Frequency of diabetic remission, predictors of remission and survival in cats using a low-cost, moderate-intensity, home-monitoring protocol and twice-daily glargine.

OBJECTIVES: The aim of the present study was to retrospectively assess remission rates and survival in diabetic cats managed using a moderate-intensity, low-cost protocol of home blood glucose measurements and insulin adjustment by clients of a cat-only practice, and to determine if predictors of remission, relapse or survival could be identified. METHODS: The records of a cat-only practice were used to identify 174 cats with newly diagnosed diabetes managed using only pre-insulin home blood glucose measurements for insulin dose adjustments based on a protocol provided to clients aimed at maintaining pre-insulin blood glucose in the range of 6.5-11.9 mmol/l (117-214 mg/dl). Cats were excluded for the following reasons: insufficient follow-up in the records; a lack of owner compliance was recorded; they were receiving ongoing corticosteroids for the management of other conditions; they were euthanased at the time of diagnosis; or they were diagnosed with acromegaly or hyperadrenocorticism. RESULTS: Using only pre-insulin blood glucose measurements at home to adjust the insulin dose to maintain glucose in the range of 6.5-11.9 mmol/l, 47% of cats achieved remission, but 40% of those cats relapsed. A minority (16%) of cats were hospitalised for hypoglycaemia. The survival time was significantly longer in cats in remission and Burmese cats. CONCLUSIONS AND RELEVANCE: The cost and time burden of treating diabetic cats may cause some clients to choose euthanasia over treatment. While the highest rates of diabetic remission have been reported in studies of newly diagnosed cats treated with intensive long-acting insulin protocols and low carbohydrate diets, these protocols may not be suitable for all clients. Nearly 50% of cats with newly diagnosed diabetes achieved remission with this low-cost, moderate-intensity, insulin dosing protocol. As remission was significantly associated with survival time, discussing factors in treatment to optimise remission is important, but it is also important to offer clients a spectrum of options. No cats that started treatment in this study were euthanased because the owner did not wish to continue the diabetes treatment.

Measures of insulin sensitivity, leptin, and adiponectin concentrations in cats in diabetic remission compared to healthy control cats.

Objectives: Firstly, to compare differences in insulin, adiponectin, leptin, and measures of insulin sensitivity between diabetic cats in remission and healthy control cats, and determine whether these are predictors of diabetic relapse. Secondly, to determine if these hormones are associated with serum metabolites known to differ between groups. Thirdly, if any of the hormonal or identified metabolites are associated with measures of insulin sensitivity. Animals: Twenty cats in diabetic remission for a median of 101 days, and 21 healthy matched control cats. Methods: A casual blood glucose measured on admission to the clinic. Following a 24 h fast, a fasted blood glucose was measured, and blood sample taken for hormone (i.e., insulin, leptin, and adiponectin) and untargeted metabolomic (GC-MS and LC-MS) analysis. A simplified IVGGT (1 g glucose/kg) was performed 3 h later. Cats were monitored for diabetes relapse for at least 9 months (270 days). Results: Cats in diabetic remission had significantly higher serum glucose and insulin concentrations, and decreased insulin sensitivity as indicated by an increase in HOMA and decrease in QUICKI and Bennett indices. Leptin was significantly increased, but there was no difference in adiponectin (or body condition score). Several significant correlations were found between insulin sensitivity indices, leptin, and serum metabolites identified as significantly different between remission and control cats. No metabolites were significantly correlated with adiponectin. No predictors of relapse were identified in this study. Conclusion and clinical importance: Insulin resistance, an underlying factor in diabetic cats, persists in diabetic remission. Cats in remission should be managed to avoid further exacerbating insulin resistance.

Cutpoints for screening blood glucose concentrations in healthy senior cats.

