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Use of Glargine and Lente Insulins in Cats with Diabetes Mellitus

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Use of Glargine and Lente Insulins in Cats with Diabetes Mellitus J Vet Intern Med 2006;20:234–238 Use of Glargine and Lente Insulins in Cats with Diabetes Mellitus Kelli E. Weaver, Elizabeth A. Rozanski, Orla M. Mahony, Daniel L. Chan, and Lisa M. Freeman 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 5 7, Glargine, n 5 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 5 3; Glargine, n 5 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. Key words: Carbohydrate; Diet; Fructosamine; Lantus; Protein. iabetes mellitus is a common endocrinopathy in injections to regulate blood glucose concentrations. This D cats with a reported frequency ranging from 1 in represents a significant commitment on the part of the 50 to 1 in 400 animals.1,2 Diagnosis is based on clients, and thus may result in lower compliance rates or identification of clinical signs including polyuria, poly- a higher risk of complications. dipsia, and weight loss despite good appetite, and by Recently, an innovative new human insulin analog, laboratory findings including persistent fasting hyper- Glargine (LantusH), has been developed for use in glycemia and glucosuria. Treatment options for diabetes people as once-daily basal insulin. Glargine was mellitus in cats include insulin therapy, dietary manage- approved for use in people by the U.S. Food and Drug ment, and oral hypoglycemic agents. Of these, insulin Administration in April 2000.7 It was developed by therapy is the most effective means of achieving glycemic recombinant DNA technology using Escherichia coli control. A number of different types of insulin, including plasmid DNA.7 Glargine insulin is produced by animal origin and human recombinant products, are substituting the amino acid asparagine with glycine at available for use in cats. Feline endogenous insulin is position A21 of the human insulin molecule and by the considered to be most homologous to bovine insulin.3 addition of 2 positively charged arginine molecules at Most cats with diabetes mellitus require insulin therapy the C terminus of the B chain.7,8 These modifications administered twice daily to prevent symptomatic hyper- result in decreased solubility of Glargine at a neutral pH glycemia and the development of ketosis.3 Protamine such as that found in subcutaneous tissue. This leads to zinc insulin (PZI) has been used in cats as a once-daily microprecipitate formation in the subcutaneous tissue, insulin, but one study noted that twice-daily adminis- which permits a slower absorption rate and therefore tration of PZI was necessary to maintain adequate a slower onset of action and relatively constant peakless glycemic control.4 Other insulin types, including beef- basal insulin supply.7 The effect observed is a steady pork and human recombinant neutral protamine Hage- action profile relatively free from peaks and troughs. dorn (NPH), Ultralente, and Lente insulin have been This effect has been demonstrated in people by use of used successfully to manage diabetes mellitus in cats but the euglycemic clamp technique.7 Glargine also has been also require twice-daily administration due to inade- proposed for use in cats. The theoretical benefits of this quate duration of action.3,5 One report demonstrated no insulin in the treatment of cats with diabetes mellitus difference in glycemic control in cats among Ultralente, include 24-hour maintenance of near normal glycemia Lente, and NPH insulin types.6 Thus, the insulin resulting in improved glycemic control with possible preparations currently available are considered less than resolution of diabetes, the ability for once-daily insulin ideal because most cats require twice daily insulin administration, prevention of hypoglycemic episodes, and potentially, the prevention of long-term complica- tions or euthanasia due to treatment failures. The use of From the Department of Clinical Sciences, Cummings School of Glargine insulin has not been widely described in Veterinary Medicine, Tufts University, North Grafton, MA. Oral animals. A clinical trial of Glargine in diabetic cats abstract presented at the 2005 ACVIM Forum, Baltimore, MD. showed that it was effective when used at a dosage of Reprint requests: Elizabeth A. Rozanski, DVM, DACVIM, 0.5 U/kg ideal body weight q12h in combination with DACVECC, Department