[Immunosuppression with cyclosporin induces clinical remission and improved beta cell function in patients with newly diagnosed insulin-dependent diabetes. A national and international multicenter study].
A prospective, randomized, double-blind, placebo-controlled international multicenter trial including 188 newly diagnosed insulin-dependent diabetic (IDDM) patients was undertaken with the aim of investigating whether immunosuppression for one year with ciklosporin (Cs) could induce and maintain clinical remission and improvement of beta-cell function. The relative odds for non-insulin-requiring remission at one year were increased approximately five times in the Cs-treated group. After three months Cs-treated patients achieved more than a doubling of beta-cell function compared to baseline than did placebo-treated patients, and the Cs-treated group maintained this improvement in beta-cell function for 12 months, whereas the placebo-group lost beta-cell function during the same period. Short duration of disease (less than or equal to six weeks of symptoms, less than or equal to two weeks of insulin treatment) was associated positively with remission, as was an elevated proinsulin/C-peptide ratio, especially in patients with the tissue-type HLA-DR 3,4; 4,X and X,X. Cs-treatment inhibited the formation of antibodies against insulin and islet cell components, but islet cell antibody status at entry was not predictive of remission. Cs-treatment caused a reversible decrement of kidney function as measured with serum creatinine and the calculated creatinine clearance, but studies of renal physiology and kidney biopsies performed on a limited subset of patients indicated that Cs treatment in IDDM patients for one year induced a slight chronic nephropathy in some of these.(ABSTRACT TRUNCATED AT 250 WORDS)
Mandrup-Poulsen
T R
TR
Niels Steensens Hospital, Gentofte.
Mølvig
J C
JC
Andersen
V
V
Bendtzen
K
K
Binder
C
C
Brøns
M
M
d'Amore
F A
FA
Dieperink
H
H
Enk
B
B
Frandsen
N E
NE
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D003524:Cyclosporins / Q000008:administration & dosage*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology; D008297:Male; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction / Q000379:methods*
D003524:Cyclosporins; D007166:Immunosuppressive Agents
Immunosuppression med ciklosporin inducerer klinisk remission og forbedret beta-cellefunktion hos patienter med nykonstateret insulinkraevende diabetes. En national og international multicenterundersøgelse. The Canadian-European Randomized Control Trial Group.