Abstracts

Brianceau P, Chester T, Smith A and others. (2008) Efficacy and safety of porcine insulin zinc suspension (izs-p) for reducing hyperglycemia and associated clinical signs in cats with diabetes mellitus. 22nd ACVIM Forum San Antonio, Texas, 4-7 June, 2008:

Abstract:
An open, unmasked study was conducted to provide substantial evidence of the clinical effectiveness and safety of porcine insulin zinc suspension (IZS-P, Vetsulin®) for reducing hyperglycemia and its associated signs in cats with diabetes mellitus. The study was conducted in the US in accordance with the current FDA, CVM and VICH Guidance on Good Clinical Practice. Cats were enrolled based on elevated fasting blood glucose (>250 mg/dL on two occasions) with concurrent glycosuria and clinical signs of diabetes mellitus. Cats that met specified criteria on prior treatment or with coexisting primary diseases were excluded. A baseline blood glucose curve (Day 0) was completed (Accu-Chek® Advantage®) and IZS-P therapy (approximately 1 to 2 IU per subcutaneous injection q 12 h) initiated. Glucose curves and clinical signs were re-evaluated on Days 7, 14, 30, 60 and 180 and the dose was adjusted accordingly. Overall response to treatment in each cat was recorded on a visual analogue scale (VAS). Additional examinations to assess the long-term safety were carried out at 90, 120 and 150 days. Complete blood count (CBC) and serum chemistry were performed during the course of the study and urinalysis prior to enrollment. Mean VAS score decreased from 93.8 mm on Day 0 to 31.2 mm and 25.0 mm on Days 60 and 180 , respectively (p<0.001 both days). This was mirrored by a substantial reduction in polyuria, polydipsia and polyphagia. Mean blood glucose decreased from 394.1 mg/dL on Day 0 (n=77) to 216.7 mg/dL (n=76) and 219.5 mg/dL (n=73) on Days 60 and 180, respectively (p<0.001 both days). Mean glucose nadir decreased from 343.3 mg/dL on Day 0 to 145.7 mg/dL and 155.9 mg/dL on Days 60 and Day 180, respectively (p<0.001 both days). Blood glucose was <300 mg/dL in 5.2%, 75.0% and 71.2% of the cats and blood glucose nadir <200 mg/dL in 0%, 72.4% and 69.9% of the cats on Days 0, 60 and 180, respectively. Mean fructosamine concentration decreased from 604.3 µmol/L on Day 0 to 451.3 µmol/L and 448.4 µmol/L on Days 60 and 180, respectively (p<0.001 both days). Diabetes remission occurred in four cats. Less than 3% (2/77) of the cats failed to respond to treatment. Hypoglycemia (blood glucose concentration <50 mg/dl) was reported as an adverse event associated with clinical signs (lethargy, diarrhea, vomiting, and/or hypothermia) in 13/78 cats and without clinical signs in 17/78 cats, 11 of the latter received oral glucose replacement. Five cats experienced more than one hypoglycemic event. Polyneuropathy was documented in 5.1% (4/78) of the cats. Two injection site reactions were reported (mild bruising at the injection site, mildly thickened subcutis). These results confirm that IZS-P is effective and safe for reducing hyperglycemia and its associated clinical signs in cats with diabetes mellitus.

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Casella M, Wess G, Reusch CE. (2002) Measurement of capillary blood glucose concentrations by pet owners: a new tool in the management of diabetes mellitus. J Am Anim Hosp Assoc. 38(3):239-245.

Abstract: Recently a new method for capillary blood sampling from the ears of dogs and cats was described, which allows the measurement of glucose concentration by means of portable glucose meters. The authors of this report evaluated the suitability of this method for use by pet owners and the potential technical problems. The owners of seven healthy dogs and seven healthy cats were asked to perform two glucose curves (measuring blood glucose concentration every 2 hours for a total of 12 hours). All dog owners and three cat owners were able to perform a reliable blood glucose curve. The most frequently encountered problems were inadequate formation of a blood drop due to excessive digital pressure on the pinna, repeatedly depressing the plunger of the lancet device instead of allowing the negative pressure to slowly build up, and failure to fill the test strip up to the mark. The authors conclude that these steps of the procedure need to be stressed during technique demonstration and that home monitoring of blood glucose concentrations may serve as a new tool in the management of diabetic dogs and cats.

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Catchpole B, Ristic JM, Fleeman LM and others. (2005) Canine diabetes mellitus: Can old dogs teach us new tricks? Diabetologia 48(10):1948-1956.

