Elevated insulin levels in response to insulin resistance may be responsible for the increased risk of colorectal cancer (CRC) among patients with type 2 diabetes mellitus (DM). Insulin-requiring type 2 DM patients are exposed to even higher systemic insulin levels due to the inefficiency of injected insulin in controlling hyperglycemia. We recently reported that the risk of CRC is over 2-fold higher among type 2 DM patients receiving insulin therapy than among other type 2 DM patients. In addition, preliminary cross-sectional data from us and others have suggested that exogenous insulin therapy may be associated with an increased prevalence of colorectal adenoma. We hypothesize that insulin therapy may increase the risk of advanced adenoma recurrence among type 2 DM patients. Specifically, we hypothesize that insulin users who are regarded as "low-risk" (i.e, 1 or 2 small tubular adenomas) in a post-polypectomy surveillance program may be at a higher risk of developing recurrent adenoma and may require surveillance colonoscopies at a shorted interval than what is currently recommened. The primary aims are 1) to estimate the absolute risk of advanced adenoma recurrence according to insulin exposure status and diabetes status and 2) to determine whether insulin exposure predicts advanced adenoma recurrence, among a cohort of veterans and non-veterans with type 2 DM who are undergoing post- polypectomy surveillance colonosocopy. Study patients will be identified from the electronic medical record systems of two closely affiliated institutions: the Philadelphia Veteran's Administration Medical Center and the University of Pennsylvania Health System. Patients from the two sites will be analyzed both separately and pooled together. Outcome data will be extracted from the electronic endoscopy and medical databases. Information on exposure to insulin therapy and other covariates will be obtained by database query and a patient interview. Our preliminary data indicated that we have the necessary personnel, environment, data source, and sample size to achieve our aims. CRC is the second most lethal cancer in the U.S. In the meantime, there is an epidemic of type 2 DM in the U.S., particularly among the veterans with 20% prevalence. Furthermore, 37% of the patients with DM in the VA system are on insulin therapy, and most of the remaining patients will eventually require insulin for adequate glucose control. Due to a lack of direct evidence, the current CRC surveillance guidelines do not recommend shorter surveillance intervals for these patients. The proposed study is the first study specifically designed to investigate this important question. Its findings will have the potential to change the post-polypectomy surveillance practices among the enormous population of insulin users in the veteran and the US population.

Public Health Relevance

Existing evidence suggests that diabetes patients receiving insulin may have a much higher likelihood of developing a form of colon polyps that can quickly progress to colorectal cancer. The risk can be eliminated if these polyps are removed by performing regular colonoscopies. However, due to lack of direct evidence, the current colonoscopy guideline does not recognize this possibility. The current study is the first study specifically designed to investigate this potentially increased risk. If it reveals the increased risk as suspected, it will provide direct scientific evidence to support an increase of colonoscopy examinations in this high risk patient population. As such, it will reduce the risk of colorectal cancer among the enormous population of veterans with diabetes requiring insulin therapy. Because of the exceedingly low number of female veterans in the VA system, we propose to expand the study to a university health system that is closely affiliated with the Philadelphia VA Medical Center so that we can generate more accurate data and data that can be applied to females.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Epidemiology (EPID)
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Philadelphia VA Medical Center
United States
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