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  • Author or Editor: Duncan C. Ferguson x
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Abstract

Objective—To determine whether changes in concentrations of hormones involved in glucose and fatty acid homeostasis are responsible for the increased probability that neutered cats will develop obesity and diabetes mellitus.

Animals—10 male and 10 female weight-maintained adult cats.

Procedure—Results of glucose tolerance tests and concentrations of hormones and nonesterified fatty acids (NEFA) were examined before and 4, 8, and 16 weeks after neutering.

Results—Caloric requirements for weight maintenance were significantly decreased 8 and 16 weeks after neutering in females. Glucose concentrations during a glucose tolerance test did not change in neutered females or males. The area under the curve (AUC) for insulin was significantly higher in males, compared with females, before neutering. However, the AUC for insulin increased and was significantly higher 4 and 8 weeks after neutering in females. The AUC for insulin did not change in neutered male cats. Leptin concentrations did not change in females but increased significantly in males 8 and 16 weeks after neutering. Thyroxine concentrations did not change after neutering; however, free thyroxine concentration was significantly higher in females than males before neutering. Baseline concentrations of NEFA were significantly higher in female than male cats before but not after neutering. Suppression of NEFA concentrations after glucose administration decreased successively in male cats after neutering, suggesting decreased insulin sensitivity.

Conclusionss and Clinical Relevance—Changes in NEFA suppression, caloric intake, and leptin concentrations may be indicators of, and possible risk factors for, the development of obesity in cats after neutering. (Am J Vet Res 2002;63:634–639)

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in American Journal of Veterinary Research

Abstract

Objective—To examine the effect of darglitazone, a compound of the thiazolidinedione class, on glucose clearance and lipid metabolism in obese cats.

Animals—18 obese and 4 lean adult neutered female cats.

Procedure—IV glucose tolerance tests with measurements of glucose, insulin, and nonesterified fatty acid (NEFA) concentrations were performed before and 42 days after daily administration of darglitazone (9 obese cats) or placebo (9 obese and 4 lean cats). Additionally, cholesterol, triglyceride, leptin, and glycosylated hemoglobin concentrations were measured.

Results—Darglitazone-treated cats had significantly lower cholesterol, triglyceride, and leptin concentrations, compared with placebo-treated obese cats. A significant decrease in the area under the curve for NEFAs, glucose, and insulin during an IV glucose tolerance test was seen in darglitazone-treated cats. The drug was well tolerated.

Conclusions and Clinical Relevance—The response of obese cats to darglitazone was similar to the response to thiazolidinediones in obese humans and rodents Darglitazone was effective in improving insulin sensitivity and glucose and lipid metabolism in obese cats. (Am J Vet Res 2003;64:1409–1413)

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in American Journal of Veterinary Research

Abstract

Objective—To examine whether obese cats, compared with lean cats, have alterations in lipoprotein metabolism that might lead to a decrease in glucose metabolism and insulin secretion.

Animals—10 lean and 10 obese adults cats (5 neutered males and 5 neutered females each).

Procedure—Intravenous glucose tolerance tests with measurements of serum glucose, insulin, and nonesterified fatty acid (NEFA) concentrations were performed. Lipoprotein fractions were examined in serum by isopycnic density gradient ultracentrifugation.

Results—Obese cats had insulin resistance. Plasma triglyceride and cholesterol concentrations were significantly increased in obese cats, compared with lean cats. Very low density lipoprotein (VLDL) concentrations were increased in obese cats, compared with lean cats; however, the composition of various fractions remained unchanged between obese and lean cats, indicating greater synthesis and catabolism of VLDL in obese cats. Serum high density lipoprotein (HDL) cholesterol concentrations were increased in obese cats, compared with lean cats. Serum NEFA concentrations were only significantly different between obese and lean cats when separated by sex; obese male cats had higher baseline serum NEFA concentrations and greater NEFA suppression in response to insulin, compared with lean male cats.

Conclusions and Clinical Relevance—Lipid metabolism changes in obese cats, compared with lean cats. The increase in VLDL turnover in obese cats might contribute to insulin resistance of glucose metabolism, whereas the increase in serum HDL cholesterol concentration might reflect a protective effect against atherosclerosis in obese cats. (Am J Vet Res 2003;64:299–303)

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in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetics of troglitazone in healthy cats after IV and oral administration of a single dose of the drug.

Animals—5 healthy ovariohysterectomized adult cats.

Procedure—Using a randomized crossover design, cats were given 5 mg of troglitazone/kg of body weight IV and 40 mg of troglitazone/kg orally. Blood and urine samples were collected after drug administration, and concentrations of troglitazone in plasma and urine were determined by use of high-performance liquid chromatography.

