Proceeding of the NAVC North American Veterinary Conference

Jan. 8-12, 2005, Orlando, Florida

Reprinted in the IVIS website with the permission of the NAVC http://www.ivis.org/

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The North American Veterinary Conference – 2005 Proceedings

332

INSULIN RESISTANCE

Debra L. Zoran, DVM, PhD, Diplomate ACVIM Texas A&M University

College Station, TX INTRODUCTION

There are a number of factors that must be assessed in a dog or cat with diabetes when there is not adequate glycemic control. To determine why the diabetes is not controlled, the numerous causes of insulin ineffectiveness or insulin resistance must be considered. Insulin resistance is a condition in which a normal dose of insulin produces a less than adequate clinical response. This short talk will briefly cover the approach to ruling out insulin resistance as the cause of poor glycemic control.

The major causes of insulin ineffectiveness include: • inactive insulin • diluted insulin • improper administration technique • inadequate dose • somogyi effect • inadequate frequency of insulin administration • impaired insulin absorption

(especially long acting insulins) • anti-insulin antibody

These causes are relatively common and easily uncovered

causes for poor glycemic control that should be ruled out before an investigation for causes of insulin resistance is initiated. Because there are so many insulins available and issues of insulin effect are important early considerations, a few comments are in order. KEY FACTS ABOUT INSULIN SOURCES

• Human insulin (such as human recombinant insulin – Humulin) are most similar to pork insulin

• Beef source insulin is most structurally similar to feline insulin – thus, cats that do not respond well to human insulin, or may have antibody, should be tried on a beef or beef-pork insulin (e.g. PZI)

• Pork insulin is most structurally similar to canine insulin – thus, pork Lente may be the best choice for dogs that are suspected of having insulin antibody interference

• Most dogs do well on human insulin due to its similarity to pork insulin

Once the causes of insulin ineffectiveness have been

ruled out, the major causes of insulin resistance must be considered, and they include:

• diabetogenic drugs (e.g. glucocorticosteroids, progestins)

• hyperadrenocorticism (dogs > cats) • diestrus (dogs – any unspayed dog will have insulin

resistance) • acromegaly (cats) • infection (periodontal disease, UTI) • hypothyroidism (dogs) • hyperthyroidism (cats) • renal insufficiency • liver insufficiency • cardiac insufficiency

• glucagonoma (dog) • pheochromocytoma • chronic inflammation, especially pancreatitis • exocrine pancreatic insufficiency • severe obesity • hyperlipidemia • neoplasia

It is important to recognize that there is no insulin dose that

clearly defines insulin resistance; however, for most dogs (and cats), good control can be achieved with a dose of insulin near or less than 1 U/kg/dose, and insulin resistance should be suspected if the dog or cat has poor glycemic control and is receiving a dose of insulin greater than 1.5 u/kg/dose. In addition, there is no definitive fructosamine level that defines insulin resistance, but levels greater than 700 mg are suspicious and suggests further evaluation is warranted. Because insulin resistance can be mild, and thus easily overcome by increasing the insulin dosage, recognition of the problem can be difficult. Alternatively, severe insulin resistance is easier to detect, as the animal is typically not responsive to any type or dosage of insulin.

The most common causes of insulin resistance in dogs is hyperadrenocorticism or exogenous steroids, bacterial infection, hypothyroidism, and diestrus (in that order). Thus, in dogs, an appropriate work-up would include testing for hyperadrenocorticism (ACTH stimulation test or low dose dexamethasone suppresstion test), hypothyroidism (free T4, TSH levels), pancreatitis (ultrasound examination, cPLI), and treatment of any infections (e.g. periodontal disease, UTI, dermatitis, etc). Adrenal function testing can be most difficult, as the presence of illness can result in abnormally high ACTH stimulation test results or elevated urine cortisol to creatinine ratios. However, in most dogs, the cortisol levels obtained during a low dose dexamethasone suppression test will suppress if the dog does not have hyperadrenocorticism. Nevertheless, the diagnosis should not be made on the basis of these tests alone, but in conjunction with appropriate clinical signs, ultrasound findings of adrenomegaly, and significant insulin resistance.

There is a different group of problems that cause insulin resistance in cats. Acromegaly, hyperadrenocorticism, obesity and renal failure are the most common causes of insulin resistance in cats (with similar prevalences of 15-18%), and hyperthyroidism, infection and steroids are in the next group (with a 9% prevalence). In all cases where insulin resistance is suspected, these disorders should be carefully ruled out before consideration of the less common causes of the problem. Because many of the feline diseases causing insulin resistance can be much more challenging to control, management of the diabetes may be difficult in these cats. This is particularly true in diabetic cats with chronic renal failure or acromegaly. REFERENCES 1. Feldman and Nelson’s Small Animal Endocrinology and

Reproduction 3rd ed., 2004 2. in feline diabetics: 17 cases (1995-2001). J Vet Emerg

Cri Care 14(1): 30, 2004 3. Chastain CB et al. Concurrent disorders in dogs with

diabetes mellitus: 221 cases (1993-1998). Sm Anim Clin Endocrin 11(2):14, 2001.

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