Use of glargine and lente insulins in cats with diabetes mellitus

The goals of this study were to compare the efficacy of once-daily administered Glargine insulin to twice-daily administered Lente insulin in cats with diabetes mellitus and to describe the use of a high-protein, low-carbohydrate diet designed for the management of diabetes mellitus in cats. All cats with naturally occurring diabetes mellitus were eligible for inclusion. Baseline testing included a physical examination, serum biochemistry, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were fed the high-protein, low-carbohydrate diet exclusively. Cats were randomized to receive either 0.5 U/kg Lente insulin q12h or 0.5 U/kg Glargine insulin q24h. Re-evaluations were performed on all cats at weeks 1, 2, 4, 8, and 12, and included an assessment of clinical signs, physical examination, 16-hour blood glucose curve, and serum fructosamine concentrations. Thirteen cats completed the study (Lente, n = 7, Glargine, n = 6). There was significant improvement in serum fructosamine and glucose concentrations in all cats but there was no significant difference between the 2 insulin groups. Four of the 13 cats were in complete remission by the end of the study period (Lente, n = 3; Glargine, n = 1). The results of the study support the use of once-daily insulin Glargine or twice-daily Lente insulin in combination with a high-protein, low-carbohydrate diet for treatment of feline diabetes mellitus.     

Feline diabetes mellitus: low carbohydrates versus high fiber?

Treatment of diabetes mellitus (DM) in the cat relies primarily on the adequate insulin therapy and controlled dietary intake. The goals of managing DM in the cat have changed from attaining glycemic control to achieving diabetic remission (transient diabetes) in a large proportion of cases. Remission rates of up to 68% have been published. The used of low-carbohydrate foods for cats improves the odds of achieving diabetic remission by fourfold. Nonetheless, some cats show an improved response to high-fiber food. Clinical judgement, trial, and personal preference to currently dictate which diet to offer an individual animal.     

Use of low carbohydrate, high protein diets in cats with diabetes mellitus

The goal of this randomized, double‐blind study was to compare the effects of feeding a low carbohydrate, high protein diet versus a maintenance diet in a group of cats with diabetes mellitus treated with insulin glargine twice daily. All cats with naturally occurring diabetes mellitus not currently treated with insulin glargine or diabetogenic drugs or being fed a low carbohydrate, high protein diet were eligible for inclusion. Baseline testing included a physical examination, complete blood count, serum biochemistry profile, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were treated with insulin glargine (starting dose of 0.25 U/kg) twice daily. Insulin was adjusted as needed for glucose regulation. Cats were randomized to receive either a low carbohydrate, high protein diet or a feline maintenance diet. Re‐evaluations were performed on all cats at weeks 1, 2, 4, 6 and 10, and included an assessment of clinical signs, physical examination, 12‐h blood glucose curve, and serum fructosamine concentrations. Changes in continuous variables over the course of the study were analyzed using analysis of variance with repeated measures. p < 0.05 was considered statistically significant. Ten cats have completed the study. There were no significant differences between diet groups at baseline for age, gender, weight, body condition score, serum glucose or fructosamine concentrations. Although there was not a significant difference over time in clinical signs, insulin doses, or peak or nadir glucose concentrations between diet groups, diet did have a significant effect on serum fructosamine concentrations (p = 0.01). Six of the 10 cats that have completed the study achieved complete remission by the end of the study period, with no statistical difference between diets. The study's results indicate that diet can have significant effects on glucose regulation in cats receiving insulin glargine for treatment of feline diabetes mellitus.     

Effects of insoluble and soluble dietary fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus

OBJECTIVE: To evaluate the effects of diets differing in type and quantity of fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 7 dogs with well-regulated naturally occurring insulin-dependent diabetes mellitus. PROCEDURE: Dogs were fed 1 of 3 diets for 1 month each in 1 of 6 randomized diet sequences. Diets included a low-fiber diet (LF) and 2 high-fiber diets; 1 contained only insoluble fiber (HIF), and 1 contained soluble fiber in addition to insoluble fiber (HSF). Caloric intake was unchanged throughout the study. Glycemic control was assessed after each feeding trial by measuring serum fructosamine concentration and performing 5 serial measurements of blood glucose concentration every 2 hours after the morning feeding and insulin injection. RESULTS: Significant differences were not detected in body weight, required insulin dosage, or albumin concentration among dogs fed the HIF, HSF, and LF diets. Mean and maximum blood glucose concentrations and area under the blood glucose curve were significantly lower in dogs fed the HIF diet, compared with values in the same dogs fed the HSF or LF diet. Fructosamine concentration was significantly lower in dogs fed the HIF or HSF diet, compared with values in the same dogs fed the LF diet. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with naturally occurring insulin-dependent diabetes mellitus, a dry, high insoluble-fiber diet may aid in glycemic control.     

