Relationship between Baseline Phenotype and Measures of Insulin Sensitivity and Beta-Cell Responses in the GRADE Cohort

Abstract

Factors associated with β-cell dysfunction in type 2 diabetes (T2D) are not well understood. We examined the association between OGTT-derived estimates of insulin sensitivity, insulin/C-peptide responses and β-cell function with baseline phenotypic characteristics in the GRADE cohort. The cohort comprised 5,047 adults with T2D <10 y, treated with metformin alone. Subjects were 63.6% men, 57.2±10 y/o (mean±SD), with BMI 34.3±6.8 kg/m2, weight 99.9±22.3 kg, waist circumference (circ) 112.3±15.8 cm, HbA1c 7.5±0.5% and T2D duration 4.2±2.8 y. Racial composition was 66% white, 20% African Americans, 4% Asian, 3% American Indian, and 7% Other. Insulin sensitivity did not differ between men and women, but women had higher insulin/C-peptide responses and disposition index (DI) (p<0.001 for all). The associations between insulin sensitivity, insulin/C-peptide responses and DI with age, BMI, weight, waist circ and T2D duration are provided in Table 1. Insulin sensitivity, insulin/C-peptide responses and DI differed by racial category (p<0.001 for all). In summary, among GRADE participants, sex, race and obesity are associated with β-cell function. Although statistically significant, the associations of insulin sensitivity and β-cell responses with age and T2D duration are not as strong.Table 1- The Spearman correlation (upper line) and p value (lower line) between baseline phenotypic characteristics and insulin sensitivity, insulin/C-peptide responses and DI.AgeWeightBMIWaist circT2D DurationMatsuda Index0.07<0.001-0.40<0.001-0.46<0.001-0.45<0.0010.08<0.001HOMA-S Index0.12<0.001-0.47<0.001-0.50<0.001-0.49<0.0010.09<0.001Insulin responseδinsulin 0-30/δglucose 0-300.04=0.010.26<0.0010.32<0.0010.29<0.001-0.13<0.001C-peptide responseδC-peptide 0-30/δglucose 0-300.07<0.0010.14<0.0010.19<0.0010.18<0.001-0.08<0.001Disposition Index(δinsulin 0-30/δglucose 0-30)/fasting insulin0.13<0.001-0.13<0.001-0.11<0.001-0.13<0.001-0.03=0.09 Disclosure N. Rasouli: Consultant; Self; AstraZeneca, Intarcia Therapeutics, Inc. R.M. Cohen: Stock/Shareholder; Self; Bristol-Myers Squibb Company. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc. S. Inzucchi: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Novo Nordisk Inc., Sanofi, Lexicon Pharmaceuticals, Inc.. Consultant; Self; VTV Therapeutics. Other Relationship; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc., Alere Inc.. F. Ismail-Beigi: 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. K. Utzschneider: Consultant; Self; Novo Nordisk Inc. J. Lachin: Board Member; Self; AbbVie Inc., Celgene Corporation. N. Younes: None. 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.