Dataset Information

Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins.

ABSTRACT: The associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood.We aimed to characterize circulating metabolite excursions during an oral glucose tolerance test (OGTT) and evaluate whether the metabolomic signatures of BMI discordance coassociate with LF content.We measured 80 metabolite parameters by nuclear magnetic resonance, together with glucose and insulin, during a 2-hour OGTT in 64 monozygotic (MZ) and 73 dizygotic (DZ) twin pairs (aged 22.8 to 36.2 years). Metabolite excursions during the OGTT were compared within BMI-discordant (intrapair difference, BMI ? 3 kg/m2) cotwins separately within MZ and DZ pairs. Insulin-based indices were calculated from the OGTT. LF was measured by magnetic resonance spectroscopy in 25 BMI-discordant MZ pairs. Metabolite profiles were compared with respect to LF discordance (?LF% ? 2%).We replicated many previously reported OGTT-induced metabolite excursions in all 274 individuals and report novel lipoprotein excursions. The associations between some metabolite excursions and BMI differed in MZ and DZ twins. In BMI-discordant MZ pairs (mean ?BMI = 4.9 kg/m2) who were concordant for LF (?0.2%), few metabolites differed between the cotwins: very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B were elevated, and high-density lipoprotein size and concentration were decreased in the cotwins with higher BMI. In contrast, in BMI-discordant MZ pairs (?BMI = 6.1 kg/m2) who were discordant for LF (?6.8%), cotwins with higher BMI exhibited lower insulin sensitivity and widespread metabolomic differences: elevations in small VLDL and low-density lipoprotein particles, fatty acids (FAs), and isoleucine. Within all 64 MZ twin pairs, lower insulin sensitivity associated with higher levels of VLDLs, triglycerides, FAs, and isoleucine.BMI-discordant MZ twin pairs who also are discordant for LF have more pronounced within-pair differences in metabolomics profiles during an OGTT than BMI-discordant pairs without LF discordance.

SUBMITTER: Ramo JT

PROVIDER: S-EPMC6287394 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins.

Rämö Joel T JT Kaye Sanna M SM Jukarainen Sakari S Bogl Leonie H LH Hakkarainen Antti A Lundbom Jesper J Lundbom Nina N Rissanen Aila A Kaprio Jaakko J Matikainen Niina N Pietiläinen Kirsi H KH

The Journal of clinical endocrinology and metabolism 20170101 1

<h4>Context</h4>The associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood.<h4>Objective</h4>We aimed to characterize circulating metabolite excursions during an oral glucose tolerance test (OGTT) and evaluate whether the metabolomic signatures of BMI discordance coassociate with LF content.<h4>Design, setting, and participants</h4>We measured 80 metabolite parameters by nuclear magnetic resonance, together with glucose ...[more]

PMID: 27809652

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Project description:BackgroundFat deposition is associated with adverse outcomes. Waist-to-hip (WHR) ratio is a simple feasible index to assess fat distribution. Lipoprotein particle composition in relation to WHR and to what extent their association is mediated by insulin sensitivity are less investigated.MethodsIn 504 randomly recruited Flemish (mean age: 48.9 years; women: 51.6%), we analyzed the lipoprotein particle constitutions using nuclear magnetic resonance spectroscopy. WHR obesity described a WHR of ≥ 0.85 for women or 0.9 for men. Insulin sensitivity was evaluated by the homeostasis model assessment-estimated insulin resistance (HOMA-IR). SCORE-2 risk algorithm was applied to estimate 10-year cardiovascular risk. Statistical methods included multivariable-adjusted linear regression analysis, logistic regression analysis, and mediation analysis.ResultsThe prevalence of WHR obesity was 54.6%, approximately 3 times of BMI-determined obesity (19.1%). Individuals with WHR obesity had significantly higher metabolic complications, such as hypertension (57.1%), dyslipidemia (61.8%), and insulin resistance (14.2%). WHR and WHR obesity were positively associated with total very-low-density lipoprotein (VLDL) particle concentration, remnant cholesterol, and triglycerides, but were negatively associated with VLDL particle size (P ≤ 0.027), independent of body mass index and other covariates. WHR was inversely associated with total high-density lipoprotein (HDL) particle concentration, whereas WHR obesity was inversely associated with HDL cholesterol (P ≤ 0.039). Neither WHR nor WHR obesity was associated with the concentration of total low-density lipoprotein (LDL) particles, LDL particle size, and LDL cholesterol (P ≥ 0.089). In the mediation analysis, insulin sensitivity significantly mediated the effect of WHR on total VLDL particle concentration (mediation percentage: 37.0%), remnant cholesterol (47.7%), and HDL cholesterol (41.1%). Individuals with WHR obesity were at increased cardiovascular risk, regardless of LDL cholesterol (P ≤0.028). In WHR obesity, higher total VLDL particle concent36ration and remnant cholesterol, and lower HDL cholesterol were associated with an increased cardiovascular risk (P≤ 0.002).ConclusionsUpper-body fat deposition was independently associated with an unfavorable lipoprotein profile, and insulin sensitivity significantly mediated this association. LDL cholesterol might underestimate lipid abnormality for people with upper-body obesity and lowering VLDL particles and remnant cholesterol might potentially reduce the residual cardiovascular risk.

Dataset Information

Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins.

Publications

Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins.

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