Relationship between b-cell responsiveness and fasting plasma glucose in Caucasian subjects with newly presenting Type 2 diabetes R. Hovorka*, A. Albarrak*, L. Chassin*, S. D. Luzio², R. Playle² and D. R. Owens² Abstract Aims b-cell responsiveness was related to fasting plasma glucose to gain further understanding of pathophysiology of Type 2 diabetes. Methods An insulin secretion model gave fasting b-cell responsiveness M 0 (ability of fasting glucose to stimulate b-cell) and postprandial b-cell responsiveness M I (ability of postprandial glucose to stimulate b-cell) by analysing glucose and C-peptide time-concentration curves sampled every 10± 30 min over 240 min during a meal tolerance test (MTT; 75 g CHO, 500 kcal). Caucasian subjects with newly presenting Type 2 diabetes according to WHO criteria (N = 83, male/female: 65 : 18, age: 54 6 10 years, body mass index (BMI): 30.9 6 5.2 kg/m 2 , fasting plasma glucose (FPG): 11.0 6 3.2 mmol/L; mean 6 SD) and Caucasian healthy subjects (N = 54, m/f: 21 : 33, age: 48 6 9 years, BMI: 26.1 6 3.7 kg/m 2 , FPG: 5.1 6 0.4 mmol/L) were studied. Results A continuum inverse relationship between M I and FPG was observed. In the diabetes group, M I was closely related to FPG (r s = ±0.74, P < 0.0001) and explained 60% intersubject FPG variability with the use of an exponential regression model. Conclusions In newly presenting Type 2 diabetes in Caucasian subjects a close inverse association exists between postprandial b-cell responsiveness and FPG. Diabet. Med. 18, 797±802 (2001) Keywords fasting plasma glucose, Type 2 diabetes, pancreatic b-cell responsiveness, meal tolerance test, C-peptide, mathematical modelling Introduction Type 2 diabetes results from the inability of the pancreas to augment insulin secretion in the presence of insulin resistance [1,2]. Various methods have been developed to measure pancreatic b-cell responsiveness: hyperglycaemic clamp [3]; intravenous glucose tolerance test with model- independent assessment [4] or with minimal model or combined model of C-peptide and insulin secretion [5,6]; homeostasis model assessment (HOMA) [7]; and con- tinuous infusion of glucose with model assessment (CIGMA) [8]. We have recently developed an insulin secretion model based on the analysis of glucose and C-peptide time- concentration pro®les during meal tolerance test [9]. The model gives two mechanistic b-cell indices. The ®rst index represents fasting C-peptide secretion normalized (divided) by fasting glucose (fasting b-cell responsiveness M 0 ). The second index represents the ability of postpran- dial glucose to stimulate C-peptide secretion and corres- ponds to the increment in secretion per unit elevation of postprandial glucose (postprandial b-cell responsiveness Correspondence to: Dr Roman Hovorka, Metabolic Modelling Group, Centre for Measurement and Information in Medicine, City University, Northampton Square, London EC1V OHB. E-mail: r.hovorka@soi.city.ac.uk *Metabolic Modelling Group, Centre for Measurement and Information in Medicine, City University, Northampton Square, London, EC1V OHB, UK, and ²Diabetes Research Unit, University of Wales College of Medicine, Academic Centre, 1st Floor, Llandough Hospital & Community NHS Trust, Penlan Road, Penarth CF64 2XX, South Glamorgan, UK Accepted 19 April 2001 ã 2001 Diabetes UK. Diabetic Medicine, 18, 797±802 797