Higher fasting plasma free fatty acid levels are associated with lower insulin secretion in children and adults and a higher incidence of type 2 diabetes.

CONTEXT: There are limited data in humans on the association between fasting free fatty acid (FFA) levels and pancreatic β-cell function.

OBJECTIVE

Our objective was to examine this association in children and adults with normal glucose tolerance and to explore fasting FFA levels in relation to subsequent risk of impaired glucose tolerance (IGT) and type 2 diabetes (T2D).

DESIGN

We measured FFA, glucose, and insulin levels after an overnight fast and 30 min after an oral glucose load in 797 children aged 8 yr in the Avon Longitudinal Study of Parents and Children and 770 adults aged 44-71 yr in the Medical Research Council Ely Study. We calculated the homeostasis model assessment to estimate fasting insulin sensitivity, the insulinogenic index to estimate insulin secretion, and the disposition index to assess insulin secretion corrected for insulin sensitivity.

RESULTS

Higher fasting FFA levels were associated with lower insulin secretion in children (boys, P = 0.03; girls, P = 0.001) and adults (men, P = 0.03, women, P = 0.04). Associations with insulin sensitivity were more variable, but after adjustment for insulin sensitivity, higher fasting FFA levels remained associated with lower insulin secretion (disposition index). Compared with adults in the lowest tertile of fasting FFA levels, those in the middle and highest tertiles had a 3-fold higher incidence of IGT or T2D over the following 5-8 yr.

CONCLUSIONS

Higher fasting FFA levels were consistently associated with lower insulin secretion in children and adults with normal glucose tolerance. Furthermore, higher fasting FFA levels were prospectively associated with a greater risk of subsequent IGT and T2D.