Excessive Intrapancreatic Fat Deposition and Risk of Pancreatic Diseases: Longitudinal Cohort Evidence From a Systematic Review With Population-Attributable Fraction Analysis
Chani-Brynn Leybourne, Yutong Liu, Maxim S. Petrov
Abstract
INTRODUCTION: Intrapancreatic fat deposition (IPFD) is closely linked to digestive and metabolic health. However, the impact of excessive IPFD remains insufficiently defined, largely because most evidence comes from cross-sectional studies, the proportion of disease risk attributable to excessive IPFD is unknown, and the influence of potential confounders is not characterized. The aim of this study was to systematically examine published longitudinal studies of IPFD and address these knowledge gaps. METHODS: A systematic review, prospectively registered in PROSPERO, was conducted to examine longitudinal cohort studies investigating IPFD. Three electronic databases were systematically searched. Population-attributable fractions and E -values were calculated. RESULTS: A total of 23 studies met the eligibility criteria. Excessive IPFD at baseline was associated with a 4-fold higher risk of acute pancreatitis, a 3-fold higher risk of pancreatic cancer, and a 2-fold higher risk of diabetes mellitus in the general population during follow-up. Furthermore, 34% of acute pancreatitis cases, 23% of pancreatic cancer cases, and 21% of diabetes mellitus cases could be avoided if excessive IPFD were eliminated. Unmeasured confounders were unlikely to explain away the statistically significant associations in the studies of acute pancreatitis ( E -value = 36), pancreatic cancer ( E -value = 16) but not the studies of type 2 diabetes mellitus ( E -value = 11). DISCUSSION: Longitudinal evidence generally supports the hypothesized role of excessive IPFD as a key contributor to the risk of major pancreatic diseases. The potential benefits of reducing IPFD appear to be greatest for pancreatitis and pancreatic cancer.