Abstract: Background: Diabetes is common in dogs, with an estimated prevalence of 0.32% in the UK. Clinical signs, as in man, include polydipsia, polyuria and weight loss, associated with hyperglycaemia and glucosuria. Diabetes typically occurs in dogs between 5 and 12 years of age, and is uncommon under 3 years of age. Breeds predisposed to diabetes include the Samoyed, Tibetan Terrier and Cairn Terrier, while others such as the Boxer and German Shepherd Dog seem less susceptible. These breed differences suggest a genetic component, and at least one dog leucocyte antigen haplotype (DLA DRB1*009, DQA1*001, DQB1*008) appears to be associated with susceptibility to diabetes. Methods: Canine diabetes can be classified into insulin deficiency diabetes (IDD), resulting from a congenital deficiency or acquired loss of pancreatic beta cells, or insulin resistance diabetes resulting mainly from hormonal antagonism of insulin function. Results: There is no evidence for a canine equivalent of human type 2 diabetes. Adult-onset IDD, requiring insulin therapy, is the most common form, with pancreatitis and/or immune-mediated beta cell destruction considered to be the major underlying causes of the disease. Discussion: Autoantibodies to insulin, recombinant canine GAD65 and/or canine islet antigen-2 have been identified in a proportion of newly diagnosed diabetic dogs, suggesting that autoimmunity is involved in the pathogenesis of disease in some patients. Conclusion: The late onset and slow progression of beta cell dysfunction in canine diabetes resembles latent autoimmune diabetes of the adult in man.

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Catchpole B, Kennedy LJ, Davison LJ and others (2008) Canine diabetes mellitus: From phenotype to genotype. J Small Anim Pract 49(1):4-10.

Abstract: Breed differences in susceptibility to diabetes mellitus in dogs suggest an underlying genetic component to the pathogenesis of the disease. There is little evidence for an equivalent of human type 2 diabetes in dogs, and it has been proposed that canine diabetes is more comparable to the type 1 form of the disease. Certain immune response genes, particularly those encoding major histocompatibility complex molecules involved in antigen presentation, are important in determining susceptibility to human type 1 diabetes. We tested the hypothesis that canine major histocompatibility complex genes (known as the dog leucocyte antigen) are associated with diabetes in dogs. A total of 530 diabetic dogs and more than 1000 controls were typed for dog leucocyte antigen, and associations were found with three specific haplotypes. The DLA-DRB1*009/ DQA1*001/DQB1*008 haplotype shows the strongest association with diabetes in the UK dog population. This haplotype is common in diabetes-prone breeds (Samoyed, cairn terrier and Tibetan terrier) but rare in diabetes-resistant breeds (boxer, German shepherd dog and golden retriever), which could explain differences in the prevalence of diabetes in these different breeds. There is evidence that the DLA-DQA1*001 allele is also associated with hypothyroidism, suggesting that this could represent a common susceptibility allele for canine immune-mediated endocrinopathies.

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Davison LJ, Herrtage ME, Catchpole B. (2005) Study of 253 dogs in the United Kingdom with diabetes mellitus. Veterinary Record 156(15):467-471.

Abstract: Clinical information and blood samples were collected from 253 dogs with naturally occurring diabetes mellitus. Over half of them were labrador retrievers, collies, Yorkshire terriers or crossbred dogs, and approximately 80 per cent of them were diagnosed between the ages of five and 12 years. The majority of the dogs were receiving insulin therapy once a day, but in the dogs receiving insulin injections twice a day there was a trend for lower serum fructosamine concentrations, suggesting better glycaemic control. The proportion of female dogs with diabetes was lower than in previous surveys. The disease was diagnosed more commonly in the winter months, a seasonal pattern also observed in human beings with diabetes, suggesting that similar environmental factors might be involved in the disease.

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Davison LJ, Herrtage ME, Catchpole B. (2011) Autoantibodies to recombinant canine proinsulin in canine diabetic patients Res Vet Sci 91(1):58-63.

Abstract: Objective: To determine whether dogs with spontaneously-occurring diabetes mellitus demonstrate serological reactivity to proinsulin. Sample population: Serum samples were collected from 15 newly-diagnosed diabetic, 15 insulin-treated diabetic and 15 non-diabetic control dogs. Procedures: Canine proinsulin was cloned into a prokaryotic expression vector to generate recombinant poly-histidine-tagged protein in Escherichia coli. A Western blotting assay was developed for detection of proinsulin autoantibodies in canine sera. Results: Reactivity to canine proinsulin was detected in 3 of 15 control dogs, 8 of 15 newly-diagnosed diabetic dogs and 6 of 15 insulin-treated diabetic patients. Of these reactors, only 1 control dog, 1 newly-diagnosed diabetic dog and 3 insulin-treated diabetic dogs recognised porcine insulin by ELISA, suggesting that the remaining proinsulin reactors might have been recognising proinsulin-specific epitopes. Conclusions and clinical relevance: This study suggests that proinsulin autoantibodies are present in a proportion of diabetic dogs. Further work is required to refine the assay and clarify the significance of these autoantibodies.

