A stable isotope minimal model protocol with oral glucose administration.

A protocol for investigating glucose metabolism whereby stable isotope tracer is given intravenously after an oral glucose challenge is described. Frequent sampling of plasma glucose and insulin allows the tracer disappearance to be interpreted on the basis of established minimal models. We have investigated the glucose effectiveness and insulin sensitivity parameters and their reproducibility in a group of six healthy adults, each studied twice.

13C- and 2H-labelled glucose compared for minimal model estimates of glucose metabolism in man.

In the present study, we have investigated the use of 1-[(13)C]glucose and GC/combustion/isotope-ratio MS as an alternative to 6,6-[(2)H(2)]glucose and GC/MS in the determination of parameters of glucose metabolism using the IVGTT (intravenous glucose tolerance test) interpreted by labelled (hot) minimal models. The study has been done in four populations, normoglycaemics (subdivided into lean and obese individuals), subjects with impaired glucose tolerance and those with diabetes mellitus. Although the use of carbon label may in some circumstances be compromised by substrate recycling, our hypothesis was that this would not be an issue under the condition of suppression of hepatic glucose production during the short timescale of an IVGTT.

Glycogenesis and glucose oxidation during an intravenous glucose tolerance test in man.

The quantity of deuterated glucose customarily given in labelled IVGTTs (intravenous glucose tolerance tests) changes the isotopic composition of the subject's body water enough to be detected by mass spectrometric techniques. Glucose undergoing direct glycogenesis does not contribute label to the body water pool, and isotope incorporated into it must have come from glucose that has either been oxidized or undergone indirect glycogenesis. By subtracting the amount of label found in body water from the total amount of glucose utilized, as calculated from the minimal model of glucose disappearance, it should be possible to study the partitioning of the dose given between direct glycogenesis in skeletal muscle and other metabolic pathways.

Measurement of insulin sensitivity indices using 13C-glucose and gas chromatography/combustion/isotope ratio mass spectrometry.

Important aspects of glucose metabolism can be quantified by using the minimal model of glucose kinetics to interpret the results of intravenous glucose tolerance tests. The power of this methodology can be greatly increased by the addition of stable isotopically labelled tracer to the glucose bolus dose. This allows the separation of glucose disposal from endogenous glucose production and also increases the precision of the estimates of the physiological parameters measured.