Hypoglycemia (Low Blood Sugar): Causes

Pathogenesis (development of disease)

Hypoglycemia is the result of a disturbance in the coordination or regulation between glucose delivery by the liver, ie, from the glycogen reservoir or by gluconeogenesis, and glucose uptake by the consuming organs. Regulation is by insulin and glucagon: insulin is responsible for promoting the uptake of glucose from the blood. It also ensures the conversion of glucose into glycogen, which is an important storage form for glucose. In this form, glucose can be stored in the liver and muscles without increasing glucose serum levels. The glucose serum level (blood glucose level) is usually within narrow limits between 70 and 110 mg/dl (3.9-6.1 mmol/l). Thus, insulin ensures that the glucose serum level remains constant. Another type of cells are the A cells. They synthesize glucagon. Among other things, this hormone stimulates specific enzymes that convert glycogen back into glucose. This increases the glucose serum level. The insulin of the B cells and the glucagon of the A cells thus have an antagonistic effect. Even after 24-72 hours of fasting (fasting test), the glucose serum level is maintained above 3 mmol/l thanks to the counter-regulatory hormones (glucagon, adrenaline) and gluconeogenesis (new sugar formation) from glucoplastic amino acids. In addition to glucagon, epinephrine, growth hormone, and cortisol have counterregulatory effects in hypoglycemia:

  • Adrenaline release is the most important response in the presence of impaired glucagon response (e.g., in prolonged diabetes mellitus, type 1)
  • Growth hormone (STH) and cortisol (stress hormone) are released only in prolonged (prolonged) hypoglycemia

The most common cause of hypoglycemia is an overdose of diabetes medications.

Etiology (causes)

Behavioral causes

  • Diet
    • Malnutrition (malnutrition) – results in a decreased supply of glucose (carbohydrate: monosaccharide; simple sugar).
  • Pleasure food consumption
    • Coffee
    • Alcohol – hypoglycemia induced by alcohol during food fasting (abstaining from food intake) is due to depletion of glycogen stores (carbohydrate stores) and inhibition of gluconeogenesis (new sugar formation from noncarbohydrate precursors, such as amino acids). In healthy people, alcohol can cause hypoglycemia after fasting, in liver patients even after a shorter time.
  • Physical activity
    • Increased muscle work – leads to increased consumption of glucose.

Causes related to disease

Certain conditions originating in the perinatal period (P00-P96).

  • Children of pregnant women with gestational diabetes in the first hours of life.

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

  • Failure of the anterior pituitary lobe (HVL) (anterior lobe of the pituitary gland (pituitary gland)).
  • Failure of the adrenal cortex
  • Diabetes mellitus (diabetes) type 1 + 2
    • Diabetes mellitus type 2; esp. susceptible are patients with:
      • Severe hypoglycemic history (medical history) (5.6-fold).
      • Sulfonylureas (6.7-fold) and/or insulin (basal insulin: 12.5-fold; blus insulin: 23.2-fold; both types of insulin: 27.7-fold)
      • HbA1c (long-term glucose level) <6%; in another study.
        • Very low values (HbA1c ≤ 5.6 percent): +45 percent.
        • Extremely high values (HbA1c ≤ 10 percent): +24 percent
      • Increasing comorbidity (concomitant diseases: COPD, dementia, heart failure and infarction, liver cirrhosis, renal insufficiency (stage 3 and above), peripheral neuropathy, tumor disease (cancer), tendency to fall, cerebrovascular disease).
  • Diabetes renalis – genetic dysfunction of the kidneys characterized by persistent glucosuria (excretion of glucose in the urine) with normal glucose tolerance and non-elevated serum glucose (blood glucose) levels.
  • Fructose intolerance (fructose intolerance).
  • Galactosemia – increased occurrence of the sugar galactose in the blood.
  • Glycogen storage diseases such as glycogenoses type-1 (von Gierke) and type-3 (Cori).
  • Addison’s disease (primary adrenocortical insufficiency) – adrenal insufficiency leading to failure of mainly cortisol production.
  • Severe form of malnutrition

Infectious and parasitic diseases (A00-B99).