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Davison LJ, Walding B, Herrtage ME and others. (2008) Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations J Vet INern Med 22(6):1317-1325.

Abstract: Background: Anti-insulin antibodies (AIA) occur in diabetic dogs after insulin therapy, although their clinical significance is unclear. Hypothesis: Treatment of diabetic dogs with heterologous insulin is more likely to stimulate production of AIA than is treatment with homologous insulin. Animals: Diabetic dogs sampled before insulin therapy (n = 40), diabetic dogs sampled following treatment with porcine (homologous) insulin (n = 100), bovine (heterologous) lente insulin (n = 100), or bovine protamine zinc (PZI) insulin (n = 20), and nondiabetic control dogs (n = 120). Methods: Prospective observational study. Sera were analyzed by ELISA for antibodies against porcine insulin, bovine insulin, insulin A, B, or C peptides, and control antigens; canine distemper virus (CDV) and canine thyroglobulin (TG). Canine isotype-specific antibodies were used to determine total and anti-insulin IgG1 : IgG2 ratios. Results: There was no difference in CDV or TG reactivity among the groups. AIA were detected in 5 of 40 newly diagnosed (untreated) diabetic dogs. There was no significant difference in AIA (ELISA optical density reactivity) comparing control and porcine insulin-treated diabetic dogs (P > .05). Anti-insulin reactivity was most prevalent in bovine PZI insulin-treated dogs (90%; P < .01), and bovine lente insulin-treated dogs (56%; P < .01). AIA induced by treatment were enriched for the IgG1 isotype. Conclusions and Clinical Importance: This study indicates that bovine insulin is more immunogenic than porcine insulin when used for treatment of diabetic dogs. Copyright © 2008 by the American College of Veterinary Internal Medicine.

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Fall T, Hamlin HH, Hedhammar Å and others. (2007) Diabetes mellitus in a population of 180,000 insured dogs: Incidence, survival, and breed distribution J Vet Intern Med 21(6):1209-1216.

Abstract: Background: Canine diabetes mellitus (DM) is a common endocrinopathy with an unclear etiology. For a better understanding of the underlying mechanisms, there is a need for comprehensive epidemiologic studies. Earlier studies have shown that the risk of disease is higher in certain dog breeds. Hypothesis: Incidence, age of onset, survival and sex proportion of DM vary by breed. Animals: Data from a cohort of 182,087 insured dogs aged 5-12 years accounting for 652,898 dog-years at risk were studied retrospectively. Methods: Incidence rates by sex, breed, and geography were calculated with exact denominators. Age-specific incidence and survival after 1st DM claim were computed with Cox's regression and Kaplan-Meier survival function. Multivariable survival analysis was performed for the outcome diagnosis of DM with age, sex, and geography tested as fixed effects, previous endocrine or pancreatic diseases tested as time-dependent covariates, and breed tested as a random effect. Results: The mean age at 1st insurance claim for the 860 DM dogs (72% females) was 8.6 years. The incidence of DM was 13 cases per 10,000 dog-years at risk. Australian Terriers, Samoyeds, Swedish Elkhounds, and Swedish Lapphunds were found to have the highest incidence. The proportion of females with DM varied significantly among breeds. Swedish Elkhounds, Beagles, Norwegian Elkhounds, and Border Collies that developed DM were almost exclusively females. The multivariable model showed that breed, previous hyperadrenocorticism, and female sex were risk factors for developing DM. Median survival time was 57 days after 1st claim. Excluding the 223 dogs that died within 1 day, the median survival time was 2 years after 1st claim of DM. Conclusion: The significant breed-specific sex and age differences shown in this study indicate that genetic variation could make breeds more or less susceptible to different types of DM.

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Graham PA, Nash AS and McKellar QA. (1997)
Pharmacokinetics of a porcine insulin zinc suspension in diabetic dogs.
Journal of Small Animal Practice 38(10):434-8.

Abstract:

Ten dogs with naturally occurring diabetes mellitus were injected with a highly purified porcine insulin zinc suspension at a dose according to their expected requirement. Plasma insulin and glucose concentrations were measured at two-hourly intervals over 24 hours following injection.

There were either one or two peaks in plasma insulin concentration: one at about 4 hours (mean 4.3 +/-1.3 [SD]) and another at about 11 hours (mean 11 +/- 1.85) after the injection. The second insulin peak was seen in only eight dogs. Persistence of elevated plasma insulin concentrations ranged from 14 to 24 hours (mean 17.4 +/- 3.65).