Effect of the alpha-glucosidase inhibitor acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus

OBJECTIVE: To evaluate effect of acarbose on control of glycemia in dogs with diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 5 dogs with naturally acquired diabetes mellitus. PROCEDURE: Dogs were treated with acarbose and placebo for 2 months each: in 1 of 2 randomly assigned treatment sequences. Dogs that weighed < or = 10 kg (22 lb; n = 3) or > 10 kg (2) were given 25 or 50 mg of acarbose, respectively, at each meal for 2 weeks, then 50 or 100 mg of acarbose, respectively, at each meal for 6 weeks, with a 1-month interval between treatments. Caloric intake, type of insulin, and frequency of insulin administration were kept constant, and insulin dosage was adjusted as needed to maintain control of glycemia. Serum glucose concentrations, blood glycosylated hemoglobin concentration, and serum fructosamine concentration were determined. RESULTS: Significant differences in mean body weight and daily insulin dosage among dogs treated with acarbose and placebo were not found. Mean preprandial serum glucose concentration, 8-hour mean serum glucose concentration, and blood glycosylated hemoglobin concentration were significantly lower in dogs treated with insulin and acarbose, compared with insulin and placebo. Semisoft to watery feces developed in 3 dogs treated with acarbose. CONCLUSIONS AND CLINICAL RELEVANCE: Acarbose may be useful as an adjunctive treatment in diabetic dogs in which cause for poor glycemic control cannot be identified, and insulin treatment alone is ineffective.     

Comparison of serum fructosamine and blood glycosylated hemoglobin concentrations for assessment of glycemic control in cats with diabetes mellitus.

OBJECTIVE: To correlate serum fructosamine concentrations with established measures of glycemic control and to compare serum fructosamine and blood glycosylated hemoglobin (GHb) concentrations as a means for assessing glycemic control in diabetic cats. DESIGN: Longitudinal cohort study. ANIMALS: 26 healthy cats, 5 cats with stress-induced hyperglycemia, 15 untreated diabetic cats, and 36 treated diabetic cats. PROCEDURE: Control of glycemia was classified and monitored and serum fructosamine and blood GHb concentrations were measured for 12 poorly controlled diabetic cats before and after improving glycemic control, 8 well-controlled treated diabetic cats before and after glycemic control deteriorated, and 5 cats with diabetes mellitus before and after onset of stress-induced hyperglycemia. RESULTS: Mean serum fructosamine and blood GHb concentrations were significantly higher in untreated diabetic cats, compared with healthy cats, and in 24 poorly controlled diabetic cats, compared with 12 well-controlled diabetic cats. Mean serum fructosamine and blood GHb concentrations decreased significantly in 12 poorly controlled diabetic cats after improving glycemic control and increased significantly in 8 well-controlled diabetic cats after glycemic control deteriorated. A significant stress-induced increase in mean blood glucose concentration was evident 12 hours after insulin administration, but not in 5 docile diabetic cats that became fractious. CLINICAL IMPLICATIONS: Serum fructosamine and blood GHb concentrations are clinically useful tools for monitoring control of glycemia in cats with diabetes mellitus.     

Fructosamine

Fructosamines are glycated serum proteins that, depending on their life span, reflect glycemic control over the previous 2 to 3 weeks. The nitroblue tetrazolium reduction method adapted to autoanalysis appeared to be a practical means to assay fructosamine quickly, economically, and accurately. The upper limit of the reference range is 374 μmol/L in dogs (95% percentile) and 340 μmol/L in cats (95% percentile). Newly diagnosed diabetic dogs and cats that had not undergone previous insulin therapy had significantly higher fructosamine concentrations than nondiabetic animals. In diabetic dogs that were receiving insulin therapy, the fructosamine test reflected the glycemic state far more accurately than did individual blood glucose measurements. Animals with satisfactory metabolic control revealed fructosamine concentrations within the reference range, whereas fructosamine concentrations above 400 μmol/L indicated insufficient metabolic control. On the basis of fructosamine concentrations, cats with a transitory hyperglycemia and cats with diabetes mellitus were differentiated. The fructosamine test is a valuable parameter for the diagnosis and metabolic control of diabetes mellitus in dogs and cats.     

