Abdominal Obesity Phenotypes and Incidence of Type 2 DM, Cardiovascular Outcomes and All-Cause Mortality-A Systematic Review and Meta-Analysis.

Abstract

The global rise in obesity, a major driver of metabolic diseases, has prompted scrutiny of distinct obesity phenotypes. While overall obesity is concerning, abdominal obesity demonstrates a stronger association with metabolic dysfunction, type 2 diabetes (DM2), and cardiovascular disease (CVD). This review examines the risk of DM2, CVD, and mortality in adults with a metabolically healthy abdominal obese phenotype. A systematic search of PubMed/MEDLINE, Web of Science, Cochrane Library, and ProQuest was conducted on April 7, 2025, to identify prospective cohort studies in adults. Eligible studies compared MHAO individuals to metabolically healthy, non-abdominally obese (MHNAO) controls, focusing on outcomes including incident T2DM, fatal and non-fatal CVD events, and all-cause mortality. Pooled estimates were calculated using random-effects meta-analysis, and heterogeneity was assessed using the I ² statistic. Six prospective cohort studies ( n = 98,329) were included. Metabolically unhealthy individuals, regardless of abdominal obesity status, had significantly increased risks of T2DM (RR 9.00, 95% CI 7.51-10.50 for MUHAO; RR 5.03, 95% CI 4.11-5.94 for MUHNAO), CVD, and all-cause mortality (HR 1.67, 95% CI 1.42-1.93 for MUHAO; HR 1.58, 95% CI 1.36-1.79 for MUHNAO). In contrast, MHAO individuals did not show significantly elevated risks of T2DM (RR 2.44, 95% CI 0.95-3.94), CVD, or all-cause mortality (HR 1.07, 95% CI 0.88-1.27) compared to MHNAO controls. Substantial heterogeneity ( I ² > 50%) was observed, partly explained by differences in outcome definitions and metabolic classifications. While metabolically unhealthy phenotypes are strongly associated with adverse health outcomes, individuals with MHAO appear to have risk profiles comparable to their metabolically healthy, non-abdominally obese counterparts. Nevertheless, abdominal adiposity and metabolic status remain critical determinants of long-term health, and the MHAO phenotype may not be entirely benign. Trial Registration: PROSPERO (CRD42019111056).