Prospective risk of Type 2 diabetes in 99 892 Nordic women with polycystic ovary syndrome and 446 055 controls: national cohort study from Denmark, Finland, and Sweden
Authors: Glintborg Dorte , Ollila Meri-Maija , Møller Jens-Jakob Kjer , Pesonen Paula , Persson Sofia , Elenis Evangelia , Rubin Katrine Hass , Gissler Mika , Andersen Marianne Skovsager , Sundström-Poromaa Inger , Piltonen Terhi 
Published: June 2024

Abstract

STUDY QUESTION
What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls?

SUMMARY ANSWER
A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries.

WHAT IS KNOWN ALREADY
The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited.

STUDY DESIGN, SIZE, DURATION
This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin.

PARTICIPANTS/MATERIALS, SETTING, METHODS
The study cohort included women originating from Denmark (PCOS Denmark, N = 27 016; controls, N = 133 994), Finland (PCOS Finland, N = 20 467; controls, N = 58 051), and Sweden (PCOS Sweden, N = 52 409; controls, N = 254 010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0–14.8), 9.8 (5.1–15.1), and 6.0 (2.0–10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education.

MAIN RESULTS AND THE ROLE OF CHANCE
The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98–4.60) in Denmark, 3.40 (3.11–3.74) in Finland, and 5.68 (5.20–6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs &lt;25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99 892; controls, N = 446 055), the crude HR for T2D in PCOS was 4.64 (3.40–5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32–3.51).

LIMITATIONS, REASONS FOR CAUTION
Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities.

WIDER IMPLICATIONS OF THE FINDINGS
The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2.

STUDY FUNDING/COMPETING INTEREST(S)
Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest.

TRIAL REGISTRATION NUMBER
N/A.