Effect of metformin therapy on circulating amino acids in a randomized trial: the CAMERA study

Preiss, D. , Rankin, N. , Welsh, P. , Holman, R.R., Kangas, A.J., Soininen, P., Würtz, P., Ala-Korpela, M. and Sattar, N. (2016) Effect of metformin therapy on circulating amino acids in a randomized trial: the CAMERA study. Diabetic Medicine, 33(11), pp. 1569-1574. (doi:10.1111/dme.13097) (PMID:26887663)

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Abstract

Aims: To investigate whether metformin therapy alters circulating aromatic and branched-chain amino acid concentrations, increased levels amino acid concentrations, increased levels of which have been found to predict Type 2 diabetes. Methods: In the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) study (NCT00723307), 173 individuals without Type 2 diabetes, but with coronary disease, were randomized to metformin (n=86) or placebo (n=87) for 18 months. Plasma samples, taken every 6 months, were analysed using quantitative nuclear magnetic resonance spectroscopy. Ten metabolites consisting of eight amino acids [three branched-chain (isoleucine, leucine, valine), three aromatic (tyrosine, phenylalanine, histidine) and two other amino acids (alanine, glutamine)], lactate and pyruvate were quantified and analysed using repeated-measures models. On-treatment analyses were conducted to investigate whether amino acid changes were dependent on changes in weight, fat mass or insulin resistance estimated using homeostasis model assessment (HOMA-IR). Results: Tyrosine decreased [−6.1 μmol/l (95% CI −8.5, -3.7); P<0.0001], while alanine [42 umol/l (95% CI 25, 59); P<0.0001] increased in the metformin-treated group compared with the placebo-treated group. Decreases in phenylalanine [−2.0 μmol/l (95% CI −3.6, −0.3); P=0.018] and increases in histidine [2.3 μmol/l (95% CI 0.1, 4.6); P=0.045] were also observed in the metformin group, although these changes were less statistically robust. Changes in these four amino acids were not accounted for by changes in weight, fat mass or HOMA-IR values. Levels of branched-chain amino acids, glutamine, pyruvate and lactate were not altered by metformin therapy. Conclusions: Metformin therapy results in a sustained and specific pattern of changes in aromatic amino acid and alanine concentrations. These changes are independent of any effects on weight and insulin sensitivity. Any causal link to metformin's unexplained cardiometabolic benefit requires further study.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Welsh, Dr Paul and Rankin, Dr Naomi and Preiss, Dr David and Sattar, Professor Naveed
Authors: Preiss, D., Rankin, N., Welsh, P., Holman, R.R., Kangas, A.J., Soininen, P., Würtz, P., Ala-Korpela, M., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diabetic Medicine
Publisher:Wiley
ISSN:0742-3071
ISSN (Online):1464-5491
Published Online:03 March 2016

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
468871Effect of metformin on progression of carotid atherosclerosis in non-diabetic patients with CHD optimally treated with conventional risk reducing agentsNaveed SattarScottish Executive Health Department (SEHHD-CSO)CZB/4/613RI CARDIOVASCULAR & MEDICAL SCIENCES
612031Cardiac biomarkers and CVD risk screening: a cost-effective public health measure?Paul WelshBritish Heart Foundation (BHF)FS/12/62/29889RI CARDIOVASCULAR & MEDICAL SCIENCES
603151EMIFNaveed SattarEuropean Commission (EC)115372RI CARDIOVASCULAR & MEDICAL SCIENCES