Glycosylated Hemoglobin Concentration for Assessment of Glycemic Control in Diabetic Cats

Blood glycosylated hemoglobin (GHb) concentration was quantified in 84 healthy cats, 9 cats with stress-induced hyperglycemia, 37 cats with newly diagnosed diabetes mellitus, and 122 diabetic cats treated with insulin or glipizide. Diabetic control was classified as good or poor in insulin-treated or glipizide-treated cats based on review of history, physical examination findings, changes in body weight, and measurement of blood glucose concentrations. Blood GHb concentration was determined using an affinity chromatography assay. Mean blood GHb concentration was similar for healthy normoglycemic cats and cats with transient, stress-induced hyperglycemia, but was significantly (P < .001) higher in untreated diabetic cats when compared with healthy normoglycemic cats. Mean blood GHb concentration was significantly (P < .001) higher in 84 cats with poorly controlled diabetes mellitus when compared with 38 cats in which the disease was well controlled. Mean blood GHb concentration decreased significantly (P < .01) in 6 cats with untreated diabetes mellitus after insulin and dietary treatment. A similar significant (P < .01) decrease in mean blood GHb concentration occurred in 7 cats with poorly controlled diabetes mellitus after diabetic control was improved by an increase in insulin dosage from 1.1 ± 0.9 to 1.4 ± 0.6 U/kg/ 24 h and by feeding a diet containing increased fiber content and in 6 cats with transient diabetes mellitus 8.2 ± 0.6 weeks after discontinuing insulin treatment. There was a significant (P< .01) stress-induced increase in mean fasting blood glucose concentration and mean blood glucose concentration for 12 hours after administration of insulin or glipizide but no change in mean blood GHb concentration in 5 docile diabetic cats 12.2 ± 0.4 weeks after the cats became fractious as a result of frequent hospitalizations and blood samplings. Results of this study suggest that evaluation of blood GHb concentration may be a clinically useful tool for monitoring glycemic control of diabetes in cats.     

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.     

Evaluation of bexagliflozin in cats with poorly regulated diabetes mellitus

The aim of this study was to investigate the effect of bexagliflozin on glycemic control in poorly regulated diabetic cats and to evaluate for adverse events associated with this medication.Sodium-glucose cotransporter 2 inhibitors are a newer class of drugs used in the management of humans with type 2 diabetes mellitus. The objective of this study was to evaluate the effect of the orally administered drug, bexagliflozin in a group of poorly regulated diabetic cats over a 4-week study period. Five client-owned cats with poorly controlled diabetes mellitus receiving insulin therapy were enrolled. Bexagliflozin was administered once daily. Serum fructosamine, serum biochemistry profile, and 10-hour blood glucose curves were assessed at baseline (Day 0), Day 14, and Day 28. All cats had a significant reduction in insulin dose requirement (P = 0.015) and insulin was discontinued in 2 cats. There was a significant decrease in blood glucose concentration obtained from blood glucose concentration curves during the study period (P = 0.022). Serum fructosamine decreased in 4 of the 5 cats with a median decrease of 152 μmol/L (range: 103 to 241 μmol/L), which was not statistically significant (P = 0.117). No cats had any documented episodes of hypoglycemia. Adverse effects were mild. The addition of bexagliflozin significantly improved diabetic management in this group of cats.     

Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the management of feline diabetes mellitus

This study compared the effects of a moderate carbohydrate-high fiber (MC-HF) food and a low carbohydrate-low fiber (LC-LF) food on glycemic control in cats with diabetes mellitus. Sixty-three diabetic cats (48 male castrated, 15 female spayed) were randomly assigned to be fed either a canned MC-HF (n = 32) food or a canned LC-LF (n = 31) food for 16 weeks. Owners were blinded to the type of diet fed. CBC, urinalysis, serum chemistry panel, fructosamine concentration and thyroxine concentration were determined on initial examination, and a complete blood count, serum chemistry panel, urinalysis and serum fructosamine concentration were repeated every 4 weeks for 16 weeks. Insulin doses were adjusted as needed to resolve clinical signs and lower serum fructosamine concentrations. Serum glucose (P = 0.0001) and fructosamine (P = 0.0001) concentrations significantly decreased from week 0 to week 16 in both dietary groups. By week 16, significantly more of the cats fed the LC-LF food (68%, 22/31), compared to the cats fed the MC-HF food (41%, 13/32), had reverted to a non-insulin-dependent state (P = 0.03). Cats in both groups were successfully taken off of insulin regardless of age, sex, type of insulin administered or duration of clinical disease before entering the study. There was no significant difference in the initial or final mean body weights or in the mean change in body weight from week 0 to week 16 between dietary groups. Diabetic cats in this study were significantly more likely to revert to a non-insulin-dependent state when fed the canned LC-LF food versus the MC-HF food.     

