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Diabetes Care, Vol 18, Issue 11 1487-1490, Copyright © 1995 by American Diabetes Association

ARTICLES

Cyclosporin A does not delay insulin dependency in asymptomatic IDDM patients

B Rakotoambinina, J Timsit, I Deschamps, K Laborde, J Jos, C Boitard, R Assan and JJ Robert
Department of Pediatric Diabetology and Inserm U 30, Hopital Necker-Enfants Malades, Paris, France.

OBJECTIVE: To measure the effects of cyclosporin A (CyA) with no insulin therapy on glucose tolerance and beta-cell function in the preclinical phase of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: beta-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 beta-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 beta-cell secretory capacity and newer nontoxic intervention strategies are required for the prevention of IDDM.
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