Weight Change as a Predictor of Incidence and Remission of Insulin Resistance

OBJECTIVE The objective of this study was to assess the longitudinal relationship of weight change on incidence and remission of insulin resistance (IR). METHODS We performed a cohort study in apparently healthy Korean men, 30 to 59 years of age, who underwent a health checkup and were followed annually or biennially between 2002 and 2009. The computer model of homeostasis model assessment, HOMA2-IR, was obtained at each visit, and IR was defined as HOMA2-IR ≥75th percentile. RESULTS For IR development, 1,755 of the 6,612 IR-free participants at baseline developed IR (rate 5.1 per 100 person-years) during 34,294.8 person-years of follow-up. The hazard ratios (95% confidence intervals) for incident IR with weight changes of <-0.9 kg, 0.6-2.1 kg and ≥2.2 kg from visit 1 to visit 2 (average 1.8 years) compared to weight change of -0.9-0.5 kg (reference) were 0.78 (0.68-0.90), 1.19 (1.04-1.35) and 1.26 (1.11-1.44), respectively. This association persisted in normal-weight individuals or those without any metabolic syndrome traits and remained significant after introducing weight categories and confounders as time-dependent exposures (P-trend <0.001). For IR remission, 903 of 1,696 IR participants had no IR (remission rate 10.3 per 100 person-years) during 8,777.4 person-years of follow-up. IR remission decreased with increasing quartiles of weight change (P-trend <0.001) and this association persisted in normal-weight individuals. CONCLUSIONS Weight gain was associated with increased IR development and decreased IR remission regardless of baseline BMI status. Preventing weight gain, even in healthy and normal-weight individuals, is an important strategy for reducing IR and its associated consequences.