OBJECTIVE: We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore.
DESIGN AND PARTICIPANTS: This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging.
MAIN OUTCOME MEASURES: Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays.
RESULTS: Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1.
CONCLUSIONS: The relationships between abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship between abdominal adiposity and insulin resistance in South Asians, but not in Malays or Chinese.
METHODS: Medline and Embase databases were searched without date restriction on May 2022 for articles that examined EAT and cardiovascular outcomes. The inclusion criteria were (1) studies measuring EAT of adult patients at baseline and (2) reporting follow-up data on study outcomes of interest. The primary study outcome was major adverse cardiovascular events. Secondary study outcomes included cardiac death, myocardial infarction, coronary revascularization, and atrial fibrillation.
RESULTS: Twenty-nine articles published between 2012 and 2022, comprising 19 709 patients, were included in our analysis. Increased EAT thickness and volume were associated with higher risks of cardiac death (odds ratio, 2.53 [95% CI, 1.17-5.44]; P=0.020; n=4), myocardial infarction (odds ratio, 2.63 [95% CI, 1.39-4.96]; P=0.003; n=5), coronary revascularization (odds ratio, 2.99 [95% CI, 1.64-5.44]; P<0.001; n=5), and atrial fibrillation (adjusted odds ratio, 4.04 [95% CI, 3.06-5.32]; P<0.001; n=3). For 1 unit increment in the continuous measure of EAT, computed tomography volumetric quantification (adjusted hazard ratio, 1.74 [95% CI, 1.42-2.13]; P<0.001) and echocardiographic thickness quantification (adjusted hazard ratio, 1.20 [95% CI, 1.09-1.32]; P<0.001) conferred an increased risk of major adverse cardiovascular events.
CONCLUSIONS: The utility of EAT as an imaging biomarker for predicting and prognosticating cardiovascular disease is promising, with increased EAT thickness and volume being identified as independent predictors of major adverse cardiovascular events.
REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42022338075.
METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP-1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta-analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects.
RESULTS: Thirty-one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight-related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34). As compared to placebo, tirzepatide and GLP-1 RA across all doses had significant increases in gastrointestinal adverse effects.
CONCLUSIONS: The superiority of tirzepatide and GLP-1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity.
METHODS AND RESULTS: Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males.
CONCLUSIONS: This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.