Prevalence of pituitary tumors among diabetic cats with insulin resistance

OBJECTIVE: To determine prevalence of pituitary tumors, detectable by means of computed tomography or magnetic resonance imaging, in cats with insulin resistance suspected to have acromegaly or hyperadrenocorticism versus cats with well-controlled diabetes mellitus. DESIGN: Case series. ANIMALS: 16 cats with insulin resistance that were also suspected to have acromegaly (n = 12) or pituitary-dependent hyperadrenocorticism (4) and 8 cats with well-controlled diabetes mellitus. PROCEDURE: Computed tomography was performed on all 16 cats with insulin resistance and 2 cats in which diabetes mellitus was well-controlled. The remaining 6 cats in which diabetes mellitus was well-controlled underwent magnetic resonance imaging. Images were obtained before and immediately after i.v. administration of contrast medium. RESULTS: Computed tomography revealed a mass in the region of the pituitary gland in all 16 cats with insulin resistance. Maximum width of the masses ranged from 4.4 to 12.7 mm; maximum height ranged from 3.1 to 12.6 mm. Results of computed tomography performed on 2 cats with well-controlled diabetes and magnetic resonance imaging performed on the remaining 6 cats were considered normal. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats with insulin resistance suspected to have acromegaly or pituitary-dependent hyperadrenocorticism are likely to have a pituitary mass detectable by means of computed tomography or magnetic resonance imaging.     

Hypertriglyceridemia with increased plasma insulin concentrations in cats

Metabolite, insulin and adiponectin concentrations and LDH, AST and ALT activities were measured in plasma of 142 client-owned cats (1–13 years old, 16 breeds) to set up a new criterion of hypertriglyceridemia (hyper-TG) with increased plasma insulin concentrations for early diagnosis of lipid metabolism abnormality including obesity. 25 cats with over 165 mg/dl of plasma triglyceride (TG) concentrations were decided as hyper-TG with increased plasma insulin concentrations, and prevalence of hyper-TG was 16.7% in young (1–6 years old) and 18.3% in old (>7 years old) cats examined. In the hyper-TG cats, their plasma TG concentrations increased to 6.6–7.4-fold of the values of control cats with 35–50 mg/dl of plasma TG and their plasma cholesterol, FFA and insulin concentrations and LDH and ALT activities increased significantly, whereas their plasma adiponectin concentrations decreased significantly compared to those in the control cats. Hyper-TG cats with significantly increased body weights and plasma insulin and decreased plasma adiponectin seemed to be in early stage of obesity accompanying increased plasma insulin concentrations. Increased TG, insulin, LDH and ALT and decreased adiponectin values in plasma seemed to be key factors for diagnosis of lipid metabolism abnormality at early stage in cats.     

Experimental Salmonella-associated conjunctivitis in cats.

Cats were infected experimentally with Salmonella typhimurium via the conjunctiva. Clinical signs consisted of lacrimation, conjunctivitis, blepharospasm, prominent nictitating membrane and scleral injection. These signs were accompanied by an absolute neutrophilia and conjunctival smears indicative of moderate to severe suppurative inflammation. Ocular signs disappeared by day 6 postinfection. Salmonella typhimurium was cultured intermittently from the inoculated conjunctivae and rectal swabs through day 7. At necropsy, mesenteric and cervical lymph nodes were enlarged. Histopathological findings included chronic conjunctivitis and lymphoid hyperplasia in cervical and mesenteric lymph nodes. This study confirms that S. typhimurium can cause a primary conjunctivitis and that the ocular route of infection can lead to fecal excretion of Salmonella, in the absence of other clinical manifestations.     

