卡介苗可长期改善1型糖尿病患者的血糖
创作:szx 审核:szx 2018年07月18日
  • 纳入282名受试者(包括211名1型糖尿病患者),52名进行卡介苗临床研究,230名进行体外实验;
  • 使用卡介苗3年后,患者的血红蛋白A1c(HbA1c)显著降低,在接下来的5年间可降至正常水平附近;
  • 卡介苗导致糖代谢由氧化磷酸化向有氧糖酵解的转化,后者利用的葡萄糖更多;
  • 另外,卡介苗可通过表观遗传调节途径,重塑6个Treg核心基因的表达,从而对免疫耐受进行重编程。
主编推荐语
szx
一个世纪依赖,卡介苗被用于预防肺结核。在npj Vaccines上发表的一项最新研究中,报道了卡介苗的另一潜在作用——改善1型糖尿病患者的血糖。研究发现,卡介苗可能是通过改变糖代谢的方式,将氧化磷酸化转变为有氧糖酵解,以消耗更多的葡萄糖,已达到降血糖作用。
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npj Vaccines [IF:5.699]

Long-term reduction in hyperglycemia in advanced type 1 diabetes: the value of induced aerobic glycolysis with BCG vaccinations

对晚期1型糖尿病患者的长期降糖作用:卡介苗免疫诱导有氧糖酵解

10.1038/s41541-018-0062-8

2018-06-21, Article

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Mycobacterium are among the oldest co-evolutionary partners of humans. The attenuated Bacillus Calmette Guérin (BCG) strain has been administered globally for 100 years as a vaccine against tuberculosis. BCG also shows promise as treatment for numerous inflammatory and autoimmune diseases. Here, we report on a randomized 8-year long prospective examination of type 1 diabetic subjects with long-term disease who received two doses of the BCG vaccine. After year 3, BCG lowered hemoglobin A1c to near normal levels for the next 5 years. The BCG impact on blood sugars appeared to be driven by a novel systemic and blood sugar lowering mechanism in diabetes. We observe a systemic shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis, a state of high glucose utilization. Confirmation is gained by metabolomics, mRNAseq, and functional assays of cellular glucose uptake after BCG vaccinations. To prove BCG could induce a systemic change to promote accelerated glucose utilization and impact blood sugars, murine data demonstrated reduced blood sugars and aerobic induction in non-autoimmune mice made chemically diabetic. BCG via epigenetics also resets six central T-regulatory genes for genetic re-programming of tolerance. These findings set the stage for further testing of a known safe vaccine therapy for improved blood sugar control through changes in metabolism and durability with epigenetic changes even in advanced Type 1 diabetes.

First Authors:
Willem M Kühtreiber

Correspondence Authors:
Denise L Faustman

All Authors:
Willem M Kühtreiber,Lisa Tran,Taesoo Kim,Michael Dybala,Brian Nguyen,Sara Plager,Daniel Huang,Sophie Janes,Audrey Defusco,Danielle Baum,Hui Zheng,Denise L Faustman

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