Pathogenesis of canine diabetes mellitus
Diabetes mellitus is a paradox: simultaneous extracellular hyperglycemia and intracellular glucose deficiency. The consequences of insulin deficiency or receptor insensitivity are reduced peripheral tissue utilization of glucose, amino acids, and fatty acids. This results in the accumulation of glucose in the blood (hyperglycemia). Glucose is a small molecule and is freely filtered through the glomerulus in the kidney. In normal dogs, the renal tubules will reabsorb the filtered glucose.
However, if the blood glucose rises above the renal threshold (approximately 180 mg/dL [10 mmol/L]), these tubular reabsorption mechanisms are overwhelmed and glucose appears in the urine. Glucose exerts an osmotic diuretic effect that leads to polyuria. To compensate, water consumption increases (polydipsia). Diabetic dogs tend to lose weight due to caloric loss with glucosuria and reduced peripheral tissue anabolism. Despite hyperglycemia, there is hypothalamic intracellular hypoglycemia that results in the stimulation of the hunger center and polyphagia. The consequences of this paradox are reflected in Figures 1 and 2.
Untreated or unrecognized diabetes mellitus may progress to diabetic ketoacidosis. In the absence of sufficient insulin, diabetic dogs will switch from glucose to fat metabolism for cellular energy. While fats are initially beneficial energy sources, lipid waste products (ketone bodies) accumulate in the blood and invoke severe and potentially life-threatening metabolic abnormalities.
Diabetic ketoacidotic dogs can present with severe clinical signs (severe depression, anorexia, vomiting, dyspnea, collapse, or coma). Dog owners may not have recognized or reported that the classic diabetic clinical signs were present. Without aggressive and determined management, ketoacidotic dogs may die.