Learn about the relationship between insulin resistance and PCOS.
In women with polycystic ovary syndrome (PCOS), there are several risk factors that have been identified for the development of type 2 diabetes. In this video—the third and final video in our series on women’s health and diabetes—Andrea Dunaif, MD, discusses the connections between diabetes and PCOS and offers insight into ongoing research.
Polycystic Ovary Syndrome: it affects about 5–15% of pre-menopausal women worldwide, without much racial or ethnic variation in its prevalence. The link between PCOS and diabetes is still being investigated. We know that there is insulin resistance in the majority of women with PCOS. Why this leads to diabetes in PCOS is less clear.
Despite how common PCOS is, there is a frequent failure to diagnose it. Women with PCOS see on average four physicians and take up to two years to have an accurate diagnosis established.
I think a key message for healthcare providers is that, in reality, PCOS is very easy to diagnose. About 80–90% of young women who are skipping menstrual cycles on a chronic basis—usually having fewer than 8–10 menses per year—will have PCOS.
It’s a syndrome, so it’s just classified by its features, which are
reproductive abnormalities leading often to chronic anovulation, which is characterized by not getting menses in a regular pattern.
increased male hormone production; the symptom of that is usually increased abnormal hair growth in women. It can be acne. It can be hair loss.
In about the 1980s, it was noticed that PCOS was associated with insulin resistance and an increased risk for type 2 diabetes. So, it has a whole metabolic side. And the big research question since that time has been, why are metabolic abnormalities associated with reproductive abnormalities?
The research on the relationship between insulin resistance and PCOS has led to some very important insights that insulin itself is a reproductive hormone and can directly stimulate the ovaries in synergy with LH, luteinizing hormone, to produce more androgens and that insulin resistance in the brain can lead to disruption of ovulation—at least from the animal models we know that. So, it’s a very intimate inter-relationship.
The incidence of type 2 diabetes in women with PCOS has not been well-studied. However, we know the prevalence is about 10% and another 30%, at least in the United States, have prediabetes or impaired glucose tolerance.
In women with PCOS, there are several risk factors that have been identified for the development of type 2 diabetes. Certainly obesity, so the prevalence rate really goes up in women whose BMIs are 30 and greater. However, it’s important to note that we still see type 2 diabetes and increased risk for type 2 diabetes in lean women with PCOS. Another risk factor for type 2 diabetes and PCOS is family history of type 2 diabetes.
There are racial disparities in the prevalence of metabolic complications of PCOS, so we see more metabolic syndrome and prediabetes in African American women with PCOS.
However, as with so many of the metabolic issues in PCOS, the studies are not where we would like them to be. We really need large, population-based studies to better outline risk in PCOS of type 2 diabetes, cardiovascular disease, and other metabolic issues.
We treat type 2 diabetes in women with PCOS very similar to recommendations for individuals with type 2 diabetes in general, which is to reduce weight, to exercise moderately. And if women with PCOS have prediabetes, we often prescribe metformin. In fact, metformin is really one of our go-to medications because it has additional benefits reproductively in women with PCOS.
I believe that the most exciting research being done with PCOS is on its genetic susceptibility. We know that PCOS runs in families and that sisters of women with PCOS have an increased risk of developing PCOS. And to date, about 20 susceptibility genes have been discovered.
Some additional, very exciting new findings in PCOS are the identification of subtypes of PCOS that seem to have distinct genetic causes. So, this is research that my group has been doing for the last several years. And we find, using machine learning techniques such as cluster analysis, that we can identify subsets of women with PCOS who have different hormonal profiles. And then when we do genetic analysis with these subsets, we’re discovering new genes. And our most recent work is that these subsets are present in several ethnic groups.
Another area of increasing focus is the idea that there are disease subtypes within these common syndromes, like type 2 diabetes, that’s also starting to be seen in obesity. And in PCOS, subtypes have been clearly identified, and there appears to be a subtype with more metabolic features and with unique genes associated with it. So, PCOS may be a special phenotype of type 2 diabetes, where it may be possible to discover novel diabetes genes and novel pathways that could be targets for therapy. So, PCOS really should be a condition that’s of overarching interest to investigators in diabetes, obesity, and metabolism, as well as to reproductive scientists.