Glucose tolerance and insulin response in normal-weight and obese cats

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 less than 0.01; glucose disappearance coefficient--0.95 +/- 0.10 vs 1.44 +/- 0.10%/min, P less than 0.01; insulinogenic index--0.20 +/- 0.02 vs 0.12 +/- 0.01, P less than 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 less than 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P less than 0.02), second 60 minutes (P less than 0.001), and total 120 minutes (P less than 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 beta-cell responsiveness to stimuli (ie, glucose).     

Assessment of the influence of fatty acids on indices of insulin sensitivity and myocellular lipid content by use of magnetic resonance spectroscopy in cats

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 non-esterified 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. CONCLUSION 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.     

Influence of glucose dosage on interpretation of intravenous glucose tolerance tests in lean and obese cats

Intravenous glucose tolerance tests (IVGTTs) are used in cats and other species to assess insulin sensitivity. Several dosages have been reported but the dosage that maximally stimulates insulin secretion in cats has not been determined nor has it been compared in lean and obese animals. IVGTTs were performed in 4 lean and 4 obese spayed female cats with 5 glucose dosages: 0.3 (A), 0.5 (B), 0.8 (C), 1.0 (D). and 1.3 (E) g/kg body weight (BW). Each cat received each dosage in a random design. The glucose disposal rate was significantly different only between lean and obese cats at the highest glucose dosage. The area under the curve for insulin increased significantly among A, B, C, and D in lean and among A, B, and C in obese cats but not between D and E in lean and among C, D, and E in obese cats. Baseline insulin secretion was significantly higher (P = .03) and 1st peak insulin secretion was approximately 50% lower in obese as compared to lean cats (P = .03). Lean but not obese cats reached baseline insulin concentrations at all dosages at 120 minutes. We conclude that the glucose dosage for maximal insulin secretion is 1.0 g/ kg BW in lean and 0.8 g/kg BW in obese cats, supporting routine use of 1 g/kg BW to maximally stimulate insulin secretion regardless of body composition. Obese cats showed an abnormal insulin secretion pattern, indicating a defect in insulin secretion with obesity and insulin resistance.     

Acute insulin response to intravenous arginine in nonobese healthy cats

The purpose of this study was to document and characterize insulin response to intravenous administration of arginine, a nonglucose secretagogue, and compare it to insulin response during intravenous glucose tolerance tests (IVGTTs) in clinically healthy nonobese cats. In addition, we examined the influence of plasma glucose level on insulin response to arginine in cats. Five dosages of 10% L-arginine hydrochloride (0.015, 0.025, 0.05, 0.1, and 0.2 g/kg of body weight) were administered to 5 cats. All doses of arginine elicited an abrupt insulin response that peaked at 2-4 minutes and returned to basal concentrations within 30 minutes. Mean insulin peak response (IPR) and mean area under the curve of plasma insulin concentration evaluated for the initial 10 minutes after administration (AUC10) increased with each progressive increase in arginine dosage. An asymptotic maximal response estimated by mean insulin AUC10 reached plateau at 0.1-0.2 g arginine/kg. Arginine at 0.2 g/kg induced hypersalivation in 2 of 4 cats. No adverse effects were evident at lower doses. Mean insulin AUC10 produced by equimolar amount of glucose (0.086 g/kg) was only 42% of that seen in response to 0.1 g arginine/kg, and mean IPR was much lower (18 +/- 7 versus 61 +/- 17 microU/mL). Mild hyperglycemia (211 +/- 6 mg/dL) induced by variable infusion rate of glucose resulted in a significant (P < .05) potentiation of insulin response to arginine; mean insulin AUC10 increased 287 +/- 26 to 551 +/- 167 microU/mL/10 minutes. These findings indicate that the arginine challenge is a more meaningful tool than is the IVGTT for evaluating the insulin secretory capacity in cats.     