These results compare favourably with those published for other intermediate-acting insulin preparations used to treat canine diabetes mellitus and suggest that this preparation has useful properties for the successful management of many canine diabetics.

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Horn B and Mitten RW(2000)
Evaluation of an insulin zinc suspension for control of naturally occurring diabetes mellitus in dogs.
Australian Veterinary Journal 78(12):831-4.

Abstract:

A trial to evaluate duration of action of Caninsulin (an insulin zinc
suspension) in spontaneously occurring cases of canine diabetes mellitus and its suitability for once daily administration.

Eight client-owned dogs with diabetes mellitus were included in a prospective pilot study. All dogs had been treated with Caninsulin for a minimum of 2 months and were considered on clinical grounds to be adequately stabilised.

The dogs were hospitalised for a 24 hour period. Blood was collected every 2 hours via indwelling venous catheters for blood glucose determination.

Caninsulin administration once daily failed tomaintain glycaemic control for greater than 13 h in five of eight dogs. Acceptable blood glucose concentrations were maintained for 22 h and greater than 24 h in two others.
The results from one of the dogs were not used as the animal became distressed during hospitalisation.

It was concluded that most diabetic dogs may require twice daily administration of Caninsulin for satisfactory glycaemic control, but once daily administration may be adequate in some animals.

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Lederer R, Rand JS, Jonsson NN, Hughes IP and others. (2009) Frequency of feline diabetes mellitus and breed predisposition in domestic cats in Australia. Vet J 179(2):254-258. Abstract: The frequency of diabetes mellitus is described for cats that received veterinary care from two large feline-only clinics in Brisbane, Australia. Frequency was estimated using period prevalences (the proportion of the population at risk that was affected by diabetes at any point during a specified time period). Of the 12,576 study cats, 93 were affected with diabetes during the 5-year study period, resulting in a 5-year period prevalence of 7.4 per 1000 cats. Period prevalence was significantly higher in Burmese cats (22.4 cats per 1000) than domestic short and longhaired cats (7.6 cats per 1000) and the mean age at first diagnosis during the study period was significantly higher amongst Burmese cats (13.6 years) compared to domestic short and longhaired cats (10.9 years). Further investigations into the apparent predisposition of Burmese cats to diabetes mellitus are indicated.

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Martin GJ and Rand JS(2001)
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.
Journal of Feline Medicine and Surgery 3(1):23-30

Abstract

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.

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Martin GJ and Rand JS. (2007)
Control of diabetes mellitus in cats with porcine insulin zinc suspension.
Veterinary Record 161:88-94.

Abstract:
The required dose rate of porcine insulin zinc suspension to control the signs of diabetes mellitus in 25 cats was assessed, and their response to insulin treatment was investigated over 12 months. The cats required a median dose of 0·5 iu/kg bodyweight twice a day, and only two of the cats required doses higher than 1·0 iu/kg twice a day. Their lowest blood glucose concentration was on average significantly higher during the night than during the day. Seven of the cats went into diabetic remission during the study, and the control of the clinical signs in the others was either excellent or good by the end of the study.

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Martin GJ and Rand JS. (2007)
Comparisons of different measurements for monitoring diabetic cats treated with porcine insulin zinc suspension.
Veterinary Record 161:52-58.

Abstract:
Clinical measurements, including a subjective clinical score and water intake, and biochemical measurements, including blood glucose, fructosamine, beta-hydroxybutyrate, cholesterol, triglycerides, triglycerides corrected for free glycerol, glycerol and urine glucose were compared for monitoring diabetic cats treated with porcine insulin zinc suspension. The data were grouped by subjective clinical score and the sensitivity of each measurement in differentiating the grouped data was assessed. None of the measurements was able to differentiate between the ranked clinical score groups, but two-hourly measurements of blood glucose over 24 hours, water intake, urine glucose and fructosamine were useful in differentiating cats that subjectively had the water and food consumption and general appearance of a normal cat from cats in which the signs of diabetes were less well controlled. Measurements of plasma lipids were not well correlated with the other measurements. The measurements that were most closely correlated with apparently perfect clinical control were the J index, water intake and maximum and mean blood glucose concentrations. In practice, water intake, maximum blood glucose concentration, mean blood glucose concentration and urine glucose would be the most useful indicators of clinical control in diabetic cats treated with porcine insulin zinc suspension.

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Martin GJ, Rand JS and Hickey SA (2006)
Separation of serum glycated proteins by agarose gel electrophoresis and nitroblue tetrazolium staining in diabetic and normal cats
Veterinary Clinical Pathology 35(3):307-310

Abstract:

Background: The total glycated protein (fructosamine) concentration in serum consists mainly of glycated albumin and lipoproteins. Measurement of fructosamine is used to diagnose and monitor diabetes mellitus in cats.