Effect of dietary insoluble fiber on control of glycemia in cats with naturally acquired diabetes mellitus

OBJECTIVE: To evaluate effects of dietary insoluble fiber on control of glycemia in cats with naturally acquired diabetes mellitus. DESIGN: Randomized controlled crossover trial. ANIMALS: 16 cats with naturally acquired diabetes mellitus. PROCEDURE: Cats were fed a diet high in insoluble fiber (HF) containing 12% cellulose (dry-matter basis) or a diet low in insoluble fiber (LF) for 24 weeks; they were fed the other diet for the subsequent 24 weeks. Caloric intake and insulin treatment were adjusted to maintain stable body weight and control of glycemia, respectively. Cats were allowed an adaptation period of 6 weeks after initiation of a diet, after which control of glycemia was evaluated at 6-week intervals for 18 weeks. Variables assessed included serum glucose concentration measured during the preprandial state, blood glycated hemoglobin concentration, serum glucose concentration measured at 2-hour intervals for 12 hours beginning at the time of the morning insulin injection, 12-hour mean serum glucose concentration, and mean fluctuation in serum glucose concentration from the 12-hour mean serum glucose concentration. RESULTS: Mean daily caloric intake, body weight, or daily insulin dosage did not differ significantly between cats when fed HF and LF diets. Mean preprandial serum glucose concentration, most post-prandial serum glucose concentrations, and the 12-hour mean serum glucose concentration were significantly lower when cats consumed the HF diet, compared with values when cats consumed the LF diet. CONCLUSIONS AND CLINICAL RELEVANCE: These results support feeding a commercially available diet containing approximately 12% insoluble fiber (dry-matter basis) to cats with naturally acquired diabetes mellitus.     

Evaluation of serum fructosamine concentration as an index of blood glucose control in cats with diabetes mellitus.

Fructosamine, a glycated serum protein, was evaluated as an index of glycemic control in normal and diabetic cats. Fructosamine was determined manually by use of a modification of an automated method. The within-run precision was 2.4 to 3.2%, and the day-to-day precision was 2.7 to 3.1%. Fructosamine was found to be stable in serum samples stored for 1 week at 4 C and for 2 weeks at -20 C. The reference range for serum fructosamine concentration in 31 clinically normal colony cats was 2.19 to 3.47 mmol/L (mean, 2.83 +/- 0.32 mmol/L). In 27 samples from 16 cats with poorly controlled diabetes mellitus, the range for fructosamine concentration was 3.04 to 8.83 mmol/L (mean, 5.93 +/- 1.35 mmol/L). Fructosamine concentration was directly and highly correlated to blood glucose concentration. Fructosamine concentration also remained high in consort with increased blood glucose concentration in cats with poorly controlled diabetes mellitus over extended periods. It is concluded that measurement of serum fructosamine concentration can be a valuable adjunct to blood glucose monitoring to evaluate glycemic control in diabetic cats. The question of whether fructosamine can replace glucose for monitoring control of diabetes mellitus requires further study.     

Effect of glipizide on serum insulin and glucose concentrations in healthy cats.

