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

Metabolic Modelling Group (A.I.A., L.J.C., R.H.), Centre for Measurement and Information in Medicine, City University, London, EC1V OHB, United Kingdom; and Diabetes Research Unit (S.D.L., R.A.P., D.R.O.), University of Wales College of Medicine, Academic Centre, Llandough Hospital and Community NHS Trust, Penarth CF64 2XX, South Glamorgan, United Kingdom

Address all correspondence and requests for reprints to: Dr. Roman Hovorka, Metabolic Modeling Group, Centre for Measurement and Information in Medicine, City University, Northampton Square, London, EC1V OHB, United Kingdom. E-mail: r.hovorka{at}soi.city.ac.uk

We examined the ability of indices of insulin sensitivity and pancreatic ß-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 (S_I), 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 (M_I) pancreatic ß-cell responsiveness. Stepwise linear regression used these indices to explain interindividual variability of fasting and postprandial plasma glucose and insulin concentrations and glycated hemoglobin (HbA_1C). All measures of pancreatic ß-cell responsiveness (M₀, M_I, 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). S_I demonstrated negative correlation with FPI (P < 0.001) but failed to correlate with any glucose variable. M_I followed by disposition index (composite index of insulin sensitivity and pancreatic ß-cell responsiveness) were most informative in explaining interindividual variability. It was possible to explain 70–80% interindividual variability of fasting plasma glucose, FPI, HbA_1C, 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 ß-cell responsiveness explain fasting glucose and HbA_1C well but fail to explain postprandial glucose.

Abbreviations: AIR_G, First-phase insulin secretion; AUC_Glucose, incremental area under the curve of plasma glucose during MTT; AUC_Insulin, incremental area under the curve of insulin during MTT; BMI, body mass index; C_max,Glucose, maximum incremental plasma glucose concentration during the MTT; C_max,Insulin, maximum incremental plasma insulin concentration during the MTT; D_I, disposition index; FPG, fasting plasma glucose; FPI, fasting plasma insulin; HbA_1C, glycated hemoglobin; IVGTT, iv glucose tolerance test; M₀, fasting pancreatic ß-cell responsiveness; M_I, postprandial pancreatic ß-cell responsiveness; MTT, meal tolerance test; S_G, glucose effectiveness; S_I, insulin sensitivity.

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