Polycystic ovary syndrome and elevated body mass index independently increase type 2 diabetes risk with obesity-mediated risk dominating: a real-world data analysis of US patients.

Abstract

OBJECTIVE To study the relationship between polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) in a retrospective US cohort. DESIGN Longitudinal case-control study. SUBJECTS The study utilized data from the IBM Explorys database, a comprehensive real-world dataset containing de-identified, longitudinal patient-level electronic health records (EHRs) from approximately 400 hospitals across the United States (US). The study population consisted of women diagnosed with PCOS between 2000 and 2020, aged 25 to 55 years (n = 42,030) and control women without PCOS (n = 84,060), matched 1:2 by ethnicity, geographic region, age, and BMI. Additionally, a secondary control group (n = 42,030) was employed, matched on all covariates except BMI. EXPOSURE PCOS status was identified using ICD-coded diagnoses, while T2DM diagnosis was determined using ICD-coded diagnoses as well as Hemoglobin A1c (HbA1c) levels. MAIN OUTCOME MEASURES The incidence of T2DM. RESULTS The 3-year cumulative incidence rates of T2DM in the PCOS and non-PCOS cohorts were 9.2% (95% Confidence Interval: 8.9% - 9.5%) and 6.0% (5.8% - 6.2%), respectively. The 15-year cumulative incidence rates were 34.3% (31.4% - 37.4%) and 22.6% (21.2% - 24.1%), respectively. The adjusted hazard ratio (HR) of T2DM in women with PCOS was 1.47 (1.41 - 1.53) compared to control individuals. HRs for PCOS were found to be consistent in different BMI strata ranging from 1.37 in the obese class III subgroup to 1.78 in the subgroup with normal weight. The median BMI in the PCOS cohort was 34.86 kg/m2, in contrast to 27.26 kg/m2 in non-PCOS controls not matched for BMI. The additional HR for T2DM associated with this BMI difference of 7.6 kg/m2 is estimated to be 1.87 (1.82 - 1.92). CONCLUSIONS In the current analysis, PCOS was independently associated with increased T2DM incidence across all BMI categories. Moreover, the elevated BMI in PCOS patients confers additional T2DM risk mediated by excess adiposity. This BMI-mediated risk exceeds the risk associated with PCOS through other mechanisms, such as hyperandrogenism.