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Practical Relevance: Up to 40% of the domestic feline population is overweight or obese. Obesity in cats leads to insulin resistance via multiple mechanisms, with each excess kilogram of body weight resulting in a 30% decline in insulin sensitivity. Obese, insulin-resistant cats with concurrent beta-cell dysfunction are at risk of progression to overt diabetes mellitus., Approach to Management: In cats that develop diabetes, appropriate treatment includes dietary modification to achieve ideal body condition (for reduction of insulin resistance), and optimization of diet composition and insulin therapy (for glycemic control and the chance of diabetic remission). Initially, as many obese cats that become diabetic will have lost a significant amount of weight and muscle mass by the time of presentation, some degree of diabetic control should be attempted with insulin before initiating any caloric restriction. Once body weight has stabilized, if further weight loss is needed, a diet with ≤ 12-15% carbohydrate metabolizable energy (ME) and >40% protein ME should be fed at 80% of resting energy requirement for ideal weight, with the goal of 0.5-1% weight loss per week. Other approaches may be necessary in some cats that need either substantial caloric restriction or do not find low carbohydrate diets palatable. Long-acting insulins are preferred as initial choices and oral antidiabetic drugs can be used in combination with diet if owners are unable or unwilling to give insulin injections. Glucagon-like peptide-1 (GLP-1) agonists have recently been investigated for use as adjunctive treatment in diabetic cats and sodium-glucose cotransporter-2 (SGLT2) inhibitors are currently being evaluated in clinical trials., Evidence Base: The information in this review is drawn from: epidemiological studies on obesity prevalence; prospective longitudinal studies of development of insulin resistance with obesity; randomized controlled studies; and expert opinion regarding the effect of diet on diabetes management 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., (© 2017 John Wiley & Sons Ltd.)

Obesity in pet dogs and cats is a significant problem in developed countries, and seems to be increasing in prevalence. Excess body fat has adverse metabolic consequences, including insulin resistance, altered adipokine secretion, changes in metabolic rate, abnormal lipid metabolism, and fat accumulation in visceral organs. Obese cats are predisposed to endocrine and metabolic disorders such as diabetes and hepatic lipidosis. A connection likely also exists between obesity and diabetes mellitus in dogs. No system has been developed to identify obese pets at greatest risk for development of obesity-associated metabolic diseases, and further study in this area is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Practical Relevance: Diabetes mellitus (DM) is a common endocrinopathy in cats that appears to be increasing in prevalence. The prognosis for affected cats can be good when the disease is well managed, but clinical management presents challenges, both for the veterinary team and for the owner. These ISFM Guidelines have been developed by an independent, international expert panel of clinicians and academics to provide practical advice on the management of routine (uncomplicated) diabetic cats., Clinical Challenges: Although the diagnosis of diabetes is usually straightforward, optimal management can be challenging. Clinical goals should be to limit or eliminate clinical signs of the disease using a treatment regimen suitable for the owner, and to avoid insulin-induced hypoglycaemia or other complications. Optimising bodyweight, feeding an appropriate diet and using a longer acting insulin preparation (eg, protamine zinc insulin, insulin glargine or insulin detemir) are all factors that are likely to result in improved glycaemic control in the majority of cats. There is also some evidence that improved glycaemic control and reversal of glucose toxicity may promote the chances of diabetic remission. Owner considerations and owner involvement are an important aspect of management. Provided adequate support is given, and owners are able to take an active role in monitoring blood glucose concentrations in the home environment, glycaemic control may be improved. Monitoring of other parameters is also vitally important in assessing the response to insulin. Insulin adjustments should always be made cautiously and not too frequently--unless hypoglycaemia is encountered., Evidence Base: The Panel has produced these Guidelines after careful review of the existing literature and of the quality of the published studies. They represent a consensus view on practical management of cats with DM based on available clinical data and experience. However, in many areas, substantial data are lacking and there is a need for better studies in the future to help inform and refine recommendations for the clinical management of this common disease., (© ISFM and AAFP 2015.)

Diabetes mellitus (DM) is a common disease in dogs and cats and its prevalence is increasing in both species, probably due to an increase in obesity, although only in cats has obesity been clearly identified as a major risk factor for diabetes. While the classification of diabetes in dogs and cats has been modeled after that of humans, many aspects are different. Autoimmune destruction of beta cells, a feature of type 1 DM in people, is common in dogs; however, in contrast to what is seen in people, the disease occurs in older dogs. Diabetes also occurs in older cats but islet pathology in those species is characterized by the presence of amyloid, the hallmark of type 2 DM. Despite being overweight or obese, most naive diabetic cats, contrary to type 2 diabetic humans, present with low insulin concentrations. The physiology of carbohydrate metabolism and pathogenesis of diabetes, including histopathologic findings, in dogs and cats are discussed in this chapter., (© 2014 Elsevier Inc. All rights reserved.)

