Immunosuppression with Azathioprine and Prednisone in Recent-Onset Insulin-Dependent Diabetes Mellitus

Abstract

We randomly assigned 46 patients (mean age, 11.7 years; range, 4.5 to 32.8) with newly diagnosed insulin-dependent diabetes mellitus within two weeks of beginning insulin to receive either corticosteroids for 10 weeks plus daily azathioprine for one year or no immunosuppressive therapy. Half the 20 immunosuppressed patients completing the one-year trial had satisfactory metabolic outcomes (hemoglobin A1c less than 6.8 percent; stimulated peak C peptide greater than 0.5 nmol per liter; insulin dose less than 0.4 U per kilogram of body weight per day) as compared with only 15 percent of the controls. Three of 20 immunosuppressed patients, but no controls, were insulin independent at one year. Two of these continue to receive azathioprine without insulin after more than 27 months of follow-up. The response to immunosuppression correlated with older age, better initial metabolic status, and lymphopenia (less than 1800 lymphocytes per cubic millimeter) resulting from immunosuppression. The side effects of azathioprine included vomiting in one patient and mild hair loss in several others. Prednisone use resulted in a transient cushingoid appearance, weight gain, and hyperglycemia. The growth rate remained normal in all patients. We conclude that early immunosuppression with short-term use of corticosteroids plus daily azathioprine can improve metabolic control in some patients with insulin-dependent diabetes mellitus, but results from this unblinded study are preliminary and require further confirmation and long-term follow-up.

A Single Course of Anti-CD3 Monoclonal Antibody hOKT3γ1(Ala-Ala) Results in Improvement in C-Peptide Responses and Clinical Parameters for at Least 2 Years after Onset of Type 1 Diabetes

“…The risk-to-benefit ratio was felt to be unfavorable when the toxicities and risks of long-term immune suppression including infections or the renal toxicity of cyclosporin were considered (7). Other agents including azathioprine with prednisone or anti-lymphocyte antibody with prednisone raised similar concerns (8,9). To develop a clinically useful treatment, agents that have lasting effects or induce tolerance are needed so that continuous immunosuppressive medication is not required.…”

Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin.

“…A major impetus behind such studies has been to develop approaches that may be utilized to treat human IDDM. Clinical trials in humans have demonstrated that antigen nonspecific immunosuppression with drugs such as cyclosporine A and azathioprine can affect beta-cell destruction after diabetes onset, but such therapy is not curative and is associated with drug-related toxicities (8,9). The ability to identify patient populations at risk for diabetes (10,11) makes the development of disease-specific nontoxic forms of therapy that can be administered to prediabetics to prevent or reduce the incidence of diabetes a major therapeutic goal.…”

Induction of remission in autoimmune polyglandular syndrome type three (APS III): An old drug with new perspectives

“…However, in combination with prednisone, Aza has been associated with increased remission rates in T1DM as indicated by lower insulin requirements and improved C‐peptide levels, yet remission could not be sustained beyond 1 or 2 years and is associated with considerable side effects mainly due to prednisone 19, 20. Only one study showed that triple therapy of Aza in combination with prednisolone plus ultraviolet radiation in vitiligo was more likely to achieve 75% of skin repigmentation 4 months after treatment 21…”