Objectives The objectives of this study were to determine the reference interval for screening blood glucose in senior cats, to apply this to a population of obese senior cats, to compare screening and fasting blood glucose, to assess whether screening blood glucose is predicted by breed, body weight, body condition score (BCS), behaviour score, fasting blood glucose and/or recent carbohydrate intake and to assess its robustness to changes in methodology. Methods The study included a total of 120 clinically healthy client-owned cats aged 8 years and older of varying breeds and BCSs. Blood glucose was measured at the beginning of the consultation from an ear/paw sample using a portable glucose meter calibrated for cats, and again after physical examination from a jugular sample. Fasting blood glucose was measured after overnight hospitalisation and fasting for 18-24 h. Results The reference interval upper limit for screening blood glucose was 189 mg/dl (10.5 mmol/l). Mean screening blood glucose was greater than mean fasting glucose. Breed, body weight, BCS, behaviour score, fasting blood glucose concentration and amount of carbohydrate consumed 2-24 h before sampling collectively explained only a small proportion of the variability in screening blood glucose. Conclusions and relevance Screening blood glucose measurement represents a simple test, and cats with values from 117-189 mg/dl (6.5-10.5 mmol/l) should be retested several hours later. Cats with initial screening blood glucose >189 mg/dl (10.5 mmol/l), or a second screening blood glucose >116 mg/dl (6.4 mmol/l) several hours after the first, should have fasting glucose and glucose tolerance measured after overnight hospitalisation.

Effect of acarbose on postprandial blood glucose concentrations in healthy cats fed low and high carbohydrate diets.

OBJECTIVES: Feeding a low carbohydrate diet is recommended for diabetic cats; however, some cats may require diets containing moderate-to-high carbohydrate and may benefit from the use of therapeutic agents to improve glycemic control. The aim of the study was to determine the effect of the α-glucosidase inhibitor acarbose on postprandial plasma glucose concentration when combined with commercially available feline diets high and low in carbohydrate. METHODS: Twelve healthy, adult, non-obese, neutered cats were enrolled. Plasma glucose concentrations were assessed over 24 h after feeding high and low carbohydrate diets, with and without acarbose, during single and multiple meal tests, in a crossover study. Commercially available feline diets were used, which were high and low in carbohydrate (providing 51% and 7% of metabolizable energy, respectively). RESULTS: In cats fed the high carbohydrate diet as a single meal, mean 24 h glucose concentrations were lower when acarbose was administered. Mean glucose concentrations were lower in the first 12 h when acarbose was given once daily, whereas no significant difference was observed in mean results from 12-24 h. Acarbose had little effect in cats eating multiple meals. Compared with consumption of the high carbohydrate diet with acarbose, lower mean 24 h and peak glucose concentrations were achieved by feeding the low carbohydrate diet alone. CONCLUSIONS AND RELEVANCE: In healthy cats meal-fed diets of similar composition to the diets used in this study, acarbose has minimal effect when a low carbohydrate diet is fed but reduces postprandial glucose concentrations over 24 h when a high carbohydrate diet is fed. However, mean glucose concentrations over 24 h are still higher when a high carbohydrate diet with acarbose is fed relative to the low carbohydrate diet without acarbose. Future studies in diabetic cats are warranted to confirm these findings.

Pathogenesis of feline diabetes.

Diabetes mellitus is the result of inadequate insulin secretion. In cats this is often associated with conditions that reduce insulin sensitivity and increase the requirement for insulin secretion. Obesity, and acromegaly, and pancreatitis are common predisposing causes of diabetes in cats. The mechanisms that prevent the pancreatic ß cells from secreting adequate amounts of insulin are not well understood, but may include inflammatory mediators, reactive oxygen species, toxic intracellular protein oligomers, and toxicity from increased blood glucose concentrations.

The role of diet in the prevention and management of feline diabetes.

This article reviews the currently available evidence and focuses on how diet may play a role in lowering (or increasing) the risk of diabetes. The article also reviews the role of diet in treatment of diabetes. To the extent that it exists, evidence from published studies are cited; however, in areas where research evidence is lacking, clinical experience and physiologic principles are used as important sources of guidance.

Remission in cats: including predictors and risk factors.

This article summarizes current literature on diabetic remission in cats. Treatment options for diabetes mellitus are reviewed to highlight which protocols are most effective in achieving remission, as well as the importance of understanding the underlying pathophysiology that contributes to remission. In addition, current research into the glucose tolerance status of cats in diabetic remission and rates of relapse are discussed.

Management of diabetic cats with long-acting insulin.

This article provides an overview of the most important information regarding the long-acting insulins glargine, detemir, and protamine zinc insulin in diabetic cats. Dosing protocols are described in detail, which achieve high remission rates and optimal glycemic control. Complications and factors that typically cause insulin resistance are also examined.

Diabetes and the kidney in human and veterinary medicine.

