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Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes

Background and aims - Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2EK; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalco...

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Main Authors: Bódis, Kálmán Benedikt (Author) , Bombrich, Maria (Author) , Schön, Martin (Author) , Knebel, Birgit (Author) , Zaharia, Oana-Patricia (Author) , Bönhof, Gidon (Author) , Karusheva, Yanislava (Author) , Strassburger, Klaus (Author) , Kupriyanova, Yuliya (Author) , Kotzka, Jörg (Author) , Guthoff, Rainer (Author) , Schrauwen-Hinderling, Vera (Author) , Al-Hasani, Hadi (Author) , Burkart, Volker (Author) , Szendrödi, Julia (Author) , Wagner, Robert (Author) , Markgraf, Daniel F. (Author) , Roden, Michael (Author)
Format: Article (Journal)
Language:English
Published: September 2023
In: Nutrition, metabolism and cardiovascular diseases
Year: 2023, Volume: 33, Issue: 9, Pages: 1785-1796
ISSN:1590-3729
DOI:10.1016/j.numecd.2023.06.004
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.numecd.2023.06.004
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0939475323002375
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Author Notes:Kálmán Bódis, Maria Bombrich, Martin Schön, Birgit Knebel, Oana-Patricia Zaharia, Gidon Bönhof, Yanislava Karusheva, Klaus Strassburger, Yuliya Kupriyanova, Jörg Kotzka, Rainer Guthoff, Vera Schrauwen-Hinderling, Hadi Al-Hasani, Volker Burkart, Julia Szendroedi, Robert Wagner, Daniel F. Markgraf, Michael Roden, for the GDS study group
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Summary:Background and aims - Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2EK; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes. - Methods and results - Males with recent-onset type 2 diabetes with (TM6SF2EK: n = 16) or without (TM6SF2EE: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-2H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with 1H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2EK had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2EE. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2EE only. - Conclusions - The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.
Item Description:Online verfügbar 9 June 2023, Version des Artikels 11 August 2023
Gesehen am 06.12.2023
Physical Description:Online Resource
ISSN:1590-3729
DOI:10.1016/j.numecd.2023.06.004

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