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Pancreatic ß-Cell Responsiveness during Meal Tolerance Test: Model Assessment in Normal Subjects and Subjects with Newly Diagnosed Noninsulin-Dependent Diabetes Mellitus¹

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

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

A model-based method was developed to quantify pancreatic ß-cell responsiveness during a meal tolerance test (MTT). C peptide secretion was related in a linear fashion to glucose concentration, whereas the standard population model was used to derive transfer rate constants of the two compartmental model of C peptide kinetics. Two indexes of pancreatic ß-cell responsiveness were defined: 1) postprandial sensitivity M_I (ability of postprandial glucose to stimulate ß-cell), and 2) basal sensitivity M₀ (ability of fasting glucose to stimulate ß-cell). The method was evaluated using plasma glucose and C peptide measured over 180 min with a 10- to 30-min sampling interval during a MTT (75 g carbohydrates; 500 Cal) performed in 16 normal subjects (7 men and 9 women; age, 50 ± 10 yr; body mass index, 29.2 ± 3.6 kg/m²; fasting plasma glucose, 5.1 ± 0.5 mmol/L; mean ± SD) and 16 body mass index-matched subjects with newly diagnosed noninsulin-dependent diabetes mellitus (NIDDM; 15 men and 1 woman; age, 50 ± 9 yr; body mass index, 29.3 ± 3.7 kg/m²; fasting plasma glucose, 12.6 ± 3.2 mmol/L). M_I and M₀ indexes were estimated with very good precision (coefficient of variation, <15%). Subjects with NIDDM demonstrated lower postprandial sensitivity M_I (17.7 ± 11.4 vs. 90.0 ± 43.3 x 10^-9/min; NIDDM vs. normal, P < 0.001) and basal sensitivity M₀ (5.4 ± 2.2 vs. 10.3 ± 4.9 x 10^-9/min; P < 0.005). Deconvolution analysis documented that the relationship between C peptide secretion and glucose concentration is approximately linear during MTT in both normal subjects (plasma glucose range, 5–8 mmol/L) and subjects with NIDDM (12–17 mmol/L). We conclude that pancreatic responsiveness during glucose stimulation (M_I) and under basal conditions (M₀) can be obtained from this novel method during MTT in healthy and disease states.

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