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Autoimmunity to Islet Proteins in Children Diagnosed with New-Onset Diabetes

Departments of Medicine (B.M.B.-W., J.P.P.) and Pediatrics (C.P.), University of Washington, Seattle, Washington 98195; Department of Medicine (B.M.B.-W., J.P.P.), Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108; Benaroya Research Institute at Virginia Mason (C.J.G.); and Children’s Hospital and Regional Medical Center (C.P.), Seattle, Washington 98105

Address all correspondence and requests for reprints to: Barbara Brooks-Worrell, Ph.D., 1660 South Columbian Way (111), DVA Puget Sound Health Care System, Seattle, Washington 98108. E-mail: bbrooks{at}u.washington.edu.

Autoantibody and T cells reacting with islet proteins have been demonstrated in patients with type 1 diabetes. In recent years an increasing number of children have been clinically classified with type 2 (not ketosis prone, evidence of insulin resistance, presence of acanthosis nigricans, and obesity) or indeterminant diabetes (admixture of clinical features of types 1 and 2). In this study, we compared the islet cell autoantibody and T-cell responses to islet proteins in type 2 (n = 19) and indeterminant (n = 16) children (<18 yr of age) to classic type 1 (n = 37) diabetic patients. We observed that 37 of 37 type 1 diabetic children demonstrated autoantibody and/or T-cell reactivity to islet proteins. Fourteen of the 19 type 2 patients were positive for islet cell autoantibodies, and six of 14 were positive for T-cell responses to islet proteins. For the indeterminant patients, 11 of 16 of the patients were positive for autoantibodies, and six of 16 patients were positive for T-cell responses to islet proteins. These results demonstrate that autoimmunity to islet proteins is present in a high percentage of children classified as indeterminant or type 2 diabetes. Moreover, the presence of obesity or acanthosis nigracans does not reliably distinguish children with or without islet cell autoimmunity.

This work was supported in part by the Medical Research Service of the Department of Veterans Affairs through a VA Merit Review grant and by the following grants from the NIH: MO1 RR00037-41, P01 DK53004, and P30 DK17047.

Abbreviations: DKA, Diabetic ketoacidosis; GAD65Ab, glutamic acid decarboxylase 65-kDa autoantibody; HLA, human leukocyte antigen; IA-2, insulinoma associated protein-2 autoantibody; IAA, insulin autoantibody; ICA, islet cell antibody; PBMC, peripheral blood mononuclear cell; SI, stimulation index.

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