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Effects of metformin on the regulation of free Fatty acids in insulin resistance: a double-blind, placebo-controlled study.

Castro Cabezas M, van Wijk JP, Elte JW, Klop B - J Nutr Metab (2012)

Bottom Line: Fasting plasma glucose, FFA, and HOMA-IR tended to decrease after metformin, suggesting improved insulin sensitivity.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).Metformin most likely decreases plasma FFAs mainly by suppressing fasting FFA concentrations and not by suppression of acute stress-induced lipolysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Center for Diabetes and Vascular Medicine, Sint Franciscus Gasthuis Rotterdam, P.O. Box 10900, 3004 BA Rotterdam, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus

Mean change in glucose, insulin, and free fatty acid (FFA) concentrations during an oral glucose tolerance test (OGTT) in insulin resistant patients at baseline and six weeks after treatment with either metformin (N = 10) (a, c, and e) or placebo (N = 9) (b, d, and f). Data represent the mean ± SEM.
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fig2: Mean change in glucose, insulin, and free fatty acid (FFA) concentrations during an oral glucose tolerance test (OGTT) in insulin resistant patients at baseline and six weeks after treatment with either metformin (N = 10) (a, c, and e) or placebo (N = 9) (b, d, and f). Data represent the mean ± SEM.

Mentions: Heart rate increased by 9.8% in the metformin group (P = 0.005) and by 8.8% in the placebo group (P = 0.07) during the mental stress test with the maximum increase at 5 to 10 minutes after the start of the mental stress. During the first 60 minutes before the mental stress, FFA plasma levels did not change significantly. During mental stress, plasma FFAs increased significantly in both groups resulting in similar increments after each intervention. There were no significant effects by metformin on mental stress-induced FFA changes when compared to placebo. During the 20 minutes of mental-stress, FFA increased significantly in the metformin group by 30.9 ± 2.1% before and 29.8 ± 1.6% after treatment and in the placebo group by 31.7 ± 3.1% and 34.1 ± 3.3%, respectively. The incremental area under the FFA curve showed no significant difference between the groups (1.77 ± 0.49 mmol·min/L before and 1.39 ± 0.29 mmol·min/L after metformin versus 1.39 ± 0.38 mmol·min/L before and 1.60 ± 0.41 mmol·min/L after placebo). The variables best associated with the decrease of fasting plasma FFA after metformin were the decrease in plasma glucose (r = 0.74; P = 0.01) and in HbA1c (r = 0.70; P = 0.03).


Effects of metformin on the regulation of free Fatty acids in insulin resistance: a double-blind, placebo-controlled study.

Castro Cabezas M, van Wijk JP, Elte JW, Klop B - J Nutr Metab (2012)

Mean change in glucose, insulin, and free fatty acid (FFA) concentrations during an oral glucose tolerance test (OGTT) in insulin resistant patients at baseline and six weeks after treatment with either metformin (N = 10) (a, c, and e) or placebo (N = 9) (b, d, and f). Data represent the mean ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475305&req=5

fig2: Mean change in glucose, insulin, and free fatty acid (FFA) concentrations during an oral glucose tolerance test (OGTT) in insulin resistant patients at baseline and six weeks after treatment with either metformin (N = 10) (a, c, and e) or placebo (N = 9) (b, d, and f). Data represent the mean ± SEM.
Mentions: Heart rate increased by 9.8% in the metformin group (P = 0.005) and by 8.8% in the placebo group (P = 0.07) during the mental stress test with the maximum increase at 5 to 10 minutes after the start of the mental stress. During the first 60 minutes before the mental stress, FFA plasma levels did not change significantly. During mental stress, plasma FFAs increased significantly in both groups resulting in similar increments after each intervention. There were no significant effects by metformin on mental stress-induced FFA changes when compared to placebo. During the 20 minutes of mental-stress, FFA increased significantly in the metformin group by 30.9 ± 2.1% before and 29.8 ± 1.6% after treatment and in the placebo group by 31.7 ± 3.1% and 34.1 ± 3.3%, respectively. The incremental area under the FFA curve showed no significant difference between the groups (1.77 ± 0.49 mmol·min/L before and 1.39 ± 0.29 mmol·min/L after metformin versus 1.39 ± 0.38 mmol·min/L before and 1.60 ± 0.41 mmol·min/L after placebo). The variables best associated with the decrease of fasting plasma FFA after metformin were the decrease in plasma glucose (r = 0.74; P = 0.01) and in HbA1c (r = 0.70; P = 0.03).

Bottom Line: Fasting plasma glucose, FFA, and HOMA-IR tended to decrease after metformin, suggesting improved insulin sensitivity.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).Metformin most likely decreases plasma FFAs mainly by suppressing fasting FFA concentrations and not by suppression of acute stress-induced lipolysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Center for Diabetes and Vascular Medicine, Sint Franciscus Gasthuis Rotterdam, P.O. Box 10900, 3004 BA Rotterdam, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus