Cyclosporin A Does Not Delay Insulin Dependency in Asymptomatic IDDM Patients

Abstract

OBJECTIVE: To measure the effects of cyclosporin A (CyA) with no insulin therapy on glucose tolerance and β-cell function in the preclinical phase of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: β-cell responses to the intravenous glucose tolerance test (IVGTT), hyperglycemic clamp, intravenous arginine, and intravenous glucagon were evaluated before and after a 6-month course of CyA in seven patients (mean age 19.6 years) with asymptomatic IDDM. RESULTS: Initial insulin secretory responses were severely decreased when the patients were compared with eight healthy control subjects: IVGTT (1 + 3 min): 106 ± 16 vs. 884 ± 190 pmol/l (P < 0.001); hyperglycemic clamp: 102 ± 16 vs. 310 ± 42 pmol/l (P < 0.001); intravenous arginine: 346 ± 72 vs. 1104 ± 168 pmol/l (P < 0.01); and intravenous glucagon: 170 ± 37 vs. 247 ± 35 pmol/l (NS). The β-cell responses remained markedly abnormal after 6 months of CyA, although the response to intravenous glucose and oral glucose tolerance tests improved in three subjects. All the patients became insulin-dependent after 5–36 months. CONCLUSIONS: CyA alone is not a suitable treatment for asymptomatic IDDM. Earlier identification of subjects with substantial β-cell secretory capacity and newer nontoxic intervention strategies are required for the prevention of IDDM.