1445-P: A Glucose Fraction Independent of Insulin Secretion in Autoantibody Positive (Ab+) Individuals

Among Ab+ individuals, reports suggest glucose is atypically associated with other T1D risk factors, such as a positive association with C-peptide. Using baseline OGTT data from 6,589 Ab+ TrialNet Pathway to Prevention participants, we hypothesized this finding is explained by a glucose fraction unrelated to insulin secretion. Index60 (fasting C-peptide, 60-min AUC glucose and C-peptide) was used as an insulin secretion proxy in regression [AUC Glucose=131.0+(8.9*Index60)] to quantify two AUC glucose fractions, each present to a degree in all individuals: one dependent on insulin secretion (DEP); the other independent (INDEP). DEP equaled predicted AUC glucose; INDEP equaled actual AUC glucose - predicted AUC glucose. The phenotype of the top DEP quartile was more typical for T1D than the top INDEP quartile (Table). INDEP correlated positively with AUC C-peptide [r=0.54 (p<0.001), 29% of AUC C-peptide variance.] With C-peptide index [(30-0 min C-peptide) / (30-0 min glucose)] as the insulin secretion proxy, findings were similar. In conclusion, Ab+ individuals with high proportions of INDEP have less typical features of T1D. The INDEP AUC glucose fraction’s positive correlation with AUC C-peptide, accounting for appreciable AUC C-peptide variance, suggests that INDEP is related to insulin resistance. Those with a higher proportion of INDEP may represent an atypical subset of the at-risk population. Disclosure J.Sosenko: None. D.D.Cuthbertson: None. M.J.Redondo: None. H.M.Ismail: Consultant; Rise Therapeutics. E.K.Sims: Speaker's Bureau; Medscape, American Diabetes Association. L.M.Jacobsen: None. B.M.Nathan: None.