  • Sepsis (blood poisoning)

Mouth, esophagus (food pipe), stomach, and intestines (K00-K67; K90-K93).

  • Gastric emptying disorder in diabetes mellitus.
  • Condition after gastric resection (stomach removal) with dumping late syndrome – condition after removal of the stomach leading to hypoglycemia due to rapid carbohydrate absorption one to three hours after food intake

Neoplasms – tumor diseases (C00-D48).

  • IGF-2-producing mesenschymal tumors (insulin-like growth factor 2 (IGF-2), also called somatomedin A (SM-A), is a growth factor).
  • Insulinoma – usually benign (benign) tumor of the pancreas (pancreas), which produces increased insulin and leads to recurrent (recurrent) hypoglycemia; every tenth insulinoma is malignant as islet cell carcinoma and tends relatively early to pronounced metastasis (especially to the liver)
  • Liver tumors, unspecified
  • Liver cirrhosis – connective tissue remodeling of the liver leading to functional impairment.
  • Nesiodioblastosis (synonyms: Islet cell hyperplasia; persistent hyperinsulinemic hypoglycemia of infancy; PHHI of persistent hyperinsulinemic hypoglycemia of infancy) – it is a genetically determined islet cell hyperplasia (enlargement) of the pancreas (pancreas), which already leads to severe hypoglycemia (hypoglycemia) in newborns.
  • Severe liver disease, unspecified
  • Pancreatic tumors (tumors of the pancreas), unspecified
  • Paraneoplastic secretion of insulin-like peptides.

Psyche – Nervous System (F00-F99; G00-G99)

  • Anorexia nervosa (craving for food)

Pregnancy, childbirth, and puerperium (O00-O99).

Symptoms and abnormal clinical and laboratory findings not elsewhere classified (R00-R99)

  • Cachexia (abnormal, very severe emaciation).
  • Uremia (occurrence of urinary substances in the blood above normal values).

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

  • Severe renal disease, unspecified

Injuries, poisonings, and other consequences of external causes (S00-T98)

  • Hypoglycemia factitia – intentionally induced hypoglycemia by surreptitious injection of insulin.

Other causes

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

  • HbA1c < 6.5 percent (48 mmol/mol) in diabetic patients → increased risk of severe hypoglycemia.

Medication

  • Analgesics (painkillers)
    • Opioids: propoxyphene (in renal insufficiency/renal impairment), tramadol.
  • Antiarrhythmics
    • Quinidine
    • Disopyramide
  • Antibiotics
  • Antidiabetic drugs
    • Glinides (nateglinide, repaglinide)
    • Insulin overdose (esp. higher hypoglycemic tendency in women).
    • Overdose of sulfonylureas (SH) – glibenclamide, gliclazide, glimepiride, glipizide, gliquidone, tolbutamide.
    • SH (glipizide or glimepiride) in combination with a vitamin K antagonist (VKA; in this case, warfarin):
      • 22% increased risk of hypoglycemia (odds ratio [OR] 1.22); aged 65-74 years (OR 1.54) and in quarters with first-time warfarin use (OR 2.47).
      • 47% increased risk of fall-related fractures (broken bones) that brought patients to the emergency department or led to hospitalization (OR 1.47)
      • 22% increased risk for cognitive impairment (reductions in mental performance) (OR 1.22)
  • Quinine (a naturally occurring chemical compound in cinchona bark from the group of alkaloids).
  • Haloperidol (neuroleptic/nerve depressant from the butyrophenone group).
  • Combination of multiple antidiabetic agents
  • Pentamidine (active ingredient from the group of antiparasitics).
  • Salicylates (salts of salicylic acid)

Environmental pollution – intoxications (poisoning).

  • Alcohol excess, especially in the presence of severe concomitant diseases.
  • Alcohol in diabetes mellitus
  • Fungal toxins
  • Ackee fruit