With the recent identification of non-insulin-dependent diabetes mellitus (NIDDM) in cats, new possibilities arise for the use of oral hypoglycaemic agents in the treatment of feline NIDDM, similar to their use in humans. To identify the future applicability of the oral hypoglycaemic agent, glipizide, in the treatment of feline NIDDM, its effects on serum insulin and glucose concentrations in healthy cats was examined. In addition, adverse effects seen clinically or on bloodwork following short-term use of the drug were looked for. Serum insulin and glucose concentrations were evaluated after the oral administration of 2.5, 5.0 and 10.0 mg glipizide and placebo in 10 healthy cats. For each drug trial, blood was obtained five minutes before, immediately before, and 7.5, 15, 30, 45, 60, 90 and 120 minutes after glipizide or placebo administration. Mean serum insulin concentration increased after glipizide administration, with peak mean serum insulin concentration occurring 15 minutes after administration and declining to baseline by 60 minutes. There was no significant difference in peak mean serum insulin concentration, mean serum insulin concentration at 60 minutes after glipizide administration, or mean total insulin secretion between the three glipizide dosages. Mean serum glucose concentration decreased within 15 minutes of glipizide administration, with the glucose nadir occurring 60 minutes after glipizide administration. Placebo trials showed no significant change in mean serum insulin or glucose concentrations from baseline concentrations.     

Use of insulin glargine in dogs with diabetes mellitus

The objective of this study was to evaluate the safety and efficacy of insulin glargine in dogs with diabetes mellitus (DM). Twelve client-owned dogs with DM were included. All dogs received insulin glargine every 12 hours for at least six months, re-evaluations were performed after one, two, four, eight, 12 and 24 weeks and included clinical signs, blood glucose curves (BGCs) and measurement of serum fructosamine concentrations. Mean blood glucose concentrations were significantly lower after two weeks of treatment and remained significantly lower for the duration of the study. By week 24, polyuria/polydipsia had improved in 91 per cent of the dogs. No clinical signs that could have been caused by hypoglycaemia were observed. Based on BGCs and remission of the clinical signs for judging the success of the treatment, 58, 33 and 8 per cent of the dogs attained good, moderate and poor glycaemic control by week 24 of the study, respectively. Insulin glargine administered subcutaneously twice daily is a possible and safe method of treatment for dogs with naturally occurring DM. Although only a few studies are available on the use of other types of insulin in dogs, their success rate is somewhat greater than that with insulin glargine.     

Serum Fructosamine Concentration as an Index of Glycemia in Cats With Diabetes Mellitus and Stress Hyperglycemia

The purpose of this study was to evaluate fructosamine concentrations in clinically healthy cats, sick cats with stress hyperglycemia, and untreated diabetic cats to determine the usefulness of this test in diagnosing diabetes mellitus in cats, and in differentiating the disease from stress-induced hyperglycemia. In addition, we evaluated if the degree of glycemic control in cats treated for diabetes influenced their serum fructosamine concentrations. In the 14 sick cats with stress hyperglycemia, the median serum fructosamine concentration (269 μmol/L) was not significantly different from the median value in the 26 clinically normal cats (252 μmol/L). Two of the 14 cats with stress hyperglycemia (14.3%) had serum fructosamine concentrations above the upper limit of the reference range (175 to 400 μmol/U; on the basis of these results, the test specificity was calculated as 0.86. In 30 cats with untreated diabetes mellitus, the median serum fructosamine concentration was 624 μmol/L, markedly higher than the value in either the normal cats or the cats with stress hyperglycemia. All but 2 of the 30 untreated diabetic cats (6.7%) had serum fructosamine concentration above the upper limit of the reference range; on the basis of these results, the sensitivity of serum fructosamine concentration as a diagnostic test for diabetes mellitus was 0.93. When 30 diabetic cats receiving treatment were divided into 3 groups according to their response to treatment (ie, poor, fair, and good), the 16 cats that had a good response to treatment had significantly lower serum concentrations of both glucose and fructosamine compared with cats that had either a fair or poor response to treatment. A significant correlation (r_s= .70, n = 100, P < .001) was found between serum concentrations of glucose and fructosamine. Results of this study indicate that quantification of serum fructosamine concentration is a meaningful test for the diagnosis of diabetes, for differentiating diabetes from stress hyperglycemia; and for monitoring the metabolic control in treated diabetic cats.     

Effects of high carbohydrate and high fat diet on plasma metabolite levels and on i.v. glucose tolerance test in intact and neutered male cats

