Definitions of metabolic health and risk of future type 2 diabetes in body mass index categories: a systematic review and network meta-analysis

Abstract

Objective: Various definitions of metabolic health have been proposed to explain differences in the risk of type 2 diabetes within body mass index (BMI) categories. The goal of this study was to assess their predictive relevance. Research Design and Methods: We performed systematic searches of MEDLINE records for prospective cohort studies of type 2 diabetes risk in categories of BMI and metabolic health. In a two-stage metaanalysis, relative risks (RR) specific to each BMI category were derived by network meta-analysis and the resulting RRs of each study were pooled using random effects models. Hierarchical summary receiver operating characteristic curves were used to assess predictive performance. Results: In a meta-analysis of 140,845 participants and 5,963 incident cases of type 2 diabetes from 14 cohort studies, being classified as metabolically unhealthy was associated with higher relative risk of diabetes in all BMI categories (RR compared with healthy individuals [95% confidence interval, CI]: lean, 4.0 [3.0 – 5.1]; overweight, 3.4 [2.8 – 4.3]; obese, 2.5 [2.1 – 3.0]). Metabolically healthy obese individuals had a high absolute risk of type 2 diabetes (10-year cumulative incidence [95% CI]: 3.1% [2.6 – 3.5%]). Current binary definitions of metabolic health had high specificity (pooled estimate [95% CI]: 0.88 [0.84 – 0.91]) but low sensitivity (0.40 [0.31 – 0.49]) in lean individuals and satisfactory sensitivity (0.81 [0.76 – 0.86]) but low specificity (0.42 [0.35 – 0.49]) in obese individuals. However, positive (< 3.3 in all BMI categories) and negative (> 0.4) likelihood ratios were consistent with insignificant to small improvements in prediction. Conclusions: Although individuals classified as metabolically unhealthy have a higher relative risk of type 2 diabetes compared with individuals classified as healthy in all BMI categories, current binary definitions of metabolic health have limited relevance to the prediction of future type 2 diabetes.