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

Autor:	Kühtreiber WM; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Tran L; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Kim T; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Dybala M; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Nguyen B; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Plager S; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Huang D; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Janes S; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Defusco A; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Baum D; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA., Zheng H; 2Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02115 USA., Faustman DL; 1Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th Street, Boston, MA 02116 USA.
Jazyk:	angličtina
Zdroj:	NPJ vaccines [NPJ Vaccines] 2018 Jun 21; Vol. 3, pp. 23. Date of Electronic Publication: 2018 Jun 21 (Print Publication: 2018).
DOI:	10.1038/s41541-018-0062-8
Abstrakt:	Mycobacterium are among the oldest co-evolutionary partners of humans. The attenuated Mycobacterium bovis 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. Competing Interests: The authors declare no competing interests.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu