Effectiveness and safety of bifidobacteria and berberine in people with hyperglycemia: study protocol for a randomized controlled trial

Jie Ming, Shaoyong Xu, Chun Liu, Xiangyang Liu, Aihua Jia, Qiuhe Ji, Jie Ming, Shaoyong Xu, Chun Liu, Xiangyang Liu, Aihua Jia, Qiuhe Ji

Abstract

Background: Berberine is one of the most important examples of a Chinese traditional medicine that has hypoglycemic effects but there have been no randomized controlled trials of the drug in a larger sample. In addition, the use of probiotic biotherapy to maintain an appropriate intestinal flora may represent an effective early intervention for hyperglycemia. Unfortunately, there has been a shortage of relevant research on this possibility at the population level. This study was designed to determine the hypoglycemic effect and safety of both bifidobacteria and berberine administration to newly diagnosed patients with pre-diabetes or diabetes mellitus.

Methods/design: This is a multicenter, double-blind, randomized, and parallel-controlled study that includes a run-in period of 2 weeks and a treatment period of 16 weeks, which will be conducted between June 2015 and October 2018. The 300 randomized patients will be assigned to the following four groups for 16 weeks' treatment: Bifidobacterium, berberine, Bifidobacterium combined berberine, and placebo control groups. The primary outcome is the absolute value of fasting plasma glucose compared with baseline after 16 weeks of treatment.

Discussion: This is the first randomized controlled trial to determine the hypoglycemic effect and safety of both bifidobacteria and berberine administration to newly diagnosed patients with pre-diabetes or diabetes mellitus. It may provide support for the use of berberine and bifidobacteria in the treatment of diabetes.

Trial registration: ClinicalTrials.gov, ID: NCT03330184 . Retrospectively registered on 18 October 2017.

Keywords: Berberine; Bifidobacteria; Chinese population; Diabetes; Hyperglycemia; Pre-diabetes; Randomized trials.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the independent Ethics Committee of the First Affiliated Hospital of the Fourth Military Medical University (ID: KY20150611-3) and registered (registration date: 18 October 2017 – retrospectively registered) at the National Institutes of Health Clinical Research Trials Register (ClinicalTrials.gov, identifier: NCT03330184). The findings of this trial will be submitted to a peer-reviewed journal. Abstracts will be submitted to relevant national and international conferences.

Each subject has provided signed and dated informed consent before conducting any procedure associated with the study. Participation in this study is strictly confidential. Any information that is published will not reveal the identity of the subjects.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Inclusion criteria and interventions
Fig. 2
Fig. 2
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure. Specific research plan and implementation steps. Note: Laboratory safety assessment assays were completed by sub-center laboratories, while the validity assessment laboratory assays and the intestinal indices were completed by the central laboratory. OGTT oral glucose tolerance test, BG blood glucose, SMBG self-monitoring of blood glucose, BMI Body Mass Index

