Metabolic Function in 5,047 Adults with Type 2 Diabetes on Metformin Alone Based on Oral Glucose Tolerance Test (OGTT) Data from the GRADE Cohort
Authors: UTZSCHNEIDER KRISTINA , BANERJI MARY ANN , BARZILAY JOSHUA I. , GONZALEZ ERICA V. , ISMAIL-BEIGI FARAMARZ , MATHER KIEREN J. , RASKIN PHILIP , YOUNES NAJI , KAHN STEVEN E. ,   GRADE RESEARCH GROUP
Published: June 2018

Little data exist on the relationship between glycemic variables, insulin sensitivity and insulin and C-peptide responses in subjects with T2DM. We assessed these relationships using baseline OGTT data from the Glycemia Reduction Approaches in Diabetes, A Comparative Effectiveness study (GRADE) cohort. Eligibility included T2DM &lt;10 y, HbA1c 6.8-8.5% treated with metformin alone. Glucose, insulin and C-peptide were measured at 0, 15, 30, 60, 90 and 120 minutes in 5047 OGTTs. Insulin sensitivity was measured by HOMA-S and insulin and C-peptide responses were estimated using δhormone/δglucose0-30 and incremental area under the curve (incAUC) hormone/glucose0-120. Subjects were 63.6% men, 57.2±10 y old (mean±SD), with HbA1c 7.5±0.5% and T2DM duration 4.2±2.8 y. Insulin and C-peptide responses were inversely associated with HOMA-S in a curvilinear manner (p&lt;0.001 for all). Glycemic variables were all inversely associated with HOMA-S and insulin and C-peptide responses (Table, p&lt;0.001 for all). The weakest association was between HbA1c and HOMA- S and the strongest between 2h glucose and incAUC C-peptide. Even in established diabetes there is measurable β-cell function and these measures remain proportional to glycemic responses. We plan to use these baseline measures of β-cell function as potential determinants of treatment outcomes in GRADE.
Table: Adjusted Regression DataHOMA-SδI/δG0-30δCP/δG0-30incAUC I/G0-120incAUC CP/G0-120Fasting glucose-0.28-0.20-0.21-0.28-0.322hr glucose-0.18-0.25-0.27-0.34-0.44incAUC-G0-120-0.10-0.16-0.16-0.16-0.18HbA1c-0.07-0.10-0.09-0.13-0.15Regression models are presented as signed R2 adjusted for sex, age, race, BMI, T2DM duration, eGFR and metformin dose. I = insulin, G = glucose, CP = C-peptide

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.