The Presence of GAD and IA-2 Antibodies in Youth With a Type 2 Diabetes Phenotype

Results from the TODAY study

  1. for the TODAY Study Group
  1. 1Barbara Davis Center and the Children's Hospital, University of Colorado Denver, Aurora, Colorado;
  2. 2George Washington University Biostatistics Center, Rockville, Maryland;
  3. 3Pittsburgh Children's Hospital University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;
  4. 4University of Oklahoma College of Medicine, Oklahoma City, Oklahoma;
  5. 5Rainbow Babies and Children's Hospital University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio;
  6. 6University of Southern California and the Children's Hospital Los Angeles, Los Angeles, California;
  7. 7Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts;
  8. 8Department of Medicine, University of Washington, Seattle, Washington;
  9. 9St. Louis University Health Sciences Center, St. Louis, Missouri;
  10. 10SUNY Upstate Medical University and Department of Veterans Affairs Medical Center, Syracuse, New York;
  11. 11National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
  1. Corresponding author: Georgeanna J. Klingensmith, georgeanna.klingensmith{at}ucdenver.edu.

Abstract

OBJECTIVE To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings.

RESEARCH DESIGN AND METHODS Children (10–17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations.

RESULTS Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P < 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P < 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects.

CONCLUSIONS Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes.

Footnotes

  • Clinical trial reg. no. NCT00081328, clinicaltrials.gov.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Received February 25, 2010.
  • Accepted May 24, 2010.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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  1. Diabetes Care vol. 33 no. 9 1970-1975
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