of Clinical Sciences, Cummings School of a high-protein low-carbohydrate diet. Pharmacokinetic Veterinary Medicine, Tufts University, 200 Westboro Road, North studies in normal cats demonstrated that the duration of Grafton, MA 01536; e-mail: [email protected]. Submitted April 15, 2005; Revised June 21, 2005, July 21, 2005, action is longer with Glargine compared with that of August 26, 2005; Accepted August 26, 2005. PZI or Lente, and that a dosage of 0.25 U/kg q12h Copyright E 2006 by the American College of Veterinary Internal produced a longer glucose lowering effect in comparison Medicine to 0.5 U/kg q24h.a In a small pilot study, high remission 0891-6640/06/2002-0003/$3.00/0 rates were observed, which were believed to be due to Once-Daily Glargine in Cats 235 improved glycemic control leading to decreased glucose Table 1. Type of diet before enrollment. toxicity.b Appropriate dietary therapy in addition to insulin Diet Lente Group Lantus Group therapy is believed essential for optimal control of High-protein, low-carbohydrate 2 3 diabetes mellitus in cats. Recent studies suggest that High fiber 2 3 a commercial high-protein, low-carbohydrate diet is beneficial in the management of some cats with diabe- tes.9,b Cats are obligate carnivores and therefore are well number of cats with effective control between the 2 insulin groups suited to use protein rather than carbohydrates as a source were compared using chi-square analysis. Changes from baseline to the end of the study between insulin groups were compared using of glucose. High-protein, low-carbohydrate diets have Mann-Whitney U analyses. Glucose and fructosamine concentra- been shown to reduce insulin requirements and lead to tion changes over time between the 2 insulin groups were compared 9 early diabetic remission in some cats with diabetes. using analysis of variance with repeated measures. A value of P , The purpose of this study was to prospectively .05 was considered significant. Commercial statistical software was evaluate the effects on glycemic control of once-daily used for all analyses.d administered insulin Glargine in comparison to twice- daily administered Lente insulin in cats with naturally Results occurring diabetes mellitus in combination with a com- mercial high protein, low carbohydrate diet. Seventeen privately owned cats were enrolled in the study. Breeds included Domestic shorthair and longhair Materials and Methods (n 5 16) and Abyssinian (n 5 1). Nine cats were castrated males and 8 were spayed females. Ages ranged from 7 to All cats with naturally occurring diabetes mellitus that were 16 years (median, 10 years), BW ranged from 3.2 to patients at the Foster Hospital for Small Animals at Cummings 10 kg (median, 5.9 kg), and BCS ranged from 3 to 9 School of Veterinary Medicine at Tufts University were eligible for (median, 8). All cats were diagnosed with naturally inclusion of the study. The study was approved by the Tufts occurring diabetes mellitus based on detection of Institutional Animal Care and Use Committee, and all owners consistent clinical signs including polyuria, polydipsia, signed an informed consent form before enrolling cats in the study. weight loss and increased appetite, hyperglycemia (blood At the initial visit (day 0) history, physical examination including body weight (BW) and body condition scores (BCS; 1– glucose .250 mg/dL), and glucosuria. Eight cats were 9) was performed, and CBC, serum biochemical profiles, serum newly diagnosed and untreated, and 9 cats were being thyroxine concentrations, serum fructosamine concentrations, and treated with insulin with poor glycemic control. Types of urinalyses and urine cultures were obtained. Cats were randomized insulin being used before enrollment in the study included to receive either Glargine or human recombinant Lente insulin recombinant human NPH (n 5 5), Lente (n 5 2), using a computer-generated randomization program. The insulin Glargine (n 5 1), and PZI (n 5 1). Types of diets starting dosages were 0.5 U/kg (actual BW) Lente SQ q12h or previously fed either alone or in combination included 0.5 U/kg (actual BW) Glargine SQ q24h. The clients and the a high-protein, low-carbohydrate diet (n 5 5), a high- attending clinician were not blinded as to the type of insulin fiber diet (n 5 5), and a typical adult maintenance dry diet received by the cats. All cats were fed Purina DMH, a commercial (n 5 4) (Table 1).
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