Development of a feline proinsulin immunoradiometric assay and a feline proinsulin enzyme-linked immunosorbent assay (ELISA): a novel application to examine beta cell function in cats

The prevalence of feline diabetes mellitus has increased several-fold over the last three decades. In humans, progression from obesity to diabetes is marked by changes in the release of proinsulin. A specific proinsulin (FPI) assay has not been available to examine similar changes in cats. The goal of this study was to develop a proinsulin assay for the analysis of beta cell function in cats. Monoclonal antibodies were developed against recombinant FPI and used in a two-site sandwich immunoradiometric assay (IRMA) and enzyme-linked immunosorbent Assay (ELISA). The antibody pair had negligible cross-reactivity with bovine insulin and feline C-peptide. The working range was 11-667pmol/L for the IRMA and 11-1111pmol/L for the ELISA. An intravenous glucose tolerance test was performed in six long-term obese and six lean adult healthy cats and serum glucose, insulin, and FPI concentrations were determined. The proinsulin and insulin secretion pattern in response to glucose was significantly different between lean and obese cats but the pattern was similar within a group. Both groups had similar baseline proinsulin/insulin ratios; however, obese cats showed a significantly higher proinsulin/insulin ratio during the first 15min of the IVGTT and a much lower ratio during the last 30min suggesting a time-delayed adjustment to the increased insulin demand. In conclusion, we report the development and validation of an IRMA and an ELISA for FPI. This novel assay is useful to elucidate FPI secretion and can be used similar to a C-petide assay to evaluate residual beta cell function in cats.     

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets.During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation.     

Effect of Weight Gain and Subsequent Weight Loss on Glucose Tolerance and Insulin Response in Healthy Cats

The effects of weight gain and subsequent weight loss on glucose tolerance and insulin response were evaluated in 12 healthy cats. Intravenous glucose tolerance tests (IVGTT) were performed at entry into the study, after a significant gain of body weight induced by feeding palatable commercial cat food ad libitum, after a significant loss of body weight induced by feeding a poorly palatable purified diet to discourage eating and promote fasting, and after recovery from fasting when body weight had returned to pre-study values and cats were eating commercial foods. A complete physical examination with measurement of body weight was performed weekly, a CBC and serum biochemistry panel were evaluated at the time of each IVGTT, and a liver biopsy specimen obtained 2 to 4 days after each IVGTT was evaluated histologically for each cat. Mean serum glucose and insulin concentrations after glucose infusion and total amount of insulin secreted during the second 60 minutes and entire 120 minutes after glucose infusion were significantly (P > .05) increased after weight gain, as compared with baseline. At the end of weight loss, cats had hepatic lipidosis and serum biochemical abnormalities consistent with feline hepatic lipidosis. There was a significant (P > .05) increase in mean serum glucose concentration and t_1/2, and a significant (P > .05) decrease in mean serum insulin concentration and the glucose disappearance coefficient (K) after glucose infusion for measurements obtained after weight loss, compared with those obtained after weight gain and at baseline. Insulin peak response, insulino-genic index, and total amount of insulin secreted during the initial 10 minutes, 20 minutes, and 60 minutes after glucose infusion were decreased markedly (P > .05), compared with measurements obtained after weight gain and at baseline. In addition, the total amount of insulin secreted for 120 minutes after glucose infusion was decreased markedly (P > .05) in measurements obtained after weight loss, compared with those obtained after weight gain. At the end of recovery, all cats were voluntarily consuming food, serum biochemical abnormalities identified after weight loss had resolved, the number and size of lipid vacuoles in hepatocytes had decreased, and results of IVGTT were similar to those obtained at baseline. These findings confirmed the reversibility of obesity-induced insulin resistance in cats, and documented initial deterioration in glucose tolerance and insulin response to glucose infusion when weight loss was caused by severe restriction of caloric intake.     

Effect of darglitazone on glucose clearance and lipid metabolism in obese cats

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 i.v. glucose tolerance test was seen in darglitazone-treated cats. The drug was well tolerated. CONCLUSION 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.     

Glucose tolerance and insulin secretion in spontaneously hyperthyroid cats

Glucose tolerance and insulin secretion after administration of a glucose load were determined in 11 clinically normal cats and 15 cats with spontaneous hyperthyroidism. In six hyperthyroid cats, a glucose tolerance test was repeated after treatment with radioactive iodine (131I). All cats had similar baseline glucose concentrations. However, the cats with hyperthyroidism had a significantly decreased glucose clearance, which was worse after treatment. Hyperthyroidism also caused a marked increase in basal and glucose-stimulated insulin secretion, which was not improved with treatment. It is concluded that hyperthyroidism in cats may lead to long-lasting alterations of glucose tolerance and insulin secretion which may not be reversed by treatment.     

