Preservation of β-Cell Function in Autoantibody-Positive Youth With Diabetes

Carla J. Greenbaum; Andrea M. Anderson; Lawrence M. Dolan; Elizabeth J. Mayer-Davis; Dana Dabelea; Giuseppina Imperatore; Santica Marcovina; Catherine Pihoker; for the SEARCH Study Group*

doi:10.2337/dc08-2326

Original Research

Preservation of β-Cell Function in Autoantibody-Positive Youth With Diabetes

Carla J. Greenbaum, MD¹,
Andrea M. Anderson, MS²,
Lawrence M. Dolan, MD³,
Elizabeth J. Mayer-Davis, PHD⁴,
Dana Dabelea, MD, PHD⁵,
Giuseppina Imperatore, MD, PHD⁶,
Santica Marcovina, PHD⁷,
Catherine Pihoker, MD⁸ and
for the SEARCH Study Group*

¹Diabetes Research Program, Benaroya Research Institute, Seattle, Washington;
²Wake Forest University School of Medicine, Winston-Salem, North Carolina;
³Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio;
⁴Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and the Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina;
⁵Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, Colorado;
⁶Division of Diabetes Translation, National Center for Chronic Disease Prevention and the Health Promotion Centers for Disease Control and Prevention, Atlanta, Georgia;
⁷Department of Medicine, University of Washington, Seattle, Washington;
⁸Department of Pediatrics, University of Washington, Seattle, Washington.

Corresponding author: Carla Greenbaum, cjgreen{at}benaroyaresearch.org.

Diabetes Care 2009 Oct; 32(10): 1839-1844. https://doi.org/10.2337/dc08-2326

Abstract

OBJECTIVE To determine the extent of β-cell function in youth with diabetes and GAD65 and/or IA2 autoantibodies.

RESEARCH DESIGN AND METHODS Fasting C-peptide levels from 2,789 GAD65- and/or IA2 autoantibody-positive youth aged 1–23 years from the SEARCH for Diabetes in Youth study were used. Preserved β-cell function was defined on the basis of cut points derived from the Diabetes Control and Complications Trial (DCCT) (fasting C-peptide ≥0.23 ng/ml) and from the U.S. adolescent population of the National Health and Nutrition Examination Survey (NHANES) 5th percentile for fasting C-peptide (≥1.0 ng/ml). We compared the clinical characteristics between those with and without preserved β-cell function.

RESULTS Within the first year of diagnosis, 82.9% of youth had a fasting C-peptide ≥0.23 ng/ml and 31.2% had values ≥1.0 ng/ml. Among those with ≥5 years of diabetes duration, 10.7% had preserved β-cell function based on the DCCT cutoff and 1.0% were above the 5th percentile of the NHANES population.

CONCLUSIONS Within the 1st year of diagnosis, four of five youth with autoantibody-positive diabetes have clinically significant amounts of residual β-cell function and about one-third have fasting C-peptide levels above the 5th percentile of a healthy adolescent population. Even 5 years after diagnosis, 1 of 10 has fasting C-peptide above a clinically significant threshold. These findings have implications for clinical classification of youth with diabetes as well as clinical trials aimed to preserve β-cell function after diabetes onset.

Footnotes

↵*A complete list of the SEARCH for Diabetes in Youth (SEARCH) Study Group can be found in the appendix.
The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases.
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 December 29, 2008.
- Accepted June 19, 2009.

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