ZHAO Jian, WANG Yuepeng, HOU Yu, MA Wangtian, MU Yiming, GU Weijun. Efficacy of UC-MSC infusion in patients with coexisting type 2 diabetes mellitus and nonalcoholic fatty liver disease: A post hoc analysis of a prospective clinical trial[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2024, 45(6): 571-577, 583. DOI: 10.12435/j.issn.2095-5227.2024.071
Citation: ZHAO Jian, WANG Yuepeng, HOU Yu, MA Wangtian, MU Yiming, GU Weijun. Efficacy of UC-MSC infusion in patients with coexisting type 2 diabetes mellitus and nonalcoholic fatty liver disease: A post hoc analysis of a prospective clinical trial[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2024, 45(6): 571-577, 583. DOI: 10.12435/j.issn.2095-5227.2024.071

Efficacy of UC-MSC infusion in patients with coexisting type 2 diabetes mellitus and nonalcoholic fatty liver disease: A post hoc analysis of a prospective clinical trial

More Information
  • Corresponding author:

    GU Weijun. Email: guweijun301@163.com

  • Received Date: February 23, 2024
  • Available Online: June 13, 2024
  • Background 

    Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are often comorbid conditions, and their coexistence can exacerbate complications and damage target organs. In recent years, stem cell therapy for metabolic diseases using mesenchymal stem cell (MSC) has been emerging both domestically and internationally. However, clinical studies on their therapeutic effects are still sparse.

    Objective 

    To investigate the therapeutic potential of umbilical cord-derived mesenchymal stem cell (UC-MSC) in the amelioration of T2DM and NAFLD comorbidity.

    Methods 

    A prospective, single-center, randomized, double-blind trial was conducted in the Endocrinology Department of the First Medical Center of Chinese PLA General Hospital from October 2015 to December 2018. A total of 65 patients with T2DM and NAFLD were enrolled and assigned on a 1:1 basis to either the UC-MSC group (33 patients) or the placebo group (32 patients). Comparisons were made between pre- and post-treatment levels of blood glucose control, insulin resistance, liver ultrasound findings, degree of liver fibrosis, and selected lipid metabolism and liver function indicators.

    Results 

    In the UC-MSC group, there were 22 males and 11 females, with an average age of 51.36±8.85 years; in the placebo group, there were 22 males and 10 females, with an average age of 50.47±8.42 years. There were no statistically significant differences in gender, age, and baseline data between the two groups (P>0.05).After 9 weeks of treatment, fasting blood glucose levels in the UC-MSC group were significantly lower than baseline ([7.46 ± 1.79] vs [8.33 ± 1.80], P=0.001), and they were also significantly lower than the placebo group at 9 and 20 weeks ([7.46 ± 1.79] vs [8.19 ± 1.95], P=0.007; [7.51 ± 1.77] vs [9.10 ± 2.78], P=0.008). Additionally, at weeks 9, 20, and 48 of treatment, a significantly higher proportion of patients in the UC-MSC group achieved the HbA1c target (<7.0%) compared to the placebo group (60.60% vs 28.10%, P=0.008; 51.50% vs 25.00%, P=0.028; 48.50% vs 12.50%, P=0.002). At week 20, a higher proportion of patients in the UC-MSC group showed improvement in liver ultrasound examinations compared to the placebo group (45.45% vs 18.75%, P=0.021). Hyperinsulinemic-euglycemic clamp test results indicated an increase in glucose infusion rates in the UC-MSC group at weeks 9 and 48 compared to baseline, with a significant difference from the placebo group at week 48 ([4.77 ± 1.70] vs [3.57 ± 1.76], P=0.007). The UC-MSC group also showed sustained improvements over baseline levels for triglycerides (TG) and gamma-glutamyl transferase (GGT), a significant reduction in total cholesterol (TC) at weeks 9 and 48, and a significant decrease in alanine transaminase (ALT) at week 20, while aspartate transaminase (AST) levels showed no significant change at any time points.

    Conclusion 

    UC-MSC therapy can improve glycemic control to some extent, enhance hepatic structure and function, boost insulin sensitivity, and modulate lipid metabolism in patients with concurrent T2DM and NAFLD.

