Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age

Abstract Background It is not clear if conventional liver fat cutoff of 5.56% weight which has been used for identifying fatty liver in western populations is also applicable for Asians. In Asian women of reproductive age, we evaluate the optimum metabolic syndrome (MetS)-linked liver fat cutoff, th...

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Main Authors: Priti Mishra, Suresh Anand Sadananthan, Jadegoud Yaligar, Kok Hian Tan, Yap Seng Chong, Peter D. Gluckman, Keith M. Godfrey, Marielle V. Fortier, Johan G. Eriksson, Jerry Kok Yen Chan, Shiao-Yng Chan, Dennis Wang, S. Sendhil Velan, Navin Michael
Format: Article
Language:English
Published: BMC 2024-11-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-024-03779-0
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author Priti Mishra
Suresh Anand Sadananthan
Jadegoud Yaligar
Kok Hian Tan
Yap Seng Chong
Peter D. Gluckman
Keith M. Godfrey
Marielle V. Fortier
Johan G. Eriksson
Jerry Kok Yen Chan
Shiao-Yng Chan
Dennis Wang
S. Sendhil Velan
Navin Michael
author_facet Priti Mishra
Suresh Anand Sadananthan
Jadegoud Yaligar
Kok Hian Tan
Yap Seng Chong
Peter D. Gluckman
Keith M. Godfrey
Marielle V. Fortier
Johan G. Eriksson
Jerry Kok Yen Chan
Shiao-Yng Chan
Dennis Wang
S. Sendhil Velan
Navin Michael
author_sort Priti Mishra
collection DOAJ
description Abstract Background It is not clear if conventional liver fat cutoff of 5.56% weight which has been used for identifying fatty liver in western populations is also applicable for Asians. In Asian women of reproductive age, we evaluate the optimum metabolic syndrome (MetS)-linked liver fat cutoff, the specific metabolomic alterations apparent at this cutoff, as well as prospective associations of preconception liver fat levels with gestational dysglycemia. Methods Liver fat (measured by magnetic resonance spectroscopy), MetS, and nuclear magnetic resonance (NMR)-based plasma metabolomic profiles were assessed in 382 Asian women, who were planning to conceive. Ninety-eight women went on to become pregnant and received an oral glucose tolerance test at week 26 of gestation. Results The optimum liver fat cutoff for diagnosing MetS was 2.07%weight. Preconception liver fat was categorized into Low (liver fat < 2.07%), Moderate (2.07% ≤ liver fat < 5.56%), and High (liver fat ≥ 5.56%) groups. Individual MetS traits showed worsening trends, going from Low to Moderate to High groups. Multiple plasma metabolomic alterations, previously linked to incident type 2 diabetes (T2D), were already evident in the Moderate group (adjusted for ethnicity, age, parity, educational attainment, and BMI). Both a cross-sectional multi-metabolite score for incident T2D and mid-gestational glucose area under the curve showed increasing trends, going from Low to Moderate to High groups (p < 0.001 for both). Gestational diabetes incidence was 2-fold (p = 0.23) and 7-fold (p < 0.001) higher in the Moderate and High groups relative to the Low group. Conclusions In Asian women of reproductive age, moderate liver fat accumulation below the conventional fatty liver cutoff was not metabolically benign and was linked to gestational dysglycemia. The newly derived cutoff can aid in screening individuals before adverse metabolic phenotypes have consolidated, which provides a longer window for preventive strategies.
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spelling doaj-art-67970fade8a54751814088214b4b06292024-12-01T12:29:45ZengBMCBMC Medicine1741-70152024-11-0122111510.1186/s12916-024-03779-0Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive agePriti Mishra0Suresh Anand Sadananthan1Jadegoud Yaligar2Kok Hian Tan3Yap Seng Chong4Peter D. Gluckman5Keith M. Godfrey6Marielle V. Fortier7Johan G. Eriksson8Jerry Kok Yen Chan9Shiao-Yng Chan10Dennis Wang11S. Sendhil Velan12Navin Michael13Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Academic Clinical Program in Obstetrics and Gynaecology, Duke-National University of Singapore Medical SchoolInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)NIHR Southampton Biomedical Research Centre, Southampton University Hospital NHS Foundation Trust and University of SouthamptonInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Academic Clinical Program in Obstetrics and Gynaecology, Duke-National University of Singapore Medical SchoolInstitute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR)Abstract Background It is not clear if conventional liver fat cutoff of 5.56% weight which has been used for identifying fatty liver in western populations is also applicable for Asians. In Asian women of reproductive age, we evaluate the optimum metabolic syndrome (MetS)-linked liver fat cutoff, the specific metabolomic alterations apparent at this cutoff, as well as prospective associations of preconception liver fat levels with gestational dysglycemia. Methods Liver fat (measured by magnetic resonance spectroscopy), MetS, and nuclear magnetic resonance (NMR)-based plasma metabolomic profiles were assessed in 382 Asian women, who were planning to conceive. Ninety-eight women went on to become pregnant and received an oral glucose tolerance test at week 26 of gestation. Results The optimum liver fat cutoff for diagnosing MetS was 2.07%weight. Preconception liver fat was categorized into Low (liver fat < 2.07%), Moderate (2.07% ≤ liver fat < 5.56%), and High (liver fat ≥ 5.56%) groups. Individual MetS traits showed worsening trends, going from Low to Moderate to High groups. Multiple plasma metabolomic alterations, previously linked to incident type 2 diabetes (T2D), were already evident in the Moderate group (adjusted for ethnicity, age, parity, educational attainment, and BMI). Both a cross-sectional multi-metabolite score for incident T2D and mid-gestational glucose area under the curve showed increasing trends, going from Low to Moderate to High groups (p < 0.001 for both). Gestational diabetes incidence was 2-fold (p = 0.23) and 7-fold (p < 0.001) higher in the Moderate and High groups relative to the Low group. Conclusions In Asian women of reproductive age, moderate liver fat accumulation below the conventional fatty liver cutoff was not metabolically benign and was linked to gestational dysglycemia. The newly derived cutoff can aid in screening individuals before adverse metabolic phenotypes have consolidated, which provides a longer window for preventive strategies.https://doi.org/10.1186/s12916-024-03779-0MetabolomicsMagnetic resonance spectroscopyMetabolic dysfunction-associated steatotic liver disease (MASLD)Metabolic syndromeGestational diabetes
spellingShingle Priti Mishra
Suresh Anand Sadananthan
Jadegoud Yaligar
Kok Hian Tan
Yap Seng Chong
Peter D. Gluckman
Keith M. Godfrey
Marielle V. Fortier
Johan G. Eriksson
Jerry Kok Yen Chan
Shiao-Yng Chan
Dennis Wang
S. Sendhil Velan
Navin Michael
Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age
BMC Medicine
Metabolomics
Magnetic resonance spectroscopy
Metabolic dysfunction-associated steatotic liver disease (MASLD)
Metabolic syndrome
Gestational diabetes
title Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age
title_full Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age
title_fullStr Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age
title_full_unstemmed Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age
title_short Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age
title_sort even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in asian women of reproductive age
topic Metabolomics
Magnetic resonance spectroscopy
Metabolic dysfunction-associated steatotic liver disease (MASLD)
Metabolic syndrome
Gestational diabetes
url https://doi.org/10.1186/s12916-024-03779-0
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