Use of cholesterol-lowering statins was linked to a lower risk of developing a subtype of diabetes that occurs after acute pancreatitis, according to a new report.
The benefits of statins depended on the consistency of usage, with regular users having a lower risk of developing post-pancreatitis diabetes than irregular users. The results were similar with low, moderate, and high statin doses, as well as in cases of both mild and severe acute pancreatitis.
“About 15% of patients with acute pancreatitis will develop diabetes mellitus in the next 5 years, and although we can monitor for it, we can’t do anything to prevent it,” Nikhil Thiruvengadam, MD, the lead study author and a gastroenterologist at Loma Linda University School of Medicine, Loma Linda, California, told Medscape Medical News.
“This could push you as a clinician to prescribe [a statin if you have a reason to] because it could provide two benefits instead of just one,” he said.
The study was published online in Clinical Gastroenterology and Hepatology.
Steady Use Mattered, Not Dose
Patients with acute pancreatitis face at least a twofold increased risk of developing post-pancreatitis diabetes, the study authors write. Although previous studies have shown that statins can lower the incidence and severity of acute pancreatitis, they haven’t been studied for the prevention of post-pancreatitis diabetes.
In a collaborative study with several other universities, Thiruvengadam and colleagues examined commercial insurance claims from the Optum Clinformatics database to assess the impact of statins on 118,479 patients without preexisting diabetes admitted for a first episode of acute pancreatitis between 2008 to 2020.
They compared patients who consistently used statins with irregular users and nonusers. Regular statin usage was defined as patients who had statin prescriptions filled for at least 80% of the year prior to their acute pancreatitis diagnosis. The analysis included 9048 patients (7.6%) who used statins regularly, 27,272 (23%) who used statins irregularly, and 82,159 (69.3%) nonusers.
With a median follow-up of 3.5 years, the 5-year cumulative incidence of post-pancreatitis diabetes was 7.5% among regular statin users and 12.7% among nonusers. Regular statin users had a 42% lower risk of developing post-pancreatitis diabetes compared with nonusers. Irregular statin users had a 15% lower risk of post-pancreatitis diabetes.
In addition, the 5-year cumulative incidence of insulin-dependent post-pancreatitis diabetes was 2.4% among regular statin users and 6.6% among nonusers. Regular statin users had a 52% lower risk of developing insulin-dependent diabetes as compared with nonusers.
Daily dosage didn’t demonstrate a linear dose-response relationship. That means high-dose statins may not be more effective in preventing diabetes as compared with lower doses, the study authors write.
Statin usage was effective across additional analyses, including sex, etiologies of pancreatitis, and in both mild and severe acute pancreatitis. According to the study authors, this suggests that a broad population of these patients may benefit from statins.
“We were pleasantly surprised by the variety of findings,” Thiruvengadam said. “We’re seeing strong signals, especially with consistency of usage.”
The results may seem paradoxical, the study authors write, given an epidemiologic association with a slight increase in new-onset diabetes with statin initiation. But, as other researchers have reported, post-pancreatitis diabetes and type 2 diabetes have different clinical features and underlying pathophysiology. For example, patients with post-pancreatitis diabetes have much higher rates of requiring insulin, hospitalization, and all-cause mortality, the study authors write.
In fact, post-pancreatitis diabetes is thought to be driven by chronic low-grade inflammation due to interleukin-6 and tumor necrosis factor alpha. Statins have been shown to reduce tumor necrosis factor alpha secretion and the production of C-reactive protein in response to circulating interleukin-6 in hepatocytes, they write.
The results should inform long-term prospective studies of acute pancreatitis, the study authors write, as well as randomized controlled trials of statins.
In the meantime, gastroenterologists and primary care physicians who see outpatients after hospitalization for acute pancreatitis may consider using statins, particularly in those who may have another possible indication for statin therapy, such as mild hyperlipidemia.
“There appears to be a low-dose benefit, which is another reason why providers may consider using statins, though it’s not for everyone with pancreatitis,” Thiruvengadam said. “This could be an exploratory pathway and suggested for use in the right setting.”
The Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, is conducting an observational cohort study at more than a dozen locations across the country to investigate the incidence, etiology, and pathophysiology of diabetes after acute pancreatitis.
“Diabetes is surprisingly common after even a single attack of acute pancreatitis,” Chris Forsmark, MD, professor of medicine and chief of the division of gastroenterology, hepatology, and nutrition at the University of Florida, Gainesville, told Medscape Medical News.
Forsmark, who wasn’t involved with this study, is a member of T1DAPC and one of the principal investigators in Florida.
“The reduction of risk by 42% is quite substantial,” he said. “Like all such studies, there is risk of bias and confounding in determining the actual risk. Nonetheless, the results provide a strong reason for confirmation in other datasets and for further study.”
The study didn’t report funding support. Thiruvengadam and Forsmark report no relevant financial relationships.
Clinical Gastroenterology and Hepatology. Published online June 21, 2022. Abstract