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

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

J Clin Endocrinol Metab. 2016 Nov 3;:jc20153512

Authors: Rämö JT, Kaye SM, Jukarainen S, Bogl LH, Hakkarainen A, Lundbom J, Lundbom N, Rissanen A, Kaprio J, Matikainen N, Pietiläinen KH

Abstract
CONTEXT: The associations of BMI and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood.
OBJECTIVE: To characterize circulating metabolite excursions during an oral glucose tolerance test (OGTT), and evaluate whether the metabolomic signatures of BMI-discordance co-associate with LF content.
DESIGN, SETTING AND PARTICIPANTS: We measured 80 metabolite parameters by nuclear magnetic resonance, together with glucose and insulin, during a 2-hour OGTT in 64 monozygotic and 73 dizygotic twin pairs (aged 22.8-36.2 years). Metabolite excursions during the OGTT were compared within BMI-discordant (intrapair difference, BMI>=3kg/m(2)) co-twins separately within monozygotic and dizygotic pairs. Insulin-based indices were calculated from the OGTT. LF was measured by magnetic resonance spectroscopy in 25 BMI-discordant monozygotic pairs. Metabolite profiles were compared with respect to LF discordance (ΔLF%>=2%).
RESULTS: 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 monozygotic and dizygotic twins. In BMI-discordant monozygotic pairs (mean ΔBMI 4.9kg/m(2)) who were concordant for LF (Δ0.2%), few metabolites differed between the co-twins: VLDL cholesterol and apolipoprotein B were elevated, and HDL size and concentration were decreased in the co-twins with higher BMI. In contrast, in BMI-discordant monozygotic pairs (ΔBMI 6.1kg/m(2)) who were discordant for LF (Δ6.8%), co-twins with higher BMI exhibited lower insulin sensitivity and widespread metabolomic differences: elevations in small VLDL and LDL particles, fatty acids, and isoleucine. Within all 64 monozygotic twin pairs, lower insulin sensitivity associated with higher levels of VLDLs, triglycerides, fatty acids, and isoleucine.
CONCLUSIONS: BMI-discordant monozygotic 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.

PMID: 27809652 [PubMed - as supplied by publisher]

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