Journal
DIABETIC MEDICINE
Volume 33, Issue 11, Pages 1569-1574Publisher
WILEY
DOI: 10.1111/dme.13097
Keywords
-
Categories
Funding
- Chief Scientist Office, Scotland [CZB/4/613]
- Academy of Finland
- Sigrid Juselius Foundation
- Novo Nordisk Foundation
- University of Oulu, Finland
- BHF fellowship [FS/12/62/29889]
- Finnish Diabetes Research Foundation
- Innovative Medicines Initiative [115372]
- European Union
- EFPIA
- MRC [MC_UU_12013/1, MC_U137686861] Funding Source: UKRI
- British Heart Foundation [FS/12/62/29889] Funding Source: researchfish
- Chief Scientist Office [CZB/4/613] Funding Source: researchfish
- Medical Research Council [MC_U137686861, MC_UU_12013/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10140, NF-SI-0515-10096] Funding Source: researchfish
Ask authors/readers for more resources
AimsTo 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. MethodsIn 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). ResultsTyrosine decreased [-6.1 mol/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 mol/l (95% CI -3.6, -0.3); P=0.018] and increases in histidine [2.3 mol/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. ConclusionsMetformin 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available