1447-P: Metabolic Heterogeneity of Antibody-Positive Individuals (Ab+I) with Impaired Glucose Tolerance (IGT) according to Glucose Fractions

Introduction and Objective: Among Ab+I, we examined the metabolic heterogeneity of IGT, a marker of progression toward stage 3 type 1 diabetes (T1D), using glucose fractions dependent or independent of insulin secretion. Methods: Data from Ab+I with baseline OGTTs meeting IGT criteria (2-hr glucose ≥140 to 200 mg/dl, n=1103) enrolled in TrialNet Pathway to Prevention were analyzed. AUC glucose was divided into fractions dependent (dAUCGLU) or independent (iAUCGLU) of insulin secretion, defined by the linear regression of AUC glucose vs. Index60 (as an insulin secretion proxy). dAUCGLU was the AUC glucose value predicted by Index60, while iAUCGLU was the AUC glucose residual value above or below the regression slope. Results: AUC C-peptide decreased as dAUCGLU quartiles increased, whereas AUC C-peptide increased as iAUCGLU quartiles increased (Figure). AUC C-peptide was inversely correlated with dAUCGLU (r=-0.84) and positively correlated with iAUCGLU (r=0.62) (p0.0001 for both). AUC C-peptide trended little with unfractionated AUC glucose quartiles. Conclusion: Opposite associations of AUC C-peptide with dAUCGLU and iAUCGLU indicate that AUC C-peptide was not only attributable to insulin secretion, but also to other factors (e.g. insulin resistance). It appears that among Ab+I, IGT is a heterogeneous metabolic state that may not be an optimal marker for T1D. Disclosure B.M. Nathan: None. D.D. Cuthbertson: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. L.M. Jacobsen: Advisory Panel; Insulet Corporation. E.K. Sims: Consultant; Sanofi. Board Member; American Diabetes Association. Other Relationship; American Diabetes Association, Medscape. Consultant; DRI. J. Sosenko: None. Funding National Institutes of Health (U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, UC4 DK117009)JDRF