CYCLOSPORINE-A DOES NOT DELAY INSULIN DEPENDENCY IN ASYMPTOMATIC IDDMPATIENTS

OBJECTIVE - To measure the effects of cyclosporin A (CyA) with no insu lin therapy on glucose tolerance and beta-cell function in the preclin ical phase of insulin-dependent diabetes mellitus (IDDM). RESEARCH DES IGN AND METHODS- beta-cell responses to the intravenous glucose tolera nce test (IVGTT), hyperglycemic clamp, intravenous arginine, and intra venous glucagon were evaluated before and after a 6-month course of Cy A in seven patients (mean age 19.6 years) with asymptomatic IDDM. RESU LTS - Initial insulin secretary 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); hyperglyc emic clamp: 102 +/- 16 vs. 310 +/- 42 pmol/l(P < 0.001); intravenous a rginine: 346 +/- 72 vs. 1104 +/- 168 pmol/l (P < 0.01); and intravenou s glucagon: 170 +/- 37 vs. 247 +/- 35 pmol/l(NS). The beta-cell respon ses remained markedly abnormal after 6 months of CyA, although the res ponse 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 asy mptomatic IDDM. Earlier identification of subjects with substantial be ta-cell secretory capacity and newer nontoxic intervention strategies are required for the prevention of IDDM.