Prospective Risk of Type 2 Diabetes in Normal Weight Women with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is associated with obesity and increased risk for type 2 diabetes (T2D). However, the prospective risk of T2D in normal weight women with PCOS is debated, together with the relevant prospective screening programs for T2D in normal weight women with PCOS. Aim: To review and discuss prospective risk of T2D in normal weight women with PCOS, and to give recommendations regarding prospective screening for T2D in normal weight women with PCOS. Methods: Systematic review. Results: A systematic literature search resulted in 15 published prospective studies (10 controlled studies and 5 uncontrolled studies) regarding risk of T2D in study cohorts of PCOS, where data from normal weight women with PCOS were presented separately. In controlled studies, higher risk of T2D in normal weight women with PCOS compared to controls was reported in 4/10 studies, which included one study where T2D diagnosis was based on glucose measurement, two register-based studies, and one study where diagnosis of T2D was self-reported. Six of the 10 controlled studies reported no increased risk of T2D in normal weight women with PCOS. Four of these studies based the diagnosis of T2D on biochemical measurements, which supported the risk of surveillance bias in PCOS. In uncontrolled studies, 2/5 reported a higher risk of T2D in lean women with PCOS compared to the general population. We discuss the evidence for insulin resistance and β-cell dysfunction in normal weight women with PCOS, and aggravation in the hyperandrogenic phenotype, ageing women, and women with Asian ethnicity. Impaired glucose tolerance could be an important metabolic and vascular risk marker in PCOS. Conclusions: The risk of T2D may be increased in some normal weight women with PCOS. Individual risk markers such as hyperandrogenism, age >40 years, Asian ethnicity, and weight gain should determine prospective screening programs in normal weight women with PCOS.