Premium
Twenty‐four‐hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes
Author(s) -
Isherwood Cheryl M.,
Van der Veen Daan R.,
Johnston Jonathan D.,
Skene Debra J.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700323r
Subject(s) - type 2 diabetes , endocrinology , medicine , diabetes mellitus , chemistry
Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single‐time‐point samples, ignoring time‐of‐day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24‐h day in 3 age‐matched, male groups—lean, overweight/obese (OW/OB), and OW/OB with T2DM—in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that average metabolite concentrations were significantly altered by increased body mass (90 of 130) and T2DM (56 of 130). Thirty‐eight percent of metabolites exhibited daily rhythms in at least 1 study group, and where a metabolite was rhythmic in >1 group, its peak time was comparable. The optimal time of day was assessed to provide discriminating biomarkers. This differed between metabolite classes and study groups—for example, phospholipids showed maximal difference at 5:00 am (lean vs . OW/OB) and at 5:00 pm (OW/OB vs. T2DM). Metabolites that were identified with both robust 24‐h rhythms and significant concentration differences between study groups emphasize the importance of controlling the time of day for diagnosis and biomarker discovery, offering a significant improvement over current single sampling.—Isherwood, C.M., Van der Veen, D.R., Johnston, J.D., Skene, D. J. Twenty‐four‐hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes. FASEB J. 31, 5557‐5567 (2017). www.fasebj.org