Diabetes and cancer: Associations, mechanisms, and implications for medical practice

Abstract

Both diabetes mellitus and cancer are prevalent diseases worldwide. It is evident that there is a substantial increase in cancer incidence in diabetic patients. Epidemiologic studies have indicated that diabetic patients are at significantly higher risk of common cancers including pancreatic, liver, breast, colorectal, urinary tract, gastric and female reproductive cancers. Mortality due to cancer is moderately increased among patients with diabetes compared with those without. There is increasing evidence that some cancers are associated with diabetes, but the underlying mechanisms of this potential association have not been fully elucidated. Insulin is a potent growth factor that promotes cell proliferation and carcinogenesis directly and/or through insulin-like growth factor 1 (IGF-1). Hyperinsulinemia leads to an increase in the bioactivity of IGF-1 by inhibiting IGF binding protein-1. Hyperglycemia serves as a subordinate plausible explanation of carcinogenesis. High glucose may exert direct and indirect effects upon cancer cells to promote proliferation. Also chronic inflammation is considered as a hallmark of carcinogenesis. The multiple drugs involved in the treatment of diabetes seem to modify the risk of cancer. Screening to detect cancer at an early stage and appropriate treatment of diabetic patients with cancer are important to improve their prognosis. This paper summarizes the associations between diabetes and common cancers, interprets possible mechanisms involved, and addresses implications for medical practice.

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

“…In addition, exposure to a wide range of toxins as well as type 2 diabetes (T2D) and obesity have been suggested as important mediators of the complex process of myelomagenesis (Alexander et al 2007, Lope et al 2008, Wallin & Larsson 2011. Among these latter preventable factors, T2D has attracted significant attention since it has been consistently identified as a medical condition frequently found in MM patients (Khan et al 2008, Richardson et al 2009, Castillo et al 2012 and it is thought to influence the myelomagenesis through hyperglycaemia and insulin-dependent and -independent mechanisms (Xu et al 2014). In a recent well-powered meta-analysis, Castillo et al (2012) observed that T2D was significantly associated with an increased risk of developing the disease (Castillo et al 2012).…”

“…Considering that T2D and MM have strong genetic components and share several biological pathways and markers (Xu et al 2014) and that T2D-related polymorphisms may influence the risk of developing solid cancer (Folsom et al 2008, Cheng et al 2011, we hypothesized that genetic risk factors for T2D may be associated with the risk of developing MM. So far there have not been studies evaluating the impact of diabetogenic variants on the risk of developing hematological cancers.…”

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“…Many epidemiologic findings indicate that diabetic patients are at significantly higher risk for cancer development. On the other hand, DM is a more common problem in patients with advanced cancer than in normal population 11 .…”

Diabetes and cancer: A critical appraisal of the pathogenetic and therapeutic links

“…With regards to diabetes, it appears that there is no requirement for changes in clinical practice in terms of anti-diabetic medications. By contrast, there remains the requirement for improved quantifying sub-optimal treatments and outcomes among patients with diabetes that develop cancer (30). Other factors, such as how to optimally adjust chemotherapy doses for increasingly obese patients, have received less attention (31).…”