Islet cell autoimmunity and mitochondrial DNA mutation in Korean subjects with typical and atypical Type I diabetes

. Aims/hypothesis: The 1997 American Diabetes Association classification of diabetes mellitus included a subset of Type I diabetic patients who do not need insulin for several years but eventually progress to complete insulin deficiency i. e. atypical Type I diabetes mellitus. In Caucasian populations, most Type I diabetic patients have auto-antibodies against islet cells. We examined the frequency of the auto-antibodies against islet cells and mitochondrial DNA 3243 mutation in Koreans with typical and atypical Type I diabetes mellitus. Methods: We measured plasma C-peptide level in 1870 consecutive Korean diabetic patients. Of these, 56 patients had insulin deficiency (fasting and glucagon-stimulated plasma C-peptide concentrations ≤ 0.2 nmol/l and ≤ 0.32 nmol/l, respectively), and they were subdivided into typical ( n = 26) and atypical Type I (insulin-dependent) diabetes mellitus ( n = 30) according to clinical manifestation. Islet cell antibody was measured by indirect immunofluorescence. Anti-GAD antibody and anti-ICA512 antibody were measured by radioimmunoassay. Mitochondrial DNA 3243 mutation was detected using restriction enzyme Apa-I digestion of the amplified genomic DNA. Results: The overall prevalence of auto-antibodies in the typical and atypical groups was 77 % and 57 %, respectively. Mitochondrial DNA 3243 mutation was found in 3 out of 30 (10 %) of atypical Type I (insulin-dependent) diabetic patients but not in typical Type I (insulin-dependent) diabetic patients. Conclusion/interpretation: Autoimmunity might not be the only cause of progressive insulin deficiency in Koreans. Mitochondrial DNA mutation is another identifiable cause but the cause(s) of insulin deficiency in the remainder of Type I diabetic patients without autoimmunity is not clear. [Diabetologia (2001) 44: 2187–2191]