Update on Feline Diabetes Mellitus
World Small Animal Veterinary Association World Congress Proceedings, 2006
Claudia E. Reusch, DECVIM-CA
Clinic for Small Animal Internal Medicine, University of Zuerich, Zuerich

In cats, diabetes mellitus represents one of the most common endocrinopathies. Currently it is assumed that the so-called administrative incidence is 1:100-1:400. Risk factors are increasing age, male gender, neutering and high body weight. Approximately 80% of cats seem to have type 2 diabetes mellitus (2DM) based on islet histology and clinical characteristics of the disease. 2DM is characterized by disorders of both insulin action and insulin secretion; both are usually present at the time of diagnosis. As in humans there is a strong link between obesity and 2DM, about 70-80% of cats are obviously obese at the time of diagnosis. The association with obesity is of practical and scientific importance. Obesity is the main risk factor and it is also the most obvious target for measures to prevent diabetes. From a scientific viewpoint, the mechanism by which obesity is diabetogenic remains unexplained. It has been shown that cats which increase their body weight by 2 kg had a 50% decrease in insulin sensitivity.

Administration of insulin and dietary management are the mainstays of treatment in diabetic cats. Treatment of diabetes mellitus should be initiated as soon as possible after diagnosis. Good glycemic control reverses the effect of high glucose on β-cells (glucose toxicity) and increases the chance of remission of diabetes. Glucose toxicity is a phenomenon, which should be understood when managing diabetes mellitus. It is defined as impaired insulin secretion from beta cells as a result of prolonged hyperglycemia. Initially, suppression of beta cells is reversible, later, structural changes will lead to an irreversible status. Glucose toxicity is the reason why measuring insulin concentration is usually not helpful to predict if the cat will go into diabetic remission. We recently investigated if differences in the response to arginine exist between transient and non-transient cats. Cats with DM had significantly lower insulin levels during the arginine test than healthy cats and the glucagon response was significantly higher. 5 of the 10 cats studied went into diabetic remission within 6 to 14 weeks. Insulin and glucagon response did not differ between cats with transient and non-transient course of disease.

In Zurich treatment is usually initiated with a porcine zinc insulin of intermediate action (Caninsulin®) twice daily: cats weighing < 4 kg receive 1U/cat BID, cats weighing > 4 kg usually receive 1.5-2.0 U/cats BID. Dosage changes are performed with increments of 0.5U/cat BID. Dosage changes are done no more often than every 5 to 7 days. Time until adequate regulation is achieved is somewhere between 1 and 3 months. The majority of cats is well regulated with a dosage of < 1U/kg body weight BID. In a recently performed multicenter study 72% of the cats treated with Caninsulin were considered well regulated. Initial insulin dosage was 0.34 ± 0.14 U/kg BID, after 4 months the dosage was 0.64 ± 0.32 U/kg BID. Diabetic remission was achieved in 17% of cats within the 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).

In cats only few data on the use of Glargine are available so far. According to a recently published study, once-daily Glargine may be as effective as twice-daily Lente-type insulin. Another group of investigators described a remission rate of 100% when Glargine was used BID.

During the last years opinion on diets for diabetic pets has changed. The fact, that cats are true carnivores recently came into focus again. As such they have a high protein requirement and the activity of hepatic enzymes responsible for phosphorylation of glucose for subsequent oxidation or storage is lower than in omnivores. Several studies show that using low-carbohydrate-high-protein diet results in better clinical control and increased rates of diabetic remission. In previous years, when we did not limit the type of food our remission rate was 15-25%. We were able to increase the remission rate to 50-70% by using 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. The latter includes evaluation of the owners' observations, measurement of body weight and determination of blood glucose and serum fructosamine. Cats, which eat and drink normal and do not loose 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 μmol/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. However, a variety of problems are associated with the determination of BGCs in hospitalised patients. The process is time consuming and relatively expensive and therefore, is not performed as frequently as required. Stress or lack of food intake can markedly influence BG concentrations. Cats in particular are sensitive to stress caused by an unfamiliar environment or by veterinary manipulation. Consequently, the BGC may show a continuous increase in the blood glucose concentrations, or it may be elevated from the start. When the latter occurs, it is not possible to differentiate between stress-associated hyperglycemia, insulin under-dosage and the many causes of insulin ineffectiveness and resistance. Hospitalized diabetic cats frequently refuse to eat, which may result in a marked decrease in blood glucose concentration. It is then difficult for the veterinarian to decide whether anorexia or overdose of insulin is the cause of low glucose concentration. Therefore, in-hospital BGCs can be difficult to interpret or may even be useless. During the last years, methods have been developed for obtaining capillary blood (mostly from the inner ear) by means of lancing devices manufactured for humans. Measurement of blood glucose concentration is performed using one of the many portable glucose meters (PGM). Attention should be paid to the fact that performance differs largely between the different PBG, and validation for use in cats is essential. We have positive experience with the PBGM Ascensia Elite (formerly Glucometer Elite, Bayer Diagnostics) or with the latest generation Ascensia Contour (Bayer Diagnostics). The latter currently is the smallest PBGM on the market, requires only small volumes of blood (0.6 μl) and measurement is not started when blood volume is too low, omitting the potential error of previous PBGM generations.

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. We recommend determine fasting blood glucose twice weekly (to practice blood sampling, to detect hypoglycemia) and a BGC for 12 hours at least once a month. BGC and appropriate changes in treatment are then discussed over the phone. Periodic re-assessments of the entire procedure in the hospital are mandatory. For the first months the patient is re-assessed at least once a month, later on frequency is reduced to a minimum of twice a year. Over the years we performed a variety of studies on HM regarding technical problems, comparison between blood glucose measured at home and in hospital and long-term compliance. Problems frequently encountered initially include failure to produce negative pressure with the lancing device, producing a blood drop, absorption of the blood drop, correct use of the test strip and restraining the cat. By means of repeated explanation and demonstration most problems can be solved. About 70% of our cat owners are willing and able to perform HM. Also long term compliance appears to be good. In a recent study 76% of the owners performing HM used the technique for more than one year for up to 4 years. HM did not appear to influence the frequency of re-evaluations in the hospital. Most owners did not change insulin dosages on their own, but called for advice. All cat owners believed that HM had raised their self-confidence with regard to their ability to manage the disease in their pets. 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. It is difficult to proof whether hospital or home curves reflect the true blood glucose concentrations. In our study the percentage of well regulated cats was higher than in comparable studies not using HM. Therefore we assume that curves generated at home reflect the true metabolic situation better than those performed in the hospital. The success of HM greatly depends on careful preparation and instruction of the owners. They must have ready access to veterinary support if needed. Initially, most owners call for advice, and several of them need repeated explanation or demonstration of the procedure. 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.

References

1.  Appleton DJ, Rand JS, Sunvold GD. Insulin sensitivity.decreases with obesity, and lean cats with low insulin sensitivity are at greatest risk of glucose intolerance with weight gain. Journal of Feline Medicine and Surgery 2001; 3: 211-228.

2.  Casella M, Wess G, Reusch CE. Measurement of capillary blood glucose concentrations by pet owners: a new tool in the management of diabetes mellitus. Journal of the American Animal Hospital Association 2002; 38: 239-5.

3.  Casella M, Wess G, Hässig M, Reusch CE. Home monitoring of blood glucose concentration by owners of diabetic dogs. Journal of Small Animal Practice 2003; 44: 298-305.

4.  Goossens MMC, Nelson RW, Feldman EC, Griffey SM. Response to insulin treatment and survival in 104 cats with diabetes mellitus (1985-1995). Journal of Veterinary Internal Medicine 1998; 12: 1-6.

5.  Kley S, Casella M, Reusch CE. Evaluation of long-term home monitoring of blood glucose concentrations in cats with diabetes mellitus: 26 cases (1999-2002). Journal of the American Veterinary Medical Association 2004; 25: 261-266.

6.  Marshall RD, Rand JS. Treatment with glargine results in higher remission rates than lente or protamine zinc insulins in newly diagnosed diabetic cats. Abstract. Journal of Veterinary Internal Medicine 2005; 19: 425.

7.  Rand JS, Martin GJ. Management of feline diabetes mellitus. In: Behrend EN, Kemppainen RJ (eds). The veterinary clinics of North America, Small Animal Practice, Endocrinology. 2001, Volume 31, Number 5. W.B. Saunders, Philadelphia. 881-913.

8.  Rand J. Pathogenesis of diabetes mellitus in the cat. The European Journal of Companion Animal Practice 2004; 14: 131-34.

9.  Thompson MD, Taylor SM, Adams VJ, Waldner CL, Feldman EC. Comparison of glucose concentrations in blood samples obtained with a marginal ear vein nick technique versus from a peripheral vein in healthy cats and cats with diabetes mellitus. Journal of the American Veterinary Medical Association 2002; 221: 389-92.

10. Weaver KE, Rozanski EA, Mahony OM, Chan DL, Freeman LM. Use of glargine and lente insulins in cats with diabetes mellitus. Journal of Veterinary Internal Medicine 2006; 20: 234-238.

11. Wess G, Reusch CE. Capillary blood sampling from the ear of dogs and cats and use of portable meters to measure glucose concentration. Journal of Small Animal Practice 2000; 43: 60-6.

12. Wess G, Reusch CE. Laboratory assessment of five portable blood glucose meters for use in cats. American Journal of Veterinary Research 2000; 61: 1587-92.

Speaker Information
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Claudia E. Reusch, DECVIM-CA
Clinic for Small Animal Internal Medicine
University of Zurich
Zurich, Switzerland


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