Submitted on March 26, 2008
Revised on June 2, 2008
Accepted on June 16, 2008
NEFA Minimal Model parameters estimated from the Oral Glucose Tolerance Test and the Meal Tolerance Test
Ray C Boston1* and Peter J Moate2
1 School of Veterinary Medicine, University of Pennsylvania
2 University of Pennsylvania
* To whom correspondence should be addressed. E-mail: drrayboston{at}yahoo.com.
The kinetics of non-esterified fatty acid (NEFA) metabolism in humans requires quantification to facilitate understanding of diseases like type 1 and 2 diabetes, metabolic syndrome and obesity, and the mechanisms underpinning various interventions. Oral glucose tolerance tests (OGTT) and glucose meal tolerance tests (MTT) are potentially useful procedures for enabling quantification of NEFA kinetics because they both cause transitory but substantial declines and then rebounds in plasma NEFA concentrations in response to physiologically relevant increases in plasma glucose. The Boston MINIMAL model of NEFA kinetics was developed to analyze data from the IVGTT, but in this work we present for the first time its application to modeling NEFA data from both OGTT and MTT studies. This model enables estimation of SFFA [µmol.l-1.min-1] (a parameter describing the maximum rate of lipolysis), and KFFA [%.min-1] (a parameter related to NEFA oxidation rate). The model could well describe the trajectories of NEFA concentrations following an OGTT (R2 in excess of 0.97), but was not as successful with the MTT (R2 > 0.65). Model parameters derived from analysis of OGTT and MTT data were well identified with coefficients of variation generally less than 15%. Type 2 diabetes, BMI and dietary treatment (high fat vs. high glycaemic index diets) were all shown to have significant effects on model parameters. Modeling plasma NEFA concentrations over 24 hours has helped to identify and quantify the extent that periprandial NEFA peaks and nocturnal elevation in plasma NEFA can be accounted for by our model.
