Diabetes mellitus in cats (Proceedings)
Management of the uncomplicated feline diabetic can occasionally be controlled by oral hypoglycemic agents (approximately 25-35%). This is because approximately 90% of the feline diabetic patients are similar to human Type2 diabetes mellitus (non-insulin dependent diabetes mellitus-NIDDM). However, by the time the cat is diagnosed with diabetes mellitus, the blood glucose is severely elevated (often>450 mg/dl) and many cats are ketotic, thus insulin is usually required. If oral hypoglycemic therapy is to be considered by the clinician for initial therapy, several classes of drugs may be considered. Sulphonylurea drugs are the preferred drugs in diabetic cats. They exert their hypoglycemic effect by stimulating insulin release by the beta islet cells and increase sensitivity to insulin by its receptors. This author's preferred drug is glypizide (2.5 mg bid, initially increased to 5 mg bid after 2 weeks). Glypizide therapy should only be considered in diabetic cats that are in reasonably good health (good appetite and state of nutrition/hydration). It should never be the sole therapy for cachectic, ketotic cats. Glypizide's major side effects include: anorexia and vomition. If these signs occur the drug should be withdrawn for at least 24-36 hours and readministered at a lower dose. Concerns for glypizide usage include: delayed onset of action and the potentiality of amyloid deposition in the beta islet cells, thus increasing insulin exhaustion. Other oral hypoglycemic agents extensively used in humans but relatively unproven in cats include: alpha-glucosidase inhibitors, which reduce GI glucose absorption (Acarbose), transition metals, which increase insulin sensitivity (chromium, vanadium), thiazolidinediones, which increase insulin sensitivity and biguanides which block glucose production in the liver and increase insulin sensitivity (Meformin).
Although oral glypizide therapy can be considered, insulin continues to be the treatment of choice in diabetic cats. The insulin preparation preferred by this author is bovine PZI. The cat and bovine have similar amino acid sequences in their insulin molecules and PZI has the longest duration of activity. Insulin glargine is relatively new synthetic long-acting insulin derivative which has demonstrated encouraging results in preliminary studies in felines with diabetes mellitus. This author prefers to hospitalize diabetic cats initially and start with 0.25-0.50 IU/kg. beef PZI bid depending on the degree of hyperglycemia and a serial blood glucose curve constructed for 48 hours. Client education for feline owners is similar to that of canine diabetic pet owners.
The diet should be low in carbohydrates and high in protein, and thus will reduce postprandial hyperglycemia, obviously if the cat has concurrent renal disease the clinician should recommend feeding a diet lower in protein and higher in fat content. The cat is fed bid prior to the administration of insulin and care is taken to facilitate weight loss in obese cats and to guard against hypoglycemia, similar to canine diabetics.The patient should be rechecked weekly for 4 weeks (similar to diabetic dogs) and a fructosamine level run initially at 6-8 weeks and the 2-3 times/year.
The difficult to control diabetic
As stated previously, dogs and cats do not need to be as tightly controlled with respect to glucose levels as human diabetics. However patients that remain PU/PD, urinate in the house, continue to lose weight, remain lethargic despite receiving adequate amounts of insulin (> 1.5 IU/kg per injection on bid protocols or > 2 IU/kg on sid protocols) fall into this category. Those dogs and cats that demonstrate marked fluctuations in insulin requirements and develop periods of hypoglycemia alternating with PU/PD (suggestive of hyperglycemia or the Somogyi effect) are termed "brittle diabetics". The clinician should consider 4 major causative categories in order to alleviate the problem. 1) A review with the pet owner regarding insulin administration is the first and most "mundane" step ( making sure that the insulin is fresh and not expired, making sure that the insulin is not frozen, heated, vigorously shaken, diluted). Watching the owner administer a dose of insulin to the pet provides valuable information about technique . Examining the the subcutaneous areas on the patient where the insulin is administered (they should be rotated with each injection and there should be no areas of fibrosis or scaring which would inhibit reliable absorption of insulin) also provides valuable information. 2) A review with the owner regarding the dog or cat's diet (bid, prior to each insulin injection-avoidence of snacks unless signs of mild hypoglycemia occur) and exercise regimine. 3) A thorough review by the clinician for endogenous causes ( metestrus in unsprayed females, hypothyroidism/obesity, hyperthyroidism-especially in older cats, hyperadrenocorticism, acromegaly-especially in cats, renal and hepatic insufficiency, cardiovascular disease, hypertension and disorders in lipid metabolism, inflammatory conditions-pancreatitis, UTI, pneumonia, etc.. 4) Rarer conditions ( pheochromocytoma, glucagonoma and non-endocrine neoplasia-liver, large soft-tissue sarcomas. 5) Iatrogenic (this author has encountered many patients with IMHA, IMTP, lymphosarcoma, IBD and various forms of atopy that became difficult-to-control diabetics because of their dependency on glucocorticoids). Also, the use of progestins (megesterol) to delay estrus in dogs or treat various dermatopathies in cats are potent insulin antagonists (they stimulate STH release). 6) Anti-insulin antibodies-If the diabetic dog is not receiving porcine insulin and the diabetic cat is not receiving bovine insulin, the possibility of the development of ant-insulin antibodies may exist. The true clinical signficance of anti-insulin antibodies in dogs and cats remains unclear, however in humans the presence of increased titers of anti-insulin antibodies may result in the need for extremely high insulin doses; occasionally resulting in prolonged hypoglycemic episodes due insulin being persistently released from insulin-antibody complexes. More clinical research is needed to understand the significance of this phenomenon. In poorly controlled the use of the serum fructosamine test is an extremely valuable tool in assessing the degree of glycemic dysfunction. The clinician should be diligent reviewing the history, performing a thorough physical examination, reviewing the past laboratory tests, radiographs, ultrasounds, etc.. Serial blood glucose curves should be performed to determine if there is absolute insulin resistance, marked fluctuations in glucose levels or the Somogyi effect. From the above findings the clinician should construct a diagnostic/therapeutic plan to improve the patient's glycemic control