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Previous literature indicates that pre-diagnostic diabetes and blood glucose levels are inversely related to glioma risk. To replicate these findings and determine whether they could be attributed to excess glucose consumption by the preclinical tumour, we used data from the Apolipoprotein MOrtality RISk (AMORIS) (n = 528,580) and the Metabolic syndrome and Cancer project (Me-Can) cohorts (n = 269,365). We identified individuals who were followed for a maximum of 15 years after their first blood glucose test until glioma diagnosis, death, emigration or the end of follow-up. Hazard ratios (HRs), 95% confidence intervals (CIs) and their interactions with time were estimated using Cox time-dependent regression. As expected, pre-diagnostic blood glucose levels were inversely related to glioma risk (AMORIS, P trend = 0.002; Me-Can, P trend = 0.04) and pre-diagnostic diabetes (AMORIS, HR = 0.30, 95% CI 0.17 to 0.53). During the year before diagnosis, blood glucose was inversely associated with glioma in the AMORIS (HR = 0.78, 95% CI 0.66 to 0.93) but not the Me-Can cohort (HR = 0.99, 95% CI 0.63 to 1.56). This AMORIS result is consistent with our hypothesis that excess glucose consumption by the preclinical tumour accounts for the inverse association between blood glucose and glioma. We discuss additional hypothetical mechanisms that may explain our paradoxical findings.

18 citations (Crossref) [2023-10-31] Place: England Schwartzbaum, Judith. Division of Epidemiology, College of Public Health, Ohio State University, Columbus, Ohio, 43210, United States of America. ja.schwartzbaum@gmail.com. Schwartzbaum, Judith. Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, 43210, United States of America. ja.schwartzbaum@gmail.com. Edlinger, Michael. Department of Medical Statistics, Informatics, and Health Economics, Medical University, Innsbruck, Austria. michael.edlinger@i-med.ac.at. Zigmont, Victoria. Division of Epidemiology, College of Public Health, Ohio State University, Columbus, Ohio, 43210, United States of America. Zigmont, Victoria. Department of Public Health, Southern Connecticut State University, New Haven, CT, 06515, United States of America. Stattin, Par. Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea University, Umea, Sweden. Rempala, Grzegorz A. Division of Epidemiology, College of Public Health, Ohio State University, Columbus, Ohio, 43210, United States of America. Rempala, Grzegorz A. Division of Biostatistics, College of Public Health, Ohio State University, Columbus, Ohio, 43210, United States of America. Rempala, Grzegorz A. Mathematical Biosciences Institute, Columbus, Ohio, 43210, United States of America. Nagel, Gabriele. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. Nagel, Gabriele. Agency for Preventive and Social Medicine, Bregenz, Austria. Hammar, Niklas. Medical Evidence & Observational Research, Global Medical Affairs, Astra Zeneca R&D, Molndal, 43150, Sweden. Hammar, Niklas. Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-17177, Stockholm, Sweden. Ulmer, Hanno. Department of Medical Statistics, Informatics, and Health Economics, Medical University, Innsbruck, Austria. Foger, Bernhard. Agency for Preventive and Social Medicine, Bregenz, Austria. Walldius, Goran. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-17177, Stockholm, Sweden. Manjer, Jonas. Department of Surgery, Skane University Hospital, Malmo, Sweden. Malmstrom, Hakan. Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-17177, Stockholm, Sweden. Feychting, Maria. Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-17177, Stockholm, Sweden.