To elucidate the impact of dietary influence on carbohydrate and lipid metabolism and on the development of diabetes mellitus in the carnivorous cat, a 3 weeks feeding trial was carried out on six sexually intact and six neutered adult male cats. The effects of two isonitrogenic diets, differing in carbohydrate and fat content, were investigated on plasma metabolite levels in a 24-h blood sampling trial. Plasma leptin concentrations were also determined at the beginning and at the end of the 24-h trial. Glucose and insulin response was measured in an i.v. glucose tolerance test. A 5 days long digestion trial was also performed, which revealed a high digestion capacity of both fat and carbohydrates in cats. The high fat diet induced a significant rise in the plasma triglyceride, FFA, beta-hydroxybutyrate and cholesterol concentration, while the elevation in the glucose level did not reach significance. In the glucose tolerance test no significant difference was found between the neutered and intact cats. However, independently of the sexual state, the cats on the high fat diet showed a slightly elongated glucose clearance and reduced acute insulin response to glucose administration. This is indicative of diminished pancreatic insulin secretion and/or beta-cell responsiveness to glucose. The results of this preliminary study may be the impetus for a long-term study to find out whether it is rather the fat rich ration than carbohydrate rich diet that is expected to impair glucose tolerance and thus might contribute to the development of diabetes mellitus in cats. Whether the alteration in glucose metabolism is due to altered leptin levels remains to be determined.     

Evaluation of the oral antihyperglycemic drug metformin in normal and diabetic cats

Metformin is an oral antidiabetic drug that improves control of glycemia primarily by inhibiting hepatic gluconeogenesis and glycogenolysis. This study evaluated the usefulness of metformin for the treatment of diabetes mellitus in cats. The study consisted of 3 phases. Phase I was a dose-finding study performed in healthy cats that were randomly administered varying doses of metformin to determine the approximate dose that would yield plasma concentrations known to be effective in humans. Phase 2 was a 3-week safety study performed in healthy cats to determine if cats could tolerate the daily oral dose and administration protocol identified during phase 1. Phase 3 was a clinical trial evaluating the clinical response of diabetic cats to oral metformin treatment. Five cats with newly diagnosed, naturally acquired diabetes mellitus were enrolled in phase 3. Plasma metformin concentrations in the therapeutic range of 0.5-2 microg/mL were achieved with doses of 50 mg/cat PO q12h without dramatic drug accumulation. Intermittent lethargy, inappetence, vomiting, and weight loss were identified, and the results of the CBC, serum biochemical analysis, plasma lactate concentration, and urinalysis remained within the reference range during phase 2 of the study. During phase 3, control of glycemia was achieved in 1 of 5 diabetic cats after 8 weeks of metformin treatment; 3 cats failed to respond to metformin, and treatment with insulin was initiated after 7-8 weeks of metformin treatment; 1 cat died unexpectedly 11 days after starting metformin treatment. The cause of death was not determined. The serum insulin concentration was within or greater than the reference range in the responder diabetic cat and was undetectable or at the low end of the reference range in the nonresponder diabetic cats. The results of this study suggest that metformin is beneficial only in those diabetic cats with detectable concentrations of insulin at the time metformin treatment is initiated.     

Effects of diet on glucose control in cats with diabetes mellitus treated with twice daily insulin glargine

The purpose of this study was to evaluate the effects of dietary modification in addition to twice daily insulin glargine. Cats were treated with insulin glargine twice daily and randomized to receive either a low carbohydrate, high protein (LCHP) diet (n=6) or a control diet (n=6) for 10 weeks. Re-evaluations of clinical signs, blood glucose curves, and serum fructosamine concentrations were performed at weeks 1, 2, 4, 6, and 10. Two of 12 cats achieved complete remission by the end of the study but remission rate was not different between diet groups. Using twice daily insulin glargine and frequent monitoring, all cats in both diet groups achieved successful glycemic control. Frequent monitoring is key to achieving glycemic control in diabetic cats; potential benefits of dietary modification require further evaluation.     

Cryohypophysectomy used in the treatment of a case of feline acromegaly

A 10-year-old female spayed cat was diagnosed with acromegaly secondary to a pituitary tumour. At the time of diagnosis, the cat had insulin-resistant diabetes mellitus and its insulin-like growth factor-I levels were elevated. Clinical signs included polyuria, polydipsia and weight gain. Persistent hyperglycaemia and glucosuria were identified, and fructosamine levels remained elevated. Magnetic resonance imaging of the brain showed a pituitary tumour. Transsphenoidal cryohypophysectomy was used to treat the pituitary tumour. Postoperatively, the serum insulin-like growth factor-I levels decreased and the diabetes mellitus was controlled with routine levels of insulin. To the authors' knowledge, this is the second reported case of acromegaly treated with cryohypophysectomy, and the first that reports a favourable long-term outcome. Cryohypophysectomy may be a safe and effective treatment for cats with a pituitary mass resulting in acromegaly.