High BMI and obesity are risk factors for type 2 diabetes mellitus and gallstones or gallbladder disease, as well as risk factors for pancreatitis [25–27]. However, it is not clear that there is a relationship between obesity and pancreatitis. MR analysis was performed using three different estimation methods (weighted difference, median method and MR-Egger regression). Our study showed that there may be possible causes of the relationship between BMI and pancreatitis. Although MR estimates from IVW, Egger's MR and weight center analysis were not consistent, IVW analysis supports the relationship between BMI and RA. Given that the IVW estimate is useful for maintaining a high precision of estimates compared to the MR-Egger in the central analysis, the MR analysis takes into account the effect of BMI on RA risk. Therefore, our study confirmed the association found during clinical trials.
Meta-analysis found a 34–43% risk of obesity-related obesity or acute pancreatitis [28, 29]. On the other hand, a study showed that the relationship between waistline and pancreatitis is stronger than BMI when adjusted independently [30] There are ways in which BMI can affect the appearance of pancreatitis. A higher BMI indicates that there may be more fat cells in the pancreas scattered around pancreatic secretory cells [31]. In acute pancreatitis, pancreatic lipase hydrolyzes and transports triglycerides and free fatty acids that accumulate in the pancreas, which can damage the pancreatic duct. The cause of ischemia creates an acidic environment and increases the toxicity of free fatty acids [2, 32]. It has been suggested that obesity does not cause chronic pancreatitis but is a risk factor for CP, for example Ammann et al. found that the progression of CP decreased over time in a group of older patients when the patient had a BMI > 25 and had premature ejaculation [33]. Some studies have found that obesity is associated with higher levels of inflammatory cytokines (including tumor necrosis factor-α and interleukin-6) and pro-inflammatory adipokines (such as leptin) [6, 34]. Animal studies reported that obesity induced PGC-1α defects in the pancreas, which increased NF-kB-mediated IL-6 in the pancreas, resulting in an inflammatory response [35].
MR is a critical tool to investigate causality between specific exposures and established outcomes. Although observational studies themselves may be biased by confounding or change factors, MR reduces these possibilities [36]. However, MR remains sensitive to the bias of genetic variation associated with multiple outcomes, a condition known as pleiotropy [18, 37]. To avoid pleiotropy, we not only performed multivariate MR to explain the confounding effect of BMI, but also performed a sensitivity analysis of necessary variables to test the validity of the conclusions obtained from the MR analysis. Another advantage of the study is that we included a large number of subjects with different genetic variants, which allowed us to identify any cause-and-effect relationships in our study. The results of the present study may provide an opportunity to determine the possible mechanisms of BMI and the risk of pancreatitis.
This study has some limitations. First, the effect of genetic variation on specific exposures is limited; Second, patients with insulitis are classified according to non-cancer criteria: self-report, which may introduce a possible cause; Third, the study of BMI and insulitis is based on participants of European heritage, and because it depends on the ethnic group and selection criteria, more MR studies are needed with others. As a complex disease, it can be said that it is a pancreatic disease caused by biological, mental, environmental or other factors. In light of these arguments, MR imaging can provide definitive evidence. However, due to the complex nature of population structure, no general research method has been developed and the structural design of the system can lead to more flexibility [38]. Furthermore, these publicly available data do not provide sufficient information to assess the impact of population structure.
In summary, the results of the MR examination support BMI as a factor in the high risk of pancreatitis. Our results show that obesity may play an important role in the development of pancreatitis. Current research may provide an opportunity to identify mechanisms that may contribute to the effect of obesity on the risk of pancreatitis. This MR study shows that BMI is associated with pancreatitis and that pancreatic disease can be prevented with weight loss goals.