References

    1. Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, et al. Prevalence of diabetes among men and women in China. N Engl J Med. 2010;362:1090–101. doi: 10.1056/NEJMoa0908292.
    1. EI-Kaissi S, Sherbeeni S. Pharmacological management of type 2 diabetes mellitus: an update. Curr Diabetes Rev. 2011;7:392. doi: 10.2174/157339911797579160.
    1. Goldberg RB, Temprosa M, Haffner S, Orchard TJ, Rater RE, Fowler SE, et al. Effect of progression from impaired glucose tolerance to diabetes on cardiovascular risk factors and its amelioration by lifestyle and metformin intervention: the Diabetes Prevention Program randomized trial by the Diabetes Prevention Program Research Group. Diabetes Care. 2009;32:726–32. doi: 10.2337/dc08-0494.
    1. Tuomilehto J, Lindstrom J, Hellmich M, Lehmacher W, Westermeier T, et al. Development and validation of a risk-score model for subjects with impaired glucose tolerance for the assessment of the risk of type 2 diabetes mellitus—The STOP-NIDDM risk-score. Diabetes Res Clin Pract. 2010;87:267–74. doi: 10.1016/j.diabres.2009.11.011.
    1. Zhang J, Tang H. Berberine progress in clinical application. Pharm Clin Res. 2015;3:287–90.
    1. Zhang L, Ji Y. Application of berberine in diabetes treatment. J Pract Med. 1999;13:22.
    1. Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004;10:1344–51. doi: 10.1038/nm1135.
    1. Lee YS, Kin KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55:2256–64. doi: 10.2337/db06-0006.
    1. Kupeli E, Kosar M, Yesilada E, Husnu K, Baser C. A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberis species. Life Sci. 2002;72(6):645–57. doi: 10.1016/S0024-3205(02)02200-2.
    1. Tang LQ, Wei W, Chen LM, Liu S. Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats. J Ethnopharmacol. 2006;108:109–15. doi: 10.1016/j.jep.2006.04.019.
    1. Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008;93:2559–65. doi: 10.1210/jc.2007-2404.
    1. Yin J, Hu R, Chen M, Tang J, Li F, Yang Y, et al. Effects of berberine on glucose metabolism in vitro. Metabolism. 2002;51:1439. doi: 10.1053/meta.2002.34715.
    1. Zhou L, Chen M, Song H. Effect of berberine on glucose transfer in fat cells and its mechanism. J Chin Endocr Metab. 2003;19:479–82.
    1. Zhou L, Yang Y. Effect of berberine on the glucose metabolism of fat cells. J Shanghai First Med Univ. 2002;22:412–4.
    1. Zhou L, Yang Y, Wang X, Liu S, Shang W, Yuan G, et al. Berberine stimulates glucose transport through a mechanism distinct from insulin. Metabolism. 2007;56:405–12. doi: 10.1016/j.metabol.2006.10.025.
    1. Bustanji Y, Taha MO, Yousef AM, Al-Bakri AG. Berberine potently inhibits protein tyrosine phosphatase 1B: investigation by docking simulation and experimental validation. J Enzyme Inhib Med Chem. 2006;21:163–71. doi: 10.1080/14756360500533026.
    1. Cani PD, Delzenne NM. Gut microflora as a target for energy and metabolic homeostasis. Curr Opin Clin Nutr Metab Care. 2007;10:729–34. doi: 10.1097/MCO.0b013e3282efdebb.
    1. Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009;15(13):1546–58. doi: 10.2174/138161209788168164.
    1. Wu X, Ma C, Han L, Nawaz M, Gao F, Xu Z, et al. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol. 2010;61:69–78. doi: 10.1007/s00284-010-9582-9.
    1. Creely SJ, Mcternan PG, Kusminski CM, Fisher FM, Da Silva NF, Khanolkar M, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;292:740–7. doi: 10.1152/ajpendo.00302.2006.
    1. Mahowald MA, Rey FE, Seedorf H, Turnbaugh PJ, Fulton RS, Wollam A, et al. Characterizing a model human gut microbiota composed of members of its two dominant bacterial. Proc Natl Acad Sci U S A. 2009;106:5859–64. doi: 10.1073/pnas.0901529106.
    1. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374–83. doi: 10.1007/s00125-007-0791-0.
    1. Abbud W, Habinowski S, Zhang JZ, Kendrew J, Elkairi FS, Kemp BE, et al. Stimulation of AMP activated protein kinase (AMPK) is associated with enhancement of Glut1-mediated glucose transport. Arch Biochem Biophys. 2000;380:347. doi: 10.1006/abbi.2000.1935.
    1. Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism. 2009;58:109. doi: 10.1016/j.metabol.2008.08.013.
    1. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57:712. doi: 10.1016/j.metabol.2008.01.013.
    1. Dong H, Wang L, Lu Z. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654. doi: 10.1155/2012/591654.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir