Etiological Approach to Characterization of Diabetes Type
The SEARCH for Diabetes in Youth Study
- Dana Dabelea, MD, PHD1,
- Catherine Pihoker, MD2,
- Jennifer W. Talton, MS3,
- Ralph B. D’Agostino Jr, PHD3,
- Wilfred Fujimoto, MD4,
- Georgeanna J. Klingensmith, MD5,
- Jean M. Lawrence, PHD6,
- Barbara Linder, MD7,
- Santica M. Marcovina, PHD8,
- Elizabeth J. Mayer-Davis, PHD9,
- Giuseppina Imperatore, MD, PHD10,
- Lawrence M. Dolan, MD11 and
- for the SEARCH for Diabetes in Youth Study*
- 1Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
- 2Department of Washington, University of Washington, Seattle, Washington
- 3Department of Biostatistical Sciences, Wake Forest University, School of Medicine, North Carolina
- 4Kuakini Medical Center, Honolulu, Hawaii
- 5Barbara Davis Center and Department of Pediatrics, University of Colorado Denver, School of Medicine, Aurora, Colorado
- 6Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
- 7National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
- 8Department of Medicine, University of Washington, Seattle, Washington
- 9Departments of Nutrition and Medicine, University of North Carolina, Chapel Hill, North Carolina
- 10Division of Diabetes Translation, Centers for Diseases Control and Prevention, Atlanta, Georgia
- 11Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
- Corresponding author: Dana Dabelea, .
OBJECTIVE To describe an etiologic approach to classification of diabetes types in youth based on the 1997 American Diabetes Association (ADA) framework, using data from the SEARCH for Diabetes in Youth Study.
RESEARCH DESIGN AND METHODS SEARCH conducted a comprehensive assessment of 2,291 subjects aged <20 years with recently diagnosed diabetes. Using autoimmunity (at least one of two diabetes autoantibodies) and insulin sensitivity (equation validated against hyperinsulinemic-euglycemic clamps) as the main etiologic markers, we described four categories along a bidimensional spectrum: autoimmune plus insulin-sensitive (IS), autoimmune plus insulin-resistant (IR), nonautoimmune plus IS, and nonautoimmune plus IR. We then explored how characteristics, including genetic susceptibility to autoimmunity (HLA genotypes), insulin deficiency, and clinical factors varied across these four categories.
RESULTS Most subjects fell into either the autoimmune plus IS (54.5%) or nonautoimmune plus IR categories (15.9%) and had characteristics that align with traditional descriptions of type 1 or type 2 diabetes. The group classified as autoimmune plus IR (19.5%) had similar prevalence and titers of DA and distribution of HLA risk genotypes similar to those in the autoimmune plus IS group, suggesting that it includes individuals with type 1 diabetes who are obese. The group classified as nonautoimmune plus IS (10.1%) likely includes individuals with undetected autoimmunity but may also include those with monogenic diabetes and thus requires further testing.
CONCLUSIONS The SEARCH study offers researchers and clinicians a practical application for the etiologic classification of diabetes type and at the same time identifies a group of youths who would benefit from further testing.
- Received December 12, 2010.
- Accepted April 21, 2011.
- © 2011 by the American Diabetes Association.
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