Background: Pioglitazone is a thiazolidinedione (TZD) insulin sensitizer approved for use in human type 2 diabetes mellitus. Therapeutic options for diabetes in cats are limited., Objective: To evaluate the effects of pioglitazone in obese cats, which are predisposed to insulin resistance, to assess its potential for future use in feline diabetes mellitus., Animals: A total of 12 obese purpose-bred research cats (6 neutered males and 6 spayed females, 5-7 years of age, weighing 5.4-9.8 kg)., Methods: Randomized, placebo-controlled 3-way crossover study. Oral placebo or pioglitazone (Actos™; 1 or 3 mg/kg) was administered daily for 7-week periods, with IV glucose tolerance testing before and after each period., Results: Three mg/kg pioglitazone significantly improved insulin sensitivity (geometric mean [95% CI] 0.90 [0.64-1.28] to 2.03 [1.49-2.78] min⁻¹pmol⁻¹L; P = .0014 versus change with placebo), reduced insulin area under the curve during IVGTT (geometric mean [range] 27 [9-64] to 18 [6-54] min∙nmol/L; P = .0031 versus change with placebo), and lowered serum triglyceride (geometric mean [range] 71 [29-271] to 48 [27-75] mg/dL; P = .047 versus change with placebo) and cholesterol (geometric mean [range] 187 [133-294] to 162 [107-249] mg/dL; P = .0042 versus change with placebo) concentrations in the obese cats. No adverse effects attributable to pioglitazone were evident in the otherwise healthy obese cats at this dosage and duration., Conclusions and Clinical Importance: Results of this study support a positive effect of pioglitazone on insulin sensitivity and lipid metabolism in obese cats, and suggest that further evaluation of the drug in cats with diabetes mellitus or other metabolic disorders might be warranted.

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.

(1)H magnetic resonance spectroscopy ((1)H MRS) is the preferred technique for noninvasive quantification of hepatic triglyceride in humans. Domestic cats are subject to liver lipid accumulation, but MRS has not been investigated for quantification of liver fat in cats. The purpose of this project was to explore a technique for (1)H MRS measurement of hepatic triglyceride in lean and obese cats. Hepatic (1)H MRS was performed, using a 3T imaging unit and a single-voxel spin-echo spectroscopy sequence, on 6 lean (3.3-4.6 kg) and 12 obese cats (5.2-9.8 kg). Median liver fat percentages in lean and obese cats were 1.3% and 6.8%, respectively. Results are biologically plausible, based on chemical assay in a separate group of cats; however, full validation of the method is necessary before other conclusions can be drawn. This report should provide a foundation for the further development of spectroscopic techniques for studying hepatic lipid accumulation in cats., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Pioglitazone is a thiazolidinedione insulin sensitizer that has shown efficacy in Type 2 diabetes and nonalcoholic fatty liver disease in humans. It may be useful for treatment of similar conditions in cats. The purpose of this study was to investigate the pharmacokinetics of pioglitazone in lean and obese cats, to provide a foundation for assessment of its effects on insulin sensitivity and lipid metabolism. Pioglitazone was administered intravenously (median 0.2 mg/kg) or orally (3 mg/kg) to 6 healthy lean (3.96 ± 0.56 kg) and 6 obese (6.43 ± 0.48 kg) cats, in a two by two Latin Square design with a 4-week washout period. Blood samples were collected over 24 h, and pioglitazone concentrations were measured via a validated high-performance liquid chromatography assay. Pharmacokinetic parameters were determined using two-compartmental analysis for IV data and noncompartmental analysis for oral data. After oral administration, mean bioavailability was 55%, t(1/2) was 3.5 h, T(max) was 3.6 h, C(max) was 2131 ng/mL, and AUC(0-∞) was 15 556 ng/mL · h. There were no statistically significant differences in pharmacokinetic parameters between lean and obese cats following either oral or intravenous administration. Systemic exposure to pioglitazone in cats after a 3 mg/kg oral dose approximates that observed in humans with therapeutic doses., (© 2011 Blackwell Publishing Ltd.)

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.

