It is well-documented in humans and cats that obesity results in insulin resistance. Type 2 diabetes manifests when either insulin resistance or inadequate insulin secretion no longer allows blood glucose to be regulated effectively, resulting in hyperglycemia. In many instances dieting and exercise, as well as dietary modification, can reverse this. Experimental work has shown that dogs made obese by feeding high-calorie diets also develop insulin resistance, though they do not tend to develop Type 2 diabetes. Many of these studies are short term with obesity induced within weeks to months and it is uncertain if the same changes occur in pet dogs that may have been obese for years. Insulin Resistance Researchers from the School of Veterinary Medicine at the University of Queensland, Australia, investigated insulin resistance and insulin production in six spontaneously obese dogs with a body condition score of 8 out of 9.1.1 The control group consisted of six age- and gender-matched lean dogs with a BCS of 4 or 5. A bolus of intravenous glucose (1g/kg) was given and frequent blood samples were collected over a three-hour period. Resting insulin concentration was almost four times higher in obese than in lean dogs. Most obese dogs had resting blood glucose concentrations similar to the lean dogs, however. Glucose Challenge The glucose challenge resulted in a rise in insulin as was to be expected, though insulin sensitivity in the obese dogs was only half that seen in the lean dogs. Unlike cats, it appears that obese dogs can increase insulin secretion sufficiently in response to decreased insulin sensitivity and thereby compensate for insulin resistance. Whether obesity plays a role in the eventual development of diabetes in dogs has not been investigated adequately.2 It would, however, appear prudent to advocate weight loss in obese dogs given the metabolic derangements seen with this correctable condition. Feline Diabetes and Glargine Insulin A variety of new recombinant insulins have come on the market for humans recently. Some are short- and some are long-acting. Insulin glargine is a long-acting compound that has generated much interest in veterinary medicine. Unlike other insulins, this compound is less soluble at normal body pH, resulting in slow delivery of insulin. In humans this compound is used as a basal insulin given once a day at bedtime. Human diabetics then supplement this with short-acting insulins before eating meals. At the 2005 ACVIM Forum in Baltimore, two abstracts presented data on the use of glargine in spontaneously diabetic cats. Abstracts at the ACVIM Forum in 2004 had involved small numbers of cats that showed considerable improvement in their diabetes and at times resolution of the disease. Glargine vs. Lente The first abstract was presented by researchers from Tufts University.3 In this study, once-daily glargine was compared to twice-daily lente insulin therapy. All cats were also placed on the same low-carbohydrate/high-protein commercial diet designed for managing diabetes mellitus in cats. Cats were either newly diagnosed diabetics or had been poorly responsive to current therapy. Initial dose of insulin was 0.5 U/kg of either insulin. The cats were frequently rechecked over the next 12 weeks and insulin dosages adjusted accordingly. Thirteen cats completed the study, with seven being treated with lente and six with glargine. Four achieved remission and two had a marked reduction in insulin requirement during the study period. This study did not show any difference between the two types of insulin. Naturally, being able to administer a single dose would be preferable to two injections in cats. Researchers from Australia presented data on the use of glargine that suggested it was superior to lente or protamine zinc (PZI) insulin.4 This study encompassed 24 newly diagnosed diabetic cats, eight in each group. Initial dosage of insulin was 0.5 U/kg BID if blood glucose concentration was >360 mg/dL and 0.25 U/kg if blood glucose was <360 mg/dL at initial presentation. All cats were also fed the same commercial low-carbohydrate/high protein diet formulated for the management of diabetes mellitus. Insulin dosage was adjusted based upon followup examinations and blood glucose curves. The mean blood glucose concentration in glargine-treated cats was significantly lower at four weeks (239±61 mg/dL) than in cats given PZI (389±20 mg/dL0) or lente insulin (410±38 mg/dL). Remission Fructosamine levels were also lower in glargine-treated cats in comparison to baseline; this did not occur in PZI or lente-treated cats. All the cats treated with glargine went into diabetic remission (normoglycemia) for at least two weeks after cessation of insulin therapy within four months of initiating therapy. In comparison, three PZI-treated cats and two lente-treated cats went into remission. The remission has been durable with followup anywhere from three to 27 months. Glargine dosage was reduced in seven of eight cats in the first three days to on average of 0.3±0.04U/kg. None of the glargine-treated cats became clinically hypoglycemic, whereas two lente- and one PZI-treated cat showed signs. Both studies show that glargine is a promising therapy in diabetic cats, though there are differences in the outcomes from these two studies. The Australian study appears to suggest that glargine is a superior insulin to either PZI or lente, whereas the Tufts study suggests that used once daily it is merely as good as lente insulin. There are, however, differences in the studies that might explain this disparity. The Australian study used glargine twice daily whereas the Tufts study used it once daily, which might result in tighter glycemic control. The Australian study also included only newly diagnosed cats, while the Tufts study also included cats that were poorly responsive to other therapies. It is not possible to ascertain from the abstract how many poorly responsive cats were in the 13 cats that completed the Tufts study. Therapy Plus Diet It has been previously shown that standard insulin therapy together with a low carbohydrate/high protein diet can result in diabetic remission in newly diagnosed cases of diabetes. This may be because cats tend to have Type 2 diabetes where environmental changes (diet and body weight) can result in normalization of insulin resistance and resolution of clinical diabetes. Glargine continues to be of great interest as a potential first-line insulin for use in diabetic cats. The abstracts presented at the 2005 ACVIM Forum certainly show great promise for this therapy, especially in newly diagnosed diabetic cats. But the number of cats treated in these studies is still quite small; it will take more time before we have a clearer picture of what role this type of insulin will play in the treatment of feline diabetes mellitus. Anthony Carr, DVM, Dipl. ACVIM, is an associate professor at the Western College of Veterinary Medicine in Saskatoon, Saskatchewan, Canada. <HOME> REFERENCES: 1. Verkest KR, Fleeman LM, et al. Insulin sensitivity is halved and fasting insulin concentration increased four times in spontaneously obese dogs. JVIM 19;424-425:2005. 2. Rand JS, Fleeman LM, et al. Canine and feline diabetes mellitus: nature or nurture? J Nutr 134; 2072S-2080S:2004. 3. Weaver KE, Rozanski EA, et al. Comparison of glargine and lente insulins in cats with diabetes mellitus. JVIM 19;425:2005 4. Marshall RD, Rand JS. Treatment with glargine results in higher remission rates than lente or protamine zinc insulins in newly diagnosed diabetic cats. JVIM 19;425:2005 03-19-2007
