Body Mass Index, Triglycerides, and Risk of Acute Pancreatitis

A Population-Based Study of 118 000 Individuals

Signe E. J. Hansen; Christian M. Madsen; Anette Varbo; Børge G. Nordestgaard

Disclosures

J Clin Endocrinol Metab. 2020;105(1) 

In This Article

Abstract and Introduction

Abstract

Objective: The incidence of acute pancreatitis is rising worldwide and currently no curative treatment exists. Clarification of preventable risk factors is important for the reduction of morbidity and mortality from acute pancreatitis. In this study, we tested the hypothesis that the risk of acute pancreatitis associated with body mass index (BMI) is partly mediated through elevated triglycerides.

Design: We included 118 085 individuals from 2 prospective cohort studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, with BMI measured at baseline. Diagnosis of acute pancreatitis was assessed from the national Danish registries, as hospitalization or death due to acute pancreatitis.

Results: Higher BMI was associated with higher risk of acute pancreatitis with a multivariable-adjusted hazard ratio of 1.4 (95% CI, 1.1–1.8) for BMI of 25–29.9, 2.1 (1.6–2.9) for BMI of 30–34.9, and 2.8 (1.8–4.3) for BMI > 35, compared with individuals with BMI of 18.5–24.9. Triglycerides mediated 29% (95% CI, 12%–46%; P = 0.001) of the association between BMI and risk of acute pancreatitis in the age- and sex-adjusted model and 22% (6%–39%; P = 0.008) in the multivariable-adjusted model.

Conclusion: Higher BMI is associated with higher risk of acute pancreatitis in individuals from the general population, partly mediated through higher triglycerides. This indicates a potential for preventing acute pancreatitis by reducing BMI and triglycerides in individuals with high values.

Introduction

Acute pancreatitis is one of the most common admission diagnoses in gastroenterology departments in the United States,[1] and the incidence of acute pancreatitis is rising, with an estimated global incidence of 34 cases per 100 000 person-years.[2] Most cases of acute pancreatitis are mild and self-limiting, but as many as 20% of patients develop severe disease with risk of systemic inflammatory response syndrome and organ failure, leading to death in 10% to 30% of severe cases.[1]

The exact pathogenesis of acute pancreatitis is still not fully understood, but cellular stress is believed to be involved in activating local and—in severe cases— systemic inflammation.[3,4] In Western countries, gallstone disease and excessive prolonged alcohol intake are the 2 most common causes, responsible for up to 75% of all cases of acute pancreatitis.[5] However, only up to 8% of individuals with gallstone disease[6] and only up to 3% of individuals with chronic excessive alcohol intake develop acute pancreatitis,[7] indicating that other, overlooked factors in disease pathogenesis are involved.

The globally rising incidence of acute pancreatitis has occurred simultaneously with the worldwide obesity epidemic,[8] indicating that higher BMI could be an independent, and potentially preventable risk factor of acute pancreatitis. This question has been investigated in 4 cohort studies of respectively 33 000,[9] 36 000,[10] 68 000,[8] and 513 000[11] individuals and in 1 case-control study with 462 cases.[12] Although these studies have provided contradictory results, yielding somewhat unclear evidence of high BMI as an independent risk factor for acute pancreatitis, the recent Korean study of 513 000 individuals strongly supports the premise that higher BMI is associated with higher risk of acute pancreatitis.[11]

BMI is strongly positively correlated with plasma triglycerides and severe hypertriglyceridemia is a known cause of acute pancreatitis.[13] In addition, recent observational studies have shown that even mild-to-moderate hypertriglyceridemia (2–5 mmol/L, 177–443 mg/dL) is associated with higher risk of acute pancreatitis.[14–17] Hence, a possible association between higher BMI and higher risk of acute pancreatitis could be mediated through higher plasma triglycerides.

In this study of 118 000 individuals from the Copenhagen General Population Study and the Copenhagen City Heart study we tested the hypothesis that the risk of acute pancreatitis associated with BMI is partly mediated through higher plasma triglycerides.

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