AIMS: To explore whether the pre-clinical findings that metformin improves lipid metabolism, possibly through modulation of intrahepatic partitioning of fatty acids towards oxidation and away from re-esterification and resecretion as triglycerides (TGs), can be translated to a human setting. MATERIALS AND METHODS: We performed a 3-month randomized, placebo-controlled, parallel-group clinical trial in patients with type 2 diabetes (T2D; n = 24) and healthy controls (n = 12). Patients with T2D received either placebo (placebo group) or 1000 mg metformin twice daily (metformin group), while healthy subjects were all treated with metformin (control group). Hepatic fatty acid metabolism was measured by [11 C]palmitate positron-emission tomography, hepatic TG secretion and peripheral oxidation by ex vivo labelled [1-14 C]VLDL-TG and VLDL particle size by TG/apolipoprotein B ratio. Body composition was assessed by dual-energy X-ray and whole-body lipid oxidation by indirect calorimetry. RESULTS:Metformin treatment for 3 months produced the anticipated decrease in fasting plasma glucose (FPG) in the metformin group (FPG 7.9 ± 1.8 mM [study day 1] vs 6.4 ± 1.1 mM [study day 2]), whereas patients in the placebo group and healthy controls had similar FPG levels before and after the trial (mixed model group vs time interaction; P = .003); however, contrary to our hypothesis, metformin treatment did not affect hepatic lipid metabolism or peripheral oxidation. CONCLUSION: The observed beneficial effects on lipid metabolism during metformin treatment in humans appear to be secondary to long-term alterations in body composition or glucose homeostasis.
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AIMS: To explore whether the pre-clinical findings that metformin improves lipid metabolism, possibly through modulation of intrahepatic partitioning of fatty acids towards oxidation and away from re-esterification and resecretion as triglycerides (TGs), can be translated to a human setting. MATERIALS AND METHODS: We performed a 3-month randomized, placebo-controlled, parallel-group clinical trial in patients with type 2 diabetes (T2D; n = 24) and healthy controls (n = 12). Patients with T2D received either placebo (placebo group) or 1000 mg metformin twice daily (metformin group), while healthy subjects were all treated with metformin (control group). Hepatic fatty acid metabolism was measured by [11 C]palmitate positron-emission tomography, hepatic TG secretion and peripheral oxidation by ex vivo labelled [1-14 C]VLDL-TG and VLDL particle size by TG/apolipoprotein B ratio. Body composition was assessed by dual-energy X-ray and whole-body lipid oxidation by indirect calorimetry. RESULTS:Metformin treatment for 3 months produced the anticipated decrease in fasting plasma glucose (FPG) in the metformin group (FPG 7.9 ± 1.8 mM [study day 1] vs 6.4 ± 1.1 mM [study day 2]), whereas patients in the placebo group and healthy controls had similar FPG levels before and after the trial (mixed model group vs time interaction; P = .003); however, contrary to our hypothesis, metformin treatment did not affect hepatic lipid metabolism or peripheral oxidation. CONCLUSION: The observed beneficial effects on lipid metabolism during metformin treatment in humans appear to be secondary to long-term alterations in body composition or glucose homeostasis.
Authors: Jean Farup; Jesper Just; Frank de Paoli; Lin Lin; Jonas Brorson Jensen; Tine Billeskov; Ines Sanchez Roman; Cagla Cömert; Andreas Buch Møller; Luca Madaro; Elena Groppa; Rikard Göran Fred; Ulla Kampmann; Lars C Gormsen; Steen B Pedersen; Peter Bross; Tinna Stevnsner; Nikolaj Eldrup; Tune H Pers; Fabio M V Rossi; Pier Lorenzo Puri; Niels Jessen Journal: Cell Metab Date: 2021-10-21 Impact factor: 31.373
Authors: Charlotte J Green; Thomas Marjot; John Walsby-Tickle; Catriona Charlton; Thomas Cornfield; Felix Westcott; Katherine E Pinnick; Ahmad Moolla; Jonathan M Hazlehurst; James McCullagh; Jeremy W Tomlinson; Leanne Hodson Journal: Eur J Endocrinol Date: 2022-02-07 Impact factor: 6.664
Authors: Anila K Madiraju; Yang Qiu; Rachel J Perry; Yasmeen Rahimi; Xian-Man Zhang; Dongyan Zhang; João-Paulo G Camporez; Gary W Cline; Gina M Butrico; Bruce E Kemp; Gregori Casals; Gregory R Steinberg; Daniel F Vatner; Kitt F Petersen; Gerald I Shulman Journal: Nat Med Date: 2018-07-23 Impact factor: 53.440