ACE Inhibitors Can Protect Diabetics From Cancer, Peptic Ulcer

Angiotensin-converting enzyme (ACE) inhibitor therapy appears to be associated with a lower than expected prevalence of cancer and peptic ulcer disease in adults with diabetes, researchers report.

Dr. Benjamin Littenberg and associates at the University of Vermont, Burlington, surveyed a randomly selected subset of 1,003 diabetics regarding comorbid illnesses and current medications.

They observed that ACE inhibitor users were less likely than non-users to report a history of cancer, except non-life-threatening skin cancers. Ten percent of ACE users reported a history of cancer compared with 15% of non-users (odds ratio, 0.59; p = 0.01).

ACE inhibitor users were also less likely than non-users to have a history of stomach ulcers or peptic ulcer disease (12% vs 16%; odds ratio, 0.70; p=0.06).

After correcting for multiple potential confounders, ACE inhibitor use remained significantly inversely associated with a history of cancer (odds ratio, 0.59) and peptic ulcer disease (odd ratio, 0.68), the investigators report.

This research, Dr. Littenberg stated, “raises the possibility that (ACE inhibitors) might actually protect against the development of those diseases.

“We had some sense,” he added, “that ACE inhibitor drugs would protect against cancer based on previous literature and our own studies in cell cultures.” For example, the ACE inhibitor captopril has been shown to inhibit proliferation of a variety of cell types, including breast cancer, and to reduce tumor growth in experimental models of cancer, the investigators note.
“The peptic ulcer finding was more surprising,” Dr. Littenberg said. “However, it also has some support in the published literature.”

Dr. Littenberg and colleagues emphasize that their study has significant methodologic limitations, including the lack of clinical confirmation of the comorbid diagnoses, and lack of information on the timing and duration of ACE inhibitor treatment relative to the onset of comorbidities.

“As in any cross-sectional study, unmeasured confounders may be responsible for the apparent associations found,” the team notes.

“We believe that these findings should represent a hypothesis warranting more study rather than a conclusion meriting clinical action,” Dr. Littenberg said. “Neither clinicians nor patients should change their strategies as a result of this study.”
Clinical Context:

Use of ACE inhibitors is associated with reduced morbidity and mortality rates associated with congestive heart failure, myocardial infarction, and diabetes, with nephropathy being reduced in patients with diabetes, and a reduced risk for cancer has also been observed.

This is a cross-sectional study conducted in 69 community-based practices in Vermont, New Hampshire, and New York to examine the association between ACE inhibitor use and cancer and peptic ulcer disease in patients with diabetes.

Practice Pearls:

• In patients with diabetes, ACE inhibitor use is associated with being male, having a higher HbA1c level, a higher BMI, being a nondrinker, and having a greater number of prescriptions.
• ACE inhibitor use in patients with diabetes is associated with a reduced risk for cancer and peptic ulcer disease.

BMC Endocr Disord. Published online December 5, 2008