Associations of Glucose Control with Insulin Sensitivity and Pancreatic β-Cell Responsiveness in Newly Presenting Type 2 Diabetes

Abstract

We examined the ability of indices of insulin sensitivity and pancreatic β-cell responsiveness to explain interindividual variability of clinical measures of glucose control in newly presenting type 2 diabetes. Subjects with newly presenting type 2 diabetes (n = 65; 53 males and 12 females; age, 54 ± 1 yr; body mass index, 30.5 ± 0.7 kg/m2; mean ± se) underwent an insulin-modified iv glucose tolerance test to determine minimal model-derived insulin sensitivity (SI), glucose effectiveness, first-phase insulin secretion, and disposition index. Subjects also underwent a standard meal tolerance test (MTT) to measure fasting/basal (M0) and postprandial (MI) pancreatic β-cell responsiveness. Stepwise linear regression used these indices to explain interindividual variability of fasting and postprandial plasma glucose and insulin concentrations and glycated hemoglobin (HbA1C). All measures of pancreatic β-cell responsiveness (M0, MI, and first-phase insulin secretion) were negatively correlated with fasting plasma glucose (P < 0.01) and positively correlated with fasting plasma insulin (FPI) and insulin responses to MTT (P < 0.05). SI demonstrated negative correlation with FPI (P < 0.001) but failed to correlate with any glucose variable. MI followed by disposition index (composite index of insulin sensitivity and pancreatic β-cell responsiveness) were most informative in explaining interindividual variability. It was possible to explain 70–80% interindividual variability of fasting plasma glucose, FPI, HbA1C, and insulin responses to MTT, and only 25–40% interindividual variability of postprandial glucose. In conclusion, postprandial insulin deficiency is the most powerful explanatory factor of deteriorating glucose control in newly presenting type 2 diabetes. Indices of insulin sensitivity and pancreatic β-cell responsiveness explain fasting glucose and HbA1C well but fail to explain postprandial glucose.