Glutamic acid decarboxylase and islet antigen 2 antibody profiles in people with adult-onset diabetes mellitus: a comparison between mixed ethnic populations in Singapore and Germany

Abstract

Aim: To gain insight into the presence of islet cell autoimmunity in an ethnic Asian compared with a white European population.

Methods: For this cross-sectional study we recruited people with adult-onset diabetes (age of diagnosis 20-60 years), at tertiary referral centres in Germany (n=1020) and Singapore (n=1088). Glutamic acid decarboxylase and islet antigen 2 antibodies were measured according to Islet Autoantibody Standardization Program protocols.

Results: The prevalence of glutamic acid decarboxylase antibody positivity was 13.9% (95% CI 12.1-16.0; P<0.001) in the white European cohort compared with 6.8% (95% CI 5.5-8.4; P<0.001) in the Asian cohort. Glutamic acid decarboxylase antibody positivity was 11.4% (95% CI 7.7-16.6) in Indian, 6.0% (95% CI 3.6-9.9) in Malay and 5.8% (95% CI 4.3-7.7; P<0.001) in Chinese participants. In the white European participants, the prevalence of islet antigen 2 antibody positivity was 7.8% (95% CI 6.4-9.4) compared with 14.8% (95% CI 12.8-17.0; P<0.001) in the Asian cohort as a whole, and among the three ethnicities in the Asian cohort it was 12.4% (95% CI 8.6-17.7) in Indian, 16.8% (95% CI 12.6-22.2) in Malay and 15.7% (95% CI 13.2-18.6) in Chinese participants. Double antibody positivity was seen in 5.7% (95% CI 4.5-7.1) of white European participants compared with 1.6% (95% CI 1.0-2.5; P<0.01) of Asian participants. In the white European cohort, those who were glutamic acid decarboxylase autoantibody-positive had a lower BMI than those who were autoantibody-negative, but this trend was absent in the Asian cohort.

Conclusions: A marked prevalence of islet cell autoimmunity was observed in people with adult-onset diabetes. While glutamic acid decarboxylase antibodies were more frequent in the European cohort, islet antigen 2 antibody positivity was highest in the three ethnic groups in Singapore, suggesting ethnic-specific differences in antibody profiles.

Figure 1

Islet cell antibody prevalence in Asian and white European participants with diabetes. (a) Glutamic acid decarboxylase (GAD) antibodies and (b) islet antigen 2 (IA2) antibody distribution in white European participants. (c) GAD antibodies and (d) IA2 antibody distribution in ethnic Asian participants. Ethnic‐specific GAD antibodies positivity for Chinese (e), Malay (g) and Indian (i) participants; IA2 antibody distribution for Chinese (f), Malay (h) and Indian (j) participants. *P < 0.01, **P < 0.001 compared with white European cohort using the t‐test. DK units, arbitrary National Institute of Diabetes and Digestive and Kidney Diseases units.

Figure 2

Islet cell antibody prevalence of glutamic acid decarboxylase (GAD) and/or islet antigen 2 (IA2) antibodies in relation to age of disease onset. (a) White European (linear regression slope= ‐0.38±0.03) and (b) ethnic Asian (linear regression slope= ‐0.012±0.05) participants with increasing age of onset. Distribution box plots showing antibody titre distribution in participants with increasing age of onset: (c) GAD antibodies in white European participants (P<0.001) and (d) IA2 antibodies in white European participants (P=0.096; non‐significant) in comparison with (e) GAD antibodies in the Singapore cohort (P=0.534; non‐significant) and (f) IA2 antibodies in the Singapore cohort (P= 0.399; non‐significant). Total population in each age group=100%. P values compared with cohort in 20–29‐year age group using one‐way anova. DK units, arbitrary National Institute of Diabetes and Digestive and Kidney Diseases units.