CI 1.22–2.10, p adj = 0.001). Conclusions These findings indicate that metabolic disturbances, reflected by glycolysis-related metabolites, are associated with short-term mortality in STEMI patients, suggesting their potential prognostic value.
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.
