INTRODUCTION: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. METHODS: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning–based framework called nnUNet. The prevalence of fatty change of the pancreas (FP) was determined using sex- and age-specific thresholds. Associations between IPFD and pancreatic diseases were assessed with multivariate Cox-proportional hazard model adjusted for age, sex, ethnicity, body mass index, smoking and drinking status, central obesity, hypertension, dyslipidemia, liver fat content, and spleen fat content. RESULTS: Of the 42,599 participants included in the analysis, the prevalence of FP was 17.86%. Elevated IPFD levels were associated with an increased risk of acute pancreatitis (hazard ratio [HR] per 1 quintile change 1.513, 95% confidence interval [CI] 1.179–1.941), pancreatic cancer (HR per 1 quintile change 1.365, 95% CI 1.058–1.762) and diabetes mellitus (HR per 1 quintile change 1.221, 95% CI 1.132–1.318). FP was also associated with a higher risk of acute pancreatitis (HR 3.982, 95% CI 2.192–7.234), pancreatic cancer (HR 1.976, 95% CI 1.054–3.704), and diabetes mellitus (HR 1.337, 95% CI 1.122–1.593, P = 0.001). DISCUSSION: FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas.

INTRODUCTION: Hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is one of the most common etiologies of acute pancreatitis (AP) worldwide. Compared with other etiologies, patients with HTG-AP may develop more severe AP, but previous studies yielded controversial conclusion due to the lack of adequate adjustment for the confounders. Therefore, the aim of this study was to examine the possibility and risk factors of developing severe AP in HTG-AP. METHODS: Data from patients with an established diagnosis of AP were collected from January 2013 to December 2023 using a predesigned data collection form and were gathered from 5 tertiary cross-regional centers of China. HTG-AP was defined as serum triglyceride levels >500 mg/dL and excluded other etiologies. The possibility and risk factors of severe AP were assessed by multivariable logistic regressions after adjusting potential confounders. A prediction model was established and validated. RESULTS: Between 2013 and 2023, we identified a total of 6,996 patients with AP, of whom 4,378 were included in the final analysis. Compared with other etiologies, patients with HTG-AP had a higher risk of developing severe AP (odds ratio: 1.897; 95% confidence interval: 1.380–2.608; P < 0.001) and organ failure. HTG-AP patients showed higher possibility for developing respiratory and circulation failure but renal failure compared with other etiologies. In HTG-AP patients, risk factors of severe AP included age, fasting blood glucose, white blood cell counts, and presence of pleural effusion. TG level was found not significantly associated with severity in HTG-AP patients. A prediction model incorporating these risk factors demonstrated an area under the curve (AUC) of 0.837 in the training and 0.883 in the testing set, with adequate calibration. DISCUSSION: Using a multicenter cross-regional cohort, we demonstrated that HTG-AP had a higher risk of developing severe AP and organ failure. A risk prediction model for predicting severe AP was developed and effectively stratified patients.

Acute pancreatitis (AP) is the most common pancreatic disease. Predicting the severity of AP is critical for making preventive decisions. However, the performance of existing scoring systems in pre...

Background: Twenty-three percent of patients are diagnosed with diabetes mellitus after the first episode of acute pancreatitis. The incidence of post-acute pancreatitis diabetes mellitus is significantly higher than that of type 1 diabetes mellitus. Some studies have concluded that the all-cause mortality and worse prognosis of diabetes after pancreatitis are higher. We predicted that number of recurrences of pancreatitis would be significantly associated with the incidences of metabolic syndrome, abdominal obesity, and post-acute pancreatitis diabetes mellitus. Methods: Patients admitted to our hospital for hypertriglyceridemic acute pancreatitis from 2013–2021 were selected for a cross-sectional study. Statistical analysis methods were used to analyze the effect of recurrences on the long-term prognosis of patients with hypertriglyceridemic acute pancreatitis. Results: In this study, 101 patients with hypertriglyceridemic acute pancreatitis were included: 60 (59.41%) in the recurrent acute pancreatitis group and 41 (40.59%) in the only one episode of acute pancreatitis group. Among all hypertriglyceridemic acute pancreatitis patients, approximately 61.4% were diagnosed with abdominal obesity, 33.7% of patients are diagnosed with metabolic syndrome, 34.7% of patients are diagnosed with diabetes mellitus, and 21.8% of patients are diagnosed with post-acute pancreatitis diabetes mellitus. Recurrent acute pancreatitis were independent risk factors for post-acute pancreatitis diabetes mellitus in patients with hypertriglyceridemic acute pancreatitis (odds ratio [OR] = 3.964, 95% confidence interval [CI] = 1.230–12.774) and the risk of post-acute pancreatitis diabetes mellitus in patients with three or more recurrent episodes was 6.607 times higher than that in patients without recurrent episodes (OR = 6.607, 95% CI = 1.412–30.916). Conclusions: Recurrence is an independent risk factor for the development of post-acute pancreatitis diabetes mellitus and is significantly associated with the number of recurrences.

Background: Acute pancreatitis in pregnancy (APIP) is a life‐threatening disease for both mother and fetus. To date, only three patients with recurrent hypertriglyceridemia‐induced APIP (HTG‐APIP) have been reported to carry rare variants in the lipoprotein lipase (LPL) gene, which encodes the key enzyme responsible for triglyceride (TG) metabolism. Coincidently, all three patients harbored LPL variants on both alleles and presented with complete or severe LPL deficiency.Methods: The entire coding regions and splice junctions of LPL and four other TG metabolism genes (APOC2, APOA5, GPIHBP1, and LMF1) were analyzed by Sanger sequencing in a Han Chinese patient who had experienced two episodes of HTG‐APIP. The impact of a novel LPL missense variant on LPL protein expression and activity was analyzed by transient expression in HEK293T cells.Results: A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient. This variant did not affect protein synthesis but significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein.Conclusion: This report describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG‐APIP. Our findings confirm a major genetic contribution to the etiology of individual predisposition to HTG‐APIP.

Severe acute pancreatitis (SAP) is characterized by high mortality rates and various complications, including skeletal muscle atrophy, which significantly exacerbates its outcomes. Despite its clinical relevance, the mechanistic understanding of the relationship between skeletal muscle and the pancreas in SAP remains limited. Our study aimed to elucidate this “organ crosstalk” and its potential implications. We established an SAP mouse model through pancreatic duct ligation (PDL) and evaluated pancreatic necrosis, skeletal muscle atrophy, and myonectin expression levels. Recombinant myonectin protein was administered in vivo and in vitro to assess its effects on acinar cell necrosis. Mechanistic insights were gained through RNA-seq data analysis and experimental validation. Serum samples from AP patients and healthy controls were collected to investigate the correlation between serum myonectin levels and disease severity. The mouse model exhibited severe pancreatic necrosis, skeletal muscle atrophy, and elevated myonectin levels, with myonectin administration exacerbating model severity. We identified iron accumulation-induced ferroptosis as a key pathway contributing to myonectin-mediated acinar cell necrosis. A total of 22 healthy controls and 52 patients with varying degrees of AP were included in the serum samples and clinical data (36.5% females, age 49.79 ± 16.53). Analysis of serum samples revealed significantly higher myonectin levels in AP patients, correlating with disease severity (R = 0.28, P = 0.041). Our findings underscore the significant role of myonectin in SAP progression and its potential as a prognostic marker for disease severity in AP patients. This study contributes to a deeper understanding of the pathophysiology of SAP and highlights potential therapeutic targets for intervention.