2型糖尿病患者维生素D与血管紧张素转化酶2及炎症因子的相互作用研究

Effect of vitamin D deficiency on ACE2 and inflammatory factors in patients with type 2 diabetes

目的 分析2型糖尿病患者维生素D、血管紧张素转化酶(ACE)、ACE2及炎症因子等的水平及相关性,探讨维生素D与ACE2及炎症因子的相互作用及对糖尿病发生发展的作用机制。方法 收集2021年7月至2021年11月河北省人民医院门诊及住院的2型糖尿病患者96例及非糖尿病对照87例,按照血清25-羟基维生素D水平分为非糖尿病维生素D正常组47例和维生素D不足组40例,糖尿病维生素D正常组52例和维生素D不足组44例,检测各组ACE、ACE2及白细胞介素(IL)、肿瘤坏死因子(TNF-α)等炎症指标,分析维生素D与各指标的相关性和影响因素。结果 无论非糖尿病还是糖尿病中,维生素D不足组较维生素D正常组胰岛素抵抗指数(HOMA-IR)、血管紧张素Ⅱ(AngⅡ)、IL-6、TNF-α显著升高,ACE2、IL-10显著降低(P<0.05);糖尿病维生素D不足组与非糖尿病维生素D不足组比较,维生素D缺乏严重,血糖、ACE及炎症因子等显著升高,胰岛素抵抗更为严重,ACE2、IL-10显著降低(P<0.05);Pearson相关分析显示,非糖尿病组维生素D与AngⅡ、IL-6呈负相关,与IL-10呈正相关(P<0.05);糖尿病组维生素D与ACE2、IL-10呈正相关,与ACE、AngⅡ、IL-6、TNF-α、HOMA-IR、HbA1c均呈负相关(均P<0.01)。多元线性回归分析显示,非糖尿病组中,IL-10和AngⅡ是维生素D缺乏的主要影响因素(P<0.05),共解释回归方程总变异的33.6%;糖尿病组中,ACE2、IL-6、TNF-α、IL-10、HOMA-IR是维生素D缺乏的主要影响因素(P<0.05),共解释回归方程总变异的55.8%。结论 维生素D缺乏可能会改变ACE2、ACE/AngⅡ的不当调节和炎症因子的释放,通过介导RAS系统加重胰岛素抵抗,参与糖尿病的潜在致病作用;ACE2、ACE/AngⅡ及炎症因子可作为糖尿病维生素D缺乏的易感标志物。

Objective To analyze the levels and correlation of vitamin D,ACE2,ACE and inflammatory factors in patients with type 2 diabetes mellitus and explore the interaction of vitamin D with ACE2 and inflammatory factors and the mechanism of action on the occurrence and development of diabetes.Methods A total of 87 non-diabetic controls and 96patients with type 2 diabetes mellitus were chosen,who visited Hebei People's Hospital and were hospitalized from July2021 to November 2021,and they were divided into non-diabetic normal vitamin D group(47 cases)and insufficient vitamin D group(40 cases),and diabetic normal vitamin D group(52 cases)and insufficient vitamin D group(44 cases)according to serum 25-hydroxyvitamin D level.Detect inflammatory indicators such as ACE,ACE2,IL-6 and TNF-αin each group,and analyze the correlation and influencing factors between vitamin D and each indicator.Results Compared with the normal vitamin D group,the vitamin D insufficiency group had significantly higher HOMAIR,AngⅡ,IL-6,and TNF-αlevels and significantly lower ACE2 and IL-10 levels in both non-diabetic and diabetic patients(P<0.05).Compared with the nondiabetic vitamin D insufficiency group,with the increase in severity of vitamin D deficiency,blood glucose,ACE and inflammatory factors were significantly increased,insulin resistance was more serious,and ACE2 and IL-10 were significantly decreased(P<0.05).Pearson correlation analysis showed that vitamin D was negatively correlated with AngⅡand IL-6,and positively correlated with IL-10 in the non-diabetic group(P<0.05).In the diabetic group,vitamin D was positively correlated with ACE2 and IL-10,and negatively correlated with ACE,AngⅡ,IL-6,TNF-α,HOMA-IR and Hb A1c(all P<0.01).Multiple linear regression analysis showed that IL-10 and AngⅡwere the main influencing factors of vitamin D deficiency in the non-diabetic group(P<0.05),which explained 33.6%of the total variation of the regression equation.In the diabetes group,ACE2,IL-6,TNF-α,IL-10 and HOMA-IR were the main influencing factors of vitamin D deficiency(P<0.05),which explained 55.8%of the total variation of the regression equation.Conclusions Vitamin D deficiency may lead to dysregulation of ACE2,ACE/AngⅡand increased levels of inflammatory factors.Vitamin D deficiency exacerbates insulin resistance by mediating the RAS system,which is involved in the potential pathogenesis of diabetes.ACE2,ACE/AngⅡand inflammatory factors can be used as susceptible markers of vitamin D deficiency in diabetes.