  • [1]
    Sun H,Saeedi P,Karuranga S,et al. IDF Diabetes Atlas:global,regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J]. Diabetes Res Clin Pract,2022,183: 109119. doi: 10.1016/j.diabres.2021.109119
    [2]
    Younossi Z,Anstee QM,Marietti M,et al. Global burden of NAFLD and NASH:trends,predictions,risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol,2018,15(1): 11-20. doi: 10.1038/nrgastro.2017.109
    [3]
    Younossi ZM,Golabi P,de Avila L,et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes:a systematic review and meta-analysis[J]. J Hepatol,2019,71(4): 793-801. doi: 10.1016/j.jhep.2019.06.021
    [4]
    Xia MF,Sun XY,Zheng LL,et al. Regional difference in the susceptibility of non-alcoholic fatty liver disease in China[J]. BMJ Open Diabetes Res Care,2020,8(1): e001311. doi: 10.1136/bmjdrc-2020-001311
    [5]
    Targher G,Corey KE,Byrne CD,et al. The complex link between NAFLD and type 2 diabetes mellitus—mechanisms and treatments[J]. Nat Rev Gastroenterol Hepatol,2021,18: 599-612. doi: 10.1038/s41575-021-00448-y
    [6]
    Xia MF,Bian H,Gao X. NAFLD and diabetes:two sides of the same coin?rationale for gene-based personalized NAFLD treatment[J]. Front Pharmacol,2019,10: 877. doi: 10.3389/fphar.2019.00877
    [7]
    Björkström K,Franzén S,Eliasson B,et al. Risk factors for severe liver disease in patients with type 2 diabetes[J]. Clin Gastroenterol Hepatol,2019,17(13):2769-2775.
    [8]
    中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 实用肝脏病杂志,2018,21(2): 177-186. doi: 10.3969/j.issn.1672-5069.2018.02.007
    [9]
    中华医学会内分泌学分会. 非酒精性脂肪性肝病与相关代谢紊乱诊疗共识(第二版)[J]. 中华内分泌代谢杂志,2018,4(7): 549-554. doi: 10.3760/cma.j.issn.1000-6699.2018.07.004
    [10]
    Zakrzewski W,Dobrzyński M,Szymonowicz M,et al. Stem cells:past,present,and future[J]. Stem Cell Res Ther,2019,10(1): 68. doi: 10.1186/s13287-019-1165-5
    [11]
    Song N,Scholtemeijer M,Shah K. Mesenchymal stem cell immunomodulation:mechanisms and therapeutic potential[J]. Trends Pharmacol Sci,2020,41(9): 653-664. doi: 10.1016/j.tips.2020.06.009
    [12]
    Xue J,Gao JQ,Gu YL,et al. Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes[J]. Stem Cell Res Ther,2022,13(1): 109. doi: 10.1186/s13287-022-02791-6
    [13]
    Sun XY,Hao HJ,Han QW,et al. Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance by suppressing NLRP3 inflammasome-mediated inflammation in type 2 diabetes rats[J]. Stem Cell Res Ther,2017,8(1): 241. doi: 10.1186/s13287-017-0668-1
    [14]
    中华医学会肝脏病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南[J]. 中国肝脏病杂志(电子版),2010,2(4): 43-48. doi: 10.3969/j.issn.1674-7380.2010.04.013
    [15]
    Zang L,Li YJ,Hao HJ,et al. Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes:a single-center,double-blinded,randomized,placebo-controlled phase II trial[J]. Stem Cell Res Ther,2022,13(1): 180. doi: 10.1186/s13287-022-02848-6
    [16]
    中华医学会糖尿病学分会胰岛素抵抗学组筹,李红,贾伟平. 胰岛素抵抗评估方法和应用的专家指导意见[J]. 中华糖尿病杂志,2018,4(6): 377-385. doi: 10.3760/cma.j.issn.1674-5809.2018.06.001
    [17]
    Wang JH,Xu CF,Xun YH,et al. ZJU index:a novel model for predicting nonalcoholic fatty liver disease in a Chinese population[J]. Sci Rep,2015,5: 16494. doi: 10.1038/srep16494
    [18]
    Castera L,Friedrich-Rust M,Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease[J]. Gastroenterology,2019,156(5):1264-1281.
    [19]
    Li LM,You WY,Ren W. The ZJU index is a powerful index for identifying NAFLD in the general Chinese population[J]. Acta Diabetol,2017,54(10): 905-911. doi: 10.1007/s00592-017-1024-8
    [20]
    刘捷,王永红,罗蓉,等. ZJU指数筛查对健康体检人群非酒精性脂肪肝患病风险预测的价值评估:一项基于重庆市体检人群的单中心研究[J]. 重庆医科大学学报,2017,3(2): 244-248.
    [21]
    Wang JH,Ma L,Chen SH,et al. Risk for the development of non-alcoholic fatty liver disease:a prospective study[J]. J Gastroenterol Hepatol,2018,33(8): 1518-1523. doi: 10.1111/jgh.14105
    [22]
    Ding XK,Saxena NK,Lin SB,et al. Exendin-4,a glucagon-like protein-1 (GLP-1) receptor agonist,reverses hepatic steatosis in ob/ob mice[J]. Hepatology,2006,43(1): 173-181. doi: 10.1002/hep.21006
    [23]
    Tan YJ,Zhen Q,Ding XY,et al. Association between use of liraglutide and liver fibrosis in patients with type 2 diabetes[J]. Front Endocrinol,2022,13: 935180. doi: 10.3389/fendo.2022.935180
    [24]
    Yan HL,Huang CY,Shen XJ,et al. GLP-1 RAs and SGLT-2 inhibitors for insulin resistance in nonalcoholic fatty liver disease:systematic review and network meta-analysis[J]. Front Endocrinol,2022,13: 923606. doi: 10.3389/fendo.2022.923606
    [25]
    Eslam M,Newsome PN,Sarin SK,et al. A new definition for metabolic dysfunction-associated fatty liver disease:an international expert consensus statement[J]. J Hepatol,2020,73(1): 202-209. doi: 10.1016/j.jhep.2020.03.039
    [26]
    Gastaldelli A,Cusi K. From NASH to diabetes and from diabetes to NASH:mechanisms and treatment options[J]. JHEP Rep,2019,1(4): 312-328. doi: 10.1016/j.jhepr.2019.07.002
    [27]
    Rong SX,Xia MF,Vale G,et al. DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER[J]. Cell Metab,2024,36(3):617-629.
    [28]
    Papadopoulou A,Papadopoulos KI. Successful lifestyle modifications may underlie umbilical cord-mesenchymal stromal cell effects in type 2 diabetes mellitus[J]. World J Diabetes,2023,14(3): 347-351. doi: 10.4239/wjd.v14.i3.347
    [29]
    王岳鹏,臧丽,母义明. 干细胞治疗糖尿病:未来可期[J]. 中华内科杂志,2023,62(9): 1039-1042. doi: 10.3760/cma.j.cn112138-20230626-00332

Catalog

    Article Metrics

    Article views (274) PDF downloads (49) Cited by()
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return