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.     

Immunohistochemical detection of the enzyme glutamic acid decarboxylase and hormones of the islets of Langerhans in spontaneous insulin-dependent diabetes mellitus in cattle

Immunohistochemical expression of glutamic acid decarboxylase (GAD) enzyme was detected in the pancreatic islets of 12 cattle with spontaneous insulin-dependent diabetes mellitus (IDDM). The most characteristic changes were atrophy and decreased number of pancreatic islets, enlarged islets with vacuolated beta cells, and lymphocytic islet adenitis. Atrophied islets were composed of small islet cells without cytoplasmic insulin-positive granules. Immunohistochemically, GAD was not found in the cytoplasm of atrophied islet cells. Furthermore, enlarged islets consisting of islet cells with vacuolated cytoplasm were frequently observed. The cytoplasm of vacuolated cells contained very few GAD- and insulin-positive granules, indicating beta cell destruction. Enlarged islets with mild lymphocytic infiltrates were frequently observed. These findings suggest that islet cells in cattle with IDDM lose their insulin synthesis function and their ability to regulate hormonal secretion of alpha and delta cells.     

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.     

Plasma amylin and insulin concentrations in normoglycemic and hyperglycemic cats.

The recently discovered pancreatic peptide amylin is postulated to be involved in the pathogenesis of feline diabetes mellitus. However, plasma amylin concentrations in normal and diabetic cats have not yet been published. The aim of the present study was to validate a commercial amylin radioimmunoassay kit for the measurement of feline amylin in unextracted plasma, and to measure plasma amylin concentrations in normal and diabetic cats. The kit had satisfactory specificity, sensitivity, accuracy, and precision, and can be recommended for measurement of feline amylin in unextracted EDTA plasma, when nonspecific binding of plasma samples is used in the calculation of measured amylin concentration. Fasting amylin concentration in cats with normal glucose tolerance was 97 +/- 4 pmol/L. Plasma amylin increased in parallel with insulin after glucose administration in cats with normal and impaired glucose tolerance. In contrast to cats with normal glucose tolerance, cats with impaired glucose tolerance had markedly delayed amylin and insulin secretion. Diabetic cats had basal hypoinsulinemia combined with hyperamylinemia. Hyperamylinemia may lead to reduced insulin secretion and insulin resistance, and contribute to the development of feline diabetes. In conclusion, feline amylin can be measured in unextracted EDTA plasma. Fasting amylin concentrations are approximately 100 pmol/L, and amylin and insulin are cosecreted in cats with normal and impaired glucose tolerance. Increased amylin concentrations may contribute to the development of feline diabetes mellitus.     

Diabetes mellitus in a domesticated Spanish mustang

An 18-year-old Spanish Mustang mare was referred for evaluation of progressive weight loss and persistent hyperglycemia. Clinicopathologic abnormalities included marked hyperglycemia and glycosuria. Serum cortisol concentration was appropriately decreased following administration of dexamethasone, indicating that the horse did not have pituitary pars intermedia dysfunction. Serum insulin and plasma C-peptide concentrations were low, suggesting that hyperglycemia was a result of decreased secretion of insulin by pancreatic beta cells. In addition, glucose concentration did not return to the baseline concentration until 5 hours after i.v. administration of a glucose bolus, suggesting that insulin secretion, insulin effect, or both were reduced. However, i.v. administration of insulin caused only a slight decrease in the plasma glucose concentration, giving the impression that the action of insulin was impaired. Within 5 hours after administration of a combination of glyburide and metformin, which is used to treat diabetes mellitus in humans, the glucose concentration was within reference limits. The horse was euthanized, and a postmortem examination was done. Immunohistochemical staining of sections of the pancreas revealed attenuation of the pancreatic islet beta-cell population, with beta cells that remained generally limited to the periphery of the islets. These findings indicate that, albeit rare, pancreatic beta-cell failure may contribute to the development of diabetes mellitus in horses.     

Definition of diabetes mellitus

The nomenclature of human diabetes mellitus (DM) has been revised, and this classification has been accepted throughout the medical world and literature. The major categories of diabetes are: insulin-dependent DM, type I or IDDM; noninsulin-dependent DM, type II or NIDDM; secondary DM or type S; impaired glucose tolerance, IGT; gestational diabetes; and previous abnormality of glucose tolerance, PrevAGT. A review of the literature has shown that over half of the documented diabetic dogs, with a single medical diagnosis, appear to be type I, IDDM, with a substantial proportion being type S, and the remainder being type II, NIDDM. Obesity is frequently associated with IGT and NIDDM. Diabetic cats most commonly have pancreatic islet destruction associated with pancreatic amyloidosis; they are insulin deficient, IDDM. The commonest causes of secondary diabetes in dogs are pancreatic damage, hyperadrenocorticism and hypersomatotropism secondary to persistent progesterone influence. Progestogen therapy is the most frequently reported cause of secondary diabetes in cats. Diabetes in horses is type S, usually secondary to a functional pituitary tumor but occasionally following chronic pancreatitis. The blood glucose ranges for normal, IGT and diabetic animals, and the normal serum insulin values of various species is tabulated.     

