Time-to-Peak C-Peptide and Peak Glucose during an Oral Glucose Tolerance Test (OGTT) Are Independent Risk Factors for Type 1 Diabetes (T1D) in Antibody-Positive (Ab+) Individuals

Abstract

Peak C-peptide (C-P) and glucose levels are known predictors of T1D, but T1D prediction by times to those peak levels has not been studied. We thus assessed T1D prediction by times to peak C-P or glucose during OGTTs in 709 Ab+ Diabetes Prevention Trial-type 1 participants with 2-hour OGTTs [mean age: 13.9±9.6 years; BMI percentile (%ile): 59.3±29.0; 56% male]. Log rank testing and Cox regression with adjustments for age, sex, BMI %ile, proband relation, HLA, and Ab number were used. Risks were higher for time to peak C-P >60 mins [HR: 1.96 (CI: 1.49-2.63), p<0.001)] and for time to peak glucose >30 mins [HR: 2.22 (1.67-2.94), p<0.001)]. With time to peak C-P and peak C-P as covariates, T1D associations were greater for time to peak C-P (X2=22.8 vs. 9.3, both p<0.001). Time to peak glucose and peak glucose associations also remained significant (both p<0.001). Findings were validated in Ab+ relatives in the TrialNet Pathway to Prevention study (Figure); those with a peak C-P >60 mins or a peak glucose >30 mins had higher risk (both p<0.001). In conclusion, Ab+ relatives with delayed peak C-P or glucose are at higher T1D risk, independent of peak levels. Moreover, the time to peak C-P appears to be more predictive than the peak level. Times to peak C-P and glucose have potential use as predictors of T1D and as markers for progression. Disclosure H.M. Ismail: None. P. Xu: None. C. Evans-Molina: None. J.P. Palmer: None. J. Sosenko: None.