Hyperinsulinemia, abnormal glucose tolerance and subsequent risk of cancer

Although many risk factors for cancer have been established, the causes of many cancers remain unexplained and the mechanisms underlying metabolic risk factors, such as physical activity, obesity and diet, are uncertain. It is hypothesized that hyperinsulinemia and associated abnormal glucose tolerance links these metabolic risk factors and may be associated with an increased risk of cancer. Increased insulin levels may lead to increased cancer, particularly colorectal cancer, through a decrease in insulin-like growth factor binding proteins and an increase in insulin-like growth factors. Few studies have examined the joint role of insulin, abnormal glucose tolerance and insulin-like growth-factor binding proteins on development of subsequent cancers. To test this hypothesis two studies were conducted.;The first study was a prospective cohort study using data from the NHANES II Mortality Study, a prospective study of adults examined in the Second National Health and Nutrition Examination Survey (NHANES II) to determine the association of abnormal glucose tolerance and cancer mortality. This analysis focused upon a nationally representative sample of 3,174 adults aged 30--74 years who underwent an oral glucose tolerance test at baseline (1976--1980), whose deaths were identified by searching national mortality files through 1992. These data suggest that in the general U.S. population, impaired glucose tolerance is a strong predictor of cancer mortality, particularly colon cancer.;The second study was a case-control study nested within the CLUE II cohort to determine the association of hyperinsulinemia, IGFBP-1 and subsequent colorectal cancer. CLUE II participants that were diagnosed with colorectal cancer from 1989 to 2001 (n = 173) were matched to 2 controls on age, sex, race, time of last meal and date of blood draw. At baseline, participants provided a blood sample and this stored serum was analyzed for insulin, IGBPP-1, triglycerides, and HDL cholesterol levels. Neither increasing insulin levels nor decreasing IGBP-1 levels were associated with an increased risk of colorectal cancer.;From these studies it can be concluded that impaired glucose tolerance is an independent predictor for cancer mortality, but that it is still uncertain whether this relationship is acting through increased insulin levels and/or decreased IGFBP-1 or another unknown mechanism.