Incidence of diabetes according to metabolically healthy or unhealthy normal weight or overweight/obesity in postmenopausal women: the Women's Health Initiative.

Objective: To determine the relationship of metabolic weight categories with incident diabetes mellitus (DM) in postmenopausal women.

Methods: 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).

Results: 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).

Conclusions: 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.