Diabetes and Cancer: a Review of Current Knowledge

Abstract

Diabetes mellitus (DM), one of the most common life-threatening illnesses worldwide, is a group of metabolic diseases, characterized by sustained hyperglycemia. The global prevalence of diabetes mellitus among adults reached 387 millions in 2014 and is still rising. It is suggested there is a strong association between diabetes mellitus (especially type 2 diabetes mellitus) and carcinogenesis. The possible biological links between diabetes mellitus and cancer comprise hyperinsulinemia, hyperglycemia and fat-induced chronic inflammation. Although, the strongest association refers to pancreas and liver, there are many other organs involved in carcinogenesis in diabetic patients including breast, endometrium, bladder and kidney. Recent studies suggest that there is also association between cancer incidence and anti-diabetic medications. It was observed that some medications decrease the risk of carcinogenesis and some increase that risk. The majority of studies concern metformin, a drug of choice in type 2 diabetes mellitus, and its anti-neoplastic and tumor-suppressing activity. The positive effect of metformin was found in numerous researches investigating breast, pancreas, liver, colon, ovaries and prostate tumors. Because a variety of studies have suggested that diabetes mellitus and cancer are frequently coexisting diseases, recently published studies try to explain the influence of diabetes mellitus and anti-diabetic medications on carcinogenesis in different organs. We present the review of the latest studies investigating the association between both diabetes mellitus and anti-diabetic medications and cancer incidence and prognosis. Particularly we highlight the problem of concomitant head and neck cancers in diabetics, rarely analysed and often omitted in studies.

T-helper-1, T-helper-17, T-regulatory lymphocytes in hypertensive patients with diabetes mellitus type 2 or impaired glucose tolerance: association with clinical and metabolic parameters in a case control study

“…Most probably, Th17-cells were already activated in vivo during DM2, and exhibited functional exhaustion during additional stimulation ex vivo. Exposure to chronic inflammation may diminish effector functions of T-lymphocytes, which may impair protection against infections and cause predisposition to cancer, which is typical to diabetic patients [32][33][34]. It had also been shown that patients with DM2 are characterized by lower numbers of Th17, specific to infectious pathogens [35].…”

Modification effects of genetic polymorphisms in FTO, IL-6, and HSPD1 on the associations of diabetes with breast cancer risk and survival

“…Diabetes is characterized by sustained hyperglycemia and is associated with increased cancer risk in many settings, possibly through proliferative, anti-apoptotic, and metastatic activity [1]. Therefore, a series of studies have been performed to explore the associations of type 2 diabetes mellitus (T2DM), the common type in later life (~95% of all diabetic cases), with the risk and prognosis of cancers [1].…”

“…Therefore, a series of studies have been performed to explore the associations of type 2 diabetes mellitus (T2DM), the common type in later life (~95% of all diabetic cases), with the risk and prognosis of cancers [1]. For breast cancer, the association was mainly observed in European females [2].…”

Insulin receptor plays a central role in skin carcinogenesis by regulating cytoskeleton assembly

“…The association between diabetes and cancer is currently the focus of many clinical and basic research studies (1)(2)(3)(4)(5)(6). Epidemiologic analyses have shown an increased risk in type 2 diabetes of various epithelial cancers, including cancers of the breast, colon, bladder, pancreas, liver, and endometrium, as well as nonmelanoma skin cancer and more.…”