Effects of Metformin on the Regulation of Free Fatty Acids in Insulin Resistance: A Double-Blind, Placebo-Controlled Study

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 (; ) and in fasting glucose (; ). 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

Mannose binding lectin 2 haplotypes do not affect the progression of coronary atherosclerosis in men with proven coronary artery disease treated with pravastatin

Objective: Mannose binding lectin (MBL) is one of the three initiators of complement activation. Polymorphisms of the MBL2 gene and its promoter, and especially haplotypes, determine MBL plasma levels. MBL deficiency has been associated with the development of atherosclerosis. We evaluated whether the rate of angiographic progression of coronary atherosclerosis during pravastatin treatment was associated with MBL2 haplotypes in REGRESS, a placebo-controlled 2 years intervention study. Methods: Three polymorphic sites in exon 1 (rs1800450, rs1800451 and rs5030737) of the MBL2 gene and 2 sites (rs7096206 and rs11003125) in the promoter region were genotyped in 398 subjects. Genotyping was performed using Applied Biosystems (R) TaqMan (R) Genotyping Assays. We divided the group in high, intermediate and low MBL2 secretor haplotypes. Quantitative coronary angiography was performed. Endpoints were mean segment diameter (MSD) and minimum obstruction diameter (MOD) established by quantitative coronary angiography. Results: At inclusion, 50.1, 31.7 and 17.6% of the patients in the REGRESS cohort carried the high, intermediate and low MBL2 secretor haplotypes, respectively. In 0.6% of the patients, the haplotype was not informative. There were no baseline differences between the MBL2 haplotypes for age, BMI, lipid levels, leukocyte counts, CRP, MSD and MOD. The intermediate MBL2 placebo group showed the greatest increase in MSD compared to the low MBL2 group (P = 0.03). No difference was found for the change in MOD. No significant interaction between MBL2 haplotype groups and pravastatin therapy was observed. Conclusion: In men with proven coronary artery disease, MBL2 secretor haplotypes are not associated to the rate of progression of coronary sclerosis nor does pravastatin treatment influence progression based on MBL2 haplotypes. (C) 2011 Elsevier Ireland Ltd. All rights reserve

The association between erythrocyte-bound apolipoprotein B (ery-apoB) and ABO blood group phenotypes.

<p>The prevalence of the ABO blood group phenotypes per tertile are shown (A). Tertiles are based upon ery-apoB. The first tertile represents the group with the lowest ery-apoB, whereas the third tertile represents the subjects with the highest ery-apoB. The prevalence of ABO blood group phenotypes was significantly different between the three groups (P = 0.002). Ery-apoB levels were almost two-fold increased in subjects with blood group O when compared to subjects with blood group A, B or AB (P-ANOVA <0.001) (B). *P<0.05 when compared to subjects with blood group A, B or AB.</p

Discontinuation of statin therapy did not affect erythrocyte-bound apolipoprotein B (ery-apoB).

<p>Ery-apoB was measured in subjects using statins (N = 54) at baseline and after discontinuing statin therapy for 6 weeks. Individual ery-apoB levels remained fairly stable during the 6 weeks of follow-up since ery-apoB at baseline was strongly correlated to ery-apoB after discontinuing statin therapy for 6 weeks (Spearman r: 0.828; P<0.001).</p

Characteristics of a select group of subjects with measurements of erythrocyte-bound apolipoprotein B (ery-apoB) and ABO blood group phenotype.

<p>Subjects were divided according to ABO blood group phenotype.</p>*<p>Significantly different when compared to blood group O (P<0.05).</p>**<p>Significantly different when compared to blood group A (P<0.05).</p>***<p>Significantly different when compared to blood group A, B or AB (all P<0.05).</p

Characteristics of subjects based on carotid intima media thickness and on deficiency of ery-apoB (ery-apoB ≤0.20 a.u.) and ery-apoB sufficiency (ery-apoB >0.20 a.u.).

<p>Abbreviations: BMI  =  body mass index; CIMT  =  carotid intima media thickness.</p