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

doi:10.12092/j.issn.1009-2501.2020.06.010

Abstract

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

CLC Number:

R976
R593.24

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.

References 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.