Testing the Accelerator Hypothesis
Body size, β-cell function, and age at onset of type 1 (autoimmune) diabetes
- Dana Dabelea, MD, PHD1,
- Ralph B. D’Agostino, Jr, PHD2,
- Elizabeth J. Mayer-Davis, PHD3,
- David J. Pettitt, MD4,
- Giuseppina Imperatore, MD, PHD5,
- Larry M. Dolan, MD6,
- Catherine Pihoker, MD7,
- Teresa A. Hillier, MD8,
- Santica M. Marcovina, PHD9,
- Barbara Linder, MD10,
- Andrea M. Ruggiero, MD, PHD2,
- Richard F. Hamman, MD, DRPH1 and
- for the SEARCH for Diabetes in Youth Study Group
- 1University of Colorado Health Sciences Center, Denver, Colorado
- 2Wake Forest University School of Medicine, Winston-Salem, North Carolina
- 3Department of Epidemiology, University of South Carolina, Columbia, South Carolina
- 4Sansum Medical Research Institute, Santa Barbara, California
- 5Centers for Disease Control and Prevention, Atlanta, Georgia
- 6Children’s Hospital Medical Center, Cincinnati, Ohio
- 7Children’s Hospital and Regional Medical Center, Seattle, Washington
- 8Kaiser Permanente Center for Health Research Northwest/Hawaii, Portland, Oregon
- 9Northwest Lipid Research Laboratories, University of Washington, Seattle, Washington
- 10National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
- Address correspondence and reprint requests to Dana Dabelea, MD, PhD, 4200 E. 9th Ave., Box C245, Denver, CO 80262. E-mail: dana.dabelea{at}uchsc.edu
Abstract
OBJECTIVE—The “accelerator hypothesis” predicts that fatness is associated with an earlier age at onset of type 1 diabetes. We tested the hypothesis using data from the SEARCH for Diabetes in Youth study.
RESEARCH DESIGN AND METHODS—Subjects were 449 youth aged <20 years at diagnosis who had positive results for diabetes antibodies measured 3–12 months after diagnosis (mean 7.6 months). The relationships between age at diagnosis and fatness were examined using BMI as measured at the SEARCH visit and reported birth weight, both expressed as SD scores (SDSs).
RESULTS—Univariately, BMI SDS was not related to age at diagnosis. In multiple linear regression, adjusted for potential confounders, a significant interaction was found between BMI SDS and fasting C-peptide (FCP) on onset age (P < 0.0001). This interaction remained unchanged after additionally controlling for number and titers of diabetes antibodies. An inverse association between BMI and age at diagnosis was present only among subjects with FCP levels below the median (<0.5 ng/ml) (regression coefficient −7.9, P = 0.003). A decrease of 1 SDS in birth weight (639 g) was also associated with an ∼5-month earlier age at diagnosis (P = 0.008), independent of sex, race/ethnicity, current BMI, FCP, and number of diabetes antibodies.
CONCLUSIONS—Increasing BMI is associated with younger age at diagnosis of type 1 diabetes only among those U.S. youth with reduced β-cell function. The intrauterine environment may also be an important determinant of age at onset of type 1 diabetes.
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted October 20, 2005.
- Received July 19, 2005.
- DIABETES CARE
