Evidence for heterogeneous pathogenesis of insulin-treated diabetes in black and white children.

We have previously reported differences in the prevalence of beta-cell autoantibodies (AAs) in black and white children with insulin-treated diabetes, suggesting that the disease pathogenesis may be more heterogeneous among racial groups than previously thought. To further explore this issue, we compared clinical, biochemical, and autoimmune characteristics at disease diagnosis and follow-up treatment in an expanded number of black and white children with and without the presence of AAs. The study cohort of 130 black children and adolescents, aged <19 years, diagnosed with diabetes and treated with insulin at time of diagnosis (January 1979 to December 1998) were matched with an equal number of white children by age at onset, sex, and year of diagnosis. The black children had a higher prevalence of obesity (43 vs. 11%) and acanthosis nigricans (21 vs. 1%) than white children and a lower prevalence of AAs. Compared with black children who had AAs, those with no AAs were older and had a higher prevalence of obesity, acanthosis nigricans, and parental diabetes. However, one of four of the black children with AAs was obese and/or had acanthosis nigricans. Among white children, the absence of AAs was not associated with any differences in terms of obesity or acanthosis nigricans compared with those with AAs. Similar to their black counterparts, white children without antibodies were older and had a higher prevalence of parental diabetes. Although treatment with an insulin sensitizer was used, insulin therapy was rarely discontinued on follow-up. These pediatric subjects, irrespective of autoimmunity, often showed characteristics associated with type 2 diabetes. These characteristics were more frequently displayed in black than in white children. Our data suggest that childhood diabetes may constitute a spectrum of pathogenic mechanisms that may overlap, including those typically associated with both type 1 and type 2 diabetes. This finding could have therapeutic implications.