Abstract

To determine the relationship of metabolic weight categories with incident diabetes mellitus (DM) in postmenopausal women. The Women's Health Initiative (WHI) enrolled 161,808 postmenopausal women aged 50 to 79 years. We included those with cardiovascular disease (CVD) biomarkers and free of CVD and prevalent DM (n = 17,043) at baseline. Normal weight was defined as a body mass index (BMI) ≥18.5 and <25 kg/m, and waist circumference (WC) <88 cm and overweight/obesity as a BMI ≥25 kg/m or WC ≥88 cm. Metabolically healthy was based on <2 and metabolically unhealthy ≥2 traits of the following: triglycerides ≥150 mg/dL, systolic blood pressure (BP) ≥130 mm Hg or diastolic BP ≥85 mm Hg, or antihypertensives or diuretics, fasting glucose ≥100 mg/dL or DM medication, and high-density lipoprotein cholesterol <50 mg/dL. Cox regression was performed to determine the risk of incident DM among metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO). Among our sample, 2,253 (13.3%) participants developed DM over a mean ± standard deviation follow-up time of 15.6 ± 3.4 years. Compared with MHNW (n = 162 incident DM cases), an increased risk of incident DM was observed in MUHNW (n = 102 cases) (hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.74-2.88, P < 0.0001), MHO (n = 624 cases) (HR 1.68, 95% CI 1.40-2.00, P < 0.0001), and MUHO (n = 1,365 cases) (HR 4.51, 95% CI 3.82-5.35, P < 0.0001). Among postmenopausal women, MUHNW and MHO confer an approximate doubling in the risk and MUHO more than a four-fold increased risk for developing DM.

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