Diabetes mellitus is one of the most common feline endocrine diseases. The latest clinical and histological evidence now suggest that type 2 diabetes mellitus (DM) is the most frequently occurring form of DM in cats. Type 2 DM in cats is characterized by an impaired ability to secrete insulin following a glucose stimulus and is caused by both a defect in pancreatic beta cells and by peripheral insulin resistance.¹ The etiology of type 2 DM is multifactorial with obesity, genetics, diet, and amyloidosis of the islets involved in the development.¹ Epidemiologic studies have shown that physical inactivity and indoor confinement rather than the proportion of dry cat food are risk factors for diabetes in the cat;² however, the study did not take into account the fact that cats eat small prey when not confined indoors. The classic metabolic abnormalities found in type 2 DM, decreased insulin secretion and peripheral insulin resistance, may be consequences of abnormal amyloid production by pancreatic cells.³

Middle-aged to older male cats with a history of obesity (body condition score [BCS] greater than 6/9) are most at risk for the development of DM. Clinical signs of type 2 diabetes mellitus are subtle and progressive over a period of months to years until finally blood glucose rises above the renal threshold which is quite high in the cat and polyuria/polydipsia ensues. Obesity (BCS over 6/9) combined with fasting or postprandial hyperglycemia may be the only clinical "sign" of early type 2 DM.⁴ Recently, increased BCS has been associated with increased circulating concentrations of islet amyloid polypeptide (IAPP) and insulin in obese nondiabetic cats.⁵ Cats affected with diabetic neuropathy will have trouble jumping onto high surfaces such as counters and beds as the affected limbs are usually the hind limbs.⁴ The most common physical examination findings in cats are lethargy and depression, dehydration, unkempt haircoat, hepatomegaly, and muscle wasting. Diabetic cats can have a variety of clinical signs suggestive of diabetic neuropathy including pain on palpation of distal extremities, hypersensitivity, gait abnormalities, and plantigrade stance.⁴

A diagnosis of diabetes mellitus should be based on the presence of clinical signs compatible with diabetes mellitus and evidence of fasting hyperglycemia with or without glycosuria. Many cats are susceptible to "stress-induced" hyperglycemia. Serum fructosamine is formed by glycosylation of serum protein such as albumin and the concentration of fructosamine in serum is directly related to blood glucose concentration. Serum fructosamine measurement may be beneficial in differentiating early or subclinical diabetes mellitus in the cat from stress-induced hyperglycemia. In cats, normal fructosamine concentrations may vary by laboratory but one study suggested a range of 283 ± 32 μmol/L.⁶ Common clinicopathologic features of diabetes mellitus in cats include fasting hyperglycemia, hypercholesterolemia, increased liver enzymes (ALP, ALT), neutrophilic leukocytosis, proteinuria, increased urine specific gravity, azotemia and glycosuria.

The cat is an obligate carnivore and is unique in its insulin response to dietary carbohydrates. The feline liver exhibits normal hexokinase activity but glucokinase activity is virtually absent. Glucokinase converts glucose to glycogen for storage in the liver and is important in "mopping" up excess postprandial glucose. Amino acids, rather than glucose, are the signal for insulin release in cats.⁷ Furthermore, cats have recently been shown to lack the sweet taste receptor which is involved in incretin release and secondary beta cell function. Another unusual aspect of feline metabolism is the increase in hepatic gluconeogenesis seen after a normal meal. Normal cats maintain essential glucose requirements from gluconeogenic precursors (i.e., amino acids) rather than from dietary carbohydrates. As a result, cats can maintain normal blood glucose concentrations even when deprived of food for over 72 h. In summary, the cat is uniquely adapted to a carnivorous diet.⁷