Effects of the sodium‐glucose cotransporter 2 (SGLT2) inhibitor velagliflozin,a new drug with therapeutic potential to treat diabetes in cats

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta‐hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume. Indirect calorimetry, an intravenous glucose tolerance test (IVGTT; 0.8 g/kg) and insulin tolerance test (IVITT) were conducted. All cats tolerated treatment well. Significant changes with D included a decrease in the respiratory exchange ratio, an increase in cholesterol, a small increase in albumin, and a rise in BHB and NEFA. Glucose clearance was unaltered, although less insulin was secreted during the IVGTT (p = .056) suggesting improved insulin sensitivity. IVITT was unchanged. Treatment did not affect glucagon, leptin, or adiponectin. Water intake, urine output, urinary glucose excretion, and the glucose/creatinine ratio but not urinary electrolytes were significantly higher post‐D. We conclude that velagliflozin is a promising drug, which increases urinary glucose excretion in cats and could thereby be beneficial for the treatment of hyperglycemia.     

Glucose uptake in horses with polysaccharide storage myopathy

OBJECTIVE: To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose. ANIMALS: 6 horses with PSSM and 10 healthy (control) horses. PROCEDURE: Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration. RESULTS: Peak glucose concentrations during IVGTT were similar for both groups of horses, but rate of glucose clearance was 1.5 times faster in horses with PSSM than in controls. Moreover, circulating concentrations of insulin before and after glucose injection were lower in the PSSM group. Blood glucose concentrations from minute 90 to minute 300 of the OGTT were lower in horses with PSSM than in controls. The MITT resulted in acute decreases in blood glucose concentrations in both groups of horses; however, horses with PSSM sustained low blood glucose concentrations for more than 3 hours after insulin injection, whereas blood glucose concentrations in controls returned to baseline values within 2 hours. CONCLUSIONS: Quarter Horses with PSSM have enhanced cellular uptake of glucose that may be, in part, caused by an increased sensitivity to insulin. CLINICAL RELEVANCE: Horses with PSSM have an increased rate of glucose clearance in response to insulin secretion. Thus, diets low in soluble carbohydrate may be the most effective way to decrease glycogen accumulation in skeletal muscle of these horses.     

Effects of obesity on lipid profiles in neutered male and female cats

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.     

Determination of reference values for glucose tolerance, insulin tolerance, and insulin sensitivity tests in clinically normal cats

OBJECTIVE: To determine reference values and test variability for glucose tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity tests (IST) in cats. ANIMALS: 32 clinically normal cats. PROCEDURE: GTT, ITT, and IST were performed on consecutive days. Tolerance intervals (ie, reference values) were calculated as means +/- 2.397 SD for plasma glucose and insulin concentrations, half-life of glucose (T1/2 glucose), rate constants for glucose disappearance (Kglucose and Kitt), and insulin sensitivity index (Si). Tests were repeated after 6 weeks in 8 cats to determine test variability. RESULTS: Reference values for T1/2glucose, Kglucose, and fasting plasma glucose and insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37 to 104 mg/dl, and 2.8 to 20.6 microU/ml, respectively. Mean values did not differ between the 2 tests. Coefficients of variation for T1/2glucose, Kglucose, and fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%, respectively. Reference values for Kitt were 1.14 to 7.3%/min, and for SI were 0.57 to 10.99 x 10(4) min/microU/ml. Mean values did not differ between the 2 tests performed 6 weeks apart. Coefficients of variation for Kitt and SI were 60 and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: GTT, ITT, and IST can be performed in cats, using standard protocols. Knowledge of reference values and test variability will enable researchers to better interpret test results for assessment of glucose tolerance, pancreatic beta-cell function, and insulin sensitivity in cats.     

High dose intravenous glucose tolerance test and serum insulin and glucagon levels in diabetic and non-diabetic cats: relationships to insular amyloidosis

