Aims/hypothesis. Autoantibodies against CD38 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. CD38-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). CD38ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti-CD38 positive had DQB1*02 compared with 38% of anti-CD38 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-CD38 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-CD38), no mutations were detected in any of the 8 exons, 5' end of intron 1 or the 5' and 3' untranslated regions of the CD38 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-CD38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence.