An estimated 65-70% of individuals with PCOS develop hyperinsulinemia,[1] elevated levels of insulin in the blood.  More insulin is produced by the pancreas to compensate for insulin resistance, where the muscles, fat and liver can’t easily absorb glucose from your blood.[2] 

In this article we explore the link between PCOS and hyperinsulinemia, a condition that can exacerbate PCOS symptoms[3] and lead to prediabetes/diabetes and other cardiometabolic conditions.

PCOS is associated with elevated levels of androgens[4], sex hormones that are produced in the ovaries, start at puberty and play a key role in reproductive health.[5] 

• An Increase in the level of circulating androgens disrupts the way that adipose tissue, the body fat or connective tissue that extends throughout your body,[6] metabolizes glucose;[7]

• The adipose tissue produces less adiponectin, a hormone that helps with insulin sensitivity and inflammation,[8] and more leptin,[9] a hormone that causes you to feel hungry in efforts to maintain enough fat stores for long-term health;[10]

• Reduced adiponectin leads to insulin resistance, whereby the body doesn’t respond as it should to the effects of insulin;[11] and

• Insulin resistance leads to elevated production of insulin in the pancreas as a compensatory measure, leading to elevated levels in insulin in the blood or hyperinsulinemia.[12]

Hyperinsulinemia exacerbates PCOS by increasing the level of circulating androgens in a self-reinforcing cycle:[13],[14]

• Elevated levels of insulin in the blood reduce the production of sex hormone binding globulin (SHBG) in the liver;

• Less SHBG is available to bind with androgens and other sex hormones in the blood (c.65% of androgens are typically bound to SHBG, c.35% are typically bound to albumin and only 1-2% are typically “free”); and

• More androgens are then unbound and circulate in the blood as free active testosterone.

Hyperinsulinemia can lead to additional health complications, including hyperglycemia (high blood sugar), pre-diabetes and Type 2 diabetes (T2D).[15]

Risk factors, other than PCOS, for hyperinsulinemia include:[16],[17]

• Obesity, especially higher levels of visceral fat, the fat that’s stored within the abdominal cavity around the organs;[18]

• Metabolic syndrome (MeTS), the cluster of conditions that include increased blood pressure, high blood sugar, excess fat around the middle and high cholesterol levels;[19]

• Higher levels of triglycerides, a type of fat found in the blood that increase the risk of heart disease;[20]

• High levels of uric acid, a chemical that can cause gout and kidney disease and that is formed when the body breaks down purines, chemicals produced in the body and found in some food and drinks;[21]

• Atherosclerosis, where a plaque forms on the walls of the arteries and causes them to harden;[22] and

• Hypertension, high blood pressure.

Hyperinsulinemia is difficult to diagnose up until the pancreas is unable to produce additional insulin to compensate.  When diagnosing hyperinsulinemia, a clinician will consider a variety of factors including medical history, family history, symptoms and blood tests for fasting plasma glucose (FPG).[23]

Hyperinsulinemia is sometimes confused with hyperinsulinism, where an individual has elevated levels on insulin in the blood due to a tumor in the pancreas or a genetic condition.[24]  Hyperinsulinism results in low blood sugar rather than high blood sugar.[25]

Lifestyle modifications such as improved diet and increased exercise are often the preferred treatment for hyperinsulinemia and the underlying insulin resistance.  As the condition progresses, medications may be prescribed to treat high blood pressure, pre-diabetes (metformin) and high LDL cholesterol (statins).[26]

Reviewed by Riya Ganguly PhD., MBA, ICD.D, expert on technology transfer, new venture development and research facilitation

Sources

[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC5175507/

[2] https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance

[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC5175507/

[4] https://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics/

[5] https://my.clevelandclinic.org/health/articles/22002-androgens

[6] https://my.clevelandclinic.org/health/body/24052-adipose-tissue-body-fat

[7] https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-022-01091-0

[8] https://my.clevelandclinic.org/health/articles/22439-adiponectin

[9] https://my.clevelandclinic.org/health/articles/22446-leptin

[10] https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-022-01091-0

[11] https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/expert-answers/hyperinsulinemia/faq-20058488

[12] https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance

[13] https://journalofmetabolichealth.org/index.php/jmh/article/view/50/184

[14] https://pmc.ncbi.nlm.nih.gov/articles/PMC7663738/

[15] https://my.clevelandclinic.org/health/diseases/24178-hyperinsulinemia

[16] https://my.clevelandclinic.org/health/diseases/24178-hyperinsulinemia

[17] https://www.healthline.com/health/hyperinsulinemia#causes

[18] https://www.healthline.com/health/visceral-fat

[19] https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/symptoms-causes/syc-20351916

[20] https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186

[21] https://medlineplus.gov/ency/article/003476.htm

[22] https://www.mayoclinic.org/diseases-conditions/arteriosclerosis-atherosclerosis/symptoms-causes/syc-20350569

[23] https://my.clevelandclinic.org/health/diseases/24178-hyperinsulinemia

[24] https://my.clevelandclinic.org/health/diseases/24178-hyperinsulinemia

[25] https://my.clevelandclinic.org/health/diseases/24178-hyperinsulinemia

[26] https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance