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 <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<0.001 for all). Glycemic variables were all inversely associated with HOMA-S and insulin and C-peptide responses (Table, p<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 Data
| HOMA-S | δI/δG0-30 | δCP/δG0-30 | incAUC I/G0-120 | incAUC CP/G0-120 | |
| Fasting glucose | -0.28 | -0.20 | -0.21 | -0.28 | -0.32 |
| 2hr glucose | -0.18 | -0.25 | -0.27 | -0.34 | -0.44 |
| incAUC-G0-120 | -0.10 | -0.16 | -0.16 | -0.16 | -0.18 |
| HbA1c | -0.07 | -0.10 | -0.09 | -0.13 | -0.15 |
| HOMA-S | δI/δG0-30 | δCP/δG0-30 | incAUC I/G0-120 | incAUC CP/G0-120 | |
| Fasting glucose | -0.28 | -0.20 | -0.21 | -0.28 | -0.32 |
| 2hr glucose | -0.18 | -0.25 | -0.27 | -0.34 | -0.44 |
| incAUC-G0-120 | -0.10 | -0.16 | -0.16 | -0.16 | -0.18 |
| HbA1c | -0.07 | -0.10 | -0.09 | -0.13 | -0.15 |
Regression 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
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.
