Hypothyroid-Induced Insulin Resistance in Dogs

Effect of Hypothyroidism on Insulin Sensitivity
and Glucose Intolerance in Dogs

N. Hofer-Inteeworn, D. L. Panciera, W. E. Monroe, K. E. Saker,
R. Hegstad Davies, K. R. Refsal, and J.W. Kemnitz

Journal of the American Veterinary Medical Association 2012; 240: 600-605.

Hypothyroidism has been associated with poor glycemic control in diabetic dogs is thought to be an uncommon cause of insulin resistance (1). However, diabetes mellitus was the most common concurrent disease in a retrospective study of dogs with hypothyroidism (2), and hypothyroidism was one of the most commonly diagnosed concurrent disorders in dogs with diabetes mellitus in another study (3). Together, these findings suggest that insulin resistance in dogs with hypothyroidism may be more common that generally thought.

The purpose of this study by Hofer-Inteeworn et al (4) was to evaluate whether hypothyroidism causes insulin resistance and to determine the overall effect of hypothyroidism on glucose tolerance in dogs. Additional objectives of this research study were to examine the secretion profile of hormones that are counter-regulatory to insulin (including, growth hormone and cortisol) and  to determine whether insulin resistance was associated with obesity in hypothyroid dogs.

Objective
To determine the effects of hypothyroidism on insulin sensitivity, glucose tolerance, and concentrations of hormones counter-regulatory to insulin in dogs.

Animals
8 anestrous mixed-breed bitches with experimentally induced hypothyroidism and 8 euthyroid control dogs.

Procedures
The insulin-modified frequently sampled IV glucose tolerance test and minimal model analysis were used to determine basal plasma insulin and glucose concentrations, acute insulin response to glucose, insulin sensitivity, glucose effectiveness, and disposition index.

Growth hormone response was assessed by stimulation and suppression tests. Additionally, basal serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations and urine cortisol-to-creatinine concentration ratios were measured. Finally, dual energy x-ray absorptiometry was performed to evaluate body composition.

Results
Insulin sensitivity was lower in the hypothyroid group than in the euthyroid group, whereas acute insulin response to glucose was higher. Glucose effectiveness and disposition index were not different between groups. Basal serum GH and IGF-1 concentrations, as well as abdominal fat content, were high in hypothyroid dogs, but urine cortisol-to-creatinine concentration ratios were unchanged.

Conclusions and Clinical Relevance
Hypothyroidism appeared to negatively affect glucose homeostasis by inducing insulin resistance, but overall glucose tolerance was maintained by increased insulin secretion in hypothyroid dogs. Possible factors affecting insulin sensitivity are high serum GH and IGF-1 concentrations and an increase in abdominal fat. In dogs with diseases involving impaired insulin secretion such as diabetes mellitus, concurrent hypothyroidism can have important clinical implications.

My Bottom Line:

The results of this study show that hypothyroidism does indeed cause substantial —even marked—insulin resistance, as evidenced by an almost 5-fold decrease in insulin sensitivity, compared with the insulin sensitivity in euthyroid dogs (4). The pathogenesis of insulin resistance appears to be multifactorial, with high serum GH and IGF-1 concentrations probably contributing. In addition, the role of visceral fat on glucose metabolism may also be important in the development of insulin resistance in hypothyroid dogs (5,6).

Despite the fact that many hypothyroid dogs are markedly insulin resistant, their glucose tolerance is unaffected as a consequence of an increase in insulin secretion, which leads to a normalization in circulating glucose concentration.

Although hypothyroidism alone does not generally lead to overt hyperglycemia or diabetes, knowledge of a dog's thyroid function could be key in the successful management of cases of "problem" diabetes (7).

In diabetic dogs suffering from insulin resistance, hypothyroidism should always be included in the list of differential diagnoses (7). Treatment of these dogs with L-T4 replacement may help reverse the underlying insulin resistance and thereby lead to better glycemic control of their concurrent diabetic state (1,7).

References:

1. Ford SL, Nelson RW, Feldman EC, et al. Insulin resistance in three dogs with hypothyroidism and diabetes mellitus. Journal of American Veterinary Medical Association 1993;202:1478–1480. 
2. Dixon RM, Reid SW, Mooney CT. Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism. Veterinary Record 1999;145:481–487. 
3. Hess RS, Saunders HM, Van Winkle TJ, et al. Concurrent disorders in dogs with diabetes mellitus: 221 cases (1993–1998). Journal of American Veterinary Medical Association 2000;217:1166–1173.
4. Hofer-Inteeworn N, Panciera, Monroe WE, et al. Effect of hypothyroidism on insulin sensitivity and glucose intolerance in dogs. Journal of the American Veterinary Medical Association 2012; 240:600-605.
5. Gayet C, Bailhache E, Dumon H, et al. Insulin resistance and changes in plasma concentration of TNF-alpha, IGF-1, and NEFA in dogs during weight gain and obesity. Journal of Animal Physiology and Animal Nutrition (Berlin) 2004;88:157-165. 
6. German AJ, Hervera M, Hunter L, et al. Improvement in insulin resistance and reduction in plasma inflammatory adipokines after weight loss in obese dogs. Domestic Animal Endocrinology 2009;37:214-226.  
7. Peterson ME. Diagnosis and management of insulin resistance in dogs and cats with diabetes mellitus. Veterinary Clinics of North America: Small Animal Practice 1995;25:691-713.