Kantartzis K, Rettig I, Staiger H, Machann J, Schick F, Scheja L, Gastaldelli A, Bugianesi E, Peter A, Schulze M B, Fritsche A, Häring H-U, Stefan N
Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany.
Diabetes Metab. 2017 Jun;43(3):229-239. doi: 10.1016/j.diabet.2016.11.006. Epub 2017 Jan 12.
In clinical practice, there is a strong interest in non-invasive markers of non-alcoholic fatty liver disease (NAFLD). Our hypothesis was that the fold-change in plasma triglycerides (TG) during a 2-h oral glucose tolerance test (fold-change TG) in concert with blood glucose and lipid parameters, and the rs738409 C>G single nucleotide polymorphism (SNP) in PNPLA3 might improve the power of the widely used fatty liver index (FLI) to predict NAFLD.
The liver fat content of 330 subjects was quantified by H-magnetic resonance spectroscopy. Blood parameters were measured during fasting and after a 2-h OGTT. A subgroup of 213 subjects underwent these measurements before and after 9 months of a lifestyle intervention.
The fold-change TG was closely associated with liver fat content (r=0.51, P<0.0001), but had less power to predict NAFLD (AUROC=0.75) than the FLI (AUROC=0.79). Not only was the fold-change TG independently associated with liver fat content and NAFLD, but so also were the 2-h blood glucose level and rs738409 C>G SNP in PNPLA3. In fact, a novel index (extended FLI) generated from these and the usual FLI parameters considerably increased its power to predict NAFLD (AUROC=0.79-0.86). The extended FLI also increased the power to predict changes in liver fat content with a lifestyle intervention (n=213; standardized beta coefficient: 0.23-0.29).
This study has provided novel data confirming that the OGTT-derived fold-change TG and 2-h glucose level, together with the rs738409 C>G SNP in PNPLA3, allow calculation of an extended FLI that considerably improves its power to predict NAFLD.
在临床实践中，人们对非酒精性脂肪性肝病（NAFLD）的非侵入性标志物有着浓厚兴趣。我们的假设是，2小时口服葡萄糖耐量试验期间血浆甘油三酯（TG）的变化倍数（TG变化倍数）与血糖和血脂参数相结合，以及PNPLA3基因中的rs738409 C>G单核苷酸多态性（SNP），可能会提高广泛使用的脂肪肝指数（FLI）预测NAFLD的能力。
通过氢磁共振波谱对330名受试者的肝脏脂肪含量进行定量分析。在空腹和2小时口服葡萄糖耐量试验后测量血液参数。213名受试者的亚组在进行9个月生活方式干预前后进行了这些测量。
TG变化倍数与肝脏脂肪含量密切相关（r = 0.51，P < 0.0001），但预测NAFLD的能力（曲线下面积[AUC] = 0.75）低于FLI（AUC = 0.79）。TG变化倍数不仅与肝脏脂肪含量和NAFLD独立相关，2小时血糖水平和PNPLA3基因中的rs738409 C>G SNP也是如此。事实上，由这些参数和常规FLI参数生成的新指数（扩展FLI）显著提高了其预测NAFLD的能力（AUC = 0.79 - 0.86）。扩展FLI还提高了预测生活方式干预后肝脏脂肪含量变化的能力（n = 213；标准化β系数：0.23 - 0.29）。
本研究提供了新的数据，证实了口服葡萄糖耐量试验衍生的TG变化倍数和2小时血糖水平，以及PNPLA3基因中的rs738409 C>G SNP，可用于计算扩展FLI，显著提高其预测NAFLD的能力。
