Hyperinsulinism: Causes

Pathogenesis (disease development)

Hyperinsulinemia may be caused by increased secretion of insulin or by peripheral insulin resistance (= decreased or abolished action of the peptide hormone insulin in peripheral tissues). Tumors (insulinomas, rare mostly benign tumors) can also lead to an overproduction of insulin. A distinction is made between acquired hyperinsulinism and congenital hyperinsulinism. In this case, insulin secretion by the beta cells of the pancreas is pathologically (abnormally) increased. Congenital hyperinsulinism (CHI) can be divided into the following forms:

  • Focal congenital hyperinsulinism – secretion is impaired in a limited tissue area.
  • Global congenital hyperinsulinism – secretion is globally, diffusely disturbed.
  • Atypical congenital hyperinsulinism – assignment from the first two forms is not possible.

Etiology (causes)

Biographical causes

  • Genetic burden – FOXO3A rs2802292 G allele is associated with increased peripheral and hepatic insulin sensitivity, ie, absence of the G allele is a risk factor for hyperinsulinemia
  • Socioeconomic factors – low socioeconomic status.

Behavioral causes

  • Nutrition
  • Consumption of stimulants
    • Tobacco (smoking)
  • Physical activity
    • Lack of physical activity (lack of exercise).
  • Psycho-social situation
    • Sleep deprivation
    • Stress
  • Overweight (BMI ≥ 25; obesity).
  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)) is presentWhen measuring waist circumference according to the International Diabetes Federation (IDF, 2005) guideline, the following standard values apply:
    • Men < 94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

  • Intentional overdose of insulin (= hypoglycaemia factitia; clinical picture in which there is a deliberate lowering of blood sugar (hypoglycemia) by targeted self-administration of blood sugar-lowering agents (mainly sulfonylureas)).

Disease-related causes

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Obesity (obesity)
  • Autoantibodies against insulin
  • Depression
  • Diabetes mellitus type 2 (age-related diabetes) – leads to peripheral insulin resistance (decreased effectiveness of endogenous insulin at target organs skeletal muscle, adipose tissue, and liver)
  • Ectopic insulin secretion – secretion of insulin from a site other than the pancreas (pancreas).
  • Congenital hyperinsulinemia (CHI) – usually due to an ion channel mutation of the ATP-sensitive potassium channel; pathologically (pathologically) increased insulin secretion by beta cells.
  • Metabolic syndrome – clinical name for the symptom combination of obesity (overweight), hypertension (high blood pressure), elevated fasting glucose (fasting blood sugar) and fasting insulin serum levels (insulin resistance), and dyslipidemia (elevated VLDL triglycerides, lowered HDL cholesterol). Furthermore, a coagulation disorder (increased tendency to clotting), with an increased risk of thromboembolism can often be detected.

Neoplasms – tumor diseases (C00-D48).

  • Insulinoma – rare, usually benign (benign) tumor of endocrine cells (islets of Langerhans) of the pancreas (pancreas) in which increased insulin is produced.

Genitourinary system (kidneys, urinary tract – sex organs) (N00-N99).

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

Medication

  • Overdose of insulin or insulin secretagogue (repa-/nateglinide).
    • Overdose of insulin → decreased insulin resistance as a result of hyperinsulinemia and associated ever-increasing release of the hormone to keep blood glucose in balance.
  • Sulfonylureas – oral antidiabetic (drug used in diabetes mellitus type 2).