- Medical topics - Hyperinsulinemia

Girls and women with oGTT (oral glucose tolerance test) with insulinemia, are often referred to the endocrinologist. Interestingly, endocrinologist rarely request analysis of insulin during an OGTT. These are most frequently done by gynecologists, discovering signs of polycystic ovaries on ovarian ultrasound.

So, what is insulin?

Insulin is a hormone consisting of 51 amino acids. It is synthesized, stored and secreted from β cells of the pancreas. Insulin is synthesized, first as preproinsulin, from which proinsulin is separated, and then proinsulin is broken down into insulin and c-peptide. All this happens in the β cells. They secrete insulin, c-peptide and proinsulin, when needed, usually on food stimulation. The blood contains all three, and each one can be measured.

What does insulin do, in healthy people?

Insulin is anabolic. It stimulates the synthesis of proteins in the muscles and the use of glucose and fats for energy. Insulin is the most important factor which regulates carbohydrate metabolism and limits the action of hormones that raise blood glucose levels, such as glucagon, adrenaline, cortisol and growth hormone.

Normal insulin values – on empty stomach and after oGTT (75 g of glucose dissolved in 300 ml of water and drunk for 3-5 minutes, and after 12 hours of fasting):

Conditions which are associated with increased insulin in the blood

These are conditions associated with insulin resistance. Insulin resistance is a state in which the beta cell secretes more insulin to keep blood glucose level normal. These conditions are:

    • Obesity
    • Polycystic ovary syndrome
    • Taking steroids
    • Early stages of type 2 diabetes
    • Acromegaly, Cushing’s syndrome and some other diseases

    Increased levels of insulin in the blood are found in tumors that secrete insulin (insulinoma) or with the abuse of insulin secretagogue or exogenous insulin.

    What else do you need to know?

    Insulin and c-peptide are secreted in equal amounts. However, 50-60% of insulin is processed in the liver, before it reaches the systemic circulation and the half-life of insulin is only 4 minutes. C-peptide is excreted through the kidneys. Its half-life is 35 minutes, and it is used to determine the secretory function of beta cells.

    When do endocrinologists perform oGTT with inulinemia?

    When a person complains of hypoglycemia, with either symptoms of hunger, shivering and fainting, or when low glucose levels are measured with a self-meter. Then, usually, a five-hour oGTT with insulinemia is performed. If a blood glucose levels of less than 3 mmol/l are reached and increased insulin is measured, further testing is required. Then a 72-hour fasting test is done!

    Why does insulin resistance develop?

    It occurs due to the inability of cells to respond to the action of insulin, this being the transport of glucose into the muscles, liver and adipose tissue, for further metabolism. As a result, the “resistant” person secretes insulin beyond the normal limit, in order to provide glucose to its “resistant” cells. Insulin levels are then high in the blood, and this can lead to various metabolic diseases.

    The HOMA index is often calculated in the laboratory. What is that?

    HOMA indices are used for research purposes to assess insulin resistance or insulin secretion. There are 2 HOMA indices both using glucose and insulin from serum, taken after 12 hours of fasting: HOMA-IR for insulin resistance and HOMA-B for the assessment of pancreatic beta cell function. They are calculated using the following formulas:

    • HOMA-IR = (glucose in mmol/l x insulin in mIU/L) /22.5
    • HOMA-B = (20 x insulin in mIU/L) / (glucose in mmol/l – 3.5)

    HOMA index is not the complete truth! It should be interpreted in the light of body mass index, waist size and age. The synthesis of various clinical factors is better than a blind interpretation of HOMA IR.

    Is excess of insulin bad?

    Yes, “hyperinsulinemic insulin” is very effective in: increasing blood pressure, increasing triglycerides, increasing platelet aggregation and stimulating endothelial dysfunction and vasoconstriction. If such condition lasts longer, it can lead to various diseases.

    What diseases occur due to insulin resistance?

    The most common are: prediabetes and T2 diabetes, hypertension, dyslipidemia, fatty liver and atherosclerotic cardiovascular disease (ASCVD).

And where are the gynecologists in this whole story? Why is their interest directed towards hyperinsulinemia?

Women visit a gynecologist due to menstrual disorders, sterility or hirsutism, or they have an ultrasound showing polycystic ovaries. However, polycystic ovaries on ultrasound do not mean that a person has polycystic ovary syndrome. Insulin resistance and compensatory hyperinsulinemia occur in 65-70% of women with polycystic ovary syndrome, of whom 70-80% are obese (BMI>30), and 20-25% have BMI <25.

Insulin resistance can be independent of body weight, and then it is usually a genetic issue.

Insulin in polycystic ovary syndrome

This is a complex story.
In short, hyperinsulinemia may encourage the emergence of hyperandrogenism and ovulation disorders. Hyperandrogenism occurs in 80% of persons with polycystic ovaries. Hyperinsulinemia stimulates the secretion of testosterone from the ovaries. Clinically, it manifests as hirsutism, hair loss, acne and alopecia. In some women, weight loss normalizes insulinemia and reduces hirsutism and acne. Hyperinsulinemia is associated with increased LH. A cycle irregularity is usually associated with an ovulation disorder. Lifestyle changes, metformin and pioglitazone may reduce hyperinsulinemia, improve cycles and fertility.

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