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An estimated 65-70% of individuals with PCOS develop insulin resistance,[1] where the muscles, fat and liver can’t easily absorb glucose from your blood.[2]   Insulin resistance affects 70-80% of individuals who have both PCOS and obesity and 20-25% of individuals with PCOS who are lean. [3]


In this article we explore the link between PCOS and insulin resistance, a condition that can lead to hyperinsulinemia, 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]

  • When adiponectin is low, cells may not respond to insulin in an effective way;[11] and

  • This leads to insulin resistance, whereby the body doesn’t respond as it should to the effects of insulin.[12]


Initially, your body may be able to compensate for insulin resistance by producing more insulin (hyperinsulinemia) and you may not therefore experience any symptoms.[13]  As insulin resistance worsens, your pancreas may not be able to produce enough insulin to overcome the resistance, leading to elevated blood sugar (hyperglycemia).


Insulin resistance can lead to additional health complications, including:[14]

  • Hyperinsulinemia, elevated production of insulin;

  • Hyperglycemia, or high blood sugar;

  • High blood pressure or hypertension, where increased retention of sodium in the kidneys alters the renin-angiotensin-aldosterone system (RAAS) leading to increases arterial blood pressure[15] and elevated levels of insulin (through hyperinsulinemia) stimulate the sympathetic nervous system and cause thickening of the smooth muscle layers in arteries;[16] 

  • Dyslipidemia, where insulin resistance in fat cells results in the increased release of fatty acids into the blood, stimulating the liver’s production of very low density lipoprotein and leading to high levels of triglycerides, low levels of high-density lipoprotein (HDL) and small dense low-density lipoprotein (LDL);[17],[18]

  • Elevated inflammatory markers, where insulin resistance promotes the accumulation of microphages, small white blood cells, in fat cells which in turn attract, macrophages, white blood cells that stimulate the immune system;[19]

  • Endothelial dysfunction, a type of coronary artery disease,[20] where the elevated inflammatory markers increase circulating levels of free fatty acids causing vascular insulin resistance;[21]

  • A prothrombotic state, a heightened level of blood coagulation that increases the risk of thrombosis,[22] caused by changes in number and activity of white blood cells;[23] and

  • Type 2 diabetes (T2D).


Risk factors, other than PCOS, for insulin resistance include:[24],[25],[26]

  • Hormonal disorders, including Cushing’s syndrome, where your body produces excess cortisol (the “stress hormone”), Acromegaly, where you have high levels of growth hormone, and hypothyroidism, where the thyroid is underactive and slows your metabolism;

  • Some rare genetic conditions that affect metabolic function, including Type A insulin resistance syndrome, Rabson-Mendenhall syndrome, Donohue syndrome, Myotonic dystrophy, Alstöm syndrome, Werner syndrome and inherited lipdystrophy;

  • Obesity and, in particular, excess visceral fat around your organs;

  • Increasing age, with increasing risk after the age of 45;

  • Having or previously having gestational diabetes, heart disease, stroke, metabolic syndrome or sleep apnea;

  • Hormonal disorders such as Cushing’s syndrome and acromegaly;

  • Close family history of diabetes;

  • Having certain ethnic backgrounds, including African American, Indigenous Alaskan, Indigenous American, Asian, Hispanic/Latino, Hawaiian or Pacific Islander;

  • Lack of physical activity;

  • A diet of highly processed, high-carbohydrate foods and saturated fats; and

  • Certain medications, including steroids (glucocorticoids), some blood pressure medications, certain HIV treatments and antipsychotic medications.


Insulin resistance is difficult to diagnose up until the pancreas is unable to produce additional insulin to compensate.  A number of different blood tests measuring blood sugar and fat levels may be used to diagnose insulin resistance including fasting plasma glucose (FPG) / glucose tolerance test (GTT), glycated hemoglobin A1c and lipid panel (total cholesterol, low-density lipoproteins (LDL) cholesterol, high-density lipoproteins (HDL) cholesterol and triglycerides).[27]


Lifestyle modifications such as improved diet and increased exercise are often the preferred treatment for insulin resistance.[28]  As the condition progresses, medications may be prescribed to treat high blood pressure, pre-diabetes (metformin) and high LDL cholesterol (statins).[29]


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

Sources
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277302/
[2] https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277302/
[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://pmc.ncbi.nlm.nih.gov/articles/PMC1483172/
[12] https://pmc.ncbi.nlm.nih.gov/articles/PMC1483172/
[13] https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance
[14] https://www.ncbi.nlm.nih.gov/books/NBK507839/
[15] https://www.ncbi.nlm.nih.gov/books/NBK470410/
[16] https://journals.lww.com/cardiovascularendocrinology/fulltext/2014/12000/role_of_insulin_resistance_in_essential.4.aspx
[17] https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0762-4
[18] https://www.jci.org/articles/view/10762/figure/1
[19] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873875/
[20] https://my.clevelandclinic.org/health/diseases/23230-endothelial-dysfunction
[21] https://www.nature.com/articles/ncpendmet0366
[22] https://bestpractice.bmj.com/topics/en-us/889
[23] https://www.mdpi.com/2077-0383/10/11/2419
[24] https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance
[25] https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance
[26] https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance
[27] https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance
[28] https://pmc.ncbi.nlm.nih.gov/articles/PMC7235686/
[29] https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance

Want to learn more about metabolic health conditions related to PCOS? Check out the sections on hyperinsulinemia, dyslipidemia and diabetes.

Symptoms - Cardiometabolic

PCOS and Insulin Resistance

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