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Metabolic Changes With Metformin May Lower LDL-C

Possible metabolic mechanism includes activation of AMPK, FADS suppression

MONDAY, Aug. 17, 2015 (HealthDay News) — The diabetes drug metformin changes metabolic profiles of three metabolites that may lower LDL cholesterol (LDL-C), according to a study published online Aug. 5 in Diabetes Care.

Tao Xu, from Helmholtz Zentrum München in Neuherberg, Germany, and colleagues analyzed both metabolomic and genomic data from three independent cohorts, including 151 patients with type 2 diabetes (T2D) treated with metformin (mt-T2D). Fasting serum samples were used to quantify 131 metabolites.

The researchers found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings persisted when controlling for conventional risk factors of T2D and were replicated in two independent studies. Levels of these metabolites decreased significantly in patients after they started metformin treatment during seven years of follow-up. There was an association between the reduction of these metabolites and a lowered blood level of LDL-C. There was an association between variations of these three metabolites and 17 genes (including FADS1 and FADS2).

“Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C,” the authors write. “Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease.”

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