Diabetic nephropathy is a well-recognized clinical consequence of both type 1 and type 2 diabetes mellitus in humans. Major risk factors include poor glycemic control, hypertension, and microalbuminuria, as well as genetic factors. In both type 1 and 2 diabetics with nephropathy, structural changes occur in the kidneys before overt clinical disease. Studies suggest that some of the risk factors and structural renal changes of human diabetes also exist in diabetic dogs and cats. This article assembles existing information on the presence of risk factors, laboratory and histologic findings, and consequences of human diabetic nephropathy as applied to cats.

Diabetic ketoacidosis and hyperosmolar hyperglycemic state in cats.

Diabetic ketoacidosis and hyperosmolar hyperglycemic state are 2 potentially life-threatening presentations of feline diabetes mellitus. Presentations range from mildly anorexic cats with diabetic ketoacidosis to comatose cats with diabetic ketoacidosis or hyperosmolar hyperglycemic state. Such cases are the result of severe insulin deficiency and/or concurrent disease, resulting in nausea and vomiting, electrolyte and water losses, acidosis, and circulatory collapse. The condition requires careful attention to supportive care to correct fluid and electrolyte abnormalities, treatment of concurrent diseases, and reversal of the effects of insulin deficiency. However, early diagnosis of diabetes mellitus and institution of appropriate insulin therapy prevents these complications.

Intramuscular glargine with or without concurrent subcutaneous administration for treatment of feline diabetic ketoacidosis.

OBJECTIVE: To describe treatment response and outcome in 15 cats with diabetic ketoacidosis (DKA) initially stabilized with glargine administered intramuscularly (IM) with or without subcutaneous (SC) glargine. MATERIALS AND METHODS: Fifteen cats diagnosed with DKA were initially administered IM glargine (1-2 U) and in most cats (12/15 cats) this was combined with SC glargine (1-3 U). This was followed by intermittent IM glargine as required at intervals of 2 or more hours (range 2-22 h) and SC glargine (1-2 U) every 12 hours. KEY FINDINGS: All 15 cats survived and were discharged from hospital (median 4 d; range 2-5 d) and one-third (5/15) of cats subsequently achieved remission (median time 20 d; range 15-29 d). Complications included hypokalemia and hypophosphatemia, which were likely the result of DKA therapy rather than glargine treatment specifically. SIGNIFICANCE: This study demonstrates that glargine administered IM is an effective treatment for DKA in cats, and may provide an alternative to regular insulin. The same vial used for initial treatment of DKA can then be used for subsequent management with SC glargine injections. Future prospective randomized controlled trials evaluating clinical outcomes in cats with DKA using different types and routes of administration of insulin are warranted. A prospective randomized controlled trial is required to compare outcomes for IM and IV administration of glargine and regular insulin in DKA cats with or without SC glargine.

Potential predictive biomarkers of obesity in Burmese cats.

Australian Burmese cats are predisposed to diabetes mellitus and, compared to other breeds, have delayed triglyceride clearance that may result in subtle changes within cells and tissues that trigger specific alterations in gene expression within peripheral blood leucocytes (PBLs). Expression of genes involved in energy metabolism (glucose-6-phosphate dehydrogenase and malate dehydrogenase), lipogenesis (ATP citrate lyase [ACL], fatty acid synthase [FAS] and sterol regulatory binding protein-1c [SREBP-1c]), and insulin signalling (insulin receptor substrates 1 and 2, and phosphatidylinositol-3 kinase), as well as cholesterol lipoprotein subfraction profiling were carried out on PBLs from lean Burmese cats and compared with similar profiles of age and gender matched lean and obese Australian domestic shorthaired cats (DSHs) in an attempt to identify possible biomarkers for assessing obesity. For the majority of the genes examined, the lean Burmese cats demonstrated similar PBL gene expression patterns as age and gender matched obese Australian DSH cats. Lean Burmese had increased expression of ACL and FAS, but not SREBP-1c, a main upstream regulator of lipid synthesis, suggesting possible aberrations in lipogenesis. Moreover, lean Burmese displayed a 3- to 4-fold increase in the very low density cholesterol fraction percentage, which was double that for obese DSH cats, indicating an increased degree of lipid dysregulation especially in relation to triglycerides. The findings suggest that Burmese cats may have a particular propensity for dysregulation in lipid metabolism.

Postprandial glycaemia in cats fed a moderate carbohydrate meal persists for a median of 12 hours--female cats have higher peak glucose concentrations.

