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Definitions of Metabolic Health and Risk of Future Type 2 Diabetes in BMI Categories: A Systematic Review and Network
Luca A Lotta1, Ali Abbasi2, Stephen J Sharp1
1MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, U.K.
Objective:
Various definitions of metabolic health have been proposed to explain differences in the risk of type 2 diabetes within 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 meta-analysis, relative risks (RRs) 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, classification as metabolically unhealthy was associated with higher RR of diabetes in all BMI categories (lean RR compared with healthy individuals 4.0 [95% CI 3.0-5.1], overweight 3.4 [2.8-4.3], and obese 2.5 [2.1-3.0]). Metabolically healthy obese individuals had a high absolute risk of type 2 diabetes (10-year cumulative incidence 3.1% [95% CI 2.6-3.5]). Current binary definitions of metabolic health had high specificity (pooled estimate 0.88 [95% CI 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 RR 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.
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