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Cyclosporine's effect on insulin secretion in patients with kidney transplants
E Esmatjes1, M J Ricart, J P Ferrer
1Endocrinology and Diabetes Unit, Hospital Clinic, University of Barcelona, Spain.
Abstract:
Adverse effects of cyclosporine on glucose metabolism have been reported in patients with kidney transplantation, but steroids were present in all the immunosuppressive schedules evaluated. We have studied endocrine pancreatic function (OGTT measuring plasma insulin [IRI] and c-peptide [CP]) in 3 groups of patients, matched for age and body-mass index, 16-66 months after functioning Ktx. Seven patients were treated with CsA monotherapy (group I), 7 patients with CsA plus prednisone (group II), and 6 patients with azathioprine plus prednisone (group III). Seven healthy subjects formed the control group. OGTT was normal in all patients, except one in group II (impaired glucose tolerance). There were no significant differences between the 4 groups concerning fasting blood glucose and area under the glucose curve, as well as basal insulin levels, peak insulin response to glucose, and area under the insulin curve. Basal CP, peak CP response to glucose, and area under CP curve were lower in CG than in the 3 groups of patients. Basal CP in group II (4.4 +/- 2.2 ng/ml) was higher than in group I (2.8 +/- 0.6 ng/ml, P less than 0.05). Glucose/IRI molar ratio in group II (5.7 +/- 1.4, P greater than 0.05) was lower than in group I (7.3 +/- 1.8) and CG (8.0 +/- 2.1, P less than 0.025). Our results suggest that CsA at normal dosage has no clinically important effect on beta-cell function. The indirect evidence of insulin resistance observed in patients treated with CsA plus prednisone is ascribable to corticosteroid treatment.
Insights
Cyclosporine (CsA) monotherapy does not significantly impair beta-cell function after kidney transplantation. However, combined CsA and prednisone treatment may indicate insulin resistance, likely due to corticosteroids.
Area of Science:
- Nephrology
- Endocrinology
- Immunology
Background:
- Adverse effects of cyclosporine (CsA) on glucose metabolism are known in kidney transplant recipients.
- Previous studies often included steroids, confounding CsA's specific impact.
- Endocrine pancreatic function requires further investigation in CsA-treated patients.
Purpose of the Study:
- To evaluate the effect of CsA monotherapy versus combination therapy on endocrine pancreatic function.
- To compare beta-cell function in kidney transplant patients with healthy controls.
Main Methods:
- Oral glucose tolerance tests (OGTT) measuring plasma insulin and C-peptide (CP) were performed.
- Three patient groups (CsA monotherapy, CsA + prednisone, azathioprine + prednisone) and a control group were studied.
- Patients were matched for age and body-mass index, 16-66 months post-kidney transplant.
Main Results:
- OGTT was normal in most patients; one patient had impaired glucose tolerance.
- No significant differences in fasting glucose or insulin response were found between groups.
- Basal C-peptide levels were lower in controls than in all patient groups.
- Group II (CsA + prednisone) showed higher basal CP and a lower glucose/IRI ratio compared to controls.
Conclusions:
- CsA at standard doses appears to have no clinically significant adverse effect on beta-cell function.
- Insulin resistance suggested in CsA + prednisone group is likely attributable to corticosteroid effects.
- Further research into steroid-induced insulin resistance in transplant patients is warranted.