Feline Diabetes Mellitus
Claudia Reusch, DVM, Dipl. ECVIM-CA
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty University of Zurich, Switzerland
Diabetes mellitus is a common endocrinopathy in cats. The incidence of the disease is increasing, most likely due to an increase in the occurrence of risk factors, such as obesity, physical inactivity and old age. Exact numbers are difficult to collect and the dark figure is certainly high, but a recent study in an insured cat population in the UK revealed a prevalence of 0.43% (1).
Types of diabetes
Traditionally, the classification of diabetes mellitus in cats has more or less followed the schema used in human medicine. Although not all aetiopathogenic mechanisms may be identical, this approach is helpful to provide a guide for identification and differentiation of the various forms of the disease. Human diabetes is categorized as type 1, type 2, other specific types and gestational diabetes. In cats type 1 seems to be extremely rare. It is currently assumed that the vast majority (i.e. 80%) of feline diabetes is type 2 - a heterogeneous disease due to a combination of impaired insulin action (insulin resistance) and β-cell failure. For both defects to develop, environmental and genetic factors play a role. The latter have not yet been characterized in the cat, but the most convincing evidence on the existence of genetic factors has derived from studies in the Burmese cat in which the frequency of diabetes was shown to be several times higher than in domestic cats (1,2). Other risk factors are increasing age, male gender, being neutered, physical inactivity, glucocorticoid and progestin administration, and obesity. As in humans, the most important risk factor is obesity and it has been shown that obese cats are 3.9 times more likely to develop diabetes than optimal weight cats. It is important to note that although obesity induces insulin resistance not all obese cats develop diabetes. When β-cells are healthy, the adaptive response to obesity and insulin resistance is an increase in insulin secretion, so that normal glucose tolerance is maintained. However, when β-cell dysfunction is present, there is impaired glucose tolerance and finally type 2 diabetes results. It is so far not known which factors are responsible for the reduction in insulin secretion and the progression to diabetes; suggested candidates include amyloid deposition, glucotoxicity, and lipotoxicity.
• Islet amyloid is derived from amylin (or islet amyloid polypeptide), a hormone which is cosecreted with insulin from β-cells. Cats are one of the few species in which amylin tends to fold into β-pleated sheets, which is then deposited as amyloid in the islets and leads to β-cell loss (Figure 1).
• Glucose toxicity is the concept of reduction in insulin secretion by hyperglycaemia; this has been demonstrated in healthy cats where insulin secretion ceases after 3-5 days of maintaining high blood glucose levels (3). Initially, the suppression of insulin secretion is reversible, but with time‚ β-cell damage becomes permanent.
• Lipotoxicity is an analogous event involving high levels of fatty acids; however β-cell damage has not been demonstrated as convincingly as with the hyperglycaemia situation. These concepts are important to comprehend, as immediate treatment of diabetes may reverse the negative effects of glucose toxicity and increase the chance of remission. Other specific types of diabetes (formerly called secondary diabetes) in the cat account for approximately 20% of cases and include pancreatitis, pancreatic neoplasia, hypercortisolism (HC), hypersomatotropism (acromegaly) and the application of diabetogenic drugs (progestins, glucocorticoids). Gestational diabetes is of little relevance in cats.
Signalment and Clinical Manifestations
Diabetes typically occurs in middle-aged to old cats. There is a strong sex predilection since approximately 70% of diabetic cats are male. Approximately 60% of diabetic cats are overweight, 35% are normal weight and 5% underweight (Figure 2) (4). Most diabetic cats show the classical signs of diabetes, namely PU/PD, polyphagia and weight loss. About 10% of diabetic cats have overt signs of diabetic neuropathy, manifested as hindlimb weakness, decreased ability to jump and plantigrade posture (Figure 3). On rare occasions weakness of the front legs may also be seen. Lethargy and a dry, unkempt haircoat are often present, whilst physical examination may reveal hepatomegaly. In cats with concurrent or underlying disease additional clinical signs may be present. Cats with complicated diabetes (diabetic ketoacidosis, hyperosmolar non-ketotic syndrome) present with lethargy, anorexia, reduced water intake and vomiting.
