During a routine office visit or hospital admission, diabetic patients are commonly asked if they are up to date with their preventive health visits, including those to the podiatrist, ophthalmologist, and nephrologist. These screening measures are in place due to the known risk of retinopathy, neuropathy, and nephropathy in diabetic patients. The mechanisms behind these pathologic sequelae have been studied in detail; however, there is an additional link between diabetes and an associated increased risk of cancer that has been more recently recognized as one that requires further elucidation.

Meta analyses have shown that the link between diabetes (mainly Type II) and cancer depends on the diagnosis.  The strongest associations appear to be in diabetic patients who develop pancreatic, liver, endometrial, colorectal, bladder, and breast cancers. When diabetic patients develop cancer, they also have higher mortality rates compared with nondiabetics. Risk factors are often shared between diabetes and cancer, including age, weight, race, tobacco exposure, diet, and exercise. At this point, it is difficult to distinguish whether these risk factors are found in both diabetes and cancer, or if the development of diabetes, regardless of shared risk factors, leads to an increased risk of cancer. The key to answering this question could be found in the complicated molecular and signaling pathways that have been a recent focus of new drug development programs.

On a molecular level, there appear to be several possibilities of how diabetes could promote a prooncologic environment. One of the pathways that insulin activates is the protein kinase B/Akt (Akt/PKB) pathway, which works to increase glucose uptake and metabolism. In addition to its effects on blood glucose, the Akt/PKB pathway has also been implicated in inhibiting apoptosis, which could potentially increase cell number and growth.  Insulin-like growth factor-1 (IGF-1) is another hormone that is similar to insulin in its structure and function, although it appears to play a more substantial role in cell growth and transformation. Upon binding to its receptor IGF-1R, the Ras-MAPK pathway is activated, which leads to inhibition of apoptosis and increased cell growth and differentiation. Due to their similarities in structure, the insulin and IGF-1 receptors share a certain amount of overlap and nonspecificity. Technically, hyperinsulinemia could lead to activation of IGF-1 receptors and the downstream activation of antiapoptotic pathways. Activation of IGF-1 receptors could also lead to increased vasculature, which is a key component of metastasis and cancer cell survival. These pathways are not the only ones involved, and future studies will undoubtedly discover new pathways as well.

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Recently, a retrospective study conducted at Washington University and presented at Digestive Disease Week 2012 showed that diabetic patients between the ages of 40 and 49 years had a similar number of adenomas to nondiabetic patients between ages 50 and 59 years. Although this study contained only a single center and was retrospective, it helped raise the question of whether diabetics should be screened earlier for cancer compared with nondiabetics.

As discussed, the current clinical and biochemical data connecting diabetes and cancer has not allowed solid recommendations to be made as to how to adjust current cancer screening guidelines for diabetic patients. New, prospective clinical studies are needed to examine exactly how diabetes impacts cancer and vice versa. Until then, health care professionals should be proactive in inquiring about cancer screenings in diabetic patients in addition to the commonly asked retinopathy, neuropathy and nephropathy questions.

Questions to Readers

  • What have your experiences been with your diabetic patients who eventually develop cancer?
  • What are your thoughts on the potential for diabetic patients receiving cancer screening tests earlier than the rest of the population?

Readers: We’d love to hear from you in the comments section below! If you have a case study or a more extended response to this subject, click here to submit an item for us to publish