The postprandial increase in glucose concentration is typically not considered in selecting diets to manage diabetic and pre-diabetic cats. This study describes increases in glucose and insulin concentrations in 24 clinically healthy, neutered adult cats following one meal (59 kcal/kg) of a moderate carbohydrate diet (25% of energy). Median time to return to baseline after feeding for glucose was 12.2 h (1.8-≥24 h) and for insulin was 12.3 h (1.5-≥24 h). Time to return to baseline for glucose was not different between male (10.2 h) and female (17.2 h) cats. There was evidence female cats had a longer return to baseline for insulin (18.9 h versus 9.8 h) and females had higher (0.9 mmol/l difference) peak glucose than males. This demonstrates that the duration of postprandial glycaemia in cats is markedly longer than in dogs and humans, and should be considered when managing diabetic and pre-diabetic cats.

Comparison of early socialization practices used for litters of small-scale registered dog breeders and nonregistered dog breeders.

OBJECTIVE-To compare early socialization practices between litters of breeders registered with the Canine Control Council (CCC) and litters of nonregistered breeders advertising puppies for sale in a local newspaper. DESIGN-Retrospective cohort study. Animals-80 litters of purebred and mixed-breed dogs from registered (n = 40) and non-registered (40) breeders. PROCEDURES-Registered breeders were randomly selected from the CCC website, and nonregistered breeders were randomly selected from a weekly advertising newspaper. The litter sold most recently by each breeder was then enrolled in the study. Information pertaining to socialization practices for each litter was obtained through a questionnaire administered over the telephone. RESULTS-Registered breeders generally had more breeding bitches and had more litters than did nonregistered breeders. Litters of registered breeders were more likely to have been socialized with adult dogs, people of different appearances, and various environmental stimuli, compared with litters of nonregistered breeders. Litters from registered breeders were also much less likely to have been the result of an unplanned pregnancy. CONCLUSIONS AND CLINICAL RELEVANCE-Among those breeders represented, litters of registered breeders received more socialization experience, compared with litters of nonregistered breeders. People purchasing puppies from nonregistered breeders should focus on socializing their puppies between the time of purchase and 14 weeks of age. Additional research is required to determine whether puppies from nonregistered breeders are at increased risk of behavioral problems and are therefore more likely to be relinquished to animal shelters or euthanized, relative to puppies from registered breeders.

Adiponectin profiles are affected by chronic and acute changes in carbohydrate intake in healthy cats.

Adiponectin is a key adipokine that regulates carbohydrate and lipid metabolism. It circulates in stable low (LMW) and high molecular weight (HMW) forms. The aims of this study were to characterize baseline adiponectin profiles (total, LMW and HMW multimers) in healthy cats and to assess the effects of varying dietary carbohydrate content on adiponectin profiles. Cats were maintained on a diet with moderate carbohydrate content (37% metabolisable energy [ME]) for 4 weeks and then randomly allocated to either a low carbohydrate (19% ME) or high carbohydrate (52% ME) diet for 4 weeks. Fasting and postprandial plasma adiponectin profiles were measured by ELISA and sucrose gradient/Western blot. After consuming the moderate carbohydrate diet for 4 weeks, fasting total, HMW and LMW plasma adiponectin concentrations were 5.0±0.6, 2.5±0.5 and 2.6±0.2 µg/mL, respectively. After changing to the low carbohydrate diet, fasting total adiponectin was unchanged but HMW adiponectin increased and LMW adiponectin decreased. No significant postprandial changes were observed. Cats consuming the high carbohydrate diet had increased fasting total and LMW adiponectin with no change in HMW adiponectin. In the postprandial state total adiponectin was reduced and there was a trend towards a decrease in HMW (p=0.086) but not LMW multimers. These data indicate that feline adiponectin multimer profiles are similar to those reported in other species and demonstrate that changes in plasma adiponectin occur in response to chronic and acute carbohydrate intake and these reflect differential changes in adiponectin multimers.

Evaluation of beta-cell sensitivity to glucose and first-phase insulin secretion in obese dogs.

