Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey

Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III; 1988–1994), with an average follow-up of 8.5 years to death, we evaluated markers of glucose and insulin metabolism, with cancer mortality, ascertained using death certificates or the National Death Index. Plasma glucose, insulin, C-peptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical, and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity, and body mass index, for every 50 mg/dl increase in plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI) (1.07–1.87; p = 0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin-resistant individuals (HR: 1.67; 95% CI: 1.15–2.42; p = 0.01), specifically among those with lower levels of physical activity (HR: 2.06; 95% CI: 1.4–3.0; p = 0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusion, hyperglycemia and insulin resistance may be ‘high-risk’ conditions for cancer mortality. Managing these conditions may be effective cancer control tools.