1827-P: Higher Glucagon-Like Peptide-1 Response and Lower Beta-Cell Glucose Sensitivity Are Associated with Increased Glycemic Variability among Individuals with Prediabetes

Background: Increased glycemic variability (GV) is thought to represent abnormalities of glucose homeostasis in the progression from prediabetes to diabetes. We evaluated the association between GV, beta-cell function and glucagon-like peptide 1 (GLP-1) response among individuals with prediabetes. Methods: 61 individuals with prediabetes (age Mean±SD 56±9 years, 31 male) each wore a blinded continuous glucose monitor (Medtronic iPro2) for 72 hours. Standard deviation (SD) and coefficient of variation (CV) were calculated from CGM glucose. Participants underwent a 2-hour mixed-meal tolerance test with measurement of insulin, C-peptide, GLP-1 for modelling of beta-cell function. Results: Early and late GLP-1/glucose ratio were positively correlated with CGM sensor glucose SD (r = 0.29, p=0.02 and r= 0.28 p = 0.048 respectively). Beta-cell glucose sensitivity (βCGS) was negatively correlated with SD (r = -0.28, p = 0.03). In multivariate analyses, only βCGS and GLP-1 response were significant predictors of SD, while early phase insulin and insulin secretion rate predicted average sensor glucose but not indices of GV. Conclusions: Higher GLP-1 response and reduced βCGS are associated with greater glucose fluctuations in the prediabetic range. Disclosure E. Chow: Research Support; Self; Powder Pharmaceuticals Inc., Sanofi-Aventis. A. Luk: None. J. Ling: None. A.P. Kong: Advisory Panel; Self; Lilly Diabetes. Research Support; Self; AstraZeneca, Lilly Diabetes. Speaker9s Bureau; Self; Abbott. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. E. Ferrannini: None. J.C. Chan: Board Member; Self; Asia Diabetes Foundation. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Merck Sharp & Dohme Corp., Sanofi-Aventis. Research Support; Self; Amgen Inc., AstraZeneca, Lee Powder, Lilly Diabetes, Pfizer Inc., Sanofi-Aventis. Speaker9s Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; GemVCare.