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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| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 2023
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| In: |
Nutrition, metabolism and cardiovascular diseases
Year: 2023, Jahrgang: 33, Heft: 9, Pages: 1785-1796 |
| ISSN: | 1590-3729 |
| DOI: | 10.1016/j.numecd.2023.06.004 |
| Online-Zugang: | 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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| Verfasserangaben: | 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 |
MARC
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| 100 | 1 | |a Bódis, Kálmán Benedikt |e VerfasserIn |0 (DE-588)1220950211 |0 (DE-627)1738085104 |4 aut | |
| 245 | 1 | 0 | |a Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes |c 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 |
| 264 | 1 | |c September 2023 | |
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| 520 | |a 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. | ||
| 650 | 4 | |a Hepatocellular lipid content | |
| 650 | 4 | |a Insulin sensitivity | |
| 650 | 4 | |a Nonalcoholic fatty liver disease | |
| 650 | 4 | |a Transmembrane 6 superfamily member 2 | |
| 650 | 4 | |a Type 2 diabetes | |
| 700 | 1 | |a Bombrich, Maria |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schön, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Knebel, Birgit |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zaharia, Oana-Patricia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bönhof, Gidon |e VerfasserIn |4 aut | |
| 700 | 1 | |a Karusheva, Yanislava |e VerfasserIn |4 aut | |
| 700 | 1 | |a Strassburger, Klaus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kupriyanova, Yuliya |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kotzka, Jörg |e VerfasserIn |4 aut | |
| 700 | 1 | |a Guthoff, Rainer |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schrauwen-Hinderling, Vera |e VerfasserIn |4 aut | |
| 700 | 1 | |a Al-Hasani, Hadi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Burkart, Volker |e VerfasserIn |4 aut | |
| 700 | 1 | |a Szendrödi, Julia |e VerfasserIn |0 (DE-588)1226436463 |0 (DE-627)1747448249 |4 aut | |
| 700 | 1 | |a Wagner, Robert |e VerfasserIn |4 aut | |
| 700 | 1 | |a Markgraf, Daniel F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Roden, Michael |e VerfasserIn |4 aut | |
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