Question

Uncontrolled Diabetes (high blood sugar, lack of insulin or lack of insulin signaling) can result in keto-acidosis, the blood pH is very low and this can be fatal. What is this? What molecules are involved? How does the lack of insulin contribute to this metabolic imbalance?

Answer 1

This condition is known as Diabetic ketoacidosis (A complication of Uncontrolled Diabetes mellitus)

The molecules which are involved in the occurrence of this condition are - Glucose, fatty acids, ketone bodies and cholesterol.

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS

• Large amounts of glucose may be excreted in urine (maybe 90 to 100 G/day in some cases). Loss of solute produces osmotic diuresis thus the large volume of urine (polyuria).

• Loss of fluid leads to thirst and polydipsia.

• Polyphagia: Eats more frequently. More fond of sweets. The above symptoms may persist for many months in maturity-onset diabetes. In juvenile-onset type-1, further symptoms develop if treatment is not started.

• Tissues including muscles received a liberal supply of glucose but cannot use glucose due to absolute or relative deficiency of insulin/ or transport defect to cells. This causes weakness and tiredness.

• As glucose cannot be used for fuel, fat is mobilized leading to increase FFA- in blood and liver.

• Increased acetyl-CoA is diverted for cholesterol synthesis— Hypercholesterolaemia and atherosclerosis. Xanthomas may develop.

• Increased amount of acetyl CoA and absence of insulin, channels the acetyl CoA to form ketone bodies. Increased ketone bodies lead to acidosis, which leads to hyperventilation (“air-hunger”).

• If ketosis is severe, acetone will be breathed out, giving characteristic “fruity” smell in-breath (due to acetone).

• Along with the above, there may be an excessive breakdown of tissue proteins. Deaminated amino acids are catabolized to provide energy, which accounts for Loss of weight.

• Due to ketosis, there is the development of anorexia, nausea, and vomiting. Continued loss of water and electrolytes increases dehydration.

• Ketoacidosis produces increasing drowsiness, leading to diabetic coma in untreated cases.