Markers of insulin resistance and colorectal cancer mortality.

A link between insulin metabolism and colorectal cancer has been hypothesized, supported by a series of potential physiological mechanisms, and confirmed by a number of reports in experimental animals. However, the evidence in humans is limited and mostly indirect. The aim of the present report is to analyze whether individuals with a cluster of metabolic abnormalities associated with abnormalities in insulin metabolism experience higher mortality for colorectal cancer than those without this cluster of metabolic abnormalities. A total of 21,311 men and 15,991 women 20-69 years of age were followed-up for an average of 7 years as part of the Risk Factors and Life Expectancy Project, a pooling of a number of epidemiological studies conducted in Italy. Our analyses indicate that participants with high levels of blood glucose and a cluster of metabolic abnormalities linked to insulin resistance experienced a significant increased risk of colorectal cancer mortality compared with participants without the cluster. For the presence of the cluster of metabolic abnormalities, the calculated hazard ratios and 95% CIs were 2.96 (1.05-8.31) for men, 2.71 (0.59-12.50) for women, and 2.99 (1.27-7.01) when both sexes were combined. These associations were independent from the potential confounding effect of age, drinking of alcoholic beverages, and smoking. Our findings are supportive of the hypotheses that glucose metabolism hyperinsulinemia, insulin resistance, and metabolic abnormalities associated with it may play a significant role in the etiology of colorectal cancer.