Obesity is the most common nutritional disorder of cats and is a risk factor for diabetes. Similar to developments in obese people, obese cats show peripheral tissue insulin resistance and may demonstrate glucose intolerance when challenged with pharmacological amounts of glucose. However, they compensate well for the insulin resistance and do not show elevated glucose concentrations when monitored during their regular daily routine, including postprandial periods. This is possible because obese cats in the fasted and postprandial state are able to maintain hepatic insulin sensitivity and decrease endogenous glucose production, which allows them to maintain normoglycemia. Also dissimilar to what is seen in many obese humans, cats do not develop atherosclerosis and clinical hypertension. The time course for progression to overt diabetes of obese cats is unknown. One might speculate that diabetes develops when the liver finally becomes insulin resistant and/or insulin secretion becomes too low to overcome increased glucose production. In addition, amyloid, demonstrated to be deposited in islet of chronically obese cats, may contribute to a reduction in insulin secretion by reducing functional β-cell mass., (© 2012 Diabetes Technology Society.)

Obesity and age are risk factors for feline diabetes. This study aimed to test the hypothesis that age, long-term obesity, and dietary composition would lead to peripheral and hepatorenal insulin resistance, indicated by higher endogenous glucose production (EGP) in the fasted and postprandial state, higher blood glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin concentrations. Using triple tracer-(2)H(2)O, [U-(13)C(3)] propionate, and [3,4-(13)C(2)] glucose infusion, and indirect calorimetry-we investigated carbohydrate and fat metabolic pathways in overnight-fasted neutered cats (13 young lean, 12 old lean, and 12 old obese), each fed three different diets (high protein with and without polyunsaturated fatty acids, and high carbohydrate) in a crossover design. EGP was lowest in fasted and postprandial obese cats despite peripheral insulin resistance, indicated by hyperinsulinemia. Gluconeogenesis was the most important pathway for EGP in all groups, but glycogen contributed significantly. Insulin and leptin concentrations were higher in old than in young lean cats; adiponectin was lowest in obese cats but surprisingly highest in lean old cats. Diet had little effect on metabolic parameters. We conclude that hepatorenal insulin resistance does not develop in the fasted or postprandial state, even in long-term obese cats, allowing the maintenance of euglycemia through lowering EGP. Glycogen plays a major role in EGP, especially in lean fasted cats, and in the postprandial state. Aging may predispose to insulin resistance, which is a risk factor for diabetes in cats. Mechanisms underlying the high adiponectin of healthy old lean cats need to be further explored.

The response to oral glucose was examined in 10 obese and 9 lean age-matched, neutered cats. In all cats, oral administration of 2g/kg glucose was followed by a prompt increase in glucose, insulin, and glucagon-like peptide (GLP)-1. There were significant differences between lean and obese cats in the areas under the curve for glucose, insulin, and GLP-1. However, the responses were variable, and a clear distinction between individual lean and obese cats was not possible. Therefore, this test cannot be recommended as a routine test to examine insulin resistance in individual cats as it is used in people. A further disadvantage for routine use is also the fact that this test requires gastric tubing for the correct administration of the glucose and associated tranquilization to minimize stress and that it was associated with development of diarrhea in 25% of the cats. GLP-1 concentrations were much lower in obese than lean cats. The low GLP-1 concentrations in obese cats might indicate a contribution of GLP-1 to the lower insulin sensitivity of obese cats, but this hypothesis needs to be further investigated., (Copyright 2010 Elsevier Inc. All rights reserved.)

Obesity is an important endocrine disorder in cats and is a risk factor for diabetes similar to humans. The goal of this study was to examine the effect of long-term obesity and different diets (high protein, and high carbohydrate supplemented with saturated fatty acids or n-3 polyunsaturated fatty acids) on plasma lipids in the fasted and fed states in 12 lean (LEAN) and 12 obese (OBESE) cats with ultracentrifugation, and nuclear magnetic resonance spectroscopy. OBESE had higher plasma non-esterified fatty acids and triglycerides, as well as very-low-density-lipoproteins (VLDL) consisting primarily of medium-sized particles. The concentration of low-density-lipoproteins (LDL) was comparable between the groups, although OBESE had mostly very small, whereas LEAN had mostly large particles. The concentration of high-density-lipoproteins (HDL) was lower in OBESE and consisted primarily of small particles. Plasma triglycerides, and triglycerides and cholesterol in all lipoproteins increased postprandially. Different diets had little effect on lipids. Our results show that long-term obese cats develop similar lipoprotein changes to humans, yet, hypertension and atherosclerosis have not been described in obese cats. This suggests that dyslipidemia alone is not sufficient to induce hypertension and atherosclerosis. Other anti-atherogenic factors may be present in the obese, dyslipidemic cat.

