Diabetes mellitus (DM) is a common feline endocrinopathy, which is probably increasing in prevalence. Most cases of feline DM resemble type II DM in humans, which results from a combination of insulin resistance in peripheral body tissues and abnormal insulin secretion secondary to pancreatic beta-cell dysfunction
In 2014, a Systematic Review was published with the intention of answering two big questions:
- Which factors influence the rate of diabetic remission in the cat? Specifically, what aspects of a cat’s treatment might affect the remission rate achieved?
- Which factors predict the occurrence of diabetic remission in the cat? What diagnostic test results or characteristics might predict remission in a diabetic cat?
Cochrane Collaboration (CC) guidelines were followed to answer these questions. Systematic and bibliographic online research was conducted in which twenty-two studies were selected and considered to enable us to assess the influence of the pharmaceutical approach and diet, as well as diagnostic tests and feline patient characteristics, as predictors of remission.
Most diabetic cats require daily insulin injections and frequent veterinary attention that can place an emotional and financial burden on pet owners leading to an estimated 30% of affected cats being euthanased within their first year of treatment. However, it is also recognised that a significant number of cats with type II DM can enter a state of remission and no longer require such intense veterinary attention. One main mechanism by which diabetic remission is thought to occur is through reversal of glucotoxicity. Glucotoxicity refers to the decrease in beta-cell function and mass caused by persistent hyperglycaemia and has been proposed to be the major cause of progressive beta-cell deterioration in human type II DM. Intensive glycaemic control early after diagnosis has been shown to improve long-term remission rates in people with type II DM. It is thought that effective control of hyperglycaemia in these patients decreases the deleterious effects of glucotoxicity on pancreatic beta-cells and increases the chance of remission.
Achieving diabetic remission is the ideal goal when managing feline diabetics, to limit the financial and emotional burden placed on cat owners and to reduce the euthanasia rate. Knowledge of factors that predict and determine the rate of diabetic remission would be highly beneficial to veterinarians advising clients on how likely it is that their cat will enter remission and deciding on the most effective management strategy to increase the cat’s likelihood of remission.
Included studies showed large variation in the duration of DM, levels of glycaemic control, and the presence of underlying disease in recruited cats. The effect of such concurrent diseases warrants mention since it is estimated that approximately 20% of diabetic cats have a secondary disease. Response to treatment could differ significantly between cats with (and without) underlying diseases.
Hypersomatotropism are well-recognised concurrent diseases among feline diabetics, which could affect remission rates. Excluding hypersomatotropism, at least with a reasonable degree of certainty through serum IGF-1 measurement, seems therefore to be appropriate given that cats with hypersomatotropism are highly unlikely to achieve remission with routine diabetic management alone.
Feline DM can also have iatrogenic, or secondary causes to hypercostisolism. Often in cats DM is associated with pancreatitis and may be associated with transient diabetic forms, which cease once pancreatitis has resolved, or with difficulty in diabetic control in case of chronic pancreatitis.
Diabetic remission was shown to be possible with oral glipizide treatment, however, the high rate of poor glycaemic control in these studies supports the finding that glipizide therapy provides lower glycaemic control and chances of remission than insulin treatment.
Successful diabetic remission was reported to occur in a proportion of cats with each insulin type discussed in this review. In recent years, insulin glargine has received a large amount of interest and has been proposed as the optimum insulin for diabetic cats. Glargine has a longer average duration of action than porcine lente insulin in healthy cats. This could lead to a greater chance of remission with glargine therapy, compared to porcine lente therapy, by prolonging glycaemic control and reducing glucotoxicity.
Another important factor is home glucose monitoring that would seem to help achieve tighter glycemic control and thereby improves remission rates by reducing the effect of glucotoxicity on pancreatic beta-cells.
Dietary carbohydrate reduction and increased dietary fibre have both been proposed as aids to feline diabetic control. Low carbohydrate diets can improve diabetic control in people through reducing post-prandial hyperglycaemia and a similar benefit has been proposed in feline diabetics. In human medicine, increased dietary fibre is shown to improve glycaemic control by several mechanisms, including delayed gastric emptying, alteration in the secretion of gastrointestinal tract hormones and decreased intestinal carbohydrate absorption, although mechanisms by which increased fibre might improve diabetic control in cats have not been established. Diets with ultra-low carbohydrate content of up to 6% metabolisable energy (ME) have been suggested as the optimum diet for diabetic cats. Such a low carbohydrate content is usually obtained only with wet foods.
Many studies have unfortunately been influenced by the small sample size and lack of randomization. In addition, there were no unique criteria for the diagnosis of diabetes, or diabetic remission, and poor control of confounding factors were frequent causes of poor study design. Some studies may have underestimated remission rates, which could eventually be achieved with the treatment protocols tested, due to too short follow-ups.
Many studies also failed to define diabetic remission. Of the seven studies that provided an adequate definition of remission in this review, five defined remission as normoglycaemia without antihyperglycaemic treatment for a minimum of 4 weeks to 1 month. We therefore propose adopting this as the standard definition of feline diabetic remission in future research, improving the consistency and comparability of results. Using a low-carbohydrate or other diabetes-specific diets would, for the purpose of this definition, not be considered ‘antihyperglycaemic treatment’.
Addressing these factors would significantly strengthen future research and ultimately enable a meta-analysis to be presented and more meaningful results to be achieved. It was not possible to find factors that allow us to predict remission in relation to the variety of different insulin types and protocols. Reducing carbohydrates in the diet might be helpful, but requires further study. The factors associated with remission in the cat resemble those highlighted in human medicine and support the hypothesis that glucotoxicity reversal is an important mechanism behind the remission of feline diabetes.