Development of insulin resistance in women over the menopause transition

BACKGROUND. Body weight and insulin resistance in women increase in midlife. It is not known whether this is driven by the menopause transition or solely by chronological aging. We aimed to determine the role of the menopause transition and menopause-related BMI changes in the development of insulin resistance in midlife women. METHODS. Mixed effects, linear spline modeling of longitudinal data in 1315 women, 42- to 52-years-old, pre- or early perimenopausal in 1995 to 1996 with up to 16 follow up visits by 2018. Homeostatic-model-assessed-insulin-resistance (HOMA-IR) was measured up to 12 times. Date of final menstrual period (FMP) was prospectively determined. RESULTS. HOMA-IR increased faster over a 4-year interval extending from 1.5 years prior to 2.5 years after the FMP, than in the years before or after it; p value for both slope changes < 0.0001. In the referent woman (White, age 52 years at FMP, non-smoker, body mass index [BMI] 25.6 kg/m 2 at baseline, and not on sex hormone therapy or statins), the average annualized rate of HOMA-IR increase, adjusted for covariates including changes in BMI, was 1.2%, 4.3%, and 0.9% respectively, before, during, and after the 4-year transition. CONCLUSION. Consistent with an independent effect of the menopause transition, insulin resistance increased significantly faster during the transition (from 1.5 years before the to 2.5 years after the FMP) than in the years preceding or following the transition. Future studies need to investigate mechanisms underpinning this observed association and determine the impact of lifestyle on dampening menopause-associated increases in insulin resistance. FUNDING. National Institutes of Health.