Objective: The aims of this study were to measure glycated proteins in diabetic and healthy (nondiabetic) cats using a semiquantitative technique and to determine whether measurement of any of the fractions of glycated protein could be potentially advantageous for the diagnosis and monitoring of diabetic cats.

Methods: Serum samples from 6 cats with diabetes mellitus and 10 clinically healthy adult cats were assayed for total glycated protein using a nitroblue tetrazolium (NBT) fructosamine assay. Serum proteins were separated by agarose gel electrophoresis and stained with NBT to identify individual glycated proteins within the bands. Gels were scanned by densitometry at 525 nm and the glycated protein content was calculated with reference to the total glycated protein content of the sample.

Results: Diabetic cats with increased total fructosamine concentrations had higher concentrations of glycated albumin and glycated a- and b-lipoproteins compared with healthy cats. The concentration of glycated proteins in each of the fractions had a positive linear association with the total glycated protein content of serum, but there was large variation in the relative contributions of the 3 protein fractions to the total glycated protein concentration.

Conclusions: Based on the results of this study, measurement of individual glycated fractions does not seem to offer any potential diagnostic advantage over measurement of total glycated protein (fructosamine) concentration alone. In some diabetic and healthy cats, glycated lipoproteins formed the major part of the total glycated protein, whereas in other cats albumin was the major contributor.

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McCann TM, Simpson KE, Shaw DJ and others. (2007)
Feline diabetes mellitus in the UK: the prevalence within an insured cat population and a questionnaire-based putative risk factor analysis.
J Feline Med Surg 9(4):289-299.

Abstract:
Prevalence and risk factors for the development of diabetes mellitus (DM) in cats in the United Kingdom have not previously been reported. The prevalence of DM was evaluated in a large insured population and was found to be 1 in 230 cats. In this insured cat population Burmese cats were 3.7 times more likely to develop DM than non-pedigree cats. A convenience-sampling questionnaire-based study was used in order to identify putative risk factors for the development of DM. The univariate risk factor analysis identified being male, neutered, inactive, weighing ≥5 kg and having a history of corticosteroid treatment as significant risk factors for the development of DM in these cats. In addition, male cats treated with megestrol acetate had a significantly increased risk of developing DM compared to females. In contrast, there was no difference in DM occurrence between male and female Burmese cats. A multivariate classification tree-based model on the questionnaire data looking for interactions between risk factors, identified gender as the most important overall risk factor for the development of DM with low physical activity being the next most important risk factor for female cats and breed the next most important for male cats.

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McManus K, Playford M(2001) Evaluation of an insulin-zinc suspension for control of naturally occurring diabetes mellitus in dogs. Aus Vet J 78(12):831-4. Abstract: Correspondence written in reference to the clinical paper published in the December 2000 issue of the Australian Veterinary Journal on the use of insulin-zinc suspension for diabetes mellitus in dogs (Horn B and Mitten RW Evaluation of an insulin zinc suspension for control of naturally occurring diabetes mellitus in dogs. Australian Veterinary Journal 78(12):831-4.) In the authors' experience, about 70% of dogs are stabilised and clinical signs eliminated on once-daily treatment with Caninsulin. They suggest that other factors should be taken into consideration when evaluating the 2000 clinical trial, such as patient selection criteria and evaluating the resolution of clinical signs on once daily Caninsulin treatment.

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Michiels L, Reusch CE, Boari A and others. (2008) Treatment of 46 cats with porcine lente insulin - a prospective, multicentre study J Feline Med Surg 10(5):439-451. Abstract: This prospective, multicentre, non-blinded, open study followed 46 cats with diabetes mellitus during treatment with porcine lente insulin (also known as porcine insulin zinc suspension, Caninsulin®, Intervet) for 16 ± 1 weeks (stabilization phase), with additional monitoring of some cats (n = 23) for a variable period. At least three of the following were present at initial presentation: appropriate history of clinical signs consistent with diabetes mellitus, glucosuria, blood glucose greater than 15 mmol/l and fructosamine greater than 380 μmol/l. Insulin treatment was started at a dose rate of 0.25-0.5 IU/kg body weight twice daily, with a maximum starting dose of 2 IU/injection. Twenty-eight of the cats were classed as reaching clinical stability during the study, in 23 of these cats this was during the stabilization phase. Seven cats went into remission during the stabilization phase and one of the cats in week 56. Clinical signs of hypoglycaemia, significantly associated with a dose of 3 units or 0.5 IU/kg or more per cat (twice daily), were observed in nine of the 46 cats during the stabilization phase and concomitant biochemical hypoglycaemia was recorded in most cases. Biochemical hypoglycaemia, recorded in 6% of the blood glucose curves performed during the stabilization phase, was significantly associated with a dose rate of 0.75 IU/kg or more twice daily. This further highlights the need for cautious stepwise changes in insulin dose. The protocol used in the present study is suitable for and easy to use in practice. This study confirmed the efficacy and safety of porcine lente insulin (Caninsulin®) in diabetic cats under field conditions.