Results—Area-moment analysis was used to calculate pharmacokinetic variables. Terminal phase half-life was 1.1 ± 0.1 hours. Steady-state volume of distribution was 0.23 ± 0.15 L/kg. After IV administration, clearance was 0.33 ± 0.04 L/h/kg. Drug was not detected in urine samples. Mean bioavailability of orally administered troglitazone was 6.9%.

Conclusions and Clinical Relevance—The overall disposition of troglitazone in cats was similar to that reported in other species, including humans. Troglitazone has low and variable oral bioavailability. Clearance of the compound is moderate. Little if any unchanged troglitazone is excreted in urine; thus, metabolism and biliary excretion play predominant roles in elimination of the drug. On the basis of troglitazone pharmacokinetics in healthy cats, as well as on the basis of pharmacodynamics of the drug in humans and other animals, a regimen that uses a dosage of 20 to 40 mg/kg administered orally once or twice per day to cats will produce plasma concentrations of the insulin-sensitizing agent that have been documented to be effective in humans. (Am J Vet Res 2000;61:775–778)

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in American Journal of Veterinary Research

Abstract

Objective—To determine whether dietary fatty acids affect indicators of insulin sensitivity, plasma insulin and lipid concentrations, and lipid accumulation in muscle cells in lean and obese cats.

Animals—28 neutered adult cats.

Procedure—IV glucose tolerance tests and magnetic resonance imaging were performed before (lean phase) and after 21 weeks of ad libitum intake of either a diet high in omega-3 polyunsaturated fatty acids (3-PUFAs; n = 14) or high in saturated fatty acids (SFAs; 14).

Results—Compared with the lean phase, ad libitum food intake resulted in increased weight, body mass index, girth, and percentage fat in both groups. Baseline plasma glucose or insulin concentrations and glucose area under the curve (AUC) were unaffected by diet. Insulin AUC values for obese and lean cats fed 3-PUFAs did not differ, but values were higher in obese cats fed SFAs, compared with values for lean cats fed SFAs and obese cats fed 3-PUFAs. Nineteen cats that became glucose intolerant when obese had altered insulin secretion and decreased glucose clearance when lean. Plasma cholesterol, triglyceride, and nonesterified fatty acid concentrations were unaffected by diet. Ad libitum intake of either diet resulted in an increase in both intra- and extramyocellular lipid. Obese cats fed SFAs had higher glycosylated hemoglobin concentration than obese cats fed 3-PUFAs.

Conclusions and Clinical Relevance—In obese cats, a diet high in 3-PUFAs appeared to improve long-term glucose control and decrease plasma insulin concentration. Obesity resulted in intra- and extramyocellular lipid accumulations (regardless of diet) that likely modulate insulin sensitivity. (Am J Vet Res 2004;65:1090–1099)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate intraday and interday variations in glucose concentrations in cats and to test the utility of a continuous glucose monitoring system (CGMS).

Animals—6 lean and 8 long-term (> 5 years) obese cats.

Procedures—Blood glucose concentrations were measured during the course of 156 hours by use of a laboratory hexokinase-based reference method and a handheld glucometer. Interstitial glucose concentrations were evaluated with a CGMS.

Results—Paired measures of glucose concentrations obtained with the CGMS typically were marginally higher than concentrations for the reference method and less biased than concentrations obtained with the glucometer. This was partially confirmed by the concordance correlation coefficients of the concentration for the CGMS or glucometer versus the concentration for the reference method, although the correlation coefficients were not significantly different. Mean ± SD area under the curve for the glucose concentration (AUCG) did not differ significantly between lean (14.0 ± 0.5 g/dL•h) and obese (15.2 + 0.5 g/dL•h) cats during the 156-hour period, but one of the obese cats had a much higher AUCG. Within-day glucose variability was small in both lean and obese cats.

Conclusions and Clinical Relevance—Glucose homeostasis was maintained, even in long-term obese cats, and intraday glucose fluctuations were small. One obese cat might have been classified as prediabetic on the basis of the AUCG, which was approximately 25% higher than that of the other obese and lean cats. The CGMS can be useful in the evaluation of long-term effects of drugs or diet on glucose homeostasis in cats.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare daily endogenous cortisol production rate and the pharmacokinetics of an IV bolus of hydrocortisone between neonatal foals and adult horses.

Animals—10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses.

Procedures—Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered IV to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid IV bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals.

Results—The mean ± SD 24-hour cortisol concentration was significantly lower in foals (20 ± 4 ng/mL) than in horses (26 ± 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 ± 320 ng/kg/d) than in horses (2,140 ± 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 ± 1.11 L/kg) and total body clearance (1.39 ± 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 ± 343 ng/mL) than did horses (0.58 ± 0.15 L/kg, 0.349 ± 0.065 L/kg/h, and 8,934 ± 3,843 ng/mL, respectively).

Conclusions and Clinical Relevance—Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.

Full access
in American Journal of Veterinary Research