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
Animals—10 male and 10 female weight-maintained
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)
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
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)
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)
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
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
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
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
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.
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.