Hepatic fat is not associated with β-cell function or postprandial free fatty acid response

Abstract

AbstractWe evaluated the association of hepatic fat with β-cell function estimated from the oral glucose tolerance test. In addition, we tested the hypothesis that postprandial free fatty acid (FFA) suppression after a meal tolerance test (MTT) is linked to hepatic fat. Individuals with normal glucose metabolism (NGM; n = 10 with low and n = 10 with high insulin secretion, matched for insulin sensitivity and sex), impaired glucose metabolism (IGM; n = 14), and type 2 diabetes mellitus (DM; n = 14) underwent a 75-g oral glucose tolerance test and MTT. β-Cell function estimates were calculated from C-peptide using a mathematical model. Liver fat was quantified by proton magnetic resonance (1H-MR) spectroscopy. Area under the curve (AUC) of triglycerides (TG) and FFA responses during MTT represented postprandial lipid responses. Linear regression models were adjusted for age, sex, and additionally for insulin sensitivity for IGM/DM subjects. Liver fat content was equal for the NGM groups with low and high insulin secretion: 4.5% (2.6-6.0) (median, interquartile range) and 4.9% (2.3-7.8), respectively; liver fat percentages of IGM and diabetic subjects were significantly higher: 11.2 (6.7-21.1) and 10.0 (7.8-24.5). Liver fat showed a fairly strong, significant negative association with insulin sensitivity, but was not associated with β-cell function. Significant associations of liver fat with fasting TG and AUCTG were shown in the total study population and in IGM/DM subjects separately. No relationship existed between fasting FFA or AUCFFA and liver fat. We conclude that fat accumulation in the liver is tightly linked to insulin sensitivity but not to β-cell function. Furthermore, liver fat is associated with circulating TG levels, but not with FFA concentrations.