二甲双胍联合糖皮质激素治疗伴糖耐量异常的系统性红斑狼疮患者的临床研究

doi:10.12092/j.issn.1009-2501.2020.06.010

中国临床药理学与治疗学 ›› 2020, Vol. 25 ›› Issue (6): 670-676.doi: 10.12092/j.issn.1009-2501.2020.06.010

二甲双胍联合糖皮质激素治疗伴糖耐量异常的系统性红斑狼疮患者的临床研究

李桂女¹, 任少琳¹, 沈瑞明², 季永能¹, 蔡彩荣¹, 苏若³

¹海南医学院第一附属医院药学部,海口 570102,海南;
²海南医学院第一附属医院风湿免疫科,海口 570102,海南;
³海南医学院第二附属医院药剂科,海口 570100,海南

收稿日期:2020-02-28 出版日期:2020-06-26 发布日期:2020-07-09
通讯作者: 沈瑞明,女,硕士,主治医师,研究方向:风湿免疫常见疾病及机制。Tel: 13852603301 E-mail: wsxq009@163.com
作者简介:李桂女,女,本科,主管药师,研究方向:药学方面的管理。Tel:13876097849 E-mail:441198496@qq.com
基金资助:
海南省卫生计生行业科研项目(18A200018)

Metformin combined with glucocorticoid in the treatment of SLE patients with IGT

LI Guinv¹, REN Shaolin¹, SHEN Ruiming², JI Yongneng¹, CAI Cairong¹, SU Ruo³

¹ Department of Pharmacy, the First Affiliated Hospital of Hainan Medical College, Haikou 570102, Hainan, China;
² Department of Rheumatology and Immunology, the First Affiliated Hospital of Hainan Medical College, Haikou 570102, Hainan, China;
³ Department of Pharmacy, the Second Affiliated Hospital of Hainan Medical College, Haikou 570100, Hainan, China

Received:2020-02-28 Online:2020-06-26 Published:2020-07-09

摘要/Abstract

摘要： 目的: 探究二甲双胍联合糖皮质激素治疗伴糖耐量异常(IGT)的系统性红斑狼疮(SLE)患者的临床疗效及对胰岛功能、Th17/Treg细胞失衡的影响。方法: 本院84例伴IGT的SLE患者随机分为联用组和对照组各42例,均给予生活、饮食指导,对照组给予糖皮质激素治疗,联用组联合二甲双胍治疗,1个月后观察疗效,并评估胰岛功能和Th17/Treg细胞失衡情况。结果: 联用组总有效率明显高于对照组(90.48% vs. 71.43%,P<0.05),SLE活动指数评分为(2.6±0.3)分,红细胞沉降率(ESR)为(18±4)mm/h,显著低于对照组的(3.9±0.8)分、(23±4)mm/h(P<0.05)。治疗后联用组空腹血糖(FBG)、空腹胰岛素(Fins)、稳态模型-胰岛素抵抗指数(HOMA-IR)、胰岛β功能细胞指数(HOMA-β)显著改善(P<0.05),且与对照组相比差异有统计学意义(P<0.05);联用组正常糖耐量(NGT)占比明显高于对照组(73.81% vs. 30.95%,P<0.05)。治疗后联用组Th17、Treg细胞比例为(6.2±0.9)个/μL、(31±7)个/μL,Th17/Treg为(0.20±0.05),与对照组的(7.4±1.3)个/μL、(28±7)个/μL、(0.26±0.06)相比有统计学差异(P<0.05)。治疗后SLE活动指数评分与HOMA-IR、HOMA-β及Th17细胞、Treg细胞、Th17/Treg明显相关(P<0.05),且HOMA-IR、HOMA-β与Th17细胞、Treg细胞、Th17/Treg也明显相关(P<0.05)。2组不良反应均轻微,发生率无统计学差异(P>0.05)。结论: 二甲双胍联合糖皮质激素治疗伴IGT的SLE患者疗效显著,可控制疾病活动性,降低血糖水平、改善胰岛功能及纠正Th17/Treg细胞失衡,且安全性高。

