Cross-sectional but not longitudinal associations between non-esterified fatty acid levels and glucose intolerance and other features of the metabolic syndrome

Aims Cross-sectional studies have demonstrated an association between high non-esterified fatty acid (NEFA) concentrations and glucose intolerance. However, the direction of causality in these studies is uncertain. The aim of this study was to examine whether NEFA levels predicted the development of glucose intolerance in a prospective population-based cohort study. Methods Four hundred and eighty-one women and 345 men participated in a prospective cohort study in which NEFA concentrations and glucose tolerance were measured at baseline and then repeated at follow-up 4.5 years later. Results The data do not show longitudinal relationships between baseline NEFA levels and either glucose intolerance or other features of the metabolic syndrome at follow-up. In contrast, strong cross-sectional associations were observed between NEFA measures and glucose intolerance (and other features of the metabolic syndrome) in both baseline and follow-up studies. At follow-up, fasting NEFA levels and two measures of NEFA suppression were markedly different in subjects with features of the metabolic syndrome, compared to subjects with normal glucose tolerance (NGT) (NGT vs. metabolic syndrome for each NEFA value, P < 0.001). Conclusions These results support the hypothesis that plasma NEFA levels change as a consequence of the metabolic syndrome and do not support the notion that increased NEFA levels cause either the metabolic syndrome or diabetes.