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 (TM6SF2 EK ; 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 (TM6SF2 EK : n Z 16) or without (TM6SF2 EE : n Z 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-2 H 2 ]glucose to measure whole-body-, hepatic-