Steroid-Induced Diabetes In Cats

Timmy is a 9-year-old, DSH, male cat who is very obese. He has a 9/9 body condition score and weighs 9.5 kg (20.9 pounds).

He recently presented for an inflamed, swollen prepuce, along with a moist dermatitis. The rest of his physical was not remarkable, except that he had lost about a pound of weight since his last visit about 6 months ago. The owner reported his overall activity and health had been fine. I clipped and cleaned the area, gave him an injection of dexamethasone (2 mg, IM) and had the owner treat the area topically with Panalog ointment.

Over the last 2 weeks, the owner now reports an increase in thirst and urination, as well as continued weight loss.  I'm rechecking Timmy tomorrow and planning to do a complete serum chemistry panel and urinalysis. I am very concerned that I have created a diabetic, but it seems unlikely to me that that small amount of dexamethasone could have induced diabetes mellitus.

Do you think glucocorticoid-induced diabetes is possible in this cat?

My Response
Several risk factors for feline diabetes have been identified: age, obesity, neutering and gender (1,2). The average age at diagnosis for feline diabetes is 10 years, with a peak incidence between 9 and 13 years. Obesity also increases the risk of developing diabetes 3- to 5-fold. Neutered cats have nearly twice the risk of developing diabetes, and male cats have 1.5 times the risk.  So obviously, this cat has all of the risk factors for developing diabetes: older age, male sex, neutered, and greatly obese!

Glucocorticoids, such as dexamethasone, are one of the most commonly prescribed classes of drugs in veterinary medicine, but they carry the risk of significant side effects. In comparison with other species, cats are considered relatively resistant to many of the deleterious effects of glucocorticoids, and some investigators have reported that cats require higher doses of glucocorticoids than dogs to achieve equivalent effects (3). This glucocorticoid resistance may be related, at least in part, to the lower number of glucocorticoid receptors that have been documented in the skin and liver of cats (4).

Nonetheless, side effects associated with treatment with glucocorticoids can certainly develop in cats, and can include induction of insulin resistance, glucose intolerance, and overt diabetes mellitus (5). In susceptible cats, giving glucocorticoids — even a single dose— can unmask or exacerbate a preexisting diabetic state. In this regard, the glucocorticoid administered appears to be important. In one study, dexamethasone showed a greater diabetogenic effect in cats than did an equipotent dose of prednisolone, a short-acting glucocorticoid (6).

If diabetes mellitus is confirmed in this cat, you might have a chance of "reversing" Timmy's diabetes. To do that, however, you should definitely not administer any additional glucocorticoids. In addition, we should start feeding a low-carbohydrate canned diet (less than 5-10 of daily calories), and began treatment with a long-acting insulin preparation (eg, ProZinc or insulin glargine) given twice daily.

By controlling postprandial hyperglycemia and lowering the cat's circulating blood glucose to close to normal throughout the day, this may help revert the effects of glucose toxicity on the insulin-secreting pancreatic cells and remission of the diabetic state may occur (1,7).

Follow-up Report
Well, Timmy's workup has definitely confirmed that he has nonketotic diabetes mellitus. His serum glucose concentration was 539 mg/dl (normal < 150 mg/dl) with 3+ glucosuria.  Fortunately, he was negative for urine ketone concentrations. Timmy was started on ProZinc insulin (2 units, BID) and his food changed from a dry maintenance diet to canned Purina DM diet. He definitely is starting to feel better, with less polydipsia and polyuria (PU/PD), although he has taken a while to regulate.

In retrospect, I believe he probably was diabetic at the time of the dexamethasone injection— he had lost a pound already, and I think the owner hadn't appreciated the overt signs of PU/PD yet. I believe the dexamethasone injection pushed him "over the edge" to be a clinical diabetic. Is that plausible?

My Response
I agree with your hypothesis. I hope the diabetic regulation goes smoothly now that you have started a low-carbohydrate, high-protein diet. In addition, now that the effects of the glucocorticoids are wearing off, it's possible that this cat could experience remission of his overt diabetic state and be able to go off insulin treatment.

That said, he still needs to loose a great deal of body weight, both for his diabetic state and overall health.

References:

1. Rand JS, Marshall RD. Diabetes mellitus in cats.Vet Clin North Am Small Anim Pract 2005;35:211-24.   
2. Rand JS, Fleeman LM, Farrow HA, et al. Canine and feline diabetes mellitus: nature or nurture? J Nutr 2004;134(8 Suppl):2072S-2080S.  
3. Scott DW, Kirk RW, Bentinck-Smith J. Some effects of short-term methylprednisolone therapy in normal cats. Cornell Vet 1979;69:104–115. 
4. Lowe AD, Graves TK, Campbell KL, et al. A pilot study comparing the diabetogenic effects of dexamethasone and prednisolone in cats. J Am Anim Hosp Assoc 2009;45:215-24. 
5. Middleton DJ, Watson AD. Glucose intolerance in cats given short-term therapies of prednisolone and megestrol acetate. Am J Vet Res 1985;46:2623–2625. 
6. van den Broek AH, Stafford WL. Epidermal and hepatic glucocorticoid receptors in cats and dogs. Res Vet Sci 1992;52:312-315.
7. Reusch CE, Hafner M, Tschuor F, et al. Diabetes remission in cats: a review. Schweiz Arch Tierheilkd 2011;153:495-500.  

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