Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods

Abstract

Type II (non-insulin-dependent) diabetes mellitus is characterised by a progressive functional beta-cell defect [1±5] and a precise measurement of insulin secretion is therefore important. However, an accurate evaluation of insulin secretion involves methodological difficulties [6]. Direct measurement of plasma insulin and C-peptide concentration responses or both to beta-cell stimuli is still the most commonly used method. The kinetics of insulin and C-peptide are influenced by various factors and consequently peripheral insulin or C-peptide concentrations do not always reflect the actual endogenous insulin secretion [6±14]. To overcome these problems, several mathematical methods have been developed to calculate beta-cell secretion from peripheral insulin or C-pep- Diabetologia (2001) Abstract Aims/hypothesis. We compared four methods to assess their accuracy in measuring insulin secretion during an intravenous glucose tolerance test in patients with Type II (non-insulin-dependent) diabetes mellitus and with varying beta-cell function and matched control subjects. Methods. Eight control subjects and eight Type II diabetic patients underwent an intravenous glucose tolerance test with tolbutamide and an intravenous bolus injection of C-peptide to assess C-peptide kinetics. Insulin secretion rates were determined by the Eaton deconvolution (reference method), the Insulin SECretion method (ISEC) based on population kinetic parameters as well as one-compartment and two-compartment versions of the combined model of insulin and C-peptide kinetics. To allow a comparison of the accuracy of the four methods, fasting rates and amounts of insulin secreted during the first phase (0±10 min) and the second phase (10±180 min) were calculated.Results. All secretion responses from the ISEC method were strongly correlated to those obtained by the Eaton deconvolution method (r = 0.83±0.92). The one-compartment combined model, however, showed a high correlation to the reference method only for the first-phase insulin response (r = 0.78). The two-compartment combined model failed to provide reliable estimates of insulin secretion in three of the control subjects and in two patients with Type II diabetes. The four methods were accurate with respect to mean basal and first-phase secretion response. The one-compartment and two-compartment combined models were less accurate in measuring the second-phase response. Conclusion/interpretation. The ISEC method can be applied to normal, obese or Type II diabetic patients.In patients with deviating kinetics of C-peptide the Eaton deconvolution method is the method of choice while the one-compartment combined model is suitable for measuring only the first-phase insulin secretion. [Diabetologia (2001

A matlab framework for estimation of NLME models using stochastic differential equations

“…The state I models the measured insulin concentration in the compartment and the insulin elimination is set to k e,I = 0.355 min −1 . This value has 14 been reported for a similar study, also on type II diabetic patients [18]. By having a fixed elimination rate and ISR given from the C-peptide part of the data, the information in the insulin measurement can be used to estimate the liver extraction.…”

“…The C-peptide measurement error is assumed to be additive Gaussian white noise with variance Σ. The model states are constrained to steady state at t = 0 given an initial individually (18) and the measurement equation is simply y = C 1 + , where ∈ N (0, Σ). The ML estimated population parameters are C 0 1 , Σ, σ ISR and Ω C 0 1 and based on these an optimal estimate of ISR can be found by using the Kalman smoothing algorithm.…”

Metabolic aspects of pig-to-monkey (Macaca fascicularis) islet transplantation: implications for translation into clinical practice

“…injection of glucose at 0.3 or 0.5 g/kg showed C-peptide and insulin levels intermediate between those of pigs and monkeys. The fold increases between time 0 and 5 min and between time 0 and 15 min were (range) 2.5-3.5 and 2.1-3.0 respectively for C-peptide and 6.3-11.4 and 4.0-5.0 for insulin [24][25][26][27][28][29][30].…”

Loss of beta cell function as fasting glucose increases in the non-diabetic range

“…The reference method for clinical measurement of pre-hepatic pancreatic insulin secretion is deconvolution of plasma C-peptide concentrations using rate constants and volumes of distribution derived by two-compartment modelling of the decay of plasma C-peptide concentrations after a bolus injection of synthetic C-peptide [42,43]. In a recent methodological comparison, both the combined model and population parameter deconvolution approaches to estimating pancreatic secretion rates provided secretion measures which were consistent with those from the reference method [44]. Comparison of secretion estimates from the two methods is nevertheless problematic, given that the population parameter approach utilises regression coefficients derived from C-peptide concentrations measured at single centre and that combined model measurements depend on the relative accuracy of the C-peptide and insulin measurements.…”