Cancer-related mortality for patients with type 2 diabetes exposed to oral hypoglycemics. Are there differences between agents?
Hypothesis: We suggest the following hypotheses for our research:
- People with type 2 diabetes will have an increased overall risk of developing cancer compared to people without diabetes.
- Relative to people without diabetes, people with type 2 diabetes on sulfonylureas and/or insulin therapy will have an increased risk of developing various types of cancers compared to people with type 2 diabetes on metformin therapy.
- Relative to people without diabetes, people with type 2 diabetes on sulfonylureas and/or insulin therapy will have an increased risk of cancer-related mortality compared to people with type 2 diabetes on metformin therapy.
Objectives: The objective of the proposed line of research is to assess the association between type 2 diabetes and cancer. Specifically, we would like to know if any therapeutic risk or benefit exists with treatments that increase circulating insulin, such as sulfonylureas, or reduce insulin resistance, such as metformin.
Rationale: The elevated risk of cancer among individuals with type 2 diabetes is being increasingly recognized. Several recent epidemiologic studies have identified associations between diabetes and specific forms of cancer in various populations. The association appears to be linked through the metabolic (insulin resistance) syndrome. In fact, it has been proposed that hyperinsulinemia combined with insulin resistance promotes carcinogenesis. Therapies that increase circulating insulin in type 2 diabetes should therefore have detrimental effects on the development and outcomes associated with cancer; the effects of antidiabetic agents on cancer mortality have never been studied, however.
Design: We propose a retrospective, controlled, population-based cohort study, using the administrative databases of BC Linked Health Data. We will identify a cohort of individuals with diabetes and a randomly selected control cohort without diabetes. We will then compare patients with type 2 diabetes on metformin monotherapy and patients on sulfonylurea monotherapy to patients without type 2 diabetes. We are interested in the development of various types of cancer (specifically, breast, pancreas, endometrial, colorectal, and prostate cancer) as well as cancer-related mortality. We will test our hypotheses using multivariate Cox regression, adjusting for potential confounding factors, including age, sex, frequency of physician office visits, physician specialty, and presence of comorbid conditions.
Relevance: From a public health perspective, the impact of the combination of type 2 diabetes and cancer is substantial. Both cancer and diabetes are prevalent in the general population and are chronic diseases with a relatively long duration. Cardiovascular disease, including macrovascular complications of type 2 diabetes, and cancer are two of the leading causes of death in Canada, both of which place a large economic burden on our health care system. Awareness of the relationship between diabetes, cardiovascular disease, and cancer as manifestations of an underlying metabolic syndrome, therefore, has important implications for prevention and management.
Jeffrey Johnson, Samantha Bowker, Carlo Marra, Paul Veugelers, Marilyn Borugian
New funds for this project have been obtained from a CIHR Operating Grant "Cancer incidence for patients with Type 2 Diabetes exposed to oral hypoglycemics: Are there differences between agents?"
Funding period July, 2008 to June 2010.
Bowker SL, Pohar SL, Johnson JA. A cross-sectional study of health-related quality of life deficits in individuals with comorbid diabetes and cancer. Health and Quality of Life Outcomes 2006;4:17. (http://www.hqlo.com/content/4/1/17).
Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29:254–258.
- Johnson JA, Yasui Y. Glucose-lowering therapies and cancer risk: The trials and tribulations of trials and observations. Diabetologia. 2010 Jun 1;53:1823-1826.
- Johnson JA, Gale EA. Diabetes, insulin use, and cancer risk: are observational studies part of the solution-or part of the problem? Diabetes. 2010 May 1;59:1129-1131.
Presentations at Scientific Meetings
Antidiabetic therapies and cancer mortality in type 2 diabetes: Assessing effects of time-varying exposure” at American Diabetes Association (ADA) Meeting, June 6-10, 2008 San Francisco, Californi