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Introduction: The cardiovascular efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) are well documented; however, the differences in cardiovascular efficacy among subpopulations remain unknown. This systematic review and meta-analysis aimed to explore the differences in cardiovascular efficacy of long-acting GLP-1RAs among subpopulations of patients with T2DM and to assess the drug safety. Methods: Relevant studies up to March 31, 2020 were searched for in six electronic databases, namely PubMed, Cochrane Library, Embase, Clinical Trials, Science Direct, and Web of Science. The primary outcome was three-point major adverse cardiovascular events (including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke). Subpopulations were defined using ten selected influential factors, and the differences in cardiovascular efficacy in subpopulations stratified by different influential factors were accessed by synthesizing studies with random-effects models one by one. Results: A total of six cardiovascular outcome trials of long-acting GLP-1RAs, comprising 49,936 participants, were included. Among stratified subpopulations, no significant differences in the cardiovascular efficacy of long-acting GLP-1RAs were observed across the ten characteristics of subjects (all P for interaction > 0.05). Favorable trends were observed in the subpopulation with established cardiovascular disease (CVD) compared to that without (P = 0.171). With regards to safety, long-acting GLP-1RAs did not significantly increase the risk of retinopathy (OR 1.09; 95% CI 0.92–1.29; P = 0.316), but increase the risk of serious gastrointestinal events (OR 1.37; 95% CI 1.02–1.83; P = 0.037). Long-acting GLP-1RAs did not significantly increase the risk of serious adverse events (OR 0.92; 95% CI 0.85–1.00; P = 0.039). Conclusions: Our analysis suggested no subpopulation differences in the cardiovascular efficacy of long-acting GLP-1RAs among stratified subpopulations, and favorable trends were only observed in the subpopulation with established CVD. These findings may have implications for the management of long-acting GLP-1RAs across subpopulations of patients with T2DM. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the safety of insulin lispro Mix 25 and 50 (LM25 and LM50) in hypoglycemia in patients with type 2 diabetes mellitus (T2DM). Methods: This was a post hoc analysis of a phase IV, randomized, crossover clinical trial in Chinese patients with T2DM switching from premixed human insulin 70/30 (PHI70/30) to LM25 or LM50. Eighty-one subjects received a two-stage crossover protocol of either LM25 or LM50 twice daily for 16 weeks. Habitual diet was taken, and self-monitoring of blood glucose (SMBG) was performed throughout the study period. High-carbohydrate diet (HCD), high-fat diet (HFD) and habitual diet patterns were taken, and 72 h continuous glucose monitoring (CGM) was performed at the last 3 days of each treatment stage. Results: The frequencies of nocturnal hypoglycemia in LM50 were lower than those in LM25 under a Chinese habitual diet pattern. The related factors of hypoglycemia in patients with T2DM treated with a LM25 or LM50 regimen were the weight-based daily mean insulin dose and the type of combined oral hypoglycemic agents. Under both HCD and habitual diet patterns, the optimal cut point values of bedtime glucose predicting nocturnal hypoglycemia in LM50 were lower than those in LM25. Conclusions: The risk of nocturnal hypoglycemia in the LM50 regimen was lower than that in the LM25 regimen under the HCD pattern, and the safety range of bedtime glucose for the LM50 regimen was wider than that of the LM25 regimen in Chinese T2DM patients. Premixed insulin analogs combined with acarbose were more helpful to reduce the incidence of hypoglycemia. Trial Registration: http://www.chictr.org.cn #ChiCTR-TTRCC-12002516. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to explore the association between serum UA and cellular aging markers. Design: The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings: Serum uric acid (UA), which has both antioxidant and pro-oxidant properties, is thought to be involved in cellular aging processes. Participants: There are 536 participants included in total, 65.3% of which are women. The average serum UA in women was 267.8 umol/l, lower than in men of 337.7 umol/l (P<0.001). Measurements: Serum UA, blood lipid profile, HbA1c, plasma glucose and insulin were determined. The peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using a real-time PCR assay. Logistic regressions were used to analyze the associations between serum UA and cellular aging markers. Results: In Spearman's correlation analysis, there were significantly negative correlations between serum UA and LTL in both women and men (r=−0.162, P=0.006; and r=−0.232, P=0.004, respectively). The logistic regression adjusted for age, BMI, WC, daily energy intake, HbA1c, TG, and LDL-C revealed that the ORs of shorter LTL comparing the extreme serum UA quintiles was 5.52 (95% CI 1.69–18.02; P for trend =0.025) in women and 6.49 (95% CI 1.38–30.45; P for trend =0.108) in men. Furthermore, the OR (95% CI) for shorter LTL per 1 SD increment in serum UA was 1.51(1.10–2.07) in women and 1.64(1.01–2.65) in men. In regard to mtDNAcn, the association between elevated serum UA and lower mtDNAcn only reached significance in men when comparing the second and fifth quintiles with reference quintile (OR=3.73(1.07–13.04) and 3.76(1.01–14.09), separately, and P for trend=0.066). Conclusions: Our results indicate a significant negative association between serum UA and peripheral blood cellular aging markers. Serum UA might play a role in promoting cellular aging. [ABSTRACT FROM AUTHOR]