Pathogenesis

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Pathogenesis of Feline Diabetes Mellitus

The insulin deficiency that occurs with diabetes impairs the uptake of glucose by cells, resulting in a great paradox: simultaneous extracellular hyperglycemia (elevated blood glucose) and intracellular glucose deficiency.

To compensate for the glucose deficiency, gluconeogenesis occurs. Because this process results in use of amino acids to produce glucose, there is a decrease in protein synthesis and subsequent weight loss and increased risk of infections resulting from antibody loss.

Excess glucose produced accumulates in the blood causing hyperglycemia. Small glucose molecules are freely filtered through the glomerulus in the kidney. In normal cats, the renal tubules will reabsorb the filtered glucose. However, if the blood glucose rises above the renal threshold of approximately 200 to 280 mg/dL in cats, these tubular reabsorption mechanisms are overwhelmed and glucose appears in the urine.

Glucose exerts an osmotic diuretic effect that leads to polyuria. To compensate, the cat experiences excessive thirst and polydipsia. Furthermore, the concentration of glucose in the bloodstream exerts an osmotic pressure and pulls fluid out of cells, resulting in cell dehydration. Without medical intervention, hyperglycemic coma and death can occur.

Figures 1 and 2 illustrate the consequences of the deadly paradox caused by diabetes:

Figure 1:

Figure 2:

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Important Safety Information:

Vetsulin^® should not be used in dogs known to have a systemic allergy to pork or pork products. Vetsulin is contraindicated during periods of hypoglycemia. Keep out of reach of children. As with all insulin products, careful patient monitoring for hypoglycemia and hyperglycemia is essential to attain and maintain adequate glycemic control and prevent associated complications. Overdosage can result in profound hypoglycemia and death. The safety and effectiveness of Vetsulin in puppies, breeding, pregnant, and lactating dogs has not been evaluated. See package insert for full information regarding contraindications, warnings, and precautions.

References:

1. Martin GJ, Rand JS. Pharmacology of a 40 IU/ml porcine lente insulin preparation in diabetic cats: findings during the first week and after 5 or 9 weeks of therapy. J Feline Med Surg. 2001;3(1):23–30. 2. Vetsulin^® (porcine insulin zinc suspension) [Freedom of Information Summary]. Millsboro, DE: Intervet Inc.; 2008. 3. Data on file, Merck Animal Health. 4. Graham PA, Nash AS, McKellar QA. Pharmacokinetics of porcine insulin zinc suspension in diabetic dogs. J Small Anim Pract. 1997;38(10):434–438. 5. Martin GJ, Rand JS. Pharmacokinetic and Pharmacodynamic Study of Caninsulin in Cats with Diabetes Mellitus. 2000: Internal Study Report. 6. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. 3rd ed. St. Louis, MO: Saunders; 2004:539–579. 7. Tennant B, ed. BSAVA Small Animal Formulary. 4th ed. Gloucestershire, UK: British Small Animal Veterinary Association; 2002. 8. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. 3rd ed. St. Louis, MO: Saunders; 2004:486–538. 9. Reusch C. Feline diabetes mellitus. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 7th ed. St. Louis, MO: Saunders; 2010:1796–1816. 10. Nelson RW. Canine diabetes mellitus. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 7th ed. St. Louis, MO: Saunders; 2010:1782–1796. 11. Burgaud S, Riant S, Piau N. Comparative laboratory evaluation of dose delivery using a veterinary insulin pen. In: Proceedings of the WSAVA/FECAVA/BSAVA congress; 12–15 April 2012; Birmingham, UK. Abstract 121. 12. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic dogs. In: Proceedings of the WSAVA/ FECAVA/BSAVA congress; 12–15 April 2012; Birmingham, UK. Abstract 122. 13. Burgaud S, Guillot R, Harnois-Milon G. Clinical evaluation of a veterinary insulin pen in diabetic cats. In: Proceedings of the WSAVA/FECAVA/BSAVA congress; 12–15 April 2012; Birmingham, UK. Abstract 45. 14. Davison LJ, Walding B, Herrtage ME, Catchpole B. Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations. J Vet Intern Med. 2008;22:1317-1325. 15. Banfield State of Pet Health 2016 Report. p 12-13.