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Testing the Accelerator Hypothesis

Body size, ß-cell function, and age at onset of type 1 (autoimmune) diabetes

¹ University of Colorado Health Sciences Center, Denver, Colorado
² Wake Forest University School of Medicine, Winston-Salem, North Carolina
³ Department of Epidemiology, University of South Carolina, Columbia, South Carolina
⁴ Sansum Medical Research Institute, Santa Barbara, California
⁵ Centers for Disease Control and Prevention, Atlanta, Georgia
⁶ Children’s Hospital Medical Center, Cincinnati, Ohio
⁷ Children’s Hospital and Regional Medical Center, Seattle, Washington
⁸ Kaiser Permanente Center for Health Research Northwest/Hawaii, Portland, Oregon
⁹ Northwest Lipid Research Laboratories, University of Washington, Seattle, Washington
¹⁰ National 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

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 ß-cell function. The intrauterine environment may also be an important determinant of age at onset of type 1 diabetes.

Abbreviations: FCP, fasting C-peptide • IA2, insulinoma-associated protein 2

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