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Zaharia, Oana P.; Strassburger, Klaus; Knebel, Birgit; Kupriyanova, Yuliya; Karusheva, Yanislava; Wolkersdorfer, Martin; Bódis, Kálmán; Markgraf, Daniel F.; Burkart, Volker; Hwang, Jong-Hee; Kotzka, Jörg; Al-Hasani, Hadi; Szendroedi, Julia; Roden, Michael; Roden, M.; Al-Hasani, H.; Burkart, V.; Buyken, A.E.; Eckel, J.; Geerling, G.; Hwang, J.H.; Herder, C.; Icks, A.; Jandeleit-Dahm, K.; [...]

Role of Patatin-Like Phospholipase Domain–Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes

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  • Medientyp: E-Artikel
  • Titel: Role of Patatin-Like Phospholipase Domain–Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes
  • Beteiligte: Zaharia, Oana P.; Strassburger, Klaus; Knebel, Birgit; Kupriyanova, Yuliya; Karusheva, Yanislava; Wolkersdorfer, Martin; Bódis, Kálmán; Markgraf, Daniel F.; Burkart, Volker; Hwang, Jong-Hee; Kotzka, Jörg; Al-Hasani, Hadi; Szendroedi, Julia; Roden, Michael; Roden, M.; Al-Hasani, H.; Burkart, V.; Buyken, A.E.; Eckel, J.; Geerling, G.; Hwang, J.H.; Herder, C.; Icks, A.; Jandeleit-Dahm, K.; [...]
  • Erschienen: American Diabetes Association, 2020
  • Erschienen in: Diabetes Care
  • Sprache: Englisch
  • DOI: 10.2337/dc20-0329
  • ISSN: 0149-5992; 1935-5548
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>The rs738409(G) single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain–containing 3 (PNPLA3) gene associates with increased risk and progression of nonalcoholic fatty liver disease (NAFLD). As the recently described severe insulin-resistant diabetes (SIRD) cluster specifically relates to NAFLD, this study examined whether this SNP differently associates with hepatic lipid content (hepatocellular lipids [HCL]) and insulin sensitivity in recent-onset diabetes.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>A total of 917 participants in the German Diabetes Study (GDS) underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution, and MRS.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>The G allele associated positively with HCL (β = 0.36, P &amp;lt; 0.01), independent of age, sex, and BMI across the whole cohort, but not in the individual clusters. Those with SIRD exhibited lowest whole-body insulin sensitivity compared with those with severe insulin-deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD), and severe autoimmune diabetes (SAID) clusters (all P &amp;lt; 0.001). Interestingly, the SIRD group presented with higher prevalence of the rs738409(G) SNP compared with other clusters and the glucose-tolerant control group (P &amp;lt; 0.05). HCL was higher in the SIRD group (median 13.6% [1st quartile 5.8; 3rd quartile 19.1] compared with the MOD (6.4 % [2.1; 12.4], P &amp;lt; 0.05), MARD (3.0% [1.0; 7.9], P &amp;lt; 0.001), SAID (0.4% [0.0; 1.5], P &amp;lt; 0.001), and glucose-tolerant (0.9% [0.4; 4.9), P &amp;lt; 0.001) group. Although the PNPLA3 polymorphism did not directly associate with whole-body insulin sensitivity in SIRD, the G-allele carriers had higher circulating free fatty acid concentrations and greater adipose tissue insulin resistance compared with noncarriers (both P &amp;lt; 0.001).</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Members of the SIRD cluster are more frequently carriers of the rs738409(G) variant. The SNP-associated adipose tissue insulin resistance and excessive lipolysis may contribute to their NAFLD.</jats:p> </jats:sec>
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