When type 2 diabetes occurs in cats, the metabolic adaptations to a carnivorous diet become even more deleterious, leading to severe protein catabolism; feeding a diet rich in carbohydrates may exacerbate hyperglycemia and protein wasting in these diabetic cats. A low-carbohydrate, high-protein diet, which is similar in fact to a cat's natural diet, may ameliorate some of the abnormalities associated with diabetes mellitus in the cat. Initial studies using a canned high-protein/low-carbohydrate diet and the starch blocker acarbose have shown that 58% of cats discontinue insulin injections and those with continued insulin requirements could be regulated on a much lower dosage (1–2U BID).⁸ In the only double-blinded controlled study of diet in feline DM, comparison of canned high-fiber vs. canned low-carbohydrate diets showed that cats fed low-carbohydrate diets were 3–4 times more likely to discontinue insulin injections.⁹ The most recent studies show that approximately 70–90% of newly diagnosed diabetic cats can discontinue insulin injections when fed a restricted carbohydrate diet. Cats should be fed no more than 60 kcal/kg (about 210 kcal for an average cat) of ideal body weight in two equal meals per day. Caution should be used when initially changing from dry to canned foods as insulin requirements may decrease dramatically; a reduction in insulin dosage may be required. Most canned cat food products will contain < 10% carbohydrates on a dry matter basis; whereas dry food will usually contain > 15% carbohydrate on a dry matter basis.

Studies have shown that compared with PZI and lente insulins, glargine insulin is associated with the highest remission rates.¹⁰ Another option would be to use PZI insulin, which is associated with a little lower remission rate (70%), but is easier to administer and less costly. In either case, the author uses an initial dosage of 2 U per cat BID as this dose has not been associated with hypoglycemia in the author's experience. For owners who prefer to give oral medication, glipizide has been used to successfully treat diabetes mellitus at a dosage of 2.5 mg BID when combined with a high-protein, low-carbohydrate diet.

Monitoring newly diagnosed and treated feline diabetics can be challenging. The author prefers to use a slow method of remission induction using urine glucose monitoring at home coupled with periodic (q 3 weeks) serum chemistry, urinalysis, and fructosamine monitoring. The owner agrees not to increase insulin dosage based on urine glucose, but only to decrease the dosage if the urine glucose becomes negative. Continuous glucose monitors have recently been adapted for use in cats and may be more effective in determining if the cat is going into remission, if hypoglycemia is occurring, or whether adequate glucose regulation is being achieved.

References

1.  Rand JS, Fleeman LM, Farrow HA, Appleton DJ, Lederer R. Canine and feline diabetes mellitus: nature or nurture? J Nutr. 2004;134:2072S–2080S.

2.  Slingarland LI, Fazilova VV, Plantinga EA, et al. Indoor confinement and physical inactivity rather than the proportion of dry food are risk factors in the development of feline type 2 diabetes mellitus. Vet J. 2009;179(2):247–253.

3.  O'Brien TD, Butler PC, Westermark P, Johnson KH. Islet amyloid polypeptide: a review of its biology and potential roles in the pathogenesis of diabetes mellitus. Vet Pathol. 1993;30:317–332.

4.  Greco DS. Diagnosis of diabetes mellitus in cats and dogs. Vet Clin North Am Small Anim Pract. 2001;31:845–853.

5.  Henson MS, Hegstad-Daies RL, Wang Q, et al. Evaluation of plasma islet amyloid polypeptide and serum glucose and insulin concentrations in nondiabetic cats classified by body condition score and in cats with naturally occurring diabetes mellitus. Am J Vet Res. 2011;72(8):1052–1058.

6.  Lutz TA, Rand JS, Ryan E. Fructosamine concentrations in hyperglycemic cats. Can Vet J. 1995;36:155–159.

7.  Kettlehut IC, Foss MC, Migliorini RH. Glucose homeostasis in a carnivorous animal (cat) and in rats fed a high-protein diet. Am J Physiol. 1978;239:R115–R121.

8.  Mazzaferro EM, Greco DS, Turner AS, Fettman MJ. Treatment of feline diabetes mellitus using an alpha-glucosidase inhibitor and a low-carbohydrate diet. J Feline Med Surg. 2003;5:183–189.

9.  Bennett N, Greco DS, Peterson ME. Comparison of a high fiber vs. low carbohydrate diet for the treatment of diabetes mellitus in cats. (abstract). J Vet Intern Med. 200;15(3):381.

10. Marshall RD, Rand JS, Morton JM. Treatment of newly diagnosed diabetic cats with glargine insulin improves glycaemic control and results in higher probability of remission than protamine zinc or lente insulins. J Feline Med Surg. 2009;11(8):683–691.