Evidence for Heterogeneous Pathogenesis of Insulin-Treated Diabetes in Black and White Children INGRID M. LIBMAN, MD, PHD 1 MASSIMO PIETROPAOLO, MD 2 SILVA A. ARSLANIAN, MD 1 RONALD E. LAPORTE, PHD 3 DOROTHY J. BECKER, MBBCH, FCP 1 OBJECTIVE — We have previously reported differences in the prevalence of -cell autoan- tibodies (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 characteris- tics at disease diagnosis and follow-up treatment in an expanded number of black and white children with and without the presence of AAs. RESEARCH DESIGN AND METHODS — The study cohort of 130 black children and adolescents, aged 19 years, diagnosed with diabetes and treated with insulin at time of diag- nosis (January 1979 to December 1998) were matched with an equal number of white children by age at onset, sex, and year of diagnosis. RESULTS — The black children had a higher prevalence of obesity (43 vs. 11%) and acan- thosis 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. CONCLUSIONS — These pediatric subjects, irrespective of autoimmunity, often showed characteristics associated with type 2 diabetes. These characteristics were more frequently dis- played 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. Diabetes Care 26:2876 –2882, 2003 I mmune-mediated type 1 diabetes is the most prevalent type of diabetes among children, and until recently only 1–2% of diabetic children were considered to have type 2 diabetes or other rare forms of the disease. However, recent reports have suggested that 8 – 45% of children with newly diagnosed diabetes have type 2 di- abetes or another nonclassical type of di- abetes (1–10). The majority of these children are classified as having type 2 diabetes according to clinical criteria, but increasingly more children are being identified with other types of diabetes. In particular, diagnoses of atypical diabetes and type 1.5 diabetes have been reported, especially in the black population, who seem to be disproportionately repre- sented in this heterogeneous group (11). We and others reported an increase in the incidence of insulin-treated diabetes in black adolescents in the 1990s, based on the results of population-based studies (1–3). This observation raises the ques- tion of whether this rising incidence could be the result of an increasing inci- dence of type 1 diabetes or another type of insulin-requiring diabetes, possibly with mixed pathogenesis. The Children’s Hospital of Pitts- burgh’s (CHP’s) Insulin-Dependent Dia- betes Mellitus (IDDM) Registry includes all children aged 19 years treated with insulin at diabetes diagnosis since 1965 and has been shown to be representative of the larger population-based Allegheny County IDDM registry (12). The registry offers an invaluable opportunity to ex- plore possible explanations for this in- creased incidence of insulin-treated diabetes in black children. Previous data in a small sample of this population dem- onstrated that, although 90% of white subjects had evidence of autoimmunity as measured by conventional islet cell anti- body (ICA) assays, these antibodies were frequently undetected in black subjects (12). The objective of this study was to characterize and compare clinical, bio- chemical, and autoimmune characteris- tics at diagnosis and follow-up treatment of black and white children with insulin- requiring diabetes who did or did not have islet autoantibodies (AAs). All sub- jects were from the CHP’s IDDM Registry and were diagnosed with diabetes be- tween 1979 and 1998. The hypothesis to be tested was that black children had a higher prevalence of characteristics asso- ciated with insulin resistance/type 2 dia- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 Division of Pediatric Endocrinology, Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania; the 2 Division of Immunogenetics, Rangos Research Center, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania; the 3 Diabetes Research Center, Department of Epidemiology, Gradu- ate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania. Address correspondence and reprint requests to Ingrid M. Libman, MD, PhD, Department of Pediatric Endocrinology, Children’s Hospital of Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213. E-mail: ingrid.libman@chp.edu. Received for publication 9 February 2003 and accepted in revised form 9 June 2003. Abbreviations: AA, autoantibody; CHP, Children’s Hospital of Pittsburgh; IA-2, insulinoma-associated protein 2; IAA, insulin autoantibody; ICA, islet cell antibody; MODY, maturity-onset diabetes of the young; RIA, radioimmunoassay; SDS, SD score. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. © 2003 by the American Diabetes Association. See accompanying editorial, p. 2954. Pathophysiology/Complications ORIGINAL ARTICLE 2876 DIABETES CARE, VOLUME 26, NUMBER 10, OCTOBER 2003