Integrated insulin secretion rates calculated from peripheral venous C-peptide measurements by two-compartment kinetic analysis were measured in six young normal subjects after increasing oral glucose loads of 25, 50, and 100 g and respective isoglycemic glucose infusions. The differences in B-cell secretory responses between oral and iv glucose challenges were attributed to factors other than glycemia itself (incretin effect). Both insulin and C-peptide concentrations as well as calculated integrated insulin secretion rates increased with increasing oral glucose loads. Due to the similarity in the glucose profiles after all oral loads, almost identical amounts of iv glucose (approximately 20 g) were infused in all "isoglycemic" infusion experiments, with resulting similar hormone profiles and insulin secretion rates. The percent contribution of incretin factors to total immunoreactive insulin responses after 25, 50, and 100 g glucose (85.6%, 74.9%, and 93.0%; response to oral load, 100%) was significantly higher than their contribution to integrated C-peptide responses (27.6-62.9%) or calculated integrated insulin secretion rates (19.2-61.0%). These findings indicate that the degree of incretin stimulation of insulin secretion depends on the amount of glucose ingested. A discrepancy between the estimates of the incretin effect derived from peripheral venous insulin responses, on the one hand, and C-peptide responses or calculated insulin secretion rates, on the other hand, exists. Inasmuch as peripheral insulin values reflect both insulin secretion and hepatic insulin removal, this discrepancy suggests that elimination kinetics of insulin differ between oral and iv glucose administration. This difference can be related to a significantly reduced fractional hepatic insulin extraction after oral (46.9-54.6%) compared to iv (63.4-76.5%) glucose administration when calculated by a three-compartment kinetic model. This reduction in fractional hepatic insulin extraction could be caused by gastrointestinal factors (hormones or nerves) stimulated in the course of glucose ingestion.

The prehepatic production of insulin in normal man was evaluated by kinetic analysis of connecting peptide (C-peptide) behavior in the plasma in men and women. Studies were performed during suppression of endogenous insulin secretion (induced by both fasting and exogenous insulin injection) as well as during stimulation of secretion (induced by oral glucose ingestion) and iv glucose injection. Least squares spline fitting of the C-peptide data by interactive computer analysis permitted evaluation of the precursor production of insulin using a two-compartment model for C-peptide removal. Basal prehepatic insulin production averaged 15-4 mU/70 kg.min in 20 subjects and was reduced to 0.9 +/- 2.2 mU/70 kg.min after 84 h of fasting. The injection of exogenous iv insulin resulted in suppression of endogenous production to 0 +/- 2.5 mU/70 kg.min. Maximum prehepatic insulin production induced by a 100-g oral glucose tolerance test was 91 +/- 1.2 mU/70 kg.min, with a cumulative hormone secretion of 11.4 +/- 2.0 U over the 5 h of observation. After the acute iv injection of 25 g glucose, production rose to 465 +/- 108 mU/70 kg.min at 2 min post injection and rapidly returned toward basal. Levels of insulin in the portal vein calculated from this analysis were markedly elevated relative to simultaneous peripheral venous levels. These results quantitate prehepatic insulin production and portal venous insulin concentration from an analysis of the behavior of C-peptide within the plasma in both the steady state and the nonsteady state in man.

A B S T R A C T Plasma transport of free fatty acids (FFA) and triglyceride fatty acids (TGFA) was studied in seven subjects with normal lipid metabolism, one case of total lipodystrophy, and one case of familial hyperlipemia (Type V). Studies were carried out after intravenous injection of radioactive FFA, of lipoproteins previously labeled in vitro in the triglyceride moiety, or both.Computer techniques were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for both FFA and TGFA. The results show that as much as 20-30% of FFA leaving the plasma compartment in normal subjects is transported to an exchanging extravascular pool and quickly reenters the plasma pool as FFA. The rate of irreversible delivery of FFA from plasma to tissues averaged 358 AEq/min in normals. The lipodystrophy patient, despite the virtual absence of adipose tissue (confirmed at autopsy), had a plasma FFA concentration and a total FFA transport, both more than twice normal. Total TGFA transport ranged from 25 to 81 MLEq/min in four normal controls.The rate constant for TGFA turnover in the patient with Type V hyperlipemia was so small that total transport could not be quantified from the data available; the TGFA half-life was over 500 min.In two normal subjects given injections of autologous lipoproteins labeled in vitro with triolein-"C and simultaneously given oleic acid-8H, it was shown that the time course for the disappearance of the TGFA in the in vitro labeled samples conformed almost exactly to that of the physiologically labeled lipoprotein TGFA synDr. Eaton's present address is

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Noninvasive monitoring of blood/tissue glucose concentrations has been successfully accomplished in individual diabetic subjects by using near-infrared (NIR) spectroscopy coupled with chemometric methods. Three different spectrometer configurations were tested: a) a Fourier-transform infrared spectrometer with an indium antimonide detector; b) a grating monochromator equipped with a silicon (Si) array detector, without fiber optics; and c) a grating monochromator equipped with an Si detector, with fiber-optic sampling. NIR spectra were obtained from diabetic subjects by transmission through the finger during a meal-tolerance test. The maximum range of observed plasma glucose concentrations obtained from the blood samples was 2.5-27 mmol/L. The NIR spectra were processed by using the chemometric multivariate calibration methods of partial least squares and principal component regression. The best calibration yielded a cross-validated average absolute error in glucose concentration of 1.1 mmol/L. This predictive ability suggests that noninvasive glucose determinations by NIR/chemometrics is a viable analytical method.

Abstract'[hi.,, rep_rt describe.,, an assessment of the hmg-term performance of a repository system that c, mtains deeply buried highly radi_mctive waste; the system is assumed tc) be located at the potential >lte at Yucca Mountain, Nevada.

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