Response to Intravenous Glucose-Tolerance Test and Risk of Cancer: A Long-Term Prospective Cohort Study

Background Impaired glucose regulation, measured with an oral glucose-tolerance test, has been associated with the risk of cancer. Here, we explored whether the response to an intravenous glucose-tolerance test (IVGTT) is associated with the risk of cancer. Methods A cohort of 945 healthy men, aged 40–59 years in 1972–75, was followed for 40 years. An IVGTT was performed at baseline. Blood samples for glucose determinations were drawn immediately before glucose injection and thereafter every 10 min for 1 h. Associations were assessed with incidence rate ratios (IRR) and Cox models. Findings Cancer incidence was higher among men with 10-min glucose levels below the median than in men with levels above the median (IRR: 1.5, 95% CI: 1.2–1.9). This association remained significant after adjusting for relevant confounders (HR: 1.6, 95% CI: 1.3–2.1) and when excluding the first 10 years of follow-up to minimize the possibility of reverse causality (HR: 1.5, 95% CI: 1.2–2.0). Interpretation Healthy middle-aged males that responded to an intravenous glucose injection with rapid glucose elimination during the first phase had an elevated risk of cancer during 40 years of follow-up. First phase response to a glucose load might be related to cancer development.
Highlights • Rapid elimination of plasma glucose during the first phase response was associated with a 60% elevated risk of cancer • Plasma glucose uptake during the first-phase may depend on the effectiveness of the molecular glucose-sensing apparatus • Polymorphisms critical for glucose transport into normal cells may also be crucial for transporting glucose into cancer cells In this study low levels of plasma glucose in the early phase of an intravenous glucose-tolerance test were associated with a 60% elevated risk of cancer. The glucose level in the early phase may depend on the effectiveness of the molecular glucose-sensing apparatus. The transport of glucose into cancer cells, that normally requires a constant supply of high glucose, may be rate limited by polymorphisms that are critical for plasma glucose-sensing in general. Previous research has shown that some key proteins, e.g. GLUT 1 and GLUT 2, are involved as glucose transporters into cancer cells.