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Monroe WE, Laxton DJ, Fallin EA and others(2005)
Efficacy and Safety of a Purified Porcine Insulin Zinc Suspension for Managing Diabetes Mellitus in Dogs.
19th ACVIM Forum Denver, Colorado, 23-26 May 200: Journal of Veterinary J Vet Intern Med 19:675-682.

Abstract

The objective of this study was to evaluate the safety and efficacy of a purified porcine insulin zinc suspension for treating dogs with uncomplicated diabetes mellitus.

Fifty-three dogs were treated for 60 days after an initial dose determination period. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs were determined before beginning insulin therapy (time 0), at the end of the dose determination period (time 1), 30 days after time 1 (time 2), and 60 days after time 1 (time 3). Presence of polyuria, polydipsia, and ketonuria was determined at each time point. Adequacy of control of hyperglycemia was based on 12-hour blood glucose curves and improvement in clinical variables (results of physical examinations, historic information, polyuria, polydipsia, and ketonuria). Safety was evaluated by questionnaire, performance of physical examination, CBC, serum chemistry profile, and urinalysis. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs at times 1, 2, and 3 were significantly lower compared with time 0 (P , .0001). There was a reduction in the proportion of dogs with polyuria, polydipsia, and ketonuria of 82, 86, and 80%, respectively. All of the dogs had adequate glycemic control at time 1, 66% at time 2, and 75% at time 3. At time 3, 66% of dogs required insulin injections q12h. Other than hypoglycemia, there were no important adverse effects of insulin administration. The insulin was safe and efficacious for reducing blood glucose and clinical signs in dogs with diabetes mellitus.

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Wess G, Reusch C

Capillary blood sampling from the ear of dogs and cats and use of portable meters to measure glucose concentration.

J Small Anim Pract. 2000 Feb;41(2):60-6

Abstract

Two new methods for collection of capillary blood from the ear of dogs and cats for the measurement of blood glucose concentration using portable blood glucose meters (PBGMs) are described. The first method uses a lancing device after pre-warming the ear, while the second employs a vacuum lancing device. Both methods generated blood drops of adequate size, although the latter method was faster and easier to perform. Accuracy of the two PBGMs was evaluated clinically and statistically. Although assessment of statistical accuracy revealed differences between the PBGMs and the reference method, all of the PBGM readings were within clinically acceptable ranges. Measurement of capillary blood glucose concentration is easy to perform, inexpensive and fast. It may be used by owners to determine blood glucose concentrations at home, and could serve as a new tool for monitoring diabetic dogs and cats.

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Panciera DL, Thomas CB, Eicker SW and others. (1990)
Epizootiologic patterns of diabetes mellitus in cats: 333 cases (1980-1986).
J Am Vet Med Assoc. 197(11):1504-1508.

Abstract:
Medical records from 333 cats with diabetes mellitus were studied retrospectively, using epidemiologic methods to determine the incidence of and risk factors for diabetes mellitus in this species. Abstracts were derived, using the Veterinary Medical Data Program with its 17 participating academic institutions in the United States and Canada. A reference population of 135,651 cats was derived from the same hospital population and time span (July 1980 to June 1986). The incidence of diabetes mellitus in cats was determined to be 2.45 cases/1,000 cat-years-of-risk during the 6-year study period. Breed had no detectable effect on risk for diabetes mellitus. In contrast, body weight, age, gender, and neutering had a significant (P less than or equal to 0.01) effect. Body weight of cats was categorized as being less than or greater than or equal to 6.8 kg. The higher body weight, probably indicating obesity, contributed a 2.2-fold increase in risk, even after adjustment for age and gender (adjusted odds ratio). The etiologic fraction for high body weight was 3.8%, suggesting that an estimated 3.8% of cases of diabetes mellitus was attributable to this factor alone. Over 50% of diabetic cats were greater than 10 years old, and the etiologic fraction for age greater than 7 years alone was 73.5%. Age was a significant (P less than 0.001) and the most important single risk factor for development of the disease in cats, with adjusted odds ratios of 8.3 and 14.4 for age 7 to 10 years and greater than 10 years, respectively.

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Petrie G. (2004)
Monitoring the diabetic dog. 1. Clinical signs, goals of therapy and techniques
In Practice 26(8):411-418.