Diagnosis and Work-Up
Diabetes is diagnosed on the basis of clinical symptoms, persistent hyperglycaemia and glucosuria. Most cats do not present until blood glucose concentrations exceed the renal capacity for glucose reabsorption (~ 15mmol/L - 270 mg/dL) as it is usually only at this stage of the disease that symptoms become apparent. Glucosuria alone is insufficient to diagnose diabetes, since it may also be seen with renal defects, certain drugs and stress. Stress-induced hyperglycaemia may be difficult to differentiate from diabetic hyperglycaemia. Increase in blood glucose from stress is often only mild to moderate, although glucose concentrations >15 mmol/L - 270 mg/dL can occur. In the latter situation glucosuria may also be present. Stress hyperglycaemia may be diagnosed by repeated blood glucose measurements and the demonstration of normalized glucose levels. Some cats, however, are stressed as long as they are hospitalized and glucose levels stay high. Measurement of serum fructosamine is an alternative means of diagnosis. Fructosamine concentration reflects the mean blood glucose concentration of the preceding 1-2 weeks. Reference ranges differ slightly between laboratories but are usually around 200-360 μmol/L. In the vast majority of newly diagnosed diabetic cats fructosamine levels are >400 μmol/L and may be as high as 1500 μmol/L. Since fructosamine is not affected by short term increases in blood glucose, concentrations are usually normal in cats with stress hyperglycaemia (5). However fructosamine may be normal in cats with very recent onset of diabetes and in cats suffering from concurrent hyperthyroidism or hypoproteinaemia. Any concurrent disease may worsen insulin resistance and will hinder treatment success. Therefore CBC, serum biochemical panel, urinalysis and urine culture should routinely be performed. Potential haematological and biochemical abnormalities include slight anaemia and a stress leukogram, hypercholesterolaemia, and increased ALP/ALT. In the majority of cats urine specific gravity is >1.020, and sporadic ketone bodies may be found, even in uncomplicated cases. Proteinuria is present in approximately 50% of cases and is usually mild to moderate, with urine protein: creatinine ratios <2.0. In some cases bacterial urinary tract infection is present and urine culture should always be performed. Further diagnostic procedures may be indicated (i.e. radiographs, echocardiography or abdominal ultrasonography) depending on results.
Pancreatitis is frequently associated with diabetes, but the cause and effect are as yet unknown. The diagnosis is challenging, since clinical signs are often vague and non-specific and serum amylase and lipase levels are of little diagnostic value (6). Measurement of plasma insulin concentration is not helpful to identify the type of diabetes, nor to predict if sufficient residual β-cell function is present for the possibility of remission. In cases with suspected HAC or hypersomatotropism specific diagnostic procedures should be delayed until some stabilization has been achieved with insulin therapy.
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1. McCann TM, Simpson KE, Shaw DJ, et al. Feline diabetes mellitus in the UK: the prevalence within an insured cat population and a questionnairebased putative risk factor analysis. J Feline Med Surg 2007; 9: 289-99.
2. Lederer R, Rand JS, Jonsson NN, et al. Frequency of feline diabetes mellitus and breed predisposition in domestic cats in Australia. Vet J 2009; 179: 254-8.
3. Zini E, Osto M, Franchini M, et al. Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat. Diabetologia 2009; 52: 336-46.
4. Reusch C. Feline Diabetes Mellitus. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 7th ed, Vol. 2. St. Louis, Missouri: Saunders Elsevier 2010; 1796-1816.
5. Reusch CE, Liehs MR, Hoyer M, et al. Fructosamine. A new parameter for diagnosis and metabolic control in diabetic dogs and cats. J Vet Intern Med 1993; 7: 177-82.
6. Forman MA, Marks SL, De Cock HE, et al. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis. J Vet Intern Med 2004; 18: 807-15.
7. 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 and lente insulins. J Feline Med Surg 2009; 11: 683-91.
8. Nelson RW, Henley K, Cole C. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. J Vet
Intern Med 2009; 23: 787-93.
9. Frank G, Anderson W, Pazak H, et al. Use of a high-protein diet in the management of feline diabetes mellitus. Vet Ther 2001; 2: 238-46.
10. Bennett N, Greco DS, Peterson ME, et al. Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the management of feline diabetes mellitus. J Feline Med Surg 2006; 8: 73-84.
11. Rucinsky R, Cook A, Haley S, et al. AAHA diabetes management guidelines for dogs and cats. JAAHA 2010; 46: 215-224.
12. Slingerland 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: 247-53.
13. Alt M. The effect of feeding time on the quality of metabolic control, dayto-day variability of blood glucose curves and evaluation of IGF-1 levels in cats with diabetes mellitus. Inaugural-Dissertation. Zürich: Klinik für Kleintiermedizin, Vetsuisse-Fakultät Universität Zürich, 2006; 3-43.
14. 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). J Am Vet Med Assoc 2004; 225: 261-6.
15. Reusch CE, Kley S, Casella M. Home monitoring of the diabetic cat. J Feline Med Surg 2006; 8: 119-27.
16. Zini E, Moretti S, Tschuor F, et al. Evaluation of a new portable glucose meter designed for the use in cats. SAT 2009; 151: 448-451.