Discussion
hyperglycemia, cancer, hyperinsulinemia, diabetes
COLORECTAL CANCER, CANCER, EVENT, HYPERGLYCEMIA, HYPERINSULINEMIA, INSULIN SENSITIVITY, COMPLICATIONS, DIABETES
In older people with diabetes, we found that a relationship exists between metformin and cancer prevention that may be modified by lower FBGLs. Overall, we found that people with diabetes whose physician had prescribed metformin had a lower cancer incidence risk than those whose physicians had not prescribed metformin over 4.5 years of follow up. We found no conclusive associations between metformin and cancer mortality, however, likely because of small event numbers. Furthermore, the rate of incident cancer in those on metformin was similar in ASPREE participants who did not have diabetes, indicating that the benefits associated with metformin may potentially attenuate diabetes as a risk factor for cancer.Several potential explanations exist for the risk reduction associated with metformin use that we observed. A chemoprevention effect of metformin has been attributed to several biological mechanisms, including 1) activation of the liver kinase B-1–adenyl-monophosphate protein kinase pathway and subsequent suppression of hepatic glucose production leading to a reduction in insulin requirements (Our data indicated that the beneficial associations of metformin on cancer incidence may not be observed in those with high FBGLs (>150 mg/dL), suggesting that if hyperglycemia and hyperinsulinemia persist, then metformin may have limited clinical effect on cancer risk. Although our analysis of the interaction between FBGL and metformin on cancer incidence was not conclusive, previous studies have shown that blood glucose control is essential for minimizing the risk of microvascular complications, a condition that emerging evidence shows is associated with future risk of cancer (The ASPREE clinical trial found no difference between aspirin and placebo for cancer incidence but an increased risk of cancer mortality with aspirin (Theoretically, aspirin could increase cancer risk through hyperinsulinemia. Several clinical trials conducted in the 1980s demonstrated a detrimental effect of aspirin therapy on insulin sensitivity in people with (Given that the magnitude of the elevated cancer mortality risk observed within the metformin group was pronounced and greater than the hazard ratio observed for the overall cohort (Previous meta-analyses of aspirin clinical trials conducted in middle-aged individuals (ranging in median age at randomization from 57.5 to 66.9 years) found that aspirin treatment prevented cancer, particularly colorectal cancer, over the next 20 years (