Immunoreactivity of cytotoxic T-lymphocyte antigen 2 alpha in mouse pancreatic islet cells

Cells of the pancreatic islets produce several molecules including insulin (beta cells), glucagon (alpha cells), somatostatin (delta cells), pancreatic polypeptide (PP cells), ghrelin (epsilon cells), serotonin (enterochromaffin cells), gastrin (G cells) and small granules of unknown content secreted by the P/D1 cells. Secretion mechanism of some of these molecules is still poorly understood. However, Cathepsin L is shown to regulate insulin exocytosis in beta cells and activate the trypsinogen produced by the pancreatic serous acini cells into trypsin. The structure of the propeptide region of Cathepsin L is homologous to Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2 alpha) which is also shown to exhibit selective inhibitory activities against Cathepsin L. It was thought that if CTLA-2 alpha was expressed in the pancreas; then, it would be an important regulator of protease activation and insulin secretion. The purpose of this study was, therefore, to examine by immunohistochemistry the cellular localization and distribution pattern of CTLA-2 alpha in the pancreas. Results showed that strong immunoreactivity was specifically detected in the pancreatic islets (endocrine pancreas) but not in the exocrine pancreas and pancreatic stroma. Immunostaining was further performed to investigate more on localization of Cathepsin L in the pancreas. Strong immunoreactivity for Cathepsin L was detected in the pancreatic islets, serous cells and the pancreas duct system. These findings suggest that CTLA-2 alpha may be involved in the proteolytic processing and secretion of insulin through regulation of Cathepsin L and that the regulated inhibition of Cathepsin L may have therapeutic potential for type 1 diabetes.     

Diabetes mellitus: an update

Diabetes mellitus is characterized by disturbances of carbohydrate, lipid and protein metabolism and glucose intolerance. Several factors are known to contribute to the disease, ie, obesity, immune-mediated insulin resistance, and the diabetogenic hormones glucagon, growth hormone and glucocorticoids. Recently, a number of developments have taken place in the management of human diabetes mellitus which may be applicable to dogs and cats. These include the use of diets high in soluble, non-absorbable carbohydrates which lower post-prandial increases in blood glucose. The more complex causes of instability, ie, insulin-induced hyperglycaemia, rapid metabolism of insulin and insulin resistance can be diagnosed by hospitalizing the patient and measuring blood glucose at four hour intervals for 24 hours. In human medicine, new techniques for controlling diabetes mellitus are pancreatic implants, constant infusion pumps for insulin and the use of the hormone somatostatin which suppresses glucagon secretion, but not all may be applicable to veterinary medicine.     

Diabetes mellitus in the cat: a review

About 80% of diabetic cats suffer from type 2 diabetes which is characterized by reduced insulin secretion from beta-cells and by insulin resistance. As in humans cats experienced a change in life habits and eating conditions over the last years leading to a tremendous increase in the prevalence of obesity. In both species obesity is one of the major risk factors for the development of type 2 diabetes. Treatment should be initiated immediately after diagnosis. In Zurich, therapy consists of application of an intermediate-acting insulin and dietary management. In the latter the use of diets with reduced carbohydrate content seems to be of utmost importance. We recently found that the percentage of cats with a transient course of diabetes increases from previous 25% to 50-70% when a diet with strongly reduced carbohydrate content is fed.     

Effect of glimepiride and nateglinide on serum insulin and glucose concentration in healthy cats

Glimepiride and nateglinide are two common oral hypoglycemic agents currently being used with humans suffering from Type 2 diabetes mellitus. Neither drug has been tested with cats thus far and it is currently unknown whether either of these drugs exert any effect in cats or not. The objective of this study was to determine the effect of glimepiride and nateglinide on glucose and insulin responses in healthy control cats, in order to determine their potential use in diabetic cats. The intravenous glucose tolerance tests was carried out since it is an excellent test for evaluating pancreatic β-cell function for insulin secretion. Alterations in the insulin secretion pattern can be perceived as the earliest sign of β-cell dysfunction in many species, including cats. Nateglinide demonstrated a quick action/short duration type effect with serum glucose nadiring and insulin response peaking at 60 and 20 minutes, respectively. Alternatively, glimepiride is medium-to-long acting with serum glucose nadiring and insulin response peaking at 180 minutes and 60 minutes, respectively. Nateglinide’s potency was evident allowing it to induce a 1.5–2 higher preliminary insulin peak (3.7?±?1.1 pg/ml) than glimepiride’s (2.5?±?0.1 pg/ml), albeit only for a short period of time. Because glimepiride and nateglinide have a shared mode of action, no significant differences in overall glucose AUC_0-360min (24,435?±?2,940 versus 24,782?±?2,354 mg min/dl) and insulin AUC_0-360min (410?±?192 versus 460?±?159) in healthy control cats were observed. These findings may provide useful information when choosing a hypoglycemic drug suited for the treatment of diabetic cats depending on the degree of diabetes mellitus the cat is suffering from.     

