Abstract
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, Ptrend = 0.002; Me-Can, Ptrend = 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.
Highlights
Glioma is a heterogeneous primary brain tumour for which there is no treatment that ensures long-term survival
We propose that elevated consumption of blood glucose by the preclinical tumour may account for the apparent reduction of glioma risk among people with diabetes or elevated blood glucose levels
Hazard ratios and trend test P-values in Table 2 are similar for both sexes combined in the Apolipoprotein MOrtality RISk (AMORIS) and Metabolic syndrome and Cancer project (Me-Can) cohorts, these P-values primarily reflect the hazard ratios of the highest level of glucose (≥6.1 mmol/L) (AMORIS HR = 0.59, 95% confidence intervals (CIs) 0.42 to 0.84; Me-Can HR = 0.58, 95% CI 0.32 to 1.04)
Summary
Glioma is a heterogeneous primary brain tumour for which there is no treatment that ensures long-term survival. If the preclinical tumour reduces circulating blood glucose levels one would expect an inverse association to be strongest near the time of glioma diagnosis[17]. Our rationale for evaluating age at diagnosis as a modifying factor is based on results of a previous AMORIS study of pre-diagnostic serum glucose levels and prostate cancer risk[18]. People with hyperglycaemia are selected out of the population at risk of glioma making etiological inferences based on comparisons of the prevalence of hyperglycaemia between people with and without glioma invalid To determine whether this potential source of selection bias is present, we estimated the modifying effects of age at diagnosis on the association between blood glucose levels and glioma. To further evaluate our data for the presence of competing risks, we used the sub-distribution hazards model[22, 23] which is a more formal method of identifying competing risks
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