Transient Diabetes Mellitus

8. Transient Diabetes

Transient DM occurs relatively frequently in diabetic cats. Historically, approximately 20% of diabetic cats were reported to fall into this category (Nelson et al., 1999; Nelson, 2005). However, the proportion of transiently diabetic cats seems to have increased recently (see below). Transiently diabetic cats go into spontaneous remission, that is, clinical symptoms such as polyuria and polydipsia resolve, blood glucose levels normalize and glucosuria disappears. This usually happens within one to four months after the initation of therapy (Nelson et al., 1999). At that time, specific antidiabetic glucose-lowering therapy can be discontinued. Once DM resolves, the glucose induced insulin secretion is normalized. Nevertheless, beta-cell density is still decreased and islet pathology is present. Therefore, most of these cases correspond to a subclinical phase of DM (Nelson et al., 1999).

Conditions for Diabetic Remission

The conditions that need to be fulfilled for diabetic remission to occur are not yet completely clear. Obviously, an adequate number of functional beta-cells still needs to be present (Nelson et al., 1999). One important factor seems to be the early resolution of hyperglycemia and hence the disappearance, or at least reduction, of glucotoxicity. Intensive glucose-lowering therapy, perhaps supported by an appropriate diet (see below), can terminate the vicious circle of chronic hyperglycemia leading to an impairment of pancreatic beta-cell function and decreased insulin sensitivity. Because glucotoxicity is initially reversible, it seems plausible that the earlier glucose-lowering therapy is initiated in diabetic cats, the higher the likelihood for diabetic cats to go into remission. However, hard scientific data to support this idea are lacking.

Differences Between Transient and Non-transient Diabetic Cats?

The prediction of a transient disease course in diabetic cats, e.g., via intravenous glucose tolerance or glucagon stimulation tests, has proven difficult. We have recently evaluated the possibility to prospectively predict the likelihood of diabetic cats going into remission based on their insulin response in an arginine stimulation test (AST; Tschuor et al., 2006). This test had successfully been used in human type 2 diabetics. As expected, the baseline glucose concentration was significantly higher, and the insulin response was significantly lower in the diabetic compared to healthy cats. Baseline glucagon and the glucagon response to arginine was significantly higher in diabetic cats. Despite clear differences between diabetic and healthy cats, no significant difference for any of the parameters (glucose, insulin, glucagon) were detected between transient and non-transient diabetic cats. Therefore, the AST seems unable to prospectively differentiate between a transient and a non-transient course of DM in cats (Tschuor et al., 2006) (see below and Figure 25). Another recent study investigated whether IGF-1 levels may help to predict transient DM in cats. This idea, however, had to be rejected (Alt et al., 2007).

Monitoring for the reversal of subclinical to clinical DM can easily be performed by monitoring glucosuria with a dipstick. Simply place the urine dipstick in a freshly spoiled litter mixed with a small volume of water. (© Yves Lanceau/Royal Canin - Sacré de Birmanie).

In diabetic cats that go into remission, recurrence of clinically overt DM is always possible. Islet pathology is usually present in transiently diabetic cats. Therefore, the susceptibility to revert to overt DM is probably higher than in previously healthy cats. This may be caused by additional stressors such as insulin-antagonistic drugs (e.g. glucocorticoids, megestrol acetate) or obesity. It is usually impossible to predict if or when clinical signs will recur, underlying the necessity to monitor cats in diabetic remission carefully for recurrence. In some cases, cats have been reported to revert from subclinical to clinical DM more than 3 years after the first resolution of symptoms (Nelson et al., 1999).

Evolution of the Remission Rate of Diabetic Cats

The proportion of transiently diabetic cats seemed to have increased over the last years, reaching 70% in some studies. This may be related to the recent recommendation to feed diabetic cats a diet relatively high in protein and low in carbohydrate, respectively. Whether the improvement of the metabolic situation depends on the high protein content (49 - 57% DMB in studies by Frank et al., 2001; Mazzaferro et al., 2003), the low carbohydrate (18% in the study by Bennett et al., 2006), or both, may require further investigation (see also below). We have also confirmed that the remission rate of diabetic cats is higher than previously reported when the cats were fed a highprotein diet (approx. 54% protein, 8% carbohydrate DMB; Tschuor et al., 2006). In our study, approximately 50% of insulin-treated cats went into remission within 4 weeks of intensive therapy. Interestingly, remission occurred before considerable weight loss was observed.