MEASURING PREHEPATIC INSULIN-SECRETION USING A POPULATION-MODEL OF C-PEPTIDE KINETICS - ACCURACY AND REQUIRED SAMPLING SCHEDULE

The accuracy of calculations of pre-hepatic insulin secretion were inv estigated, to provide independent validation of a population model of C-peptide kinetics. The effects of sampling frequency were also assess ed. Five normal subjects (aged 28 to 43 years; BMI (kg/m(2)) 20.5 to 2 4.5) and five subjects with non-insulin-dependent diabetes mellitus (N IDDM) treated by diet alone (aged 34 to 57 years; BMI 22.6 to 25.6) we re given a variable intravenous infusion of biosynthetic human C-pepti de (BHCP) (t = -60 to 240 min) mimicking meal stimulated C-peptide sec retion, with short-term oscillations (peak approximately every 12 min) superimposed on the infusion profile. Plasma C-peptide was measured e very 5 min (t = 0 to 240 min). The BHCP infusion was reconstructed fro m C-peptide measurements using a population model of C-peptide kinetic s and a deconvolution method. Bias, defined as the percentage differen ce between the total amount of calculated BHCP and the total amount of infused BHCP (t = 0 to 240 min), indicated that overall C-peptide sec retion can be measured with 14% [95 % confidence interval (CI) -11 to 39%] and 21% (95% CI -3 to 45 %) accuracy in normal subjects and subje cts with NIDDM respectively. Accuracy was not reduced by reducing the sampling frequency to every 30 min. The root mean square error, measur ing the average deviation between the infused and normalised calculate d BHCP profiles, was also independent of the sampling frequency [mean (95 % CI) 0.9 (0.3 to 1.6) pmol/kg per min in normal subjects; 1.0 (0. 9 to 1.1) pmol/kg per min in subjects with NIDDM]. Deconvolution emplo ying a population model of C-peptide kinetics can be used to estimate postprandial total C-peptide secretion with biases of 14% and 22% resp ectively in normal subjects and subjects with NIDDM. Plasma C-peptide samples need only be drawn every 30 minutes.