关键词: 二甲双胍, 糖耐量异常, 系统性红斑狼疮, 胰岛功能, Th17/Treg细胞

Abstract: AIM: To investigate the clinical curative effect of metformin combined with glucocorticoids in the treatment of patients with systemic lupus erythematosus (SLE) complicated with impaired glucose tolerance (IGT) and the effect on islet function and Th17/Treg cell imbalance. METHODS: Eighty-four patients with SLE complicated with IGT were randomly divided into the combined group and the control group with 42 cases in each group. All of them were given life and diet guidance. The control group was treated with glucocorticoids while the combined group was treated with metformin combined with glucocorticoids. One month later, the curative effect was observed, and islet function and Th17/Treg cell imbalance were evaluated. RESULTS: The total response rate of the combined group was significantly higher than that of the control group (90.48% vs. 71.43%, P<0.05). The SLE activity index score and the erythrocyte sedimentation rate (ESR) [(2.6±0.3) points, (18±4) mm/h] were significantly lower than those in the control group [(3.9±0.8) points, (23±4) mm/h] (P<0.05). Fasting blood glucose (FBG), fasting insulin (Fins), steady-state model-insulin resistance index (HOMA-IR) and islet β-functioning cell index (HOMA-β) in the combined group were significantly improved after treatment (P<0.05). There were statistically significant differences between the two groups (P<0.05). The proportion of NGT in the combined group was significantly higher than that in the control group (73.81% vs. 30.95%, P<0.05). The ratios of Th17 and Treg cells in the combined group were (6.2±0.9) /μL and (31±7) /μL, and Th17/Treg was (0.20±0.05). Compared with the control group [(7.4±1.3) /μL, (28±7) /μL, (0.26±0.06)], there were statistically significant differences (P<0.05). The SLE activity index scores after treatment were significantly correlated with HOMA-IR, HOMA-β and Th17 cells, Treg cells, Th17/Treg (P<0.05). Besides, HOMA-IR and HOMA-β were significantly correlated with Th17 cells, Treg cells and Th17/Treg (P<0.05). The adverse reactions in both groups were mild, and there was no statistically significant difference in the incidence (P>0.05). CONCLUSION: Metformin combined with glucocorticoids is effective in the treatment of SLE with IGT. The treatment can control disease activity, lower blood glucose levels, improve islet function and correct Th17/Treg cell imbalance with high safety.

Key words: metformin, impaired glucose tolerance, systemic lupus erythematosus, islet function, Th17/Treg cells

中图分类号:

R976
R593.24

李桂女, 任少琳, 沈瑞明, 季永能, 蔡彩荣, 苏若. 二甲双胍联合糖皮质激素治疗伴糖耐量异常的系统性红斑狼疮患者的临床研究[J]. 中国临床药理学与治疗学, 2020, 25(6): 670-676.

LI Guinv, REN Shaolin, SHEN Ruiming, JI Yongneng, CAI Cairong, SU Ruo. Metformin combined with glucocorticoid in the treatment of SLE patients with IGT[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(6): 670-676.

