Abstract
To assess the risk of type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS) in relation to body mass index (BMI) and the hyperandrogenic (HA) PCOS phenotype. Population-based cohort study. Data from six Swedish national registers, with participants being followed for a maximum of 19 years. All women with an International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of PCOS, androgen excess, or anovulatory infertility born between 1950 and 1999 (n = 52,535) were identified in the Patient Register. The HA PCOS phenotype was defined by two filled prescriptions for anti-androgenic drugs. For each woman with PCOS, five control women (n = 254,624) were randomly chosen from the Total Population Register, matched for age and geographic area. No interventions were performed. International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of T2D or prescription of antidiabetic treatment other than metformin. The cumulative incidence rates of T2D were 1.3%, 4.4%, and 14.2% in controls (non-PCOS women) and women with normoandrogenic (NA) and HA PCOS, respectively. After adjustment for BMI, women with PCOS had a twofold higher rate of T2D than non-PCOS women (adjusted hazard ratio, 2.52 [95% confidence interval, 2.15-2.96]). Women with HA PCOS had a higher rate of T2D than those with NA PCOS (adjusted hazard ratio, 3.86 [95% confidence interval, 3.16-4.72]). Polycystic ovary syndrome is an independent risk factor for T2D, even after adjustment for BMI. Women with the HA PCOS phenotype face an even higher risk of T2D than those with the NA PCOS phenotype.
Highlights
Women with NA polycystic ovary syndrome (PCOS) had more often been diagnosed with obesity than women with HA PCOS, who in turn were more often diagnosed than non-PCOS women: 16.6%, 12.7%, and 4.5%, respectively
In model 2, adjusting for obesity diagnosis (Supplemental Table 2, available online), women with NA PCOS had a higher rate of developing type 2 diabetes (T2D) than non-PCOS women
No increased rate of T2D was noted in non-PCOS women treated with anti-androgenic COCs; the adjusted hazard ratios (aHRs) were 0.83 with adjustment for obesity diagnosis and 1.26 with adjustment for body mass index (BMI)
Summary
To assess the risk of type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS) in relation to body mass index (BMI) and the hyperandrogenic (HA) PCOS phenotype. Four different phenotypes have been identified on the basis of current criteria; three of these include HA, while one is normoandro- It is unclear, whether all women with PCOS are at increased risk of T2D or only those with concomitant overweight or obesity. Two Nordic studies reported that normal-weight women with PCOS were not at increased risk of developing T2D, suggesting that the higher risk of T2D in women with PCOS is because of overweight and obesity [12, 13]. While the relationship between PCOS and T2D is well established [7,8,9,10], no previous population-based study has addressed the risk of T2D in relation to BMI and the HA phenotype in women with PCOS. On the basis of previous metabolic studies [17, 18], we further hypothesized that women with HA PCOS are at higher risk of T2D than those with NA PCOS
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