Does the Shape of the OGTT Glucose Curve Reflect Metabolic Function in Individuals with Type 2 Diabetes? Baseline Data from the GRADE Cohort

Abstract

In nondiabetic subjects a biphasic (rise, fall, rise) vs. monophasic (rise then fall) glucose pattern on OGTTs has been associated with better metabolic parameters, but data in T2DM are limited. We categorized the shape of the glucose curve from baseline OGTTs performed in the Glycemia Reduction Approaches in Diabetes Study (GRADE) into monophasic, biphasic or continuous rise and analyzed their relationship with metabolic parameters. GRADE eligibility included T2DM <10 y, HbA1c 6.8-8.5% with metformin treatment alone. OGTT glucose and insulin were measured at 0, 15, 30, 60, 90 and 120 minutes (n=5047 adults: age 57.2±10 y, 63.6% male, HbA1c 7.5±0.5%, duration T2DM 4.2±2.8 y). Most glucose profiles were monophasic. HbA1c did not differ between groups. Those with a monophasic shape were more likely to be men, had higher BMI, fasting glucose and incAUC glucose, and lower HOMA-S and disposition index (Table). Compared to the monophasic group, those with a continuous rise shape had lower fasting glucose and higher HOMA-S, but the highest 2 h glucose. Those with a biphasic pattern had intermediate insulin sensitivity, but the highest disposition index. Thus, a biphasic glucose pattern reflects better β-cell function, similar to that observed in nondiabetic subjects. Whether glucose patterns predict response to GRADE interventions will be determined on study completion.Table. Phenotypic and metabolic characteristics by OGTT glucose curve shapeMonophasicBiphasicContinuousP valueN (%)3212 (64.0)283 (5.6)1523 (30.4)Sex (%male)70.359.750.2<0.001Age (years)56.5±9.958.0±10.558.5±9.9<0.001BMI (kg/m2)35±732±633±7<0.001HbA1c (%)7.5±0.57.5±0.57.5±0.50.6Fasting glucose (mmol/L)8.5±1.78.4±1.68.3±1.7<0.0012 hour glucose (mmol/L)15.4±2.915.8±3.117.1±3.0<0.001incrementalAUC0-120 glucose (mmol/L)6.4±1.55.3±1.75.7±1.5<0.001HOMA-S (mU.mmol/L-2)0.22±0.230.25±0.210.28±0.41<0.001δInsulin/δGlucose0-30 (mU/mmol)5.3±4.46.5±5.65.1±6.10.002Disposition index (mmol/L-1)0.34±0.640.46±0.430.38±0.370.005Mean±SD. 23 had missing data and 6 were excluded with a triphasic pattern. Disposition index = δI/δG0-30 x HOMA-S. Disclosure K. Utzschneider: Consultant; Self; Novo Nordisk Inc. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc. J.I. Barzilay: Stock/Shareholder; Self; AbbVie Inc., AstraZeneca, Celgene Corporation, DuPont, Merck & Co., Inc., Teva Pharmaceutical Industries Ltd.. E.V. Gonzalez: None. F. Ismail-Beigi: None. K.J. Mather: Research Support; Self; Merck & Co., Inc., Sanofi-Aventis, Novo Nordisk A/S, Abbott. Advisory Panel; Self; Merck & Co., Inc. P. Raskin: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc., GlaxoSmithKline plc.. N. Younes: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. G. Research Group: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute. Other Relationship; Self; Bristol-Myers Squibb Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi-Aventis, Roche Diagnostics Corporation, Becton, Dickinson and Company, Centers for Disease Control and Prevention, National Diabetes Education Program.