参考文献 20

[1]	王丽平, 陈利锋, 陈芳, 等. 艾拉莫德对系统性红斑狼疮模型小鼠的影响 [J]. 医药导报, 2018, 37(3): 289-293.
[2]	Huang Q, Yan Y, Zhao H, et al. A systemic lupus erythematosus patient presenting as type B insulin resistance complicated with cryoglobulinemia [J]. Lupus, 2017, 26(1): 95-97.
[3]	Miyake CN, Gualano B, Dantas WS, et al. Increased insulin resistance and glucagon levels in mild/inactive systemic lupus patients despite normal glucose tolerance [J]. Arthritis Care Res, 2018, 70(1): 114-124.
[4]	Takei M, Ishii H, Kawai Y, et al. Efficacy of oral glucocorticoid and cyclosporine in a case of rituximab-refractory type B insulin resistance syndrome [J]. J Diabetes Invest, 2015, 6(6): 734-738.
[5]	谷丽平, 谢小琪, 平立静, 等. 二甲双胍联合雷尼酸锶治疗糖尿病性骨质疏松症的临床效果研究 [J]. 空军医学杂志, 2019, 35(2): 174-177.
[6]	Kawalec PP, Malinowski KP. The indirect costs of systemic autoimmune diseases, systemic lupus erythematosus, systemic sclerosis and sarcoidosis: a summary of 2012 real-life data from the Social Insurance Institution in Poland [J]. Expert Rev Pharmacoecon Outcomes Res, 2015, 15(4): 667-673.
[7]	Kozora E, Ellison MC, West S. Depression, fatigue, and pain in systemic lupus erythematosus (SLE): relationship to the American College of Rheumatology SLE neuropsychological battery [J]. Arthritis Rheum, 2010, 55(4): 628-635.
[8]	赵清, 楼国春. 天麦消渴片联合盐酸二甲双胍片对糖耐量异常患者胰岛素抵抗、胰岛β细胞及肝脏脂肪含量的影响 [J]. 中华中医药学刊, 2016, 34(11): 2700-2702.
[9]	何尚映, 林洁, 黄鹏, 等. 他克莫司胶囊联合醋酸泼尼松龙片治疗系统性红斑狼疮的临床研究 [J]. 中国临床药理学杂志, 2017, 33(5): 398-399.
[10]	李敏, 李雪锋, 郭毅飞, 等. 白细胞介素-17、单核细胞趋化蛋白-1与系统性红斑狼疮患者亚临床动脉粥样硬化的关系 [J]. 国际检验医学杂志, 2018, 39(16): 33-37, 41.
[11]	靳永欣, 徐萍, 高彦青, 等. 系统性红斑狼疮患者胰岛素抵抗情况及其与糖皮质激素的关系 [J]. 天津医药, 2017, 45(12): 1282-1285.
[12]	徐丽玲, 郭乾育, 蔡小燕, 等. 糖皮质激素治疗系统性红斑狼疮患者的现况调查 [J]. 中华内科杂志, 2017, 56(4): 290-294.
[13]	姜晓琳, 张兵, 侯海燕, 等. 二甲双胍联合膈下逐瘀汤对多囊卵巢综合征大鼠炎性因子及性激素水平的影响 [J]. 北京中医药大学学报, 2018, 41(1): 65-70.
[14]	Afzal MZ, Mercado RR, Shirai K. Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma [J]. J Immunother Cancer, 2018, 6(1): 64-75.
[15]	Wang H, Li T, Chen S, et al. NETs mitochondrial DNA and its autoantibody in Systemic Lupus Erythematosus and a proof-of-concept trial of metformin [J]. Arthritis Rheumatol, 2016, 67(12): 3190-3200.
[16]	刘喆, 王海婷, 王慧静, 等. 二甲双胍治疗系统性红斑狼疮的临床试验后随访研究 [J]. 上海交通大学学报(医学版), 2018, 38(10): 60-64.
[17]	Yin Y, Choi S C, Xu Z, et al. Normalization of CD4+ T cell metabolism reverses lupus [J]. Sci Transl Med, 2015, 7(274): 1565-1576.
[18]	赵凌, 杨晓帆, 周小斌, 等. SLE患者CD4＋CD25-T细胞来源的体外诱导型Treg细胞IL-10表达特征的初步研究 [J]. 南京医科大学学报: 自然科学版, 2017, 37(9): 1114-1119.
[19]	Kang KY, Kim YK, Yi H, et al. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis [J]. Int Immunopharmacol, 2013, 16(1): 85-92.
[20]	郝美华, 景晓娜, 梁赵云, 等. 二甲双胍通过调节辅助性T细胞17和调节性T细胞平衡治疗系统性红斑狼疮的应用前景 [J]. 中华风湿病学杂志, 2018, 22(7): 489-492.

二甲双胍联合糖皮质激素治疗伴糖耐量异常的系统性红斑狼疮患者的临床研究

Metformin combined with glucocorticoid in the treatment of SLE patients with IGT

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