Cyclosporine‐associated diabetes mellitus in renal transplants

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Abstract
Between August 1973 and August 1988, 463 non‐diabetic patients received renal transplants at our Hospital. Of them, 187 (40.4%) were immunosuppressed with cyclosporine plus steroids or plus steroids and azathioprine (Group 1), and 276 (59.6%) were treated with prednisolone plus azathioprine (Group 2). In Group 1, 21 (11.2%) developed diabetes mellitus (two different determinations of serum glucose > 11.1 mmol/1) as compared to 9 (3.3%) in Group 2 (p=0.0031). For Groups 1 and 2, respectively, the following data were obtained: diabetes started 4.4 ± 1.6 (SEM) and 23.3 ± 9.6 months post‐transplant (p = 0.0075), number of rejections was 0.14 ± 0.08 and 1.33 ± 0.53 (p = 0.0028), total dose of methylprednisolone was 1.7 ± 0.13 and 3.3 ± 0.8 g (p = 0.0015), total dose of prednisolone until diagnosis of diabetes was 2546 ± 648 and 9420 ± 2514 (p = 0.0054), and dose of prednisolone at the time of diagnosis was 0.51 ± 0.1 and 0.52 ± 0.2 mg per kilo (NS). There was no significant difference in age, time on dialysis prior to transplant, duration of diabetes, number of patients cured, mortality, renal function at diagnosis, or length of follow‐up between the two groups. There was a significant but unexplained predominance of males in Group 1 (19 vs. 3; p = 0.0031). Our data practically exclude steroid‐induced diabetes mellitus as a likely explanation for this complication of our patients. We conclude that immunosuppression with cyclosporine in renal transplant patients may induce or be associated with the development of diabetes mellitus; possible mechanisms could be peripheral insulin resistance, impaired insulin secretion due to beta‐cell degeneration and/or a summation of the effects of cyclosporine and steroids.