Objective and Introduction: It has been shown that AUC glucose from oral glucose tolerance tests (OGTTs) can be divided into fractions dependent or independent of insulin secretion. We assessed whether the independent fraction is predictive of incident IGT, a pre-diagnostic marker (2-hr glucose ≥140 to <200 mg/dl), and T1D among Ab+I.
Methods: AUC glucose, calculated from baseline OGTTs of 5182 normoglycemic TrialNet Pathway to Prevention participants with ≥1 Ab+, was divided into fractions dependent (dAUCGLU) or independent (iAUCGLU) of insulin secretion. Fractions were derived from linear regression of AUC glucose vs. Index60 (insulin secretion proxy). dAUCGLU was the expected AUC glucose value, while iAUCGLU was the residual value of AUC glucose above or below the regression slope. Fractions were assessed for predicting IGT and T1D.
Results: dAUCGLU and iAUCGLU were each predictive of both IGT and T1D (p<0.0001 for both, Figure). iAUCGLU was a stronger predictor of IGT, while dAUCGLU was a stronger predictor of T1D. When added to dAUCGLU in regression models, iAUCGLU contributed to the prediction (p<0.0001) of both IGT and T1D.
Conclusion: A glucose fraction independent of insulin secretion predicts both IGT and T1D in Ab+I. This merits investigation into other factors (e.g., insulin resistance) contributing to these hyperglycemic endpoints.
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.
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
