Abstract
Introduction and Objective: Although age and BMI have been included as risk factors for T1D in Ab+ individuals, a definitive association between glucose with either age or BMI has not been evident. We hypothesized that a recently identified fraction of glucose, independent of insulin secretion (INDEP), obscures associations of glucose with age and BMI. Methods: 5475 TrialNet Pathway to Prevention Ab+ participants (age: 2-50 years) were studied. Index60, a composite measure of glucose and C-peptide, was a surrogate for insulin secretion. To obtain the INDEP fraction of AUC glucose, we first determined the AUC glucose fraction dependent on insulin secretion (DEP) from the intercept and slope (DEP=130.74+11.08* Index60) of a simple linear regression model. INDEP was then calculated by subtracting DEP from total AUC glucose. Results: Unfractionated AUC glucose had a small correlation with age (r=-0.06). However, after separation into fractions, DEP was inversely correlated with age (r=-0.46), whereas INDEP was positively correlated (r=0.15). INDEP was higher in those >40.0 years (highest decade; n=524) than in those <10.0 years (lowest decade; n=2179): 7.1±24.4 vs. -3.9±19.8 mg/dL. Unfractionated AUC glucose was not corelated with BMI (r=0.00). Like age, DEP and BMI were inversely correlated (r=-0.45), whereas INDEP and BMI were positively correlated (r=0.20). INDEP was higher in those with BMI>25.0 (overweight surrogate; n=1157) than in those <15.0 (underweight surrogate; n=581): 9.0±23.2 mg/dL vs. -4.3±19.6 mg/dL. Conclusion: Positive correlations of INDEP (opposite to inverse correlations of DEP) with age and BMI contribute to the lack of association of unfractionated AUC glucose with those risk factors in Ab+ individuals. Since glucose fractions characterize heterogeneity of the relation between glucose and insulin secretion, the partitioning of glucose should be considered in studies of Ab+ individuals.