Cyclosporin A does not delay insulin dependency in asymptomatic IDDM patients.
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).


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.
Rakotoambinina
B
B
Department of Pediatric Diabetology and Inserm U 30, Hôpital Necker-Enfants Malades, Paris, France.
Timsit
J
J
Deschamps
I
I
Laborde
K
K
Jos
J
J
Boitard
C
C
Assan
R
R
Robert
J J
JJ
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000494:pharmacology; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D016572:Cyclosporine; D005934:Glucagon; D001120:Arginine