Abstract
Introduction. Impaired free fatty acid (FFA) metabolism is closely linked to insulin resistance. Our aim was to evaluate plasma FFA changes in insulin resistance in a physiological situation after improvement of insulin sensitivity by metformin. Methods. A double-blind, placebo-controlled intervention with metformin was carried out in patients with insulin resistance. Nineteen patients were randomized to receive metformin 850 mg b.i.d. during 6 weeks or placebo. Participants underwent a mental stress test and an oral glucose tolerance test (OGTT) before and after treatment. Results. Fasting plasma glucose, FFA, and HOMA-IR tended to decrease after metformin, suggesting improved insulin sensitivity. FFA concentrations during the mental stress test showed a similar pattern after metformin, albeit lower at all time points, in contrast to the placebo group. The decrease in fasting plasma FFAs was positively associated to the decrease in HbA1c (r = 0.70; P = 0.03) and in fasting glucose (r = 0.74; P = 0.01). The suppression of plasma FFAs during OGTT did not change by metformin or placebo. Conclusion. Metformin in insulin resistance did not lead to improved FFA dynamics despite a trend of improved insulin sensitivity. Metformin most likely decreases plasma FFAs mainly by suppressing fasting FFA concentrations and not by suppression of acute stress-induced lipolysis.
Highlights
Impaired free fatty acid (FFA) metabolism is closely linked to insulin resistance
Disturbances of FFA metabolism are of major importance in the pathogenesis of insulin resistance as seen in type 2 diabetes mellitus [22,23,24]
Our data are partly in line with earlier reports [26, 27], since fasting FFA were decreased by metformin, albeit not statistically significant, most likely due to the small number of subjects included in our study
Summary
Impaired free fatty acid (FFA) metabolism is closely linked to insulin resistance. Our aim was to evaluate plasma FFA changes in insulin resistance in a physiological situation after improvement of insulin sensitivity by metformin. The mechanism whereby mental stress acutely increases FFAs, is stimulation of catecholamine secretion leading to enhanced hydrolysis of intracellular triglycerides in adipose tissue [13, 14]. The counterpart of this activating system is insulin, which leads to an acute inhibition of intracellular lipolysis and suppression of FFA plasma levels [8, 13, 14]. Metformin has been proposed to acutely inhibit catecholamine-stimulated lipolysis in insulin resistant subjects [18] It remains unclear if the FFA lowering effect of metformin is based on lowering basal FFA concentrations or by improving FFA dynamics during acute lipolysis. The present investigation was a double-blind placebo controlled study, designed to determine plasma FFA dynamics under mental stress and during high insulin levels
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