Abstract
IMPORTANCE: There is limited evidence regarding the association between age at menopause and incident type 2 diabetes (T2D). OBJECTIVE: To investigate whether age at menopause and premature menopause are associated with T2D incidence in postmenopausal Korean women. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted among a nationally representative sample from the Korean National Health Insurance Service database of 1 125 378 postmenopausal women without T2D who enrolled in 2009. The median (IQR) follow-up was 8.4 (8.1-8.7) years. Data were analyzed in March 2024. EXPOSURES: Age at menopause and premature menopause (menopause onset at age <40 years). MAIN OUTCOMES AND MEASURES: The primary outcome was incident T2D. Multivariable Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% CIs for incident T2D by age at menopause, adjusting for potential confounders. RESULTS: Of 1 125 378 participants (mean [SD] age at enrollment, 61.2 [8.4] years), 113 864 individuals (10.1%) were diagnosed with T2D at least 1 year after enrollment. Women with menopause onset at ages younger than 40 years (premature menopause; HR, 1.13; 95% CI, 1.08-1.18) and ages 40 to 44 years (HR, 1.03; 95% CI, 1.00-1.06) had increased risk of T2D compared with those with onset at age 50 years or older, with adjustment for sociodemographic, lifestyle, cardiometabolic, psychiatric, and reproductive factors; a younger age at menopause was associated with increased risk of developing T2D (P for trend <.001). Body mass index, depressive disorder, and prediabetes modified the association in subgroup analyses; for example, for individuals with premature menopause vs those with menopause at ages 50 years or older, HRs were 1.54 (95% CI, 1.14-2.06) for a BMI less than 18.5 and 1.14 (95% CI, 1.00-1.30) for a BMI of 30 or greater (P < .001), 1.28 (95% CI, 1.12-1.45) for individuals with depression and 1.11 (95% CI, 1.07-1.16) for those without depression (P = .01), and 1.25 (95% CI, 1.18-1.33) for individuals who were not prediabetic and 1.04 (95% CI, 0.99-1.11) those who were prediabetic (P < .001). CONCLUSIONS AND RELEVANCE: In this study, premature and early menopause were associated with a higher risk of T2D, highlighting the need for targeted public health strategies aimed at preventing or delaying T2D among postmenopausal women.