Does PCOS Raise the Risk for Type 2 Diabetes?
Over half of women with polycystic ovary syndrome will develop type 2 diabetes by age 40. How are these two hormonal conditions connected?
Excessive hair, irregular periods, ovarian cysts, trouble conceiving or infertility, and insulin resistance. These are all symptoms of polycystic ovarian syndrome (PCOS), which affects roughly five million women in the U.S.
PCOS is a hormonal condition that affects women of childbearing age. It causes the ovaries to produce excess androgens, which are a type of sex hormone. Testosterone is one of the most common androgens.
While great for building muscle, androgens may place women at higher risk for insulin resistance. Studies have found high levels of androgens can impair the function of insulin-secreting cells (known as beta cells) in the pancreas.
Previous studies have shown that androgens interact with beta cells to stimulate insulin release, which results in much higher levels of insulin in the blood. Over time, this places chronic stress on the pancreas, impairs insulin cell signaling pathways, and can increase blood glucose levels.
Such outcomes occur in up to 70% of women with PCOS. Since PCOS strips women of their innate insulin sensitivity, it leaves them at greater risk for developing type 2 diabetes.
The link between PCOS and type 2 diabetes
More than half of women with PCOS will develop type 2 diabetes by the age of 40, according to the Centers for Disease Control and Prevention. The damage to pancreatic beta cells PCOS causes is a major contributor to this increased incidence of diabetes.
“If you have good beta cells, you could be as insulin-resistant as you want and you won't get diabetes,” said Dr. Andrea Dunaif, chief of the division of endocrinology, diabetes, and bone disease for the Mount Sinai Health System. “It’s when the beta cells can’t keep up that you’re at very high risk.”
Studies from Dunaif’s research group have identified distinct reproductive and metabolic subtypes of PCOS. It remains uncertain what genetic variations could impair beta cell function in people with PCOS as genes commonly associated with type 2 diabetes and beta cell function have not come up for PCOS, Dunaif said.
This could mean that beta cell impairment varies between PCOS and diabetes, and requires further research.
“PCOS is a complex genetic disease. Similar to type 2 diabetes, it results from a combination of multiple susceptibility genes and environmental factors,” said Dunaif.
Insulin resistance can drive PCOS risk, too
Research around insulin was how scientists first learned about the connection between PCOS and diabetes.
“In the 70s, a legendary group of scientists described a group of young girls with extreme insulin resistance and signs of PCOS,” said Dunaif. This so-called “type A insulin resistance syndrome” was found to be caused by genetic variations that affect the body’s ability to use insulin.
From this, researchers learned that insulin defects can cause excess androgens seen in certain genetic disorders. PCOS isn’t the only driver in this interaction – insulin abnormalities can increase the risk of developing PCOS as well.
Some young women (8-12 years old) experience changes to insulin secretion before they have their first period, which means their beta cells are struggling before the onset of PCOS symptoms, said Dunaif. Other signs of PCOS include excess hair growth, acne, weight gain, and irregular menstruation.
Insulin has the ability to act as a reproductive hormone, stimulating androgen production from the ovaries, alongside other hormones. It also potentially draws excess androgens from fat cells, which can result in too much insulin in the bloodstream. In this case, insulin ends up being a potential driving force for developing PCOS.
In addition, the brain sources insulin from the pancreas and uses it for many functions, including the regulation of reproductive pathways for ovulation. Impaired insulin cell signaling threatens to disrupt this pathway and drives hormonal imbalances.
“If you experimentally block insulin signaling in the brain in animal studies, you can produce PCOS symptoms,” added Dunaif.
Obesity as a risk factor for PCOS and diabetes
Studies show that obesity can cause PCOS and type 2 diabetes, but the reverse is not always true. Individuals with genetic variations associated with PCOS are not necessarily at greater risk for obesity, said Dunaif.
That said, significant weight loss can improve PCOS symptoms, even going so far as to potentially reverse metabolic abnormalities and improve reproductive health, some research finds.
For over the past decade, Dunaif has been campaigning for the use of GLP-1 receptor agonist weight loss drugs for PCOS. She said her efforts were met with resistance and lack of interest from pharmaceutical companies in investigating treatment in patients with PCOS alone.
Dunaif explained that GLP-1 agonists should be a frontline therapy for patients with type 2 diabetes and PCOS. These medicines could even dethrone metformin, which had shown benefits but is now no longer recommended as a primary treatment for PCOS.
Diagnosing and screening for PCOS
Despite PCOS being a common problem and a main cause of female infertility, it’s often misdiagnosed. Many physicians also don’t know much about PCOS, let alone its connection to diabetes, said Dunaif. She added that one of the issues is that healthcare professionals are still “fixated on what the ovaries look like and having that be the diagnostic criteria.”
“That isn’t necessary to handle any of the associated metabolic issues. And you can make the diagnosis accurately without doing an ovarian ultrasound,” she said.
As research progresses, Dunaif anticipates that the diagnostic criteria for PCOS will likely change. Genetic studies, like that from Dunaif’s group, advance the medical community’s understanding of PCOS – plus how to treat it.
In the meantime, individuals living with PCOS are charged with being proactive about their health by ensuring they receive a proper diagnosis and treatment. Treatment varies depending on a person’s age, health, severity of symptoms, and if they plan on having children, but may include:
Maintaining a healthy diet and getting regular exercise
Medications that stimulate ovulation (like letrozole)
Birth control pills
Diabetes medications like SGLT-2 inhibitors and GLP-1s
It’s also recommended that menopausal women with a history of PCOS receive regular evaluations because of the higher risk of type 2 diabetes.
Dunaif also recommends getting glucose tolerance tests – particularly for patients with PCOS and a body mass index (BMI) of over 20 – as A1C tests may fail to catch signs of impaired tolerance.
“I think there is a lot of actionable information and steps that women with PCOS and diabetes can take to protect their health,” she said.