Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin.
Preliminary data from our group indicated that cyclosporin A induced frequent remissions of insulin dependency in a group of 40 insulin-dependent (type I) diabetic children if given at the onset of clinical manifestations of diabetes. We report a 2-yr analysis of the response to cyclosporin A in the group of 81 patients included in the initial study. As observed before, a remission could be obtained in most of the patients (65%) in association with a shorter duration of symptoms, less severe hyperglycemia, lower incidence of ketoacidosis, and higher plasma C-peptide concentrations. All remissions ended during the follow-up period after a mean +/- SE duration of 316 +/- 21 days (range 31-850 days). Two parameters were linked to the duration of remissions: the mean circulating level of cyclosporin during the first 3 mo and the duration of prediagnostic polyuria. We were unable to relate the end of a remission to variations in the cyclosporin regimen, titer of autoantibodies, or progression of beta-cell failure. The euglycemic clamp technique revealed that insulin sensitivity decreases with time in patients not taking insulin. At 24 mo, the patients who had a remission of insulin dependency had better glycemic control, lower insulin dosages, and C-peptide levels two- to threefold higher than the nonremission patients and four- to sixfold higher than the historical control subjects. The cyclosporin regimen was well tolerated over the observed period: more specifically, serum creatinine remained unchanged, and kidney biopsies performed at 18-24 mo of treatment were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)
Pediatric Endocrinology and Diabetes Division, Saint Vincent de Paul Hospital, Paris, France.
P F
PF
Bougnères
P
P
Landais
C
C
Boisson
J C
JC
Carel
N
N
Frament
C
C
Boitard
J L
JL
Chaussain
J F
JF
Bach
D000293:Adolescent; D001323:Autoantibodies / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002648:Child; D003524:Cyclosporins / Q000009:adverse effects / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male
D001323:Autoantibodies; D002096:C-Peptide; D003524:Cyclosporins; D007328:Insulin; C024211:islet cell antibody; D005934:Glucagon