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.     

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.     

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.     

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.     

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.     

Cellular and Molecular Characterization of a Feline Insulinoma

Background: Insulinoma is an autonomous insulin-secreting islet cell neoplasm that is rarely diagnosed in cats. The clinical and pathological aspects of feline insulinoma have been described previously, but the molecular characteristics of these tumors have not been investigated.
Objectives: The study objectives were to characterize peptide hormone production and determine expression of selected genes involved in glucose metabolism and insulin secretion in a feline insulinoma.
Methods: Immunohistochemistry and RT-PCR were used to examine hormone and gene expression, respectively, by insulinoma cells.
Results: Immunohistochemistry examination indicated that the tumor cells expressed insulin, chromogranin A, and somatostatin but not glucagon or pancreatic polypeptide. The tumor expressed several genes characteristic of pancreatic beta cells (β cells) including insulin ( INS ), glucose transporter 2 ( GLUT2 ), and glucokinase ( GCK ). The tumor also expressed hexokinase 1 ( HK1 ), a glycolytic enzyme not normally expressed in β cells. GCK expression was higher in the insulinoma than in normal pancreas from the same cat. The GCK  :  HK1 ratio was >20-fold higher in insulinoma tissue than in normal pancreas.
Conclusions and Clinical Importance: The feline insulinoma produced several peptide hormones and expressed genes consistent with a β-cell phenotype. The pattern of hexokinase gene expression in tumor cells differed from that of normal pancreas. These findings suggest insulinoma cells may have an increased sensitivity to glucose that could contribute to the abnormal insulin secretory response observed at low serum glucose concentrations.     

Weight loss in cats which eat well

Four cats were investigated because they lost weight while eating well. One cat was found to have hypoinsulinaemic diabetes mellitus, and another had maldigestion caused by exocrine pancreatic atrophy. An enteropathy with presumed intestinal malabsorption was diagnosed in the third case. The fourth cat had hyperthyroidism and disseminated amyloidosis. The diabetic animal has been maintained satisfactorily on daily insulin injections for 2 ½ years, but treatment in the other three cases was either unsuccessful or not attempted. Weight loss is uncommon in cats which are eating well. In investigating this syndrome, it is suggested that initially urine should be tested for glucose and faeces examined for maldigestion or malabsorption. More specific tests for diabetes mellitus, pancreatic maldigestion, intestinal malabsorption or hyperthyroidism might then be indicated.     

Response to Insulin Treatment and Survival in 104 Cats with Diabetes Mellitus (1985–1995)

Medical records of 104 cats with diabetes mellitus were reviewed. Information from 54 cats that had multiple blood glucose concentrations evaluated at least 5 times over a minimum of 3 months, beginning at the time insulin treatment was initiated, was used to evaluate the efficacy of insulin in treating diabetes mellitus. Fourteen of 54 cats were treated with protamine zinc insulin (PZI), 26 with ultralente insulin, and 14 with lente insulin. Six, 29, and 19 cats had good, mediocre, and poor glycemic control, respectively, based on mean blood glucose concentrations, whereas 31, 21, and 2 owners thought clinical response was good, mediocre, and poor, respectively. No significant difference was found in glycemic control among cats treated with PZI, ultralente, or lente insulin. Glycemic control was significantly (P < .05) better in 33 cats without than in 21 cats with concurrent disease. All 104 cats were used to calculate survival data. Fifty-one of 104 cats were alive at the time of the study. Mean (± standard deviation [SD]) and median survival times were 24 (± 16) and 20 months, respectively, in the 51 cats still alive at the end of the evaluation, and 25 (± 4) and 17 months, respectively, in the 53 cats that had died during the period of evaluation. Pancreatic abnormalities identified in 37 cats that underwent necropsy included chronic pancreatitis (n = 17), acute to subacute pancreatitis (n = 2), exocrine pancreatic adenocarcinoma (n = 7) and adenoma (n = 1), islet cell atrophy and vacuolar degeneration (n = 27), and islet amyloidosis (n = 8). No association was found between glycemic control and islet amyloidosis or exocrine pancreatic neoplasia, or between survival time and chronic pancreatitis, islet amyloidosis, or exocrine pancreatic neoplasia. In conclusion, diabetic cats evaluated in this study showed a variable response to exogenously administered insulin, ranging from excellent to poor. By maintaining mean blood glucose concentrations under 300 mg/dL, clinical signs were improved, and owners were satisfied with insulin treatment. Concurrent potentially insulin-antagonistic diseases were common and deleteriously affected glycemic control and survival time.     

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.