Abstract:
A good understanding of the clinical signs, goals of therapy and available monitoring techniques is important for the successful management of dogs with diabetes mellitus. The best monitoring 'tool' is the dog's owner - despite the array of tests available to monitor diabetics, the absence of the cardinal, clinical signs of disease probably remains the most reliable indicator of good diabetic control. This article discusses the techniques that may be used, both at home and in the clinic, for monitoring diabetics, emphasising the benefit of serial glucose measurements and the 'glucose curve'. An accompanying article, on pages 421 to 430 of this issue, looks at how monitoring tests can influence management changes to restore good glycaemic control and resolve clinical signs in problem cases.

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Potschka H, Bäumer W. (2006)
Treatment of diabetes mellitus in dogs and cats - Current status [Aktueller stand in der therapie des diabetes mellitus bei hund und katze]
Tierarztliche Praxis Ausgabe K: Kleintiere - Heimtiere 34(6):425-431.

Abstract:
Due to the high incidence of diabetes mellitus in dogs and cats, the generation of an individual therapeutic scheme for treatment of diabetes mellitus is a frequent challenge in veterinary practice. The aim of an optimized therapy is the tight control of blood glucose and the prevention of secondary pathological consequences. Although etiology, pathogenesis, and symptoms of diabetes mellitus can differ to a large extent, adminstration of insulin is generally the treatment of choice. To date, only Caninsulin® is approved for the treatment of diabetes mellitus in dogs and cats. The combination of a short-acting and a longer-acting insulin in Caninsulin® allows a good basic glycemic control as well as a suppression of postprandial glucose peaks. The therapy requires an individualized adjustment of the dosing and of the administration intervals which can only be optimized based on a good collaboration between the patient's owner and the veterinarian. Thereby, the repeated control of therapeutic efficacy by generating blood glucose curves is of particular importance. If no therapeutic success is achieved in cats using Caninsulin®, insulin glargin (Lantus®) can be tested as an alternative. Especially in cats a controlled diet can reasonably complement the insulin therapy. Based on current knowledge, the use of oral antidiabetics should be restricted to individual cases.

Rand JS, Martin GJ. (2001)
Management of feline diabetes mellitus.
Vet Clinics North Am - SA Pract 31(5):881-913.

Abstract:
Up to one quarter of diabetic cats can be well controlled with oral hypoglycemic drugs, although at least 75% require insulin therapy. Most available insulins provide good clinical control but only moderate glycemic control. Because mild to moderate hyperglycemia is well tolerated by cats receiving insulin but hypoglycemia can be life threatening, conservative insulin dosing is recommended. Clinical signs and water intake indicate whether a dose adjustment is required, but serial blood glucose measurements are usually needed to determine the direction of the adjustment. Starting doses of 0.3 to 0.5 IU/kg administered twice daily (rounded down to the nearest whole unit) are usually safe. Dose adjustments should not exceed 1 IU per cat every 2 to 4 weeks unless clinical hypoglycemia has occurred. Cats with clinical hypoglycemia need to be reassessed to see if they are in remission. If not, a 50% to 75% reduction in dose is advised. Approximately 30% of cats go into diabetic remission 1 to 4 months after an adequate treatment protocol is instituted.

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Reusch CE. (2005)
Monitoring and treatment of the diabetic cat Proceedings of ECVIM-CA 15th Annual Congress, 1-3 September 2005, Glasgow, Scotland. pp. 125-127.

