Autoimmunity in South Indian Patients With IDDM

Evidence for an autoimmune pathogenesis of insulindependent diabetes mellitus (IDDM) among diabetes-prone European populations has included the presence of islet cellreactive autoantibodies, the presence of cell-mediated immunity to islet antigens, inheritance with HLA-DR3 and HLA-DR4 alleles, and association with autoimmune diseases involving the thyroid, gastric mucosa, and adrenal cortex. ' In the United States, islet cell antibodies (ICAs) are present in a significantly lower frequency among recently diagnosed Black IDDM patients compared with Caucasian IDDM patients. ' North Indian patients with IDDM have been reported to have an ICA frequency similar to that of Europeans with IDDM. We are, however, unaware of any data on organspecific autoimmunities in southern Indian patients with IDDM. Because southern Indians are largely of Dravidian origin and differ from the Aryan population of northern India, we considered it worthwhile to compare the autoimmune aspects of diabetes in the southern Indian population with those of the previously reported northern Indian patients. In previous studies, some of us have shown significant differences in the HLA-linked susceptibility between these populations. Patients met the criteria for IDDM established by the National Diabetes Data Group and presented with acute onset of symptoms, severe hyperglycemia, and marked ketonuria beginning before the age of 30 yr, with duration <5 yr. Their origins were the four southern states of India, i.e., Tamil Nadu, Karnataka, Andhra Pradesh, and Kerala. To insure that only subjects with IDDM were included, we studied only those with fasting and stimulated C-peptide responses <0.1 pmol/ml. There were 33 men and 34 women; 23 were diagnosed at <10 yr of age, 29 between 10 and 19 yr, and the rest between 20 and 30 yr of age. Diabetes duration was <6 mo in 26 patients. Patients were all from middleor upperclass families and did not have malnutrition or evidence of chronic pancreatitis. ICA, thyroid microsomal antibodies (TMA), and gastric parietal cell autoantibodies (PCA) were determined as previously described. Ten subjects had ICAs, 8 of the 26 (30.8%) with <6 mo duration of diabetes and only 2 of the 43 (4.7%) with >7 mo duration, individuals with 1 yr and 3 yr duration of insulin therapy. TMA was present in 16 (23.2%) and PCA in 8 (12.5%). Of the 35 men, only 4 had ICAs (11.4%), not statistically different from the 6 of 34 women (17.6%). Seven of the 13 TMA-positive subjects were men, as were 3 of the 7 PCA-positive individuals. The frequency of ICA during the first 6 mo of insulin requirement among young patients from southern India is comparable with that of American Black patients with IDDM and comparable with that of northern Indians. ' However, southern Indians showed a level of ICA positivity of <5% after 6 mo of diabetes compared with 20% in American Black patients with up to 5 yr duration and with the 30% frequency in northern Indians after 6 mo of diabetes. The latter group does not show an appreciable reduction of ICA positivity over periods >6 yr. These findings suggest a heterogeneity different for southern Indian (Dravidian) people with IDDM from that for the nothern Indian (Aryan) population. The similar frequency of ICA in men and women with <5 yr duration of diabetes in this study is consistent with a large study from the US. However, TMA and PCA were also similar in frequency between men and women; in the Euramerican diabetic populations, thyrogastric autoimmunity is more common among women than men. The frequencies of TMA and PCA in the southern Indian population are virtually identical to those of the northern Indians. The similarity of thyrogastric autoimmunities in the southern and northern Indian populations, although there are marked differences in the ICA frequency after 6 mo of diabetes, emphasizes that these autoimmunities are transmitted separately from IDDM despite their frequent clinical association. The frequencies of TMA and PCA in both Indian populations are virtually identical to those reported for the US Caucasian IDDM population. These studies add to the catalog of data emphasizing heterogeneity for IDDM by virtue of race.