Glucose lowering effects of inhaled insulin in healthy cats

Inhaled medications have proven effective and well tolerated in cats, and inhaled insulin has been used successfully for the management of diabetes mellitus in humans. Thus, we hypothesize that delivery of aerosolized regular insulin can lower blood glucose in healthy cats. Five adult cats were administered aerosolized 0.9% saline (IS), regular insulin intravenously (IV) 0.5 U/kg, and aerosolized regular insulin 15 U/kg (I15) and 25 U/kg (I25) and blood glucose was evaluated. Mean blood glucose was significantly lower at 15, 30 and 45 min in the I25 and IV groups compared to baseline. Similarly, the IV and I25 groups had a significantly greater maximal percent change in blood glucose than the IS group. Significantly more cats developed severe hypoglycemia (<50 mg/dl; 2.7 mmol/l) in the IV and I25 groups than in the IS group. Results of this study demonstrate that aerosolized insulin can effectively lower blood glucose concentrations in healthy 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.     

Overweight and impaired insulin sensitivity present in growing cats

Obesity is a growing problem in pets as well as in humans. Overweight and obesity are linked to insulin sensitivity and subsequently in older cats, to an increased risk of developing diabetes mellitus. In the experimental cat population of the Institute of Animal Nutrition of the Vetsuisse Faculty, University of Zurich, an overweight phenotype in intact cats younger than 1 year became evident. The aims of the present study were to determine whether an association between insulin sensitivity and body condition score (BCS) or feline body mass index (FBMI) is already present during young adulthood in these cats and to test the hypothesis that the phenotype lean/overweight is significantly associated with monthly body weight during the growing period. Therefore, 41 kittens from the mentioned cat breeding colony were studied. They were weighed weekly and checked monthly (third to eighth month after birth) for BCS and FBMI. At the age of 8 months, they were classified into an overweight and lean phenotype based on BCS on a scale of 9 (median; maximum and minimum: overweight male (6.4; 6.8; 6.0); overweight female (6.1; 6.2; 6.0); lean male (5.4; 5.7; 5.0); lean female (5.2; 5.6; 5.0). A significant association between the phenotype and body weight was obvious during the growing period from the third to the 8 months (p = 0.0001). At month 8, body fat content was measured by dual energy X‐ray absorptiometry and a glucose tolerance test to determine the insulin sensitivity index was performed. Insulin sensitivity was significantly associated with BCS (p = 0.0007) and body fat content (p < 0.0001) but not with sex (p = 0.61). Our data provide evidence that already in young intact cats; insulin insensitivity is significantly associated with BCS or a presumed phenotype lean/overweight.     

Decreased gene expression of insulin signaling genes in insulin sensitive tissues of obese cats

Type 2 diabetes mellitus (DM) animal models have provided ample opportunity for investigating pathogenesis, as well as to evaluate novel treatment and prevention options for the disease. Because the domestic cat shares a similar environment with humans, it is also confronted with many similar risk factors for diabetes, such as physical inactivity and obesity. Obesity is a significant risk factor for diabetes in cats, and as such, the domestic cat may serve as an ideal model for investigating obesity induced insulin resistance. This study determined changes in insulin signaling genes within insulin sensitive tissues of obese felines. Quantitative RT-PCR was performed to determine mRNA levels of three important insulin signaling genes which have been implicated with insulin resistance: insulin receptor substrate (IRS)-1, IRS-2, and phosphatidylinositol 3’-kinase (PI3-K) p85α. Obese cats had significantly lower IRS-2 and PI3-K p85α mRNA levels in liver and skeletal muscle as compared to control cats. This down regulation of insulin signaling genes in obese cats mirrors that of obese humans and rodents suffering from insulin resistance. Interestingly, preprandial blood tests indicated that our obese cats were no different from control cats with regards to glucose tolerance and insulin resistance, thus indicating that the obese cats used in our study had a moderate level of obesity. Therefore, insulin signaling gene alterations were occurring in insulin sensitive tissues of moderately obese felines before glucose intolerance was clinically evident. As such, the monitoring of key insulin signaling genes may have some important diagnostic value to determine the risk level and degree of obesity induced insulin resistance.     

Comparison of insulin signaling gene expression in insulin sensitive tissues between cats and dogs

Diabetes mellitus (DM) is a common endocrine disease in cats and dogs with increasing prevalence. Type 1 DM appears to be the most common form of diabetes in dogs whereas Type 2 DM prevails for cats. Since insulin resistance is more frequently encountered in cats than dogs, our laboratory was interested in determining whether differences at the insulin signaling pathway level and differences in glucose and lipid metabolism could be observed between cats and dogs. Insulin resistance has been positively correlated to insulin signaling pathway abnormalities. As such, this study measured insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and phosphatidylinositol 3-kinase (PI3-K) P-85α mRNA expression levels in classical insulin-responsive sensitive tissues (liver, skeletal muscle, and abdominal fat) and peripheral leukocytes between cats and dogs by qRT-PCR. Different tissues were sampled because it is currently unknown where insulin-resistance arises from. In addition, enzymes involved in glucose and lipid metabolism, malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) were also assessed since glucose and lipid metabolism differs between cats and dogs. Overall, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA tissue expression profiles demonstrated different levels of expression, in various tissues for both canines and felines, which was expected. No distinct expression pattern emerged; however, differences were noted between canines and felines. In addition, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA expression was significantly higher in canine versus feline tissues, including peripheral leukocytes. Remarkable differences in insulin signaling gene expression between felines and canines indicate that cats may have an underlying low insulin sensitivity level due to low IRS-1, IRS-2, and PI3-K P-85α mRNA expression levels which would predispose cats to develop insulin resistance. Moreover, differences in glucose and lipid metabolism related gene expression (MDH, G6DPH, and FAS) demonstrate that felines have an overall lower metabolic rate in various tissues which may be attributed to overall lower insulin signaling gene expression and a lack of physical activity as compared to canines. Therefore, a combination of genetic and environmental factors appears to make felines more prone to suffer from insulin resistance and type 2 DM than canines.     

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.     

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).     

Experimental evaluation of attachment behaviors in owned cats

Attachment, a normal behavior among social animals, is quite significant since owners worry about their pets and take care of them because of this affective connection. There are not enough research studies that focus on attachment between owners and their cats. The general objective of this study was to identify attachment behaviors, directed toward their owners, in cats of different body types, age groups, and sexes in an experimental situation.Twenty-eight cats, ranging from 1 to 7 years of age and having different body types, were used in the study without taking into account sex or reproductive status. These cats underwent an Ainsworth’s Adapted Strange Situation Test. Event frequencies and behavioral state durations in individual type behaviors such as exploration/locomotion, alertness, and inactivity were registered using direct focal sampling. For data analysis, cats were divided by body type, sex, and reproductive status. Analysis of variance (ANOVA) of locomotion/exploration revealed a statistically significant difference (N = 28, F = 13.55, P < 0.001) between the episodes with the owner, alone, and with a stranger with cats spending more time engaged in locomotion/exploration while accompanied by their owner. On the alert behavior event frequency, difference (ANOVA, F = 7.44, P < 0.05) was found, which showed a higher frequency while in the company of a stranger. Last, in the inactivity time ratio, a significant difference was found (ANOVA, F = 18.55, P < 0.001), where the time spent on this behavior was considerably higher when the animal was alone.These results are consistent with the ones obtained by Ainsworth in children attached to their mothers; therefore, it can be said that cats can manifest attachment behaviors toward their owners. Further studies are indicated to see whether cats can develop separation anxiety.     

Control of diabetes mellitus in cats with porcine insulin zinc suspension

The required dose rate of porcine insulin zinc suspension to control the signs of diabetes mellitus in 25 cats was assessed, and their response to insulin treatment was investigated over 12 months. The cats required a median dose of 0.5 iu/kg bodyweight twice a day, and only two of the cats required doses higher than 1.0 iu/kg twice a day. Their lowest blood glucose concentration was on average significantly higher during the night than during the day. Seven of the cats went into diabetic remission during the study, and the control of the clinical signs in the others was either excellent or good by the end of the study.     

Beta cell and insulin antibodies in treated and untreated diabetic cats

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.