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III.3.B.d. The symptoms of the lack of insulin

  1. In the lack of insulin, the blood Glu level increases: hyperglycemia develops.
  2. Glu is excreted by the renal tubules into the urine when the blood Glu level is abnormally high: glycosuria develops.
  3. The Glu excreted into the urine (and ketone bodies) is accompanied osmotically by a larger volume of water (the amount of urine increases): osmotic diuresis develops.
  4. The higher volume of urine (polyuria) causes increased thirst and excessive fluid intake (polydipsia).
  5. The polyuria impairs the function of the renal tubules, and electrolytes (Na+ and Cl-) are released.
  6. The loss of water (dehydration) and electrolytes causes a decrease of the extracellular liquid (blood) volume, and the development of circulatory disorders and low BP.
  7. The circulatory disorders cause the deoxygenation of tissues (hypoxia).
  8. The persisting symptoms generate hypoxia of the brain and neurological disorders.
  9. In parallel with the above-described mechanisms, other harmful processes are generated. The lack of insulin causes glucagon overexpression. (Insulin inhibits glucagon gene expression.)
  10. The increased glucagon level enhances the blood Glu level and increases the above-mentioned reactions.  
  11. Glucagon
    1. stimulates the breakdown of fat (lipolysis) and the by-products of the process;
    2.  increases the amounts of ketone bodies (β-hydroxybutyric acid, acetoacetic acid and acetone); and
    3. the increased breakdown of fat and protein induces a weight loss.
  12. Ketone bodies
    1. reduce the blood pH level: ketoacidosis develops
    2. enhance the release of renal ketone bodies and water; and
    3. the breath of patients not taking medication smells of acetone (acetone breath).
  13. Circulatory disorders develop, and the changed blood pH reduces oxygen binding (Kussmaul breathing: rapid and deep breaths).
  14. The increased ketoacidosis causes vomiting (nausea).
  15. The effects of the ketone bodies on the nervous system and the loss of Na+ lead to coma.
  16. Death.