The multiphasic profile of free fatty acids during the intravenous glucose tolerance test is unresponsive to exogenous insulin

Sumner, Anne E.; Bergman, Richard N.; Vega, Gloria Lena; Genovese, David J.; Cochran, Craig; Pacák, Karel; Watanabe, Richard M.; Boston, Ray

doi:10.1016/j.metabol.2004.03.020

Cited by 22 publications

(46 citation statements)

References 21 publications

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“…As can be seen in Figs. 2-5, and as has been reported previously (39,46), when an FSIGT is conducted in humans, especially overweight or obese humans, there is often an extended latency period before NEFA concentrations begin a precipitous decline. In contrast, in lactating dairy cows there is generally only a short latencys period (10,29).…”

Section: Methodsmentioning

confidence: 68%

“…The data used to develop this model came from two previously reported experiments involving a range of subject types and experimental protocols (Table 1). Briefly, the experiment of Sumner et al (39) involved 13 healthy, African-Americans who were administered an insulin-modified frequently sampled IVGTT (IM-FSIGT), and then, 4 wk later were administered a glucose-only IVGTT (GO-FSIGT). The experiment of Brehm et al (11) involved 13 lean, healthy, subjects who underwent in random order, an IM-FSIGT and a modified protocol (IM-FSIGT-CLAMP) during which variable-rate glucose infusions were administered to prevent plasma glucose from declining below 100 mg/dl.…”

Section: Methodsmentioning

confidence: 99%

“…1, A and C in Sumner et al (39), and Fig. 1, A and C in Brehm et al (11) were used in this analysis.…”

Section: Methodsmentioning

confidence: 99%

“…More recently, the IVGTT has been used to elucidate the relationship between plasma glucose and NEFA concentrations (39,46).…”

mentioning

confidence: 99%

“…Furthermore, the Thomaseth model assumes that the rebound plateau concentration of NEFA is the same as the initial or pre-IVGTT NEFA concentration (28). This assumption is a serious defect since NEFA concentrations often rebound to a plateau concentration Ͼ 50% higher than the initial or pre-IVGTT NEFA concentration (39). We speculate that with a number of changes, especially related to assumptions regarding initial conditions, the Thomaseth model might be modified so that it can overcome these defects.…”

mentioning

confidence: 99%

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A novel minimal model to describe NEFA kinetics following an intravenous glucose challenge

Boston

Moate²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Dynamics of nonesterified fatty acid (NEFA) metabolism in humans requires quantification if we are to understand the etiology of such diseases as type 1 and 2 diabetes, as well as metabolic syndrome and obesity, or if we are to elucidate the mechanism of action of various interventions. We present a new compartmental model that employs the pattern of plasma glucose concentrations in healthy young adults to predict dynamic changes that occur in plasma NEFA concentrations during either a glucose-only intravenous glucose tolerance test, or an insulin-modified intravenous tolerance test, or a modified protocol during which variable-rate glucose infusions were administered to prevent plasma glucose from declining below 100 mg/dl. The model described all of the major features of NEFA response to an intravenous glucose tolerance test, including an initial latency phase, a phase during which plasma NEFA concentrations plummet to a nadir, and a rebound phase during which plasma NEFA concentrations may rise to a plateau concentration, which may be substantially higher than the initial basal NEFA concentration. This model is consistent with physiological processes and provides seven adjustable parameters that can be used to quantify NEFA production (lipolysis) and utilization (oxidation). When tested on data from the scientific literature, the range in estimated rate of lipolysis was 24-36 micromol.l(-1).min(-1) and for NEFA oxidation rate was 25-54 micromol.l(-1).min(-1). All model parameters were well identified and had coefficients of variation < 15% of their estimated values. It is concluded that this model is suitable to describe NEFA kinetics in human subjects.

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