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.
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