Gavriilidis Stylianos, Andrianopoulou Rozalia, Ntenti Charikleia, Sarakapina Anna, Trakatelli Christina, Polyzos Stergios A, Goulas Antonis
First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Third Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece.
Endocrine. 2025 Jan;87(1):73-78. doi: 10.1007/s12020-024-04007-8. Epub 2024 Aug 23.
The evaluation of the effect of dulaglutide on glycated hemoglobin (HbA1c) and non-invasive indices of hepatic steatosis among different genotypes of the PNPLA3 I148M (rs738409) and CETP Taq1B (rs708272) polymorphisms in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).
Relevant data from patients with inadequately controlled T2DM, also displaying NAFLD, administered 1.5 mg dulaglutide weekly for 6 months were retrospectively retrieved. The non-invasive indices, fatty liver index (FLI) and hepatic steatosis index (HSI), were calculated. Genotyping for rs738409 and rs708272 were performed with polymerase chain reaction.
Data from 80 patients (39 females), aged 64.4 ± 9.5 years and displaying a baseline BMI of 34.5 ± 5.8 kg/m, were retrieved at baseline and after 6 months (endpoint) of dulaglutide treatment. Glycated hemoglobin (HbA1c; -0.72 ± 1.10%; p < 0.001), FLI (-5.8 ± 9.8; p < 0.001) and HSI (-1.18 ± 3.51; p = 0.004) significantly decreased after treatment. Lipid profile and liver function tests also improved after treatment. Overall, homozygotes for the reference rs738409 allele (CC) displayed a 2.4-fold decrease (p = 0.002) and heterozygotes (CG) an 1.6-fold decrease (p = 0.013) compared to GG homozygotes after treatment, but the effect was largely limited to female patients. No similar effect was observed in FLI, HSI and other relevant parameters. No association was observed between rs708272 and any of the parameters studied.
rs738409, but not rs708272, was associated with the effect of dulaglutide on HbA1c, but not on presumed hepatic steatosis or other relevant parameters. Sex-specific effects were also noticed.
评估度拉糖肽对2型糖尿病（T2DM）和非酒精性脂肪性肝病（NAFLD）患者中PNPLA3 I148M（rs738409）和CETP Taq1B（rs708272）基因多态性不同基因型患者糖化血红蛋白（HbA1c）及肝脂肪变性非侵入性指标的影响。
回顾性检索接受每周1.5mg度拉糖肽治疗6个月、T2DM控制不佳且伴有NAFLD患者的相关数据。计算非侵入性指标脂肪肝指数（FLI）和肝脂肪变性指数（HSI）。采用聚合酶链反应对rs738409和rs708272进行基因分型。
在度拉糖肽治疗的基线期和6个月（终点）后，检索到80例患者（39例女性）的数据，年龄64.4±9.5岁，基线体重指数为34.5±5.8kg/m²。治疗后糖化血红蛋白（HbA1c；-0.72±1.10%；p<0.001）、FLI（-5.8±9.8；p<0.001）和HSI（-1.18±3.51；p=0.004）显著降低。治疗后血脂谱和肝功能检查也有所改善。总体而言，与治疗后的GG纯合子相比，rs738409参考等位基因（CC）的纯合子下降了2.4倍（p=0.002），杂合子（CG）下降了1.6倍（p=0.013），但这种效应主要限于女性患者。在FLI、HSI和其他相关参数中未观察到类似效应。未观察到rs708272与所研究任何参数之间存在关联。
rs738409而非rs708272与度拉糖肽对HbA1c的影响有关，但与假定的肝脂肪变性或其他相关参数无关。还注意到了性别特异性效应。
