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  • Author or Editor: Margarethe Hoenig x
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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 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 identify variations in glucose values concurrently obtained by use of a continuous glucose monitoring system (CGMS) at the same site, reliability of results for each site, lag time for each site, and influence of site thickness on CGMS accuracy.

ANIMALS 8 random-source research dogs.

PROCEDURES In experiment 1, 8 CGMS sensors were implanted bilaterally at 1 site (4 sensors/side) in 4 dogs. In experiment 2, 2 CGMS sensors were implanted bilaterally at each of 4 sites (1 sensor/side) in 8 dogs; 4 of those 8 dogs then were subjected to a glycemic clamp technique. The CGMS results were compared among sensors and with criterion-referenced results during periods of euglycemia for all 8 dogs and during hyperglycemia and hypoglycemia for 4 dogs during the glycemic clamp procedure.

RESULTS Differences (median, −7 mg/dL; interquartile range [IQR], −18.75 to 3 mg/dL) between CGMS and criterion-referenced glucose concentrations differed significantly among dogs and sites; during euglycemia, they were not different from the expected normal variation between multiple sensors concurrently implanted at the same site. Differences (median, −35 mg/dL; IQR, −74 to −15 mg/dL) between CGMS and criterion-referenced concentrations were greater during changes in glucose concentrations. Thoracic sensors were most accurate but had the shortest mean functional life.

CONCLUSIONS AND CLINICAL RELEVANCE Significant differences were detected between CGMS and criterion-referenced glucose concentrations. Overall clinical utility of CGMS was acceptable at all sites, with most of the values from all sensors, sites, and dogs meeting guidelines for point-of-care glucometers.

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in American Journal of Veterinary Research

Abstract

Objective—To compare results of hematologic testing in nondiabetic and diabetic cats to identify possible indicators of alterations in long-term glucose control.

Design—Cross-sectional study.

Animals—117 client-owned cats (76 nondiabetic cats [25 with normal body condition, 27 overweight, and 24 obese] and 41 naïve [n = 21] and treated [20] diabetic cats).

Procedures—Signalment and medical history, including data on feeding practices, were collected. A body condition score was assigned, and feline body mass index was calculated. Complete blood counts and serum biochemical analyses, including determination of fructosamine, thyroxine, insulin, and proinsulin concentrations, were performed. Urine samples were obtained and analyzed.

Results—Glucose and fructosamine concentrations were significantly higher in the naïve and treated diabetic cats than in the nondiabetic cats. Insulin and proinsulin concentrations were highest in the obese cats but had great individual variation. Few other variables were significantly different among cat groups. Most cats, even when obese or diabetic, had unlimited access to food.

Conclusions and Clinical Relevance—Results suggested that cats at risk of developing diabetes (ie, overweight and obese cats) could not be distinguished from cats with a normal body condition on the basis of results of isolated hematologic testing. A longitudinal study is indicated to follow nondiabetic cats over a period of several years to identify those that eventually develop diabetes. Findings also suggested that dietary education of cat owners might be inadequate.

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in Journal of the American Veterinary Medical Association

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 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 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)

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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.

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate plasma glipizide concentration and its relationship to plasma glucose and serum insulin concentrations in healthy cats administered glipizide orally or transdermally.

Animals—15 healthy adult laboratory-raised cats.

Procedure—Cats were randomly assigned to 2 treatment groups (5 mg of glipizide, PO or transdermally) and a control group. Blood samples were collected 0, 10, 20, 30, 45, 60, 90, and 120 minutes and 4, 6, 10, 14, 18, and 24 hours after administration to determine concentrations of insulin, glucose, and glipizide.

Results—Glipizide was detected in all treated cats. Mean ± SD transdermal absorption was 20 ± 14% of oral absorption. Mean maximum glipizide concentration was reached 5.0 ± 3.5 hours after oral and 16.0 ± 4.5 hours after transdermal administration. Elimination half-life was variable (16.8 ± 12 hours orally and 15.5 ± 15.3 hours transdermally). Plasma glucose concentrations decreased in all treated cats, compared with concentrations in control cats. Plasma glucose concentrations were significantly lower 2 to 6 hours after oral administration, compared with after transdermal application; concentrations were similar between treatment groups and significantly lower than for control cats 10 to 24 hours after treatment.

Conclusions and Clinical Relevance—Transdermal absorption of glipizide was low and inconsistent, but analysis of our results indicated that it did affect plasma glucose concentrations. Transdermal administration of glipizide is not equivalent to oral administration. Formulation, absorption, and stability studies are required before clinical analysis can be performed. Transdermal administration of glipizide cannot be recommended for clinical use at this time. (Am J Vet Res 2005;66:581–588)

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in American Journal of Veterinary Research