Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes.
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.


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 approximately 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 beta-cell function. The intrauterine environment may also be an important determinant of age at onset of type 1 diabetes.
Dabelea
Dana
D
University of Colorado Health Sciences Center, Denver, Colorado, USA. dana.dabelea@uchsc.edu
D'Agostino
Ralph B
RB
Mayer-Davis
Elizabeth J
EJ
Pettitt
David J
DJ
Imperatore
Giuseppina
G
Dolan
Larry M
LM
Pihoker
Catherine
C
Hillier
Teresa A
TA
Marcovina
Santica M
SM
Linder
Barbara
B
Ruggiero
Andrea M
AM
Hamman
Richard F
RF
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001324:Autoantigens / Q000097:blood; D001724:Birth Weight; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood; D006801:Humans; D007223:Infant; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007527:Isoenzymes / Q000097:blood; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000097:blood; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8
D001324:Autoantigens; D007527:Isoenzymes; D008565:Membrane Proteins; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2