Women with polycystic ovary syndrome (PCOS) have a significantly increased risk of developing type 2 diabetes at a younger age compared with controls, a national registry–based Danish study confirms.
With a median follow-up of 11 years, the risk for developing type 2 diabetes was four times higher in women with PCOS compared with controls (hazard ratio [HR], 4.0; P < .001), according to Katrine Hass Rubin, PhD, associate professor at the University of Southern Denmark in Odense, and colleagues.
The type 2 diabetes event rate was also four times higher in women with PCOS than in controls (8.0 per 1000 patient-years vs 2.0 per 1000 patient-years, P < .001), they say in their report published online August 29 in the Journal of Clinical Endocrinology & Metabolism.
Dr Rubin and colleagues note that prior evidence regarding the increased risk of type 2 diabetes in PCOS has been based on observational studies; data from population based studies are limited.
They found the average age at type 2 diabetes diagnosis was 31 years in women with PCOS (82% of whom were younger than 40) and 35 years for those without PCOS (66% of whom were younger than 40 years; P < .001).
Therefore, increasing age should not be included in future guidelines as an isolated risk marker for development of type 2 diabetes in PCOS, they emphasize.
The work also shows that a higher number of pregnancies was associated with a lower risk of type 2 diabetes among women with PCOS.
“The most straightforward explanation could be that multiple pregnancies indicate a less severe PCOS phenotype and therefore also a lower risk of later developing type 2 diabetes,” the study authors say. “Future studies are needed to evaluate the effect of oral contraceptives and number of births on risk of type 2 diabetes in PCOS.”
Diabetes Screening Key for Obese Women With PCOS
It is estimated that in the United States, up to 6 million women have PCOS, considered one of the most common endocrine conditions in women of childbearing age.
“Many women with PCOS are obese, but the risk for the development of diabetes in PCOS is unknown,” pointed out corresponding author Dorte Glintborg, MD, PhD, of the Odense University Hospital, in an Endocrine Society statement.
The current study’s findings are important since diabetes may develop at a young age, she said, noting that screening for diabetes is key, “especially in women who are obese and have PCOS.”
The best predictors of type 2 diabetes development in women with PCOS were body mass index (BMI) and fasting blood glucose. However, HbA1c, 2-hour blood glucose, insulin resistance, and triglycerides were also predictive of a future diagnosis of type 2 diabetes.
The study population consisted of two groups of women with PCOS: 18,477 premenopausal women extracted from national registry records from 1995 to 2015 (PCOS Denmark); and an embedded local cohort of 1162 women with PCOS and no history of type 2 diabetes (PCOS OUH). The latter were tested for insulin and glucose levels, cholesterol, triglycerides, and testosterone levels at the Odense University Hospital.
The control group consisted of 54,680 age-matched women without PCOS or a diagnosis of type 2 diabetes who were randomly selected from the same national registries. Matched sets were created by assigning three controls to each woman with PCOS.
The investigators used diagnosis codes and records of filled medical prescriptions to look for associations between baseline clinical and biochemical characteristics and development of type 2 diabetes. They also looked at age, BMI, number of pregnancies, and prescriptions for oral contraceptives.
Oral contraceptives, often used to treat hyperandrogenism and irregular menses in PCOS, increased the risk of type 2 diabetes in the PCOS Denmark group, the study authors say, noting that 71% women in this group were taking oral contraceptives compared with 34% of controls. When gestational diabetes was excluded from type 2 diabetes diagnosis, however, and number of births was added as a predictor of type 2 diabetes development, this risk became nonsignificant.
“These results could suggest a confounding effect of pregnancies for effect of oral contraceptive treatment on development of type 2 diabetes,” Dr Rubin and colleagues say.
Findings Confirmatory
Their findings confirm those from a 2010 meta-analysis showing that the odds ratio for type 2 diabetes was 4.4 in women with PCOS compared with controls (Hum Reprod Update. 2010;16:347-363).
Data from smaller observational studies in selected populations of women with PCOS were included in the meta-analysis, the study authors note, adding that until now, few nationwide data sets examining risk for type 2 diabetes in PCOS have been available.
And in a 2015 report on morbidity and medications in the same national cohort and matched controls, Dr Rubin and colleagues found a fivefold increase in the likelihood of type 2 diabetes in women at the time of PCOS diagnosis compared with non-PCOS controls: 1.5% v s 0.4%, respectively (Eur J Endocrinol. 2015;172:627-638).
BMI was closely associated with risk of type 2 diabetes in PCOS, they say, and it was highly unusual for a woman with a normal BMI to be diagnosed with type 2 diabetes at the time of presenting with PCOS. A recent population-based Finnish study reported a synergistic effect between overweight/obesity and PCOS for increased risk development of type 2 diabetes (Hum Reprod. 2017;32:423-431).
Although women in the PCOS OUH subgroup were relatively slim — median BMI at time of PCOS diagnosis was 26.9 kg/m2 — 10% still developed type 2 diabetes.
The study authors report no relevant financial relationships.
J Clin Endocrinol Metab. Published online on August 29, 2017. Abstract
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