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.

The effect of a 2-week administration of 75microg triiodothyronine (T3) on substrate oxidation, heat production, non-esterified fatty acids, and leptin was evaluated in eight lean (three females and five males) and eight obese (five females and three males) age-matched adult neutered cats. In addition, using real-time RT-PCR, expression of muscle and adipose tissue uncoupling proteins (UCP2 and UCP3), deiodinase 1 and 2 (D1; D2), and peroxisome proliferator-activated receptor (PPAR) alpha and gamma and peroxisome-proliferator-activator receptor-gamma co-activator 1alpha (PGC1) was examined. Compared to lean cats, obese cats had increased NEFA, leptin, UCP2, and D1mRNA in muscle and UCP3mRNA levels in fat, but lower heat production, and fat PPARs and PGC1. T3 administration increased thermogenesis and NEFA in lean and obese cats, and adipose tissue PPARgamma in lean cats. It also increased muscle D1 in lean and D2 in obese cats. The increase in muscle D2 was interpreted to be reflective of the reduced serum total T4 concentration following T3 suppression of the pituitary. No effect was seen on leptin, or UCP2 and 3. This shows that T3 regulates thermogenesis but not through changes in uncoupling protein expression. It also indicates that PPARs have an important role in the pathogenesis of obesity in cats.

Obesity is a rising problem in cats. It is a risk factor for several diseases and has been linked to impaired immunity. The goal of this study was to determine the effect of body composition and effects of diet on immune function in cats. Twenty-eight short-term obese and 12 lean cats with equal gender distribution were evenly and randomly divided into two groups which were either fed a diet containing saturated (SFA) or long-chain n-3 polyunsaturated fatty acids (3-PUFA) for a period of 6 months prior to testing. Blood was collected by venipuncture from the jugular vein. Blood samples were analyzed in a double blind fashion. A complete blood count was performed and lymphocyte distribution was examined by flow cytometric analysis with specific fluorescein-conjugated subset markers. Immune function was measured as follows: the proliferative activity of different cellular fractions was tested with polyclonal mitogens such as lipopolysaccharide (LPS), phytohaemagglutinin (PHA), phorbol 12-myristate 13-acetate (PMA), Ca ionophore, and concanavalin A. Innate immune functions assessed were phagocytosis and natural killer cell (NK) cytotoxicity. A similar immune innate and adaptive immune response was elicited regardless of diet or body condition. However, there was no correlation between body condition, diet, and any of the quantitative and qualitative functional responses of the immune system. We conclude that short-term obesity and the fatty acid composition of the diet do not alter immune responses in cats.

Insulin sensitivity (SI) of glucose disposal can be quantified with the euglycemic hyperinsulinemic clamp (EHC) with tracer glucose infusion. True steady state is, however, difficult to achieve, and non-steady state analysis of EHC data is preferred. This analysis requires information on glucose kinetics that can be obtained from bolus injection of cold and tracer glucose. The aim of this study was to assess glucose kinetics in cats. Mathematical modeling and non-steady state analysis was applied to assess effects of obesity on glucose turnover, glycolysis/glycogen synthesis, SI, and inhibition of endogenous glucose production (EGP) in lean cats (L) and obese cats (O). D-[3-(3)H]-glucose kinetics and 3H-H2O production were analyzed in 4 L and 4 O with three-compartment modeling. Frequently sampled insulin-modified intravenous glucose tolerance tests (FSIGT) with minimal model analysis were performed in 5L and 3 O to assess glucose kinetics and SI. EHC was performed in 10 L and 10 O with primed-constant infusion of 3H-glucose. Data were analyzed with a modified minimal model segregating suppression of EGP by insulin using a non-linear mixed-effects population approach. FSIGT provided estimates of SI, glucose effectiveness SG, and distribution volume. EHC provided estimates of SI, SG, glycolysis, and suprabasal insulin concentration for 50% EGP inhibition. Obesity appears to affect glucose distribution but not utilization at basal insulin, and reduces SI estimated by FSIGT and EHC. Differences in SI between FSIGT and EHC depend on different descriptions of EGP inhibition by insulin. Finally, glucose disposal at basal insulin appears to occur entirely through glycolysis, whereas significant amounts of glucose are sequestrated from oxidation during EHC.