Abstract:
Administration of insulin and dietary management are still the mainstays of treatment in diabetic cats. Good glycaemic control reverses the effect of high glucose on bets cells (glucose toxicity) and increases the chance of remission of diabetes. We usually start with a porcine zinc insulin of intermediate action (Caninsulin) twice daily. Time until adequate regulation is achieved is somewhere between 1 and 3 months. In a multicenter study 72% of the cats treated with Caninsulin were considered well regulated and 17% had gone into diabetic remission at the end of a study period of 4 months. Recently, insulin analogues have been developed in order to improve pharmacodynamic properties, e.g., absorption. In humans insulin glargine, a long acting synthetic insulin analogue is thought to be a peakless insulin with a long duration of action (> 24 hours). Glargine seems to have a shorter duration of action in cats than in humans and BID application is usually required. Insulin glargine does not seem to have obvious advantages over Caninsulin and is therefore not used as first line insulin in our hospital. Several studies show that using low-carbohydrate-high-protein diet results in better clinical control and increased rates of diabetic remission. In previous years our remission rate was 15-25% by using a high fibre diet. We recently were able to increase the percentage of remission to 45-50 by switching to a low carbohydrate-high-protein-diet. Diabetes mellitus is a chronic disease, that requires continuing medical care and owner education to prevent acute complications and to enable adequate life quality. Until recently long-term management of diabetic cats relied on the owners observation of clinical signs and on periodic evaluation by a veterinarian. Cats which eat and drink normal and do not lose weight are usually well regulated. Blood glucose concentrations in well regulated cats range mostly between 15 mmol/l (prior to insulin) and 5 mmol/l (nadir), fructosamine then is either within the normal range or moderately to slightly elevated (up to 450 micromol/l). Serial blood glucose curves (BGCs) are necessary to assess insulin efficacy, glucose nadir, time of peak insulin effect, duration of the insulin effect, degree of fluctuations in blood glucose (BG) concentrations and to recognise the Somogyi phenomenon. Until recently, the vast majority of BGCs were performed in the hospital because most pet owners are unable to collect blood samples by venipuncture. In-hospital BGCs can be difficult to interpret or may even be useless. Measurement of capillary blood glucose (home monitoring, HM) has been part of the routine protocol for long-term management for diabetic cats in our clinic since 1999. Cat owners are introduced to HM about 3 weeks after starting therapy. About 70% of our cat owners are willing and able to perform HM. When blood glucose curves generated at home and in the hospital were compared with regard to treatment decisions, in about 60% of cases treatment decisions would have been the same. In 40% decisions would have been different, in some cases even completely contrary. We usually base our treatment decisions on the curves generated at home. The success of HM greatly depends on careful preparation and instruction of the owners. One of the major advantages of HM is that it enables frequent generation of BGC. In complicated cases, more than one curve can therefore be performed at home before a treatment decision is made.

Rieder J , Seipel J, Biermann K and others. (2008)
Canine and feline diabetes mellitus: A retrospective epidemiological study (1996-2006) [Kaniner und feliner Diabetes mellitus - Ein epidemiologischer Rückblick (1996-2006)]
Tierarztliche Praxis Ausgabe K: Kleintiere - Heimtiere 36(3):169-175.

Abstract:
Objective: Prevalence and risk factor analysis for diabetes mellitus in cats and dogs seen at the Tierärztliche Hochschule Hannover (Hanover Veterinary Medical School). Materials and methods: Each diabetic patient presented at the Department for Small Animals at the Hanover Veterinary Medical School between 1996 and 2006 was analysed according to weight, age, gender and breed. Results: Ten of 1000 cats and four of 1000 dogs seen between 1996 and 2006 were found to suffer from diabetes mellitus. Among all cats presented, neutered male animals had the highest prevalence. Highest risk for cats was at the age of 11 years. For dogs the female to male ratio was 2:1. Among dogs, neutered female animals represented the highest risk group with 0.79%. Concerning breed, Cairn Terriers and West Highland White Terriers had the highest incidence for diabetes mellitus whereas German Shepherds and Dachshunds had a significantly lower prevalence. Conclusion: The prevalence of diabetes mellitus is increasing in cats but not in dogs. The following risk factors were identified in the population studied: advanced age, male gender, increased weight for cats; middle age, female gender and neutered status for dogs. Clinical relevance: The pathogenesis of feline and canine diabetes mellitus is multifactorial and still poorly understood. It remains a challenge for clinicians and scientists to identify specific risk factors for diabetes mellitus in cats and dogs in order to improve prevention and therapy of diabetes in these small animals.

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Salgado D, Reusch C, Spiess B. (2000)
Diabetic cataracts: Different incidence between dogs and cats.
Schweizer Archiv fur Tierheilkunde 142(6):349-353.

Abstract:
Diabetes mellitus is one of the most common endocrinopathies in the dog and cat. Diabetic cataract primarily affects the canine species and is rarely observed in the cat. It has been proposed that the incidence of cataracts in diabetic dogs is high because many of these patients have significant hyperglycemia despite insulin therapy. Age, gender, levels of serum glucose (before and during insulin therapy) and cataract formation were evaluated, retrospectively, in 23 dogs and 22 cats with diabetes mellitus. In the canine population, the groups with the highest frequency of presentation were females and sexually intact animals. In contrast, males and neutered animals were the most prevalent groups in the feline diabetic population. Over 80 % of diabetic cats and dogs were older than 7 years. Our results confirm the almost total lack of cataracts in diabetic cats, while they were present in more than half of the dogs. A relation between the incidence of cataracts and the correspondent level of hyperglycemia in the canine and feline species could not be established. The estimation of the relative risk for the development of cataracts in diabetic dogs shows that some population groups have a higher probability for suffering from this ocular alteration. A relation between relative risk and the correspondent level of hyperglycemia in the various groups was not found. This fact indicates that other factors are involved in the unequal appearance of diabetic cataracts in dogs and cats.

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Diabetes in cats