OBJECTIVE: To compare beta-cell sensitivity to glucose, first-phase insulin secretion, and glucose tolerance between dogs with naturally occurring obesity of > 2 years' duration and lean dogs. ANIMALS: 17 client-owned obese or lean dogs. PROCEDURES: Frequently sampled IV glucose tolerance tests were performed with minimal model analysis on 6 obese dogs and matched controls. Glucagon stimulation tests were performed on 5 obese dogs and matched controls. RESULTS: Obese dogs were half as sensitive to the effects of insulin as lean dogs. Plasma glucose concentrations after food withholding did not differ significantly between groups; plasma insulin concentrations were 3 to 4 times as great in obese as in lean dogs. Obese dogs had plasma insulin concentrations twice those of lean dogs after administration of glucose and 4 times as great after administration of glucagon. First-phase insulin secretion was greater in obese dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Obese dogs compensated for obesity-induced insulin resistance by secreting more insulin. First-phase insulin secretion and beta-cell glucose sensitivity were not lost despite years of obesity-induced insulin resistance and compensatory hyperinsulinemia. These findings help explain why dogs, unlike cats and humans, have not been documented to develop type 2 diabetes mellitus.

Use of a meal challenge test to estimate peak postprandial triglyceride concentrations in dogs.

OBJECTIVE: To develop a standardized meal challenge test by assessing associations between food-withheld preprandial (ie, fasting) and postprandial triglyceride concentrations, determining the most appropriate sampling time to detect the peak concentration (highest postprandial concentration), and estimating reference intervals for fasting and postprandial concentrations in healthy dogs. ANIMALS: 12 lean healthy mixed-breed dogs. PROCEDURES: Dogs were fed a dry commercially available diet (fat, 31% metabolizable energy) for 3 weeks. After food was withheld for 23 to 24 hours, plasma triglyceride concentrations were measured 1 and 0.083 hours before and 1, 2, 3, 4, 5, 6, 9, and 12 hours after feeding of a standardized challenge meal (median amount eaten, 63 kcal/kg [127 kcal/kg°.75]). Correlation and agreement between concentrations at peak and other time points were assessed by use of correlation coefficients and Bland-Altman limits of agreement. Reference intervals were calculated by use of a robust method. RESULTS: Fasting and peak triglyceride concentrations were not closely associated. The highest concentration among samples obtained 2, 5, and 6 hours after meal consumption had closest agreement with peak concentration. In 5 of 12 dogs, concentrations 12 hours after eating were still significantly above baseline concentration (mean of each dog's fasting concentrations). CONCLUSIONS AND CLINICAL RELEVANCE: Fasting triglyceride concentration could not be used to accurately predict peak concentration. When estimating peak concentration, multiple samples should be collected 2, 5, and 6 hours after consumption of a standardized meal. Food may need to be withheld for > 12 hours when assessing fasting concentrations in healthy dogs.

Changes in blood glucose concentration are associated with relatively rapid changes in circulating fructosamine concentrations in cats.

The aim of the study was to determine the time required for plasma fructosamine concentration to increase after the onset of hyperglycaemia and decrease after resolution of hyperglycaemia. Healthy cats (n=14) were infused to maintain either moderate hyperglycaemia (n=5) (actual mean glucose 17 mmol/l) or marked hyperglycaemia (n=9) (actual 29 mmol/l) for 42 days. Fructosamine exceeded the upper limit of the reference range (331 micromol/l) after 3-5 days of marked hyperglycaemia, took 20 days to plateau and, after cessation of infusion, took 5 days to return to baseline. Fructosamine concentration for moderate hyperglycaemia took longer to exceed the reference range (7 days, range 4-14 days), and fewer days to plateau (8 days) and return to baseline (1 day). In cats with moderate hyperglycaemia, fructosamine concentration mostly fluctuated under the upper limit of the reference range. The range of fructosamine concentrations associated with a given glucose concentration was wide. The critical difference for fructosamine was 33 micromol/l.

Insulin glargine has a long duration of effect following administration either once daily or twice daily in divided doses in healthy cats.

The pharmacological effects of glargine administered once or twice daily were compared in six healthy cats. A two-way crossover study was performed with insulin and glucose concentrations measured following subcutaneous administration of glargine once daily (0.5 U/kg) or twice daily (0.25 U/kg, repeated after 12h). Nadir glucose concentration and mean daily glucose concentration did not differ significantly following insulin administration once daily or twice daily in divided doses. Time to reach last glucose nadir differed, with longer intervals occurring following twice daily dosing. Blood glucose failed to return to baseline concentration by 24h in three of six cats in each treatment group. Insulin variables were not significantly different following once or twice daily dosing. This study in healthy cats demonstrates that glargine has a long duration of action with carry-over effects to the next day likely, regardless of dosing regimen. A study in diabetic cats is required to determine the best dosing regimen.