Diabetes and cancer II: role of diabetes medications and influence of shared risk factors

Abstract

An association between type 2 diabetes mellitus (DM) and cancer has long been postulated, but the biological mechanism responsible for this association has not been defined. In part one of this review, we discussed the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. Here we review the risk factors shared by cancer and DM and how DM medications play a role in altering cancer risk. Hyperinsulinemia stands out as a major factor contributing to the association between DM and cancer, and modulation of circulating insulin levels by DM medications appears to play an important role in altering cancer risk. Drugs that increase circulating insulin, including exogenous insulin, insulin analogs, and insulin secretagogues, are generally associated with an increased cancer risk. In contrast, drugs that regulate insulin signaling without increasing levels, especially metformin, appear to be associated with a decreased cancer risk. In addition to hyperinsulinemia, the effect of DM medications on other shared risk factors including hyperglycemia, obesity, and oxidative stress as well as demographic factors that may influence the use of certain DM drugs in different populations are described. Further elucidation of the mechanisms behind the association between DM, cancer, and the role of DM medications in modulating cancer risk may aid in the development of better prevention and treatment options for both DM and cancer. Additionally, incorporation of DM medication use into cancer prediction models may lead to the development of improved risk assessment tools for diabetic patients.

Sessile serrated adenomas versus conventional adenomas. Different polyps in different populations?

“…It has been postulated that insulin resistance and hyperglycemia may induce the development of colorectal cancer and conventional adenomas through inflammatory mechanisms, production of oxidative stress or through involvement in the proliferative pathways as in the case of insulin-like growth factor (IGF) pathway [26,27]. Regarding SSA/Ps and their association with diabetes mellitus, there is only one study from Anderson et al indicating a positive association [9].…”

Breast and Prostate Cancer Survivors in a Diabetic Cohort: Results from the Living With Diabetes Study

“…19 We therefore took particular interest in determining if duration of diabetes was independently associated with cancer survivorship and found that this was not the case. This latter finding suggests that diabetes-related factors of control and complications may not be key factors influencing cancer survivorship but contribute simply to the burden of comorbidities.…”

European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer

“…However, due to the complex nature of diabetes and the broad array of available therapies, it is difficult, in observational settings, to discern whether the inverse association between metformin and cancer risk is due to an anti-neoplastic effect of metformin or might result from uncontrolled confounding, when metformin is compared to other antidiabetics [208,[216][217][218]. Several trials have recently been launched that aim to assess the potential of metformin for preventing cancer or cancer recurrence [208,215].…”