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  • Author or Editor: Margarethe Hoenig 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)

Full access
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)

Full access
in American Journal of Veterinary Research

SUMMARY

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.

Free access
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.

Full access
in Journal of the American Veterinary Medical Association

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.

Full access
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)

Full access
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)

Full access
in American Journal of Veterinary Research

Abstract

Objective

To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug.

Animals

6 healthy adult ovariohysterectomized cats.

Procedure

In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally. Blood and urine samples were collected after drug administration, and concentrations of metformin in plasma and urine were determined by use of high-performance liquid chromatography.

Results

Disposition of the drug was characterized by a three-compartment model with a terminal phase half-life of (mean ± SD) 11.5 ± 4.2 hours. Metformin was distributed to a small central compartment of 0.057 ± 0.017 L/kg and to 2 peripheral compartments with volumes of distribution of 0.12 ± 0.02 and 0.37 ± 0.38 L/kg. Steady-state volume of distribution was 0.55 ± 0.38 L/kg. After IV administration, 84 ± 14% of the dose was excreted unchanged in urine, with renal clearance of 0.13 ± 0.03 L/h/kg; nonrenal clearance was negligible (0.02 ± 0.02 L/kg). Mean bioavailability of orally administered metformin was 48%.

Conclusions

The general disposition pattern of metformin in cats is similar to that reported for humans. Metformin was eliminated principally by renal clearance; therefore, this drug should not be used in cats with substantial renal dysfunction.

Clinical Relevance

On the basis of our results, computer simulations indicate that 2 mg of metformin/kg administered orally every 12 hours to cats will yield plasma concentrations documented to be effective in humans. (Am J Vet Res 1999;60:738–742)

Free access
in American Journal of Veterinary Research

SUMMARY

Prednisone was given orally to 12 dogs daily for 35 days at an anti-inflammatory dosage (1.1 mg/kg of body weight in divided dose, q 12 h) to study its effect on thyroxine (T4) and triiodothyronine (T3) metabolism. Six of these dogs were surgically thyroidectomized (THX-Pred) and maintained in euthyroid status by daily SC injections of T4 to study peripheral metabolism while receiving prednisone; 6 dogs with intact thyroid gland (Pred) were given prednisone; and 6 additional dogs were given gelatin capsule vehicle as a control group (Ctrl).

Baseline T4 concentration after 4 weeks of treatment was not significantly different in dogs of the THX-Pred or Pred group (mean ± SEM, 2.58 ± 0.28 or 3.38 ± 0.58 μg/dl, respectively) vs dogs of the Ctrl group (2.12 ± 0.30 μg/dl). A supranormal response of T4 to thyrotropin was observed in dogs of the Pred group, but the T4 response to thyrotropinreleasing hormone was normal. Baseline T3 concentration in dogs of both steroid-treated groups was significantly (P< 0.05) lower after 2 and 4 weeks of prednisone administration vs pretreatment values, but normalized 2 weeks after prednisone was stopped. Free T3 (FT3) and T4 (FT4) fractions and absolute FT3 and FT4 concentrations were not altered by prednisone administration. Reverse T3 (rT3) concentration in vehicle-treated Ctrl dogs (26.6 ± 3.5 ng/dl) was not different from rT3 concentration in dogs of the THX-Pred (25.7 ± 4.3 ng/dl) and Pred (28.9 ± 3.8 ng/dl) groups after 4 weeks of medication. These data indicate that daily oral administration of such anti-inflammatory dose of prednisone for 1 month reduces baseline serum T3 concentration, does not alter serum T4 concentration, and enhances thyroidal sensitivity to thyrotropin.

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association