Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical... Show moreVisceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008-2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R-2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm(2) and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R-2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006-2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000-2007). Performance was comparable to the development setting in PIVUS (R-2 = 0.63, RMSE = 42.4 cm(2), calibration slope = 0.94) but lower in MESA (R-2 = 0.44, RMSE = 60.7 cm(2), calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements. Show less
Neeland, I.J.; Boone, S.C.; Mook-Kanamori, D.O.; Ayers, C.; Smit, R.A.J.; Tzoulaki, I.; ... ; Mutsert, R. de 2019
Background-Identifying associations between serum metabolites and visceral adipose tissue (VAT) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases.... Show moreBackground-Identifying associations between serum metabolites and visceral adipose tissue (VAT) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT.Methods and Results-Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross-sectional linear regression of individual-level data from participants in MESA (Multi-Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted H-1 nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted H-1 nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid-lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT (P=4.88 x 10(-20)-1.16 x 10(-3)). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched-chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT (P=1.90 x 10(-35)-8.46 x 10(-7)), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations.Conclusions-We identified and replicated a metabolite panel associated with VAT in 2 community-based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity. Show less
