A dynamic model to analyse intravenous glucose and insulin tolerance tests performed on dairy cows

Abstract

A dynamic model was developed to assess insulin sensitivity and pancreatic response in lactating dairy cows. The model is based on a simultaneous analysis of insulin and glucose intravenous tolerance tests. It comprises five compartments corresponding to insulin in portal–hepatic plasma, and insulin or glucose in both systemic plasma and in interstitial fluid. Insulin secretion rate is a sigmoidal function of glucose in plasma. Insulin is cleared from hepatic plasma and from the interstitial fluid. The glucose entry rate is constant and glucose utilization rate is a sigmoidal function of insulin in the interstitial fluid. Six parameters were estimated: two for insulin secretion rate, two for insulin clearance, one for glucose entry rate and one for glucose utilization rate. After integration of the functions, the model yielded a relative estimate of the quantities of insulin secreted and cleared, as well as the glucose entering and utilized during each test. Using an experimental dataset composed of ten pairs of tolerance tests, the explained variations for plasma insulin and glucose concentrations were 96·0 and 98·3 % and standard errors of estimates were 0·032 nmol/l and 0·14 mmol/l respectively. Except in the early stages after injection, residual errors were low. A Jackknife analysis showed that the estimated parameters exhibited low statistical bias. This model simplifies the interpretation of both tests through a simulation based on six common parameters. Compared to a classical analysis of tolerance tests, it may improve the analysis of modifications in the key functions regulating glucose homeostasis in ruminants.