Hyperinsulinemia and Insulin Resistance Linked to Colorectal Cancer

Non-insulin-dependent diabetes mellitus (NIDDM) seems to be one risk factor for
colorectal cancer. Usually, in the pre-NIDDM state, hyperinsulinemia is seen for several years. Insulin is a growth factor of epithelial and cancer cells of colon and rectum. At the Department of General Surgical Science, Gumma University, Gumma, Japan [46], patients suffering from colorectal cancer but never diagnosed for diabetes, were tested for glucose tolerance. Serum glucose and insulin levels were found to be higher in cancer patients than in controls. The authors concluded that hyperinsulinemia may be one of the causes of colorectal cancer and should be controlled to prevent recurrence of colorectal cancer even after curative resection. Mechanistically, hyperinsulinemia has been associated with insulin resistance, increased levels of growth factors, including IGF-1, and alterations in NF-B and peroxisome proliferator-activated receptor signaling, which may promote colon cancer through their effects on colonocyte kinetics. The insulin resistance colon cancer hypothesis, stating that insulin resistance may be associated with the development of colorectal cancer, represents a significant advance in colon cancer, as it emphasized the potential for this cancer to become a modifiable disease [47]. This hypothesis is supported by results from a prospective study including anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in malesmokers [48].

A cohort study on the impact of diabetes within a large randomized adjuvant
chemotherapy trial of 3,759 patients with high-risk stage II and stage III colon cancer was carried out in 2003 at the Dana-Farber Cancer Institute, Eastern Cooperative Oncology Group Statistical Center, and Channing Laboratory, Department of
Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston,
Mass., USA [49]. Patients with diabetes and high-risk stage II and stage III colon cancer experienced a significantly higher rate of overall mortality and cancer recurrence. Median survival was 6.0 and 11.3 years for diabetics and non-diabetics, respectively. In various animal models, it could be shown that insulin and insulin-like growth factor axes and insulin resistance are major determinants of proliferation and apoptosis and thus may influence carcinogenesis. Clinical conditions associated with hyperinsulinemia and increased IGF-1 levels are related to an increased risk of colon cancer. Global nutrition studies [39] indicate that dietary patterns that stimulate insulin secretion and resistance, including a high consumption of sucrose, various sources of starch, a high glycemic index and high saturated fatty acid intake, are associated w ith a higher r isk of c olon c ancer. E fforts to c ounter t hese p atterns are likely to have the most potential to reduce colon cancer incidence and tumor recurrence.