The high dose intravenous glucose tolerance test and concurrent immunoreactive serum insulin and glucagon levels were measured and the results related to the presence or absence of pancreatic insular amyloid in 16 cats, seven of which were known to be diabetic. Control values for all parameters were established using seven additional clinicopathologically normal cats. Nine of the 16 cats had normal fasting blood glucose levels (less than 120 mg/dl) and impaired glucose tolerance. These cats had attenuated (3/9) or normal (6/9) 0 to 5 minute glucose-stimulated insulin secretion, rising 45 to 60 minute insulin secretion (7/9), low mean insulin/glucose ratio, and normal mean serum glucagon. Three of the nine cats with impaired glucose tolerance had insular amyloidosis. These three cats had significantly higher mean blood glucose levels during the glucose tolerance test than did cats with impaired glucose tolerance and no insular amyloid deposits. Also, these three cats accounted for three of the four longest glucose disappearance one-half times (T1/2S), three of the four lowest glucose disappearance coefficients, and three of the four lowest 0 to 5 minute insulin responses. The seven diabetic cats (fasting blood glucose levels greater than 120 mg/dl) had either low to low normal (6/7) or above normal (1/7) fasting insulin levels, no insulin response to intravenous glucose stimulation (6/7), and elevated mean serum glucagon levels. Insular amyloid was present in six of the seven diabetic cats. Three diabetic cats with marked insular amyloid deposits had glucose disappearance T1/2 and K (coefficient) values, serum insulin levels, serum glucagon levels, and insulin/glucose ratios which were not significantly different from the other three diabetic cats with slight to moderate insular amyloidosis. These results confirm a strong association between the occurrence, but not the extent of insular amyloidosis and diabetes mellitus in adult diabetic cats, although amyloid replacement of pancreatic islets does not appear to be the primary diabetogenic event. Rather, these results appear to be consistent with our hypothesis that insular amyloid deposition is a morphologic marker of primary B-cell dysfunction that is basic to the pathogenesis of the diabetic condition, and is reflected clinically by impaired glucose tolerance.     

High-fat feeding and staphylococcus intermedius infection impair beta cell function and insulin sensitivity in mongrel dogs

As obesity is a state of low-grade inflammation, we aimed to investigate the combined effect of high-fat diet and bacterial infection on β-cell function and insulin sensitivity in dogs. We used 20 healthy, male, mongrel dogs randomly divided into four groups: control group—healthy, non-obese dogs; infected group—non-obese dogs with experimentally induced infection (Staphylococcus intermedius); obese group—obese dogs (after 90 day high-fat diet) and obese-infected group—obese dogs with experimentally induced infection (Staphylococcus intermedius). To evaluate insulin sensitivity and β-cell function an intravenous glucose tolerance test (IVGTT) was performed. Plasma insulin increased in all group after glucose infusion. The lowest values were found in obese-infected group. Blood glucose also increased on 3 min after glucose infusion and then gradually decreased. In obese-infected group glucose concentration on 30 min was still significantly higher than initial levels, while in other groups glucose concentration returned to the initial values. The lowest rate of glucose elimination was found in infected group. In dogs of obese group and obese-infected group AUC_{ins 0–60 min} was lower compared to controls. AUC_{glucose 0–60 min} values were lowest in infected group, while in obese-infectd group values were the highest. Levels of ∆I/∆G in dogs of obese-infected group were significantly lower compared to controls and infected group. In conclusion, these results reveal that infection in obese dogs leads to impaired glucose tolerance, which is result of impairment in both insulin secretion and insulin sensitivity.     

Glucose tolerance and insulin response in diabetes mellitus of dogs

The low dose intravenous glucose tolerance test (IVGTT) and the insulin response to the glucose load were performed in a series of twenty–two diabetic dogs. All diabetic dogs were characterized by glucose intolerance as expressed by an abnormal half time (Tl/2) or fractional turnover rate (k) for glucose clearance. On the basis of the initial insulin level (Io), the insulin peak response (Ip) and the insulinogenic index (I/G), the dogs were classified into three types. Type I dogs were characterized by a low Io, low Ip and low I/G in response to glucose, similar to the juvenile form of diabetes in humans. Type II dogs were characterized by a normal or high Io, but also with a low Ip and a low I/G which are some of the features of the maturity onset form. Type III dogs were characterized by a normal Io and a normal or delayed response to glucose as seen in chemical diabetes. It is suggested that these types represent stages in the natural history of the development of diabetes mellitus in dogs.     