Post-heparin plasma activity of lipoprotein lipase (LPL) and hepatic lipase (HL), and fat and muscle activity of LPL were measured in neutered lean and obese cats. Lipoprotein lipase, hormone-sensitive lipase (HSL), and tumor necrosis factor a (TNF) mRNA were measured in muscle and fat tissue with real-time PCR using primers for feline LPL, HSL, and TNF. Lipoprotein lipase plasma and fat activity and fat mRNA levels were significantly lower (50, 80, and 50%, respectively) in obese cats than lean cats, whereas the muscle/fat ratio of LPL was significantly higher in obese compared to lean cats. The activity of HL was not different between the groups. Hormone-sensitive lipase mRNA levels were significantly higher in obese than lean cats. The level of fat TNF also was significantly higher in obese cats than in lean cats, whereas the level in muscle was not different. The lower LPL activity and mRNA expression in fat and the higher LPL and HSL mRNA expression in muscle in obese cats compared to lean cats expectedly favor a redistribution of fatty acids from fat to muscle tissue where they can be deposited or used for energy in times of need. Tumor necrosis factor alpha may regulate this repartitioning process through suppression of adipocyte LPL.

The increase in obesity in people and pets has been phenomenal. As in man, obesity in pets is a risk factor for many diseases including diabetes mellitus. Recently, tissue-specific regulation of glucose metabolism in fat and muscle tissue has been identified as an important factor for insulin sensitivity and it has been hypothesized that glucose uptake into tissues is altered in obesity causing insulin resistance. The purpose of this study was to determine the expression of the glucose transporter proteins GLUT4 and GLUT1 in muscle and fat from lean and obese cats. Seventeen domestic felines were tested in the lean state and again after a 6-month period of ad libitum food intake which led to a significant increase in weight (P < 0.0001). Obese cats showed a significantly higher area under the curve (AUC) for glucose, AUC for insulin and a significant decrease in glucose percentage disappearance per min (K-value) (P = 0.013, 0.018 and 0.017, respectively) during an intravenous glucose tolerance test, but no change in baseline glucose or glycosylated hemoglobin concentrations. GLUT4 expression was decreased in biopsies of both muscle (P = 0.002) and fat (P = 0.001) in the obese animals. GLUT4 in muscle and fat significantly and negatively correlated with the insulin AUC (r2 = 0.36, P = 0.004 and r2 = 0.18, P = 0.040, respectively). GLUT1 expression showed no significant change in the obese cats in either tissue. It is concluded that the changes in GLUT4 are early derangements in obesity and occur before glucose intolerance is clinically evident.

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.

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.

Diabetes mellitus is a common disease in cats and dogs. Its incidence is increasing, possibly due to an increase in obesity in both species. Different types of diabetes have been identified in pet animals. The classification of diabetic dogs and cats is modeled after the human classification but especially in the diabetic dogs, many aspects are different. The diabetic cat, however, resembles type 2 diabetic human patients more closely. The clinical presentation, pathophysiology, and histologic findings are described for both dog and cat and possible etiological mechanisms are discussed.

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.

Beta cell and insulin antibodies are involved in the pathogenesis of diabetes in human patients. Beta cell antibodies have also been found in about 50% of newly diagnosed diabetic dogs. This study's objective was to examine these antibodies' role in feline diabetes. The serum of 26 newly diagnosed untreated diabetic cats, 29 cats on insulin therapy, 30 cats with diseases other than diabetes, and 30 healthy cats was examined for beta cell and insulin antibodies. For beta cell antibody testing, purified beta cells from a radiation-induced transplantable rat insulinoma were used. Serum from cats in which anti-beta cell antibodies were induced by injecting a purified beta cell suspension subcutaneously was used as a positive control. Following incubation with test sera, fluorescein-labeled anti-cat immunoglobulins were used to visualize binding between the beta cells and cat gamma globulins. Each serum was tested on two different tumor preparations. For the detection of insulin antibodies, a charcoal separation method was used. It was found that none of the healthy cats, none of the newly diagnosed, untreated diabetic cats and none of the cats with diseases other than diabetes had antibodies against beta cells or against endogenous insulin. Four diabetic cats (14%) that had been treated with different insulin preparations had insulin antibodies. It is concluded that immune-mediated processes are not causing diabetes in the cat. Further studies are needed to evaluate if antibodies directed against exogenous insulin alter the response of diabetic cats to insulin.

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.

Megaesophagus was diagnosed in 2 cats. Both had a history of regurgitation, and one was dyspneic. Radiography of the thorax and abdomen revealed generalized megaesophagus and gastric distention with gas. There was no esophageal motility during fluoroscopic observation. The prognosis for cats with megaesophagus is guarded. Although they may be satisfactory pets, cats with this condition should not be used for breeding because the condition is believed to be inherited through recessive genes.