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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 2017; 102(1):220-231JC

Abstract

Context

The associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood.

Objective

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.

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 (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 (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 MZ and DZ twins. In BMI-discordant MZ pairs (mean ΔBMI = 4.9 kg/m2) who were concordant for LF (Δ0.2%), 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 (ΔBMI = 6.1 kg/m2) who were discordant for LF (Δ6.8%), 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.

Conclusions

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.

Authors+Show Affiliations

Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, FI-00029, Helsinki, Finland. Institute for Molecular Medicine Finland, FI-00014, Helsinki, Finland.Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, FI-00029, Helsinki, Finland.Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, FI-00029, Helsinki, Finland.Department of Public Health, University of Helsinki, FI-00014, Helsinki, Finland.Department of Radiology, HUS Medical Imaging Center, Helsinki University Hospital, University of Helsinki, FI-00029, Helsinki, Finland.Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, 40225, Düsseldorf, Germany. German Center for Diabetes Research, Partner Düsseldorf, 40225, Düsseldorf, Germany.Department of Radiology, HUS Medical Imaging Center, Helsinki University Hospital, University of Helsinki, FI-00029, Helsinki, Finland.Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, FI-00029, Helsinki, Finland. Department of Psychiatry, Helsinki University Hospital, and University of Helsinki, 00014, Helsinki, Finland.Institute for Molecular Medicine Finland, FI-00014, Helsinki, Finland. Department of Public Health, University of Helsinki, FI-00014, Helsinki, Finland. Department of Health, National Institute for Health and Welfare, FI-00014, Helsinki, Finland; and.Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, FI-00029, Helsinki, Finland. Endocrinology, Abdominal Center, Helsinki University Hospital, and University of Helsinki, FI-00029, Helsinki, Finland.Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, FI-00029, Helsinki, Finland. Institute for Molecular Medicine Finland, FI-00014, Helsinki, Finland. Endocrinology, Abdominal Center, Helsinki University Hospital, and University of Helsinki, FI-00029, Helsinki, Finland.

Pub Type(s)

Journal Article
Twin Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27809652

Citation

Rämö, Joel T., et al. "Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins." The Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 1, 2017, pp. 220-231.
Rämö JT, Kaye SM, Jukarainen S, et al. Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins. J Clin Endocrinol Metab. 2017;102(1):220-231.
Rämö, J. T., Kaye, S. M., Jukarainen, S., Bogl, L. H., Hakkarainen, A., Lundbom, J., ... Pietiläinen, K. H. (2017). Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins. The Journal of Clinical Endocrinology and Metabolism, 102(1), pp. 220-231. doi:10.1210/jc.2015-3512.
Rämö JT, et al. Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins. J Clin Endocrinol Metab. 2017 01 1;102(1):220-231. PubMed PMID: 27809652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins. AU - Rämö,Joel T, AU - Kaye,Sanna M, AU - Jukarainen,Sakari, AU - Bogl,Leonie H, AU - Hakkarainen,Antti, AU - Lundbom,Jesper, AU - Lundbom,Nina, AU - Rissanen,Aila, AU - Kaprio,Jaakko, AU - Matikainen,Niina, AU - Pietiläinen,Kirsi H, PY - 2015/09/23/received PY - 2016/10/31/accepted PY - 2016/11/5/pubmed PY - 2017/6/21/medline PY - 2016/11/5/entrez SP - 220 EP - 231 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 102 IS - 1 N2 - Context: The associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood. Objective: 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. 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 (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 (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 MZ and DZ twins. In BMI-discordant MZ pairs (mean ΔBMI = 4.9 kg/m2) who were concordant for LF (Δ0.2%), 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 (ΔBMI = 6.1 kg/m2) who were discordant for LF (Δ6.8%), 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. Conclusions: 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. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/27809652/Liver_Fat_and_Insulin_Sensitivity_Define_Metabolite_Profiles_During_a_Glucose_Tolerance_Test_in_Young_Adult_Twins_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2015-3512 DB - PRIME DP - Unbound Medicine ER -