Interactive diabetes case 9: Management of type 1 diabetes in a patient on glucocorticoid therapy – Comment

COMMENT — While the mechanisms by which glucocorticoids cause or exacerbate hyperglycemia have been well studied, the optimal management of hyperglycemia in patients on these agents has not been well defined. This may be due in part to the heterogeneity of steroid agents used and to the diverse ways in which they are used in practice.

The clinical approach should reflect the following: the pharmacologic properties of the steroid agent used, especially the duration of action; the timing and frequency of doses; and the anticipated duration of therapy. The duration of hyperglycemic effect will differ between a short-acting glucocorticoid such as prednisone and a long-acting one such as dexamethasone. Also, a short-acting glucocorticoid agent given once a day in the morning will have a different effect on the blood glucose level than the same agent given in divided doses, as an example, every six hours. If the anticipated duration of therapy is one to two weeks, it may be sufficient to use frequent injections of a short- or very short-acting insulin and to avoid a change in the basal insulin dose, the effect of which will be difficult or impossible to assess when the insulin requirement is falling as the steroid is tapered. In some instances, especially in a patient already in the hospital, an intravenous insulin infusion may be the most efficient and fastest way to restore normoglycemia. On the other hand, if the anticipated duration of therapy is months or years, then it is advisable to adjust the doses of basal insulin as well as those of the short-acting or very short-acting insulin.

Because glucocorticoids increase insulin resistance and exacerbate postprandial hyperglycemia, it is usually necessary to increase the doses of short- or very short-acting insulin out of proportion to those of basal insulin. The ratio of short- or very short-acting insulin to basal insulin per 24 hours will exceed the usual 50:50 ratio, and one may wind up using twice as much short- or very short-acting insulin as basal insulin per 24 hours, especially in patients with type 2 diabetes. The dose adjustments required are not well defined. This will vary from patient to patient and will depend on the steroid doses. As a rule of thumb, it is reasonable to anticipate that a patient with well-controlled diabetes will experience a 50 to 100 percent increase in insulin requirement when the dose of steroids is above 20 mg a day of prednisone or equivalent. On rare occasion, a patient with type 2 diabetes on such a steroid dose will not require an increase in insulin. Because of the variability of the effect of a glucocorticoid on the insulin dose, it is prudent to begin cautiously, with an increment of 20 percent or so in the insulin dose and to adjust the dose in an iterative manner. On the other hand, the blood glucose level can rise very rapidly in a steroid-treated patient and continue to rise day after day even after adjustments in insulin dose have started. Consequently, it may be necessary to make adjustments each day for several days. Thereafter, further adjustments can be made every few days.

An intermediate-acting basal insulin (in particular, NPH insulin) given in the morning is probably the preferred basal insulin for a patient treated with a short-acting glucocorticoid such as prednisone once daily in the morning. The time course of action of NPH insulin roughly approximates the time course of the hyperglycemic effect of a short-acting glucocorticoid such as prednisone.

An intravenous insulin infusion in the hospital can be invaluable in an acutely ill patient on steroids and in any steroid-treated patient in whom the glucose values are persistently uncontrolled (eg, >180 mg/dL [10 mmol/L]) and not responsive to initial increments in the insulin dose. This is most likely to be necessary in a patient on divided doses of a glucocorticoid (eg, every 6 or 12 hours) or on a continuous glucocorticoid infusion. The use of intravenous insulin facilitates control of hyperglycemia and has additional advantages. It facilitates an estimate of the patient's 24-hour insulin requirement. As an example, if the patient requires 4 units of insulin per hour, it is reasonable to estimate that at this time the 24-hour requirement is approximately 96 units. This serves as a basis for selecting insulin doses when the patient is converted from intravenous to subcutaneous insulin. Of course, the insulin requirement may change from day to day depending on the patient's underlying condition, response (or lack of response) to treatment of the underlying condition, and changes in the steroid dose. Also, the use of intravenous insulin may shorten the length of stay in the hospital and reduce costs.

In the present case, the patient received prednisone once a day in the morning, a common practice. As noted, when a short-acting glucocorticoid such as prednisone is given in this manner, the hyperglycemic effect is most pronounced during the first 8 to 12 hours after the dose, especially after meals. Typically, the effect is minimal or absent the following morning. At the start of prednisone given in this way, it is usually appropriate to increase the doses of a short- or very short-acting insulin before breakfast and lunch. By preventing the acute rise of the blood glucose level after breakfast and before and after lunch, this approach may improve the glucose values at bedtime and the following morning. It averts the risk of hypoglycemia at night or early in the morning that may occur when the insulin doses are also increased before supper and at bedtime in patients treated with a short-acting steroid in the morning. An increase in the morning dose of NPH insulin may also be helpful.

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