Increased Risk of Gastrointestinal Malignancy in Patients with Diabetes Mellitus and Correlations with Anti-Diabetes Drugs: A Nationwide Population-based Study in Taiwan

Abstract

Objective Although the major cause of morbidity and mortality in patients with diabetes mellitus (DM) is cardiovascular disease, DM is also associated with certain site-specific cancers. However, whether DM is associated with an increased risk of cancer of the digestive tract remains undetermined. A nationwide, population-based database in Taiwan was analyzed to explore the relationship between DM and cancer of the digestive organs. Methods From 2000 to 2007, a study cohort consisting of 39,515 patients with newly diagnosed diabetes without a previous diagnosis of gastrointestinal (GI) cancer was identified from the National Health Insurance Research Database in Taiwan. A control cohort of 79,030 age-and sex-matched non-diabetic subjects was selected to compare the occurrence of GI malignancies between the two groups. The association between the incidence of GI cancers and the use of glucose-lowering therapies was also investigated. Results During the 7-year follow-up period, GI cancers developed in 929 diabetic patients (2.35%) and 1,126 subjects (1.42%) in the comparison cohort. DM was associated with a 2.75-fold (95% confidence interval (CI), 2.51-3.02) higher risk of developing GI malignancy. Among GI cancers, the incidences of stomach (adjusted hazard ratio (HR), 1.49; 95% CI, 1.16-1.92), liver (adjusted HR, 2.65; 95% CI, 2.29-3.07), colon (adjusted HR, 1.58; 95% CI, 1.28-1.94) and pancreatic cancers (adjusted HR, 4.35; 95% CI, 2.93-6.47) were significantly increased in the patients with DM. An analysis of the effects of various glucose-lowering therapies in the diabetic patients revealed the use of α-glucosidase inhibitors to be associated with a lower risk of hepatic cancer (adjusted HR, 0.62; 95% CI, 0.4-0.94). Thiazolidinedione (TZD) treatment was associated with lower stomach (adjusted HR, 0.11; 95% CI, 0.02-0.82) and hepatic cancer risks (adjusted HR, 0.46; 95% CI, 0.29-0.73), while sulfonylurea use was associated with a lower colon cancer risk (adjusted HR, 0.74; 95% CI, 0.51-1.09) and a higher pancreatic cancer risk (adjusted HR, 2.36; 95% CI, 1.21-4.61). Conclusion Patients with DM have an increased risk of GI malignancy that may be affected by the use of different categories of glucose-lowering therapies.

Use of an α-Glucosidase Inhibitor and the Risk of Colorectal Cancer in Patients With Diabetes: A Nationwide, Population-Based Cohort Study

“…These factors led to the lack of a beneficial effect of acarbose on colorectal cancer risk reduction in patients with diabetes compared with the general population. In another study by Chiu et al (20), subjects were matched by enrollment date using stratified random sampling; however, an immortal time bias might have occurred with an inappropriate accounting of the follow-up time in the study design.…”

“…In the APC gene knockout animal model, which develops multiple intestinal adenomas, acarbose had a regressive effect on the size of gastrointestinal adenomas but did not significantly decrease the number of colonic neoplasms (19). Previous smaller database studies investigating acarbose use and incident colorectal cancer have provided null results (10,20). We used the Taiwanese National Health Insurance (NHI) research database of a large cohort with diabetes to evaluate the effect of acarbose treatment on the risk of colorectal cancer.…”

Cancer risks among the users of ergot-derived dopamine agonists for Parkinson's disease, a nationwide population-based survey

“…Cancer association has been well known with the anti-diabetic agents, no matter the observations in or outside Taiwan [18,19,23,24]. Although indirect or controversial reports about the association of PD and cancer [15,16,25,26], diabetes mellitus patients still have a potential risk for PD [11,12], and the cancer risk among PD patients may be also attributed to the prescribing medicines for PD, as the story in diabetes mellitus.…”

“…However, we wonder the exogenous factors, especially our prescribed medicines, attributed to the cancer occurrence for the vast population with idiopathic PD. A mirror is the higher cancer incidence among the users of sulfonylurea for diabetes mellitus [18,19], thus we speculate anti-PD medications, particularly DAs, as the possible contributor to the cancer occurrence. Thus, the purpose of this nationwide study of PD patients was to clarify the association between the use of DAs and clinical cancer.…”

Diabetes Mellitus as a Novel Risk Factor for Gastrointestinal Malignancies

“…In addition, agonists of PPAR-γ in the TZD family may have antitumor activity in tissues that underexpress PPAR-γ, 91 and may inhibit angiogenesis and induce apoptosis by several mechanisms. [92][93][94][95] In a population-based study of patients with T2DM in Taiwan, TZD treatment was associated with lower hepatic cancer risks (adjusted hazard ratio, 0.46; 95% CI, 0.29-0.73), 29 so there remains hope that this agent will prove to be chemopreventive. The TZDs may also have a role in reversing the course of NASH.…”