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Diabetologia. 2002 Sep;45(9):1298-306. Epub 2002 Jul 24.

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes.

Author information

1
Department of Internal Medicine and Metabolism Unit of the CNR Institute of Clinical Physiology, University of Pisa, Italy.

Abstract

AIMS/HYPOTHESIS:

Autoantibodies against CD 38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i). overlaps with anti-GAD autoimmunity, (ii). identifies an insulin-deficient phenotype, (iii). is under the influence of genetic factors.

METHODS:

We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects).

RESULTS:

CD 38-autoantibodies were found in 8.4% of Type II diabetic patients ( p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD 38 ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti- CD 38 positive had DQB1*02 compared with 38% of anti-CD 38 negative ( p=0.04). On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired ( p=0.02) only in association with anti-GAD positivity (3.2+/-3.1 U/mol, mean +/- SD) but not in anti- CD 38 positive patients (5.6+/-2.9) as compared with patients free of autoimmunity (4.5+/-4.6, p=NS). In 44 Type II diabetic patients (22 negative and 22 positive for anti- CD 38), no mutations were detected in any of the 8 exons, 5' end of intron 1 or the 5' and 3' untranslated regions of the CD 38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype.

CONCLUSION:

Anti-CD 38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence.

PMID:
12242463
DOI:
10.1007/s00125-002-0886-6
[Indexed for MEDLINE]

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