Effect of dietary chromium-L-methionine on glucose metabolism of beef steers

Thirty-six crossbred steers (288 +/- 3.7 kg initial BW) were used to determine the effect of Cr, as chromium-L-methionine, on glucose tolerance and insulin sensitivity in beef calves. Calves were fed a control diet or the diet supplemented with 400 or 800 microg Cr/kg of diet as chromium-L-methionine. Calves were kept in drylots (six calves/pen; two pens/dietary treatment). Steers were caught twice a day in locking headgates and individually fed their respective diets for a period of 22, 23, or 24 d prior to the metabolic challenges. Calves received a totally mixed diet containing 54% corn, 38% cottonseed hulls, and 5% soybean meal. On d 21, 22, and 23, four calves/dietary treatment were fitted with an indwelling jugular catheter. Approximately 24 h after catheterization, an intravenous glucose tolerance test (500 mg glucose/kg of BW), followed 5 h later by an intravenous insulin challenge test (0.1 IU insulin/kg of BW), was conducted. There was no effect (P > 0.10) of dietary treatment on ADG or ADFI. During the intravenous glucose tolerance test, serum insulin concentrations were increased by supplemental chromium-L-methionine (linear effect of Cr, P < 0.05). There was a time x treatment interaction (P < 0.05) on plasma glucose concentrations after the glucose infusion. Plasma glucose concentrations of calves fed 400 microg Cr/kg of diet were lower than those of controls and calves supplemented with 800 microg Cr/kg of diet (quadratic effect of Cr, P < 0.05) 5 and 10 min after the glucose infusion. Supplemental chromium-L-methionine increased the glucose clearance rate from 5 to 10 min after the insulin challenge test (linear effect of Cr, P < 0.05). Glucose half-life from 5 to 10 min after the insulin infusion was also decreased by supplemental chromium-L-methionine (linear effect of Cr, P < 0.10). These data indicate that supplemental Cr, as chromium-L-methionine, increased glucose clearance rate after an insulin infusion and increased the insulin response to an intravenous glucose challenge in growing calves with functioning rumens.     

Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings

Insulin resistance is considered a risk factor in obesity, laminitis, exertional rhabdomyolysis, and osteochondrosis. The objective was to use the minimal model to estimate glucose effectiveness (Sg) and insulin sensitivity (Si) in nonobese to obese horses initially adapted to forage only, then adapted to forage plus supplements rich in starch and sugar (SS) or fiber and fat (FF). Ten Thoroughbred geldings, with BCS of 5 (nonobese), 6 (moderately obese), and 7 to 8 (obese), were adapted to pasture and hay, allocated to two groups, and fed SS or FF in a switch-back design with 8 wk of adaptation. Modified frequent-sampling i.v. glucose tolerance tests were applied after adaptation to forage, SS, and FF. For the tolerance tests, horses were kept in stalls overnight and provided hay, and venous catheters were placed the next morning. Baseline samples were collected, 0.3 g of glucose/kg of BW was given i.v., and blood was sampled at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 19 min. At 20 min, 30 mU of insulin/kg of BW was given, followed by sampling at 22, 23, 24, 25, 27, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 min. Plasma was analyzed for glucose and insulin, and Si, Sg, acute insulin response to glucose, and the disposition index were calculated. Normality was tested using the Shapiro-Wilk statistic. Body condition effects were analyzed using a mixed model with repeated measures. Diet effects were analyzed using a Wilcoxon signed rank test. The Sg was higher in obese than nonobese (P = 0.003) and moderately obese (P = 0.007) horses; Si was lower in obese than nonobese (P = 0.008) horses, and acute insulin response to glucose was higher in obese than nonobese (P = 0.039) horses. Effects of diet were likely confounded by body condition, but horses had lower Si (P = 0.066) when fed SS compared with FF, especially when nonobese. In conclusion, the minimal model effectively estimated Sg, Si, acute insulin response to glucose, and disposition index in horses. Obese geldings were insulin-resistant and seemed to rely primarily on Sg for glucose disposal. Feeding a diet rich in sugar and starch decreased insulin sensitivity of horses. Maintenance of body condition and avoidance of grain-based meals rich in sugar and starch would be beneficial to decrease the risk of developing insulin resistance and associated metabolic syndromes in horses, especially for horses at risk for these syndromes.     

Influence of chromium tripicolinate on growth and glucose metabolism in yearling horses

