TYG-BMI在维生素D和非酒精性脂肪肝中的中介作用

Mediating role of TYG-BMI in vitamin D and nonalcoholic fatty liver disease

目的:分析维生素D水平、甘油三酯葡萄糖-体质指数(triglyceride glucose-body mass index,TYG-BMI)与2型糖尿病(type 2 diabetes,T2DM)合并非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)患者的相关性,探讨TYG-BMI在维生素D缺乏对NAFLD影响中的作用。方法:纳入河北省人民医院内分泌科住院的434例成年T2DM患者为研究对象。收集患者的人口学基本信息和血液指标,NAFLD通过超声诊断。维生素D缺乏定义为25-羟基维生素D[25-hydroxyvitamin D,25(OH)D]<20 ng/mL。采用Spearman相关分析方法,探讨25(OH)D、TYG-BMI和T2DM合并NAFLD危险因素之间的相关性。采用多元逻辑回归分析方法探讨25(OH)D、TYG-BMI与NAFLD之间的联系。采用中介分析方法探索TYG-BMI是否介导25(OH)D和NAFLD之间的联系。结果:(1)在所有纳入的T2DM患者中,NAFLD组比无NAFLD组的25(OH)D水平更低[15.89(12.33,19.94)vs.18.27(14.05,24.63),P<0.05],TYG-BMI水平更高[213.59(191.92,237.60)vs.176.91(159.55,196.86),P<0.05],并且男性和女性均有同样的变化趋势(P<0.05)。(2)按照25(OH)D水平不同分组发现,维生素D缺乏组的NAFLD患病率(60.1%)高于维生素D不足组(45.4%)及维生素D充足组(23.3%),差异存在统计学意义(P<0.05)。(3)无论是男性患者还是女性患者,血清25(OH)D水平均与TYG-BMI呈负相关(男:r=-0.215,P<0.001;女:r=-0.271,P<0.001)。(4)采用logistic回归调整混杂因素后发现维生素D缺乏是T2DM患者发生NAFLD的危险因素(Model 1 OR=2.347,95%CI=1.423~3.871,P=0.001;Model 2 OR=2.478,95%CI=1.472~4.172,P=0.001;Model 3 OR=2.057,95%CI=1.172~3.610,P=0.012)。进一步按性别分亚组进行logistic回归分析,仅在女性中发现维生素D缺乏是T2DM患者发生NAFLD的独立危险因素(Model 1 OR=5.52,95%CI=2.008~15.177,P=0.001;Model 2 OR=5.342,95%CI=1.776-16.061,P=0.003;Model 3 OR=3.734,95%CI=1.108~12.578,P=0.034)。(5)在所有患者、男性患者和女性患者中TYG-BMI与NAFLD患病率均呈正相关(P<0.05)。(6)中介分析发现在所有患者或女性患者中,TYGBMI部分介导了25(OH)D对NAFLD患病率的间接影响(中介百分比:所有患者58.66%,女性患者38.07%),而男性没有。结论:仅在女性T2DM患者中,维生素D缺乏与T2DM合并NAFLD发病率增加相关。其中维生素D缺乏导致T2DM合并NAFLD发生率增加的原因部分由TYG-BMI介导。

Objective:To analyze the correlation between the serum vitamin D and triglyceride glucose-body mass index(TYG-BMI)of type 2 diabetes mellitus(T2DM)patients complicated with nonalcoholic fatty liver disease(NAFLD),and to explore the roles played by TYG-BMI in the vitamin D deficiency of T2DM living with NAFLD.Methods:A total of 434 patients with T2DM hospitalized at Department of Endocrinology,Hebei General Hospital were included in the study.These patients’demographics and clinical data were collected.Abdominal ultrasonography was performed to diagnose NAFLD.Vitamin D deficiency was defined as that 25-hydroxyvitamin D[25(OH)D]vitamin levels were less than 20 ng/mL.Spearman correlation was used to test for an association among 25(OH)D,TYG-BMI and risk factors of NAFLD in T2DM.Multiple logistic regression was used to determine the association in 25(OH)D,TYG-BMI and NAFLD.Mediation analysis was used to explore whether TYG-BMI mediated the association between 25(OH)D and NAFLD.Results:①In all included T2DM patients,the 25(OH)D level in patients with NAFLD was significantly lower[15.89(12.33,19.94)vs.18.27(14.05,24.63),P<0.05]and TYG-BMI was significantly higher[213.59(191.92,237.60)vs.176.91(159.55,196.86),P<0.05]compared with those without NAFLD.The data showed the same trends for males and females(P<0.05).②According to different 25(OH)D levels,the prevalence of NAFLD in the vitamin D deficiency group(60.1%)was higher than that in the vitamin D insufficiency group(45.4%)and the vitamin D sufficiency group(23.3%),and the difference was statistically significant(P<0.05).③Serum 25(OH)D level was negatively correlated with TYGBMI,both in women and in men(men:r=-0.215,P<0.001;women:r=-0.271,P<0.001).④After adjusting for confounding factors,multivariate logistic regression analysis revealed that Vitamin D deficiency was a risk factor for NAFLD in T2DM patients(Model 1 OR=2.347,95%CI=1.423-3.871,P=0.001;Model 2 OR=2.478,95%CI=1.472-4.172,P=0.001;Model 3 OR=2.057,95%CI=1.172–3.610,P=0.012).Gender-specific subgroup logistic regression analyses showed vitamin D deficiency was an independent risk factor for NAFLD in T2DM for women(Model 1 OR=5.52,95%CI=2.008-15.177,P=0.001;Model 2 OR=5.342,95%CI=1.776-16.061,P=0.003;Model 3 OR=3.734,95%CI=1.108-12.578,P=0.034).⑤TYG-BMI was positively correlated with the prevalence of NAFLD in all T2DM patients,male patients and female patients(P<0.05).⑥Mediation analysis indicated that TYG-BMI partly mediated the indirect effect of 25(OH)D on NAFLD incidence(percentage of mediation:58.66%of all patients,and 38.07%of female patients).Conclusion:Vitamin D deficiency is associated with an increased incidence of NAFLD only in female subjects with T2DM.The association between vitamin D deficiency and higher prevalence of NAFLD in T2DM may be at least partially mediated by TYG-BMI.