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Diabetes and Its Effect on Cancer

Does diabetes cause cancer, or vice versa?

The International Diabetes Federation has stated that 387 million people throughout the world have diabetes mellitus in 2014, and it will rise to 592 million in 2035. Type 2 diabetes results from the body’s unsuccessful use of insulin and comprises 90% of people with diabetes around the world. Apart from various microvascular and macrovascular complications, insulin resistance and hyperinsulinemia have been hypothesized to be associated with many kinds of tumor. Links with breast and endometrial cancer remain controversial, but a number of studies found that women with diabetes were at increased risk of breast and endometrial cancer. Kidney cancer is among the 10 most common cancers in the western world. Its etiology remains unknown but phenacetin-containing analgesics, smoking, obesity, hypertension, advanced kidney disease and genetic factors have been identified as potential risk factors.

A study conducted in China assessed cancer risk among Chinese patients with T2DM in a population-based prospective study. It was a prospective study conducted by using diabetes and cancer surveillance districts over 16 million residents. Newly diagnosed diabetes and cancer patients’ information was verified by CDC. It was then recorded in a computerized database with unique identification numbers and followed for a year. Statistical analysis was performed using SAS package version 9.2. T2DM patients numbered 327,268 whereas cancer patients numbered 7,435; they were recruited between January 1, 2007 and December 31 2013. All patients with SIR (95% CI) for the total cancer was 1.19 (1.17-1.22). 11 of the cancer sites showed significant increased SIRs for patients with T2DM. Pancreas had the highest SIRs with stomach, esophagus and cervix cancer having the lowest. Cancer risk among urban and rural area patients with T2DM were also determined with SIR, for urban area total cancer being 1.16 (95%CI 1.12-1.20). For rural area, the SIR for the total cancer was 1.20 (95% CI 1.17-1.24). Increased risk of cancer and of most site-specific cancers were observed. Pancreatic cancer showed the strongest risk in T2DM patients. Some limitations were observed, such as follow up period being short; some site specific cancer numbers were small which leads to a decreased statistical ability to examine the true association between T2DM and cancer. Also. other confounding factors like obesity and smoking were not considered.

Another study was conducted to focus on the incidence of kidney cancer and type 2 diabetes mellitus. It was a retrospective study using reimbursement from NHI database. Type 2 diabetes, unknown living region and kidney cancer diagnosis before 2003 were excluded from study. 115,655 patients with type 2 diabetes mellitus and 883,073 individuals without diabetes mellitus were followed from the beginning of 2003 to the end of 2005. Baseline characteristics between the two groups were noted and SAS statistical software version 9.3 was used. Increasing incidences of kidney cancer from 2003-2005 in both groups were calculated. Sulfonylurea and metformin were the two antidiabetic drugs mostly used. Diabetes status is significantly connected with a higher risk of kidney cancer after multivariable adjustment with an odds ratio of 1.7 (95% CI 1.3-2.1). Every year of diabetes duration caused an increased risk of approximately 10% (odds ratio 1.1, 95% CI 1.0-1.1, P<0.01).  A few weaknesses of this study include a short follow up period, lack of biochemical data such as lipid and glucose profile, insulin and C-peptide. Also confounders such as anthropometric parameters like obesity, family history, diet were not available.

Another study was to estimate the incidence of the relative risk of breast and endometrial cancer among diabetic female patients. Data was retrospectively collected from the National Health Insurance Research Database. For the exclusion criteria, patients admitted for malignant cancer between 1997 and date of ambulatory care for diabetes treatment in 2000, also cancer patients with major illness and 20 years or less. Cox proportional hazard regression model was used in the statistical analysis. 2,945 diabetic patients were admitted for breast cancer and 2,656 individuals in the control group were admitted for same diagnosis. For endometrial cancer, the diabetes group had a significant increased risk. It was found that diabetes increased the risks of both breast and endometrial cancer. There were some limitations, like reliance on the claim data which might have caused bias. Also BMI, duration and treatment regimens of diabetes and other socioeconomic characteristics were not determined.

In conclusion, patients with T2DM have an increased chance of developing cancer especially kidney, breast and endometrial cancer.

Practice Pearls:

  • Patients with T2DM suffer from a significantly higher risk of cancer involving the breast, endometrium, colorectum, liver, pancreas, bladder and lymphoid tissue.
  • Diabetes and breast cancer association was found to be more apparent among postmenopausal women.
  • Biochemical mechanisms provide biological plausibility for a causal association between T2DM and cancer.

References:

Chen, Hua-Fen et al. “Risks of Breast and Endometrial Cancer in Women with Diabetes: A Population-Based Cohort Study.” Ed. Matthew L. Anderson. PLoS ONE 8.6 (2013): e67420. PMC. Web. 19 July 2016.

Tseng, Chin-Hsiao. “Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance.” Ed. Demetrios Vavvas. PLoS ONE 10.11 (2015): e0142480. PMC. Web. 19 July 2016.

Wang, Meng et al. “Cancer Risk among Patients with Type 2 Diabetes Mellitus: A Population-Based Prospective Study in China.” Scientific Reports 5 (2015): 11503. PMC. Web. 19 July 2016.