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 and 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.

Glucose tolerance and insulin response were evaluated in 9 normal-weight and 6 obese cats after IV administration of 0.5 g of glucose/kg of body weight. Blood samples for glucose and insulin determinations were collected immediately prior to and 2.5, 5, 7.5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose infusion. Baseline glucose concentrations were not significantly different between normal-weight and obese cats; however, mean +/- SEM glucose tolerance was significantly impaired in obese vs normal-weight cats after glucose infusion (half time for glucose disappearance in serum--77 +/- 7 vs 51 +/- 4 minutes, P < 0.01; glucose disappearance coefficient--0.95 +/- 0.10 vs 1.44 +/- 0.10%/min, P < 0.01; insulinogenic index--0.20 +/- 0.02 vs 0.12 +/- 0.01, P < 0.005, respectively). Baseline serum insulin concentrations were not significantly different between obese and normal-weight cats. Insulin peak response after glucose infusion was significantly (P < 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P < 0.02), second 60 minutes (P < 0.001), and total 120 minutes (P < 0.0003) after glucose infusion was also significantly greater in obese than in normal-weight cats. Most insulin was secreted during the first hour after glucose infusion in normal-weight cats and during the second hour in obese cats. The impaired glucose tolerance and altered insulin response to glucose infusion in the obese cats was believed to be attributable to deleterious effects of obesity on insulin action and cell responsiveness to stimuli (ie, glucose).

Prednisone was administered orally for 4 weeks at a dosage of 1.1 mg/kg of body weight/d, in divided dose every 12 hours, to a group of healthy adult dogs (n = 12). Intravenous glucose tolerance testing was performed before and after the 28-day regimen in each dog, as well as in dogs of a control group (n = 6). Glucose metabolism was evaluated by measurement of preprandial plasma insulin and glucose concentrations, total insulin secretion, and fractional clearance of glucose. Mean preprandial plasma insulin and glucose concentrations were not increased after the 4-week regimen of prednisone. Total insulin secretion in response to an IV administered glucose load was not increased in treated dogs, compared with pretreatment values or with values for control dogs. The fractional clearance of glucose was also not altered in dogs given prednisone. Results indicate that anti-inflammatory doses of prednisone, given orally for 4 weeks, probably do not alter insulin sensitivity or glucose tolerance in clinically normal dogs.

After IV administration of 0.5 mg of glucagon/cat, glucose tolerance and insulin secretory response were evaluated in 10 lean cats, 10 obese cats, and 30 cats with diabetes mellitus. Blood samples for glucose and insulin determinations were collected immediately before and at 5, 10, 15, 30, 45, and 60 minutes after IV administration of glucagon. Baseline serum insulin concentration and insulin secretory response were used to classify diabetes mellitus in the 30 cats as type I or type II. Mean (+/- SEM) baseline and 30-minute serum glucose concentrations in obese cats were significantly (P < 0.05) decreased, compared with values in lean cats, but were similar at all other blood sample collection times. Serum glucose concentration in diabetic cats was significantly (P < 0.05) greater than values in obese and lean cats at all blood sample collection times. Two statistically different insulin responses to IV administration of glucagon were seen in diabetic cats. Of the 30 diabetic cats, 23 had minimal insulin secretory response after glucagon administration (ie, serum insulin concentration was at or below sensitivity of the insulin assay). Seven diabetic cats had baseline serum insulin concentration similar to that of obese cats and significantly (P < 0.05) greater than that of lean cats and of the other 23 diabetic cats. In these 7 diabetic cats, serum insulin concentration increased after glucagon administration. Total insulin secretion was not significantly different between these 7 diabetic cats and the lean and obese cats, and was significantly (P < 0.05) greater than total insulin secretion in the other 23 diabetic cats. Results support existence of type-I and type-II diabetes mellitus in cats.

In 5 horses, 13CO2/12CO2 ratios in expired air were determined using isotope mass spectroscopy to investigate metabolism of naturally occurring [13C]glucose. Oral glucose tolerance tests (OGTT) were performed using maize or beet glucose. Maize has a higher 13C concentration than that of most plants. The 13CO2/12CO2 ratios after OGTT was performed using maize glucose were compared with 13CO2/12CO2 ratios in expired air after OGTT was performed using beet glucose. The ratio also was determined during the period horses were not fed. Using OGTT, all horses were glucose tolerant. The OGTT performed using beet glucose led to minimal changes in 13CO2/12CO2 ratios. The 13CO2/12CO2 ratios decreased significantly (P less than 0.01) when horses were not fed. After oral dosing with maize glucose, 13CO2/12CO2 ratios reached maximal increases 5 hours after dosing and reached baseline values 15 hours after dosing.