Comparison of time-action profiles of insulin Glargine and NPH insulin in normal and diabetic dogs

Intermediate insulin injections are commonly used for glycemic control in insulin dependent diabetic dogs acting as a replacement for natural insulin. Neutral Protamin Hagedorn (NPH) insulin and insulin glargine are two types of injectable insulin preparations commonly used in humans. In our study, we investigated the time-action profiles of both aforementioned insulin preparations in normal dogs in order to determine whether co-administration of NPH and glargine would be of benefit to insulin dependent diabetic dogs as it is for humans suffering from insulin dependent diabetes. Time-action profiles of NPH insulin and insulin glargine in normal dogs demonstrated a clear difference between both insulin preparations confirming that NPH insulin is an intermediate-acting preparation whereas insulin glargine is a long-lasting preparation. In addition, co-administration of NPH insulin and insulin glargine resulted in tight glycemic control as compared to NPH insulin alone in insulin dependent diabetic dogs. However, co-administration result in hypoglycemia at the dosages tested.     

Pharmacodynamics of Insulin Detemir and Insulin Glargine Assessed by an Isoglycemic Clamp Method in Healthy Cats

Background: Insulin detemir and insulin glargine are synthetic long‐acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time‐action profile, while insulin detemir has significantly less within‐subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events. Objectives: To compare the pharmacodynamics of insulin detemir and insulin glargine in healthy cats. Animals: Ten young, healthy, neutered, purpose‐bred cats. Methods: Randomized, cross‐over design. Pharmacodynamics of insulin detemir and insulin glargine were determined by the isoglycemic clamp method after a 0.5 U/kg SC injection. Results: The only significant difference in the pharmacodynamics of insulin detemir and insulin glargine was onset of action (1.8 ± 0.8 and 1.3 ± 0.5 hours for insulin detemir and insulin glargine, respectively, P= .03). End of action of insulin detemir was reached at 13.5 ± 3.5 hours and for insulin glargine at 11.3 ± 4.5 hours (P= .18). Time‐to‐peak action of insulin detemir was reached at 6.9 ± 3.1 hours and for insulin glargine at 5.3 ± 3.8 hours (P= .7). The time‐action curves of both insulin analogs varied between relatively flat curves in some cats and peaked curves in others. Conclusion and Clinical Importance: Insulin detemir and insulin glargine have shorter durations of action than in people when assessed by the clamp method, but in some cats these insulin analogs could be useful as once‐a‐day drugs. Peak effects of both insulin analogs are pronounced in some cats.     

Management of canine diabetes.

The majority of diabetic dogs appear to have a form of type 1 diabetes analogous to the latent autoimmune diabetes of adults (LADA) in humans. Evidence of acute or chronic pancreatitis occurs in about 40% of diabetic dogs. Blindness caused by cataract formation eventually occurs in the majority of diabetic dogs and is not dependent on glycemic control. Insulin is the mainstay of therapy for diabetic dogs, and a conservative approach to insulin therapy is crucial. Most diabetic dogs require twice-daily dosing with lente or NPH insulin to adequately control their clinical signs. The diet fed should primarily be palatable and nutritionally balanced. Improved glycemic control may be achieved in some dogs if the diet contains increased insoluble fiber.     

Evaluation of detemir in diabetic cats managed with a protocol for intensive blood glucose control

The aim of this study was to report outcomes using detemir and a protocol aimed at intensive blood glucose control with home monitoring in diabetic cats, and to compare the results with a previous study using the same protocol with glargine. Eighteen cats diagnosed with diabetes and previously treated with other insulins were included in the study. Data was provided by owners who joined the online German Diabetes-Katzen Forum. The overall remission rate was 67%. For cats that began the protocol before or after 6 months of diagnosis, remission rates were 81% and 42%, respectively (P = 0.14). No significant differences were identified between the outcomes for the glargine and detemir studies, with the exception of three possibly interrelated factors: a slightly older median age of the detemir cohort at diabetes diagnosis, a higher rate of chronic renal disease in the detemir cohort and lower maximal dose for insulin detemir.     

Absorption kinetics of regular, isophane, and protamine zinc insulin in normal cats

Absorption kinetics of regular, isophane (NPH), and protamine zinc (PZI) insulin were evaluated in seven clinically normal domestic shorthair cats by measurement of serial serum concentrations of insulin after subcutaneous administration of each insulin preparation. These results were compared to measurements of serial serum insulin concentrations after similar dosages of regular insulin were administered intravenously. Regular insulin administered subcutaneously was better absorbed than NPH and PZI insulins (mean bioavailability index 45.4% vs. 33.0% for NPH and 27.3% for PZI), and resulted in a significantly greater maximal increase in mean circulating insulin concentrations above baseline values (3529 pM vs. 1044 pM for NPH and 344 pM for PZI, P<0.05). The mean time interval between insulin administration and time to reach peak concentrations was significantly shorter for regular insulin than for NPH or PZI insulin (0.5 hr vs. 1.6 hr for NPH and 4.1 hr for PZI, P<0.05). There was also a significant difference (P<0.05) in the mean time interval between insulin injection and return of serum insulin concentrations to baseline values between regular insulin (5.6 hr) and NPH (7.7 hr) or PZI (13.1 hr) insulins. When compared with PZI, NPH insulin showed a significantly (P<0.05) greater maximal increase in mean serum insulin concentrations over baseline values. In addition, the interval between insulin administration and time to reach peak concentrations, as well as the time between insulin injection and return of serum insulin concentrations to baseline values, were also significantly shorter with NPH insulin than with PZI. These results suggest that NPH and PZI insulins administered subcutaneously to cats may require a short time to reach peak serum insulin concentrations as well as a relatively short time for circulating insulin concentrations to return to baseline values. If the absorption kinetics are similar to that in this study, most cats with diabetes mellitus would need twice daily injection of NPH or PZI insulin to adequately control the diabetic state.     

Absorption kinetics of regular and isophane (NPH) insulin in the normal dog

Absorption kinetics of regular and isophane (NPH) insulins were evaluated in seven normal fasted dogs by measuring serial serum concentrations of insulin and glucose following the subcutaneous administration of regular and NPH insulins. These results were compared to serum insulin values determined after injecting similar doses of regular insulin intravenously. Regular insulin was better absorbed than NPH insulin (mean bioavailability index 64.6% vs. 41.1%, P less than .01) resulting in a significantly greater maximal increase in mean circulating insulin concentrations above baseline values (362.2 microU/ml vs. 147.8 microU/ml, P less than .05). The time interval between insulin injection and return of serum insulin values to basal concentrations was also significantly shorter for regular than for NPH insulin (4.9 hr vs. 8.6 hr, P less than .05). However, there were no significant differences between regular and NPH insulins in time to reach peak serum insulin concentrations, maximal reduction in serum glucose concentrations, or time of lowest circulating glucose levels. The results of this study support previously accepted values for time-action characteristics of regular insulin, but suggest that NPH insulin may have an earlier peak and shorter duration of action than has previously been proposed in the dog.     

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.     

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.     

Gentamicin pharmacokinetics in diabetic dogs

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, five normal dogs, three dogs with alloxan-induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using non-compartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 +/- 2970 min, mean +/- SD) was longer (P less than 0.01) than in diabetic dogs (136 +/- 164 min). In diabetic dogs, Cls was greater (3.01 +/- 0.86 ml/min/kg) than in normal dogs (1.45 +/- 0.11 ml/min/kg; P less than 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 +/- 0.508 l/kg) than in normal dogs (8.56 +/- 4.48 l/kg; P less than 0.01). Serum gentamicin concentrations were less than 0.020 microgram/ml by 2 days in all of the diabetic dogs, but were 0.048 +/- 0.018 microgram/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non-rodent species.     

Glucose tolerance and insulin response in diabetes mellitus of dogs

The low dose intravenous glucose tolerance test (IVGTT) and the insulin response to the glucose load were performed in a series of twenty–two diabetic dogs. All diabetic dogs were characterized by glucose intolerance as expressed by an abnormal half time (Tl/2) or fractional turnover rate (k) for glucose clearance. On the basis of the initial insulin level (Io), the insulin peak response (Ip) and the insulinogenic index (I/G), the dogs were classified into three types. Type I dogs were characterized by a low Io, low Ip and low I/G in response to glucose, similar to the juvenile form of diabetes in humans. Type II dogs were characterized by a normal or high Io, but also with a low Ip and a low I/G which are some of the features of the maturity onset form. Type III dogs were characterized by a normal Io and a normal or delayed response to glucose as seen in chemical diabetes. It is suggested that these types represent stages in the natural history of the development of diabetes mellitus in dogs.     

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.     

Glargine and protamine zinc insulin have a longer duration of action and result in lower mean daily glucose concentrations than lente insulin in healthy cats

The pharmacological effects of glargine, protamine zinc (PZI), and lente insulins were evaluated in nine healthy cats. A 3-way crossover study was performed and plasma concentrations of insulin and glucose were determined for 24 h after a single subcutaneous injection of each insulin at 3-day intervals.
Time to onset of action did not differ between insulins. Mean time to first nadir glucose was longer for glargine (14 h) relative to PZI (4 h) and lente (5 h). PZI was biphasic in action with nadirs at 4 and 14 h with the second nadir occurring at a similar time to glargine. Nadir glucose did not differ significantly between insulin types. The duration of action was similar for glargine and PZI and was longer than that for lente insulin. Mean daily glucose after glargine and PZI were also similar and were lower than after lente insulin.
Time to reach peak insulin did not differ between insulin types. Time to return to baseline insulin level for PZI was longer than glargine but did not differ significantly from lente.
In conclusion, healthy cats injected subcutaneously with glargine, compared to those injected with lente insulin, have a later glucose nadir and longer duration of action. Glargine and PZI had similar durations of action in study cats but a larger study is required to obtain precise comparisons of duration of action.     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

Hypoglycemic effects of vanadium on alloxan monohydrate induced diabetic dogs

The hypoglycemic effects after oral administration of vanadium have been studied previously in many species such as rats, mice and even humans. However, there has been no prior report on the glucose lowering effect of vanadium on diabetic dogs. Therefore, the purpose of this study was to evaluate the hypoglycemic effects of oral vanadium on diabetic dogs. Diabetes mellitus in the dogs studied was induced by alloxan monohydrate intravenous injection. The dogs were divided into two groups, one was the diabetic control (DC) group (n = 4) and the other was the vanadium treated (DV) group (n = 6). Fresh water was supplied to the dogs in the DC group, but sodium metavanadate solution (0.1~0.2 mg/ml) was given to the dogs in DV group from one week after the alloxan injection. The fasting glucose levels, fructosamine and serum chemistry profiles were compared between the two groups weekly for three weeks. The fasting blood glucose levels in DV group were significantly lower than those in the DC group (p < 0.01). Fructosamine levels in the DV group were also lower than those in the DC group (p < 0.05). The serum chemistry profiles were not significantly different in comparisons between the two groups. However, the cholesterol levels were significantly lower in the DV group compared to the DC group (p < 0.05). Our findings showed that oral vanadium administration had a hypoglycemic effect on chemically induced diabetic dogs.     

Pharmacology of a 40 IU/ml porcine lente insulin preparation in diabetic cats: findings during the first week and after 5 or 9 weeks of therapy.

The aim of this study was to measure the pharmacokinetics and pharmacodynamics of subcutaneously injected 40 IU/ml porcine lente insulin preparation (Caninsulin, Intervet BV, The Netherlands) in diabetic cats. The pharmacological properties of the insulin in poorly controlled or untreated cats were compared with those after several weeks of treatment, to determine if improved diabetic stability altered the pharmacology of this insulin. In addition, the pharmacological properties of intravenously injected 100 IU/ml regular porcine insulin (Actrapid MC, NovoNordisk, Denmark) were measured. Serial plasma samples were collected after subcutaneous injection of porcine lente insulin from 25 diabetic cats in the first week of admission to a 12-month diabetic treatment trial. Samples were also collected after 4 or 8 weeks of treatment, in those cats which had not achieved diabetic remission by this time. At this time, serial plasma samples were also collected from these cats after intravenous injection of porcine regular insulin. Plasma samples were assayed for glucose, anti-insulin antibodies were extracted using a PEG technique, and samples were assayed for insulin using an RIA kit with low sensitivity for endogenous feline insulin, but high sensitivity for exogenous porcine insulin in feline plasma. Caninsulin injected subcutaneously in diabetic cats led to a peak insulin concentration in plasma after 1.7+/-0.1 h, and a nadir of blood glucose after 4.1+/-0.3 h. Insulin and glucose concentrations returned to baseline within 12 h. There was no significant change in the onset or duration of Caninsulin action between the first week of treatment and 5 or 9 weeks of treatment. Actrapid MC injected intravenously had a peak insulin at 0.36+/-0.03 h, and a nadir of blood glucose at 1.9+/-0.3 h. Insulin and glucose returned to baseline within 6 h. It was concluded that Caninsulin injected subcutaneously has suitable pharmacological properties for the twice-daily treatment of diabetes mellitus in cats. In addition, Actrapid MC insulin injected intravenously has suitable pharmacological properties for injection every 4-6 h in diabetic cats.     

Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans

Dogs develop obesity-associated insulin resistance but not type 2 diabetes mellitus. Low adiponectin is associated with progression to type 2 diabetes in obese humans. The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S_A) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs. We compared adiponectin profiles between 10 lean dogs and 10 lean humans and between 6 lean dogs and 6 age- and sex-matched, client-owned obese dogs. Total adiponectin was measured with assays validated in each species. We measured S_A with velocity centrifugation on sucrose gradients. The effect of total and HMW adiponectin concentrations on MINMOD-estimated insulin sensitivity was assessed with linear regression. Lean dogs had total and HMW adiponectin concentrations three to four times higher than lean humans (total: dogs 32 ± 5.6 mg/L, humans 10 ± 1.3 mg/L, P<0.001; HMW: dogs 25 ± 4.5 mg/L, humans 6 ± 1.3 mg/L, P<0.001) and a higher S_A (dogs: 0.78 ± 0.05; humans: 0.54 ± 0.08, P = 0.002). Adiponectin concentrations and S_A were not lower in obese dogs (0.76 ± 0.05 in both groups; P=1). Total adiponectin, HMW adiponectin, and S_A were not associated with insulin sensitivity in dogs. We propose that differences in adiponectin profiles between humans and dogs might contribute to the propensity of humans but not dogs to develop type 2 diabetes. Dogs with chronic, naturally occurring obesity do not have selectively reduced HMW adiponectin, and adiponectin does not appear to be important in the development of canine obesity-associated insulin resistance.     

Low dose of insulin detemir controls glycaemia, insulinemia and prevents diabetes mellitus progression in the dog with pituitary-dependent hyperadrenocorticism

Diabetes is often associated with pituitary-dependent hyperadrenocorticism (PDH). Hypercortisolism causes insulin resistance and affects β-cell function. The purpose of this study was to test if daily administration of a long-acting insulin analogue during the first month of anti-PDH treatment can prevent progress to diabetes in these animals. Twenty-six PDH dogs were divided into three groups: one group with glycaemia <5.83 mmol/L and two groups with glycaemia >5.83 mmol/L and <9.35 mmol/L, one of which received insulin detemir during 4 months. Dogs with glycaemia <5.83 mmol/L and those with glycaemia >5.83 mmol/L which received insulin did not develop diabetes. In the non-insulin group, 6/7 dogs developed diabetes after the third month. There is a 13-fold higher risk of diabetes in dogs with glycaemia >5.83 mmol/L and no insulin treatment. Administering insulin detemir to dogs with PDH and glycaemia >5.83 mmol/L could prevent progression to diabetes.     

Glycated hemoglobin fractions in normal and diabetic dogs measured by high performance liquid chromatography.

We established a new analytical condition to measure the canine glycated hemoglobin by high performance liquid chromatography (HPLC) using cation exchange column. The canine hemoglobin gave five peaks consisting of 2 major and 3 minor hemoglobin fractions such as HbA1a, HbA1b and HbA1c. Measurement was done in 38 clinically normal dogs and 10 diabetic dogs. Mean HbA1c values (% of total Hb) in normal and diabetic dogs were 2.60 and 6.41%, respectively. And mean HbA1 values were 3.58 and 7.41%, respectively. The mean values of the canine HbA1c and HbA1 in diabetic dogs was higher than those in normal dogs, significantly (p less than 0.01). Advantages of the HPLC method and applicability for monitoring effectiveness of insulin therapy in the canine diabetes mellitus are discussed.     

Influence of type of starch and feeding management on glycaemic control in diabetic dogs

The present study evaluated the effects of two diets with different starch sources and two feeding methods on the glycaemic control in dogs with diabetes mellitus. The diets had similar nutrient contents (40% starch and 16% dietary fibre), one formulated with 46% of broken rice and the other with 42% sorghum and 10% lentils (as-fed). Ten client-owned diabetic dogs were fed with each diet for 2 months, in a crossover design. Five dogs received NPH human insulin and food every 12 h (feeding method 1), and the other five received insulin every 12 h but were fed three times a day (feeding method 2). In feeding method 2, morning insulin was higher than the evening dose and dogs received the second meal after 4 to 5 h of the morning insulin and meal. Parameters evaluated included insulin dosage, 12- and 8-h glycaemic curves, complete blood count, biochemical profile and urinalysis. Glycaemic curves were analysed by ANOVA with repeated measures. Glycaemic control parameters (fasting, mean, minimum and maximum glycaemia and serum fructosamine) and glucose area under the curve (AUC) were calculated and analysed by paired t test (p < 0.05). In feeding method 1, dogs fed the sorghum-based diet presented lower mean (p = 0.04) and minimum blood glucose concentrations (p = 0.03), and a tendency to lower maximum blood glucose (p = 0.06) and glucose AUC (p = 0.08) than when fed the rice-based diet. When food was provided twice a day, the ingestion of the rice-based diet resulted in higher post-prandial glucose response than the diet with sorghum and lentil. In feeding method 2, there was no effect of diet on the assessed parameters (p > 0.05). No differences in insulin dosage were observed between groups or feeding methods (p > 0.05). Providing two meals a day followed by insulin administration associated with the sorghum- and lentil-based diet improved glycaemic control in diabetic dogs.     

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 (0.5U/kg) or twice daily (0.25U/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.