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Medications> Glucose-raising>
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Steroid-induced diabetes

Rachel Derr, M.D.
08-30-2010

DEFINITION

  • Glucocorticoids (GC) such as prednisone, dexamethasone and cortisone, are potent anti-inflammatory and immunosuppressive agents, thus effective for treating a wide spectrum of diseases.
  • Hyperglycemia, primarily resulting from impaired glucose transport into muscles, is a common adverse effect (Pagano).
  • GC-induced hyperglycemia: diabetes-range hyperglycemia in subjects who have normal glucose tolerance when not taking GC.

EPIDEMIOLOGY

  • Glucocorticoids are prescribed for roughly 10% of the inpatients at tertiary care hospitals and 3% of the outpatient population >60 years old (Donihi, Choi).
  • Prevalence of glucocorticoid-induced hyperglycemia is approximately 54 - 64% among inpatients at tertiary-care hospitals without a history of diabetes treated with high-dose glucocorticoids (at least 40 mg of prednisone per day for at least 2 days) (Donihi).
  • Five-fold increased risk of hyperglycemia in critically ill patients in ICUs when glucocorticoids are used.
  • Risk of requiring a new diabetes medication was increased 2-fold among outpatients and 4-fold among inpatients with COPD when glucocorticoids were prescribed compared to when they were not (Gurwitz, Niewoehner).
  • Glucocorticoid dose is positively associated with degree of hyperglycemia and need for glucose-lowering medications (Gurwitz).

DIAGNOSIS

  • No formal criteria for diagnosing steroid-induced diabetes, but it may be considered diabetes recognized for the first time in the setting of glucocorticoid (GC) use.
  • Diagnostic criteria for diabetes are unchanged.
  • Hyperglycemia in pre-existing diabetes is usually severely worsened by GC use in any form.

SIGNS AND SYMPTOMS

  • Expected signs and symptoms of hyperglycemia: worsening of polyuria, polydipsia, polyphagia, fatigue.
  • Infections may be more prevalent due to combination of hyperglycemia and immunosuppression.
  • Other signs and symptoms may be related to chronic exogenous steroid exposure such as buffalo hump, thin skin, easy bruisability, proximal muscle weakness, or edema.

CLINICAL TREATMENT

Possible benefits of treatment

  • For hospitalized patients, improve hyperglycemia-related symptoms and decrease hospital length of stay.
  • Reduce infections: Rates of neutropenic infections during bone marrow transplant were higher in patients with higher mean glucose during the pre-neutropenic period, especially in the subset who received glucocorticoids (GC) while neutropenic (Derr).
  • Some evidence suggests improved mortality in cancer patients: In glioblastoma multiforme patients ( many receiving GC to reduce brain edema), mortality was 57% higher in patients with  the highest quartile of mean glucose compared to the lowest (Derr).
Management Strategies

  • If glucocorticoid (GC)-induced hyperglycemia is mild, metformin and thiazolidinediones may be effective by reducing insulin resistance.
  • For moderate or severe hyperglycemia and in the hospital setting, insulin is preferred because it acts immediately, allows for more flexible dosing, and is more effective.
  • Some experts recommend prescribing higher ratio of nutritional insulin to basal insulin since hyperglycemia due to GC is worse postprandially (Clement).

FOLLOW UP

  • Insulin requirements will change dramatically as glucocorticoid (GC) doses are adjusted, or effects wear off following injection. Close follow-up is required.
  • Anticipate the need for lower insulin doses when GC are weaned, to avoid hypoglycemia.
  • When GC are discontinued, glucose-lowering medications are usually no longer needed in patients with baseline normal glucose tolerance.
  • Little data on risk of progression to overt diabetes among patients with previous history of GC-induced diabetes, presumably it is a risk factor for later diabetes.

EXPERT COMMENTS

  • The effect of glucocorticoids (GC), particularly at high doses, on glucose tolerance can be dramatic and may cause symptoms or even hyperosmolar nonketotic states, as well as negatively impact outcomes in hospitalized patients.
  • Warn people with diabetes who are about to receive GC (orally or by joint injection, for example) of the anticipated hyperglycemic effect.
  • For inpatients on GC, monitor glucose at least daily; for outpatients with diabetes, increase monitoring while on GC.  

REFERENCES

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