Thoroughbred and Quarter Horse yearlings (n = 24; 335+/-7 d of age) were used in a 112-d feeding trial to determine whether chromium (Cr) supplementation would alter growth, development, and energy metabolism of growing horses on high-concentrate diets. The horses were assigned at random within breed and gender subgroups to one of four treatment groups: A) basal concentrate; B) basal plus 175 microg of Cr/kg concentrate; C) basal plus 350 microg of Cr/kg concentrate; and D) basal plus 700 microg of Cr/kg concentrate. Chromium was provided via Cr tripicolinate (Prince Agri Products, Quincy, IL). The horses were weighed, measured for withers and hip height, heart girth, and body length and underwent ultrasound evaluation for croup fat thickness. The concentrate was fed for ad libitum consumption for two, 1.5-hr feeding periods daily. Coastal bermudagrass (Cynodon dactylon) hay was group-fed (six animals/group) at 1% of BW daily. Feed intake was 60% concentrate and 40% hay, resulting in a supplemental Cr intake of 0, 105, 210, and 420 microg/kg diet for groups A, B, C, and D, respectively. Colts consumed more concentrate and total feed than did fillies (P < .05), but no dietary effect on feed intake was detected. Colts weighed more than fillies at the completion of the experiment (P = .0754), but no dietary effects on weight, body measurements, or croup fat were detected. An i.v. glucose tolerance test (.2 g of glucose/kg BW) and an i.v. insulin sensitivity test (.1 IU of insulin/kg BW) were conducted on each animal during the third 28-d period of the experiment. Plasma glucose peaked immediately following injection and decreased more rapidly in animals consuming the high-Cr diet than in those consuming the control diet (P < .01). Mean glucose fractional turnover rate values increased (P = .0369) and mean half-life of glucose decreased (P = .0634) in response to the high Cr supplementation. Plasma glucose depletions in animals fed the other two diets were between and not different from (P > .10) the depletions in control animals or in those fed high-Cr diets. No difference in insulin sensitivity was detected (P > .10). Results indicate that Cr tripicolinate supplementation of yearling horses increases the rate at which glucose is metabolized and may lower the plasma glucose concentration. No effect of Cr supplementation on development of the animals was detected.     

Transient clinical diabetes mellitus in cats: 10 cases (1989-1991)

Medical records of 10 cats with transient clinical diabetes mellitus were reviewed. At the time diabetes was diagnosed, clinical signs included polyuria and polydipsia (10 cats), weight loss (8 cats), polyphagia (3 cats), lethargy (2 cats), and inappetence (1 cat). Mean (+/- SD) fasting blood glucose concentration was 454 +/- 121 mg/dL, mean blood glucose concentration during an 8-hour period (MBG/8 hours) was 378 +/- 72 mg/dL, and glycosuria and trace ketonuria were identified in 10 and 5 cats, respectively. Baseline serum insulin concentration was undetectable (6 cats) or within the reference range (4 cats) and serum insulin concentration did not increase after i.v. glucagon administration in any cat. Insulin-antagonistic drugs were being administered to 5 cats and concurrent disorders were identified in all cats. Management of diabetes included administration of glipizide (6 cats), insulin (3 cats), or both (1 cat), discontinuation of insulin-antagonistic drugs, and treatment of concurrent disorders. Insulin and glipizide treatment was discontinued 4-16 weeks (mean, 7 weeks) after the initial diagnosis of diabetes was confirmed. At the time treatment for diabetes was discontinued, clinical signs had resolved, mean fasting blood glucose concentration was 102 +/- 48 mg/dL, MBG/ 8 hours was 96 +/- 32 mg/dL, glycosuria and ketonuria were not identified in any cat, and concurrent disorders (except mild renal insufficiency in 1 cat) had resolved. Significant (P < .05) increases occurred in postglucagon serum insulin concentrations, insulin peak response, and total insulin secretion, compared with values obtained when clinical diabetes was diagnosed. Histologic abnormalities were identified in pancreatic islets of 5 cats in which pancreatic biopsies were obtained and included decreased number of islets (4 cats), islet amyloidosis (3 cats), and vacuolar degeneration of islet cells (3 cats). Mean beta cell density was significantly (P < .001) decreased in diabetic cats compared with control cats (1.4 +/- 0.7 versus 2.6 +/- 0.5%, respectively). Cells within islets stained positive for insulin, however, the number of insulin-staining cells per islet and the intensity of insulin staining were decreased in 5 and 2 cats, respectively. Clinical diabetes had not recurred in 1 cat after 6 years, in 4 cats lost to follow-up after 1.5, 1.5, 2.0, and 2.5 years, and in 2 cats that died 6 months and 5.5 years after clinical diabetes resolved. Clinical diabetes recurred in 3 cats after 6 months, 14 months, and 3.4 years, respectively. These findings suggest that cats with transient clinical diabetes have pancreatic islet pathology, including decreased beta cell density, and that treatment of diabetes and concurrent disorders results in improved beta cell function, reestablishment of euglycemia, and a transition from a clinical to subclinical diabetic state.