Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech
Blacksburg, VA, USA
Hypothyroidism causes abnormalities in glucose homeostasis in a variety of animal species. It has been documented as a cause of insulin resistance in dogs with concurrent diabetes mellitus. While several studies have been conducted in hypothyroid dogs to determine insulin secretion and glucose concentrations during glucose tolerance tests, parameters of insulin sensitivity have not been determined to date. The purpose of the study was therefore to investigate the effect of hypothyroidism on glucose tolerance and insulin sensitivity in dogs.
Sixteen female mixed breed dogs were studied. Dogs were randomly selected and allocated into two groups. In 8 dogs, hypothyroidism was induced by administration of 1 mCi/kg 131I while the remaining 8 dogs were euthyroid controls. Hypothyroidism was confirmed by finding serum T4 < 5 nmol/L before and 4 hours after IV administration of human recombinant TSH. Experiments were performed on non-anesthetized, fasted dogs in anestrous approximately 12 months after hypothyroidism was induced. The insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) was used to determine insulin and glucose concentrations over a 3-hr time period. Data was analyzed by the Minimal Model Analysis (MINMOD) to calculate basal insulin and glucose concentrations, acute insulin response to glucose (AIRg), insulin sensitivity (Si), glucose effectiveness (the effect of glucose itself in its own disappearance, Sg) and the disposition index (DI). Student's t-test for unpaired data was used for comparisons between groups. P-values < 0.05 were considered statistically significant.
One dog in the control group was excluded from the analysis due to an exaggerated response to the exogenously administered insulin at 20 minutes. Basal glucose concentrations were mildly, but significantly higher in the control group, whereas basal insulin concentrations were significantly lower. Minimal Model Analysis revealed a lower insulin sensitivity in the hypothyroid group (P<0.001), whereas AIRg was higher (P=0.01). Glucose effectiveness and disposition index were not statistically different between groups.
The results confirm that hypothyroidism negatively affects glucose homeostasis by inducing insulin resistance. Since the disposition index, defined as the product of insulin sensitivity and secretion remained unchanged, a compensatory increase in insulin secretion as indicated by the increased AIRg occurred in hypothyroid dogs to maintain glucose tolerance. In cases with impaired insulin secretion, such as canine diabetes mellitus, concurrent hypothyroidism can have important clinical implications in the successful management of the disease.