Hypertriglyceridemic Pancreatitis Research Articles

Prospective observational study and mechanistic evidence showing lipolysis of circulating triglycerides worsens hypertriglyceridemic acute pancreatitis.

While most hypertriglyceridemia is asymptomatic, hypertriglyceridemia-associated acute pancreatitis (HTG-AP) can be more severe than other AP etiologies. The reasons underlying this are unclear. We thus studied whether lipolytic generation of non-esterified fatty acids (NEFA) from circulating triglycerides (TGs) could worsen clinical outcomes. Admission serum TGs, NEFA compositions and concentrations were analyzed prospectively in 269 patients with AP. These and demographics, clinical outcomes were compared between HTGAP (TGs >500mg/dL; American Heart Association 2018 guidelines) and other AP etiologies. Serum NEFAs were correlated with the serum triglyceride fatty acids (TGFAs) alone, and with the product of TGFA x serum lipase (NEFA-TGFA x lipase). Studies in mice, rats were done to understand the role of HTG lipolysis in organ failure and to interpret the NEFA-TGFA correlations. HTG-AP patients had higher serum NEFAs and TGs and more severe AP (19% vs. 7% p<0.03) than other etiologies. Correlations of long-chain unsaturated NEFA with corresponding TGFAs increased with TG concentrations up to 500mg/dL and declined thereafter. However, NEFA-TGFA x lipase correlations got stronger with TGs >500mg/dL. AP, and intravenous lipase infusion in rodents caused lipolysis of circulating TGs to NEFA. This led to multi-system organ failure, which was prevented by pancreatic triglyceride lipase deletion, or lipase inhibition. HTG-AP is made severe by the NEFAs generated form intravascular lipolysis of circulating TGs. Strategies that prevent TG lipolysis may be effective in improving clinical outcomes of HTG-AP. Not applicable. This project was supported by Grant numbers RO1DK092460, R01DK119646 from the NIDDK, PR191945 under W81XWH-20-1-0400 from the DOD (VPS), and R01AA031257 from the NIAAA (VPS).

Computed tomography-based body composition indicative of diabetes after hypertriglyceridemic acute pancreatitis

BackgroundPost‑acute pancreatitis prediabetes/diabetes mellitus (PPDM‑A) is one of the common sequelae of acute pancreatitis (AP). The aim of our study was to build a machine learning (ML)-based prediction model for PPDM-A in hypertriglyceridemic acute pancreatitis (HTGP). MethodsWe retrospectively enrolled 165 patients for our study. Demographic and laboratory data and body composition were collected. Multivariate logistic regression was applied to select features for ML. Support vector machine (SVM), linear discriminant analysis (LDA), and logistic regression (LR) were used to develop prediction models for PPDM-A. Results65 patients were diagnosed with PPDM-A, and 100 patients were diagnosed with non-PPDM-A. Of the 84 body composition-related parameters, 15 were significant in discriminating between the PPDM-A and non-PPDM-A groups. Using clinical indicators and body composition parameters to develop ML models, we found that the SVM model presented the best predictive ability, obtaining the best AUC=0.796 in the training cohort, and the LDA and LR model showing an AUC of 0.783 and 0.745, respectively. ConclusionsThe association between body composition and PPDM-A provides insight into the potential pathogenesis of PPDM-A. Our model is feasible for reliably predicting PPDM-A in the early stages of AP and enables early intervention in patients with potential PPDM-A.

Acute pancreatitis secondary to tamoxifen-induced hypertriglyceridemia: A systematic review.

e24105 Background: Tamoxifen can cause paradoxical effects on lipid metabolism and increase triglyceride levels. Acute pancreatitis (AP) can culminate in increased severity and morbidity. A multitude of secondary etiologies may lead to hypertriglyceridemia (HTG), including alcohol, pregnancy, diabetes mellitus, or medications. Tamoxifen is known to cause HTG, but AP as a sequel to this complication remains exceedingly rare. Methods: We performed a systematic search of MEDLINE, Cochrane, Embase, and Google Scholar by using MeSH terms and keywords "tamoxifen," "acute pancreatitis," and "hypertriglyceridemia" from tamoxifen approval in 1977 to December 2023. A total of 26 cases were identified. The diagnosis of AP was established on meeting two of the three Revised Atlanta Classification criteria. Results: A total of 17 case reports fulfilled our inclusion criteria. The mean age of included patients was 35.84 ± 5.99 years. Clinical presentation was mainly related to vomiting (65%), abdominal pain (59%), nausea (47%), and epigastric discomfort (18%). HTG (55%), diabetes mellitus (27%), and hypertension (18%) were major comorbid conditions. The mean onset delay was 11.81 ± 14.75 months, and the tamoxifen dose was 20 mg per day. AP was categorized into mild (35%), moderate (35%), or severe (30%) forms. Treatment mainly consisted of conservative measures, but intravenous insulin (24%) and plasmapheresis (6%) were used in severe cases. The overall mortality rate was 6%. Conclusions: Tamoxifen-induced hypertriglyceridemic pancreatitis is a potential complication of tamoxifen therapy. The findings underscore the need for regular monitoring of serum lipids in these patient patients, especially those with pre-existing HTG or other comorbid conditions that increase their risk of developing hypertriglyceridemic pancreatitis. By implementing these recommendations, clinicians can help reduce morbidity and mortality associated with this condition. [Table: see text]

Association of admission serum triglyceride levels with intensive care unit hospitalization rates in acute pancreatitis patients: A retrospective study.

Acute pancreatitis (AP) is a complex and unpredictable condition, of which hypertriglyceridemia (HTG) is the third most prevalent cause. This study aimed to conduct a retrospective analysis of clinical data from hospitalized AP patients to uncover a potential correlation between triglyceride (TG) levels and the necessity for intensive care unit (ICU) admission. This retrospective cohort study utilized the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV) critical care dataset, incorporating data from 698 patients with hypertriglyceridemic acute pancreatitis (HTG-AP). The analysis employed the RCS model along with univariate and multivariate logistic regression methods to affirm the association between triglyceride levels and ICU admission. Subgroup analysis was performed to investigate specific populations. The study included 698 patients with AP, 42.41% of whom experienced HTG during hospitalization. RCS analysis revealed a linear association between TG levels and risk of ICU admission (p for nonlinear = .219, p for overall = .009). Multivariate logistic regression analysis indicated an increased risk of ICU admission in the TG range of 1.7-5.65 mmol/L (aOR = 1.83, 95% CI 1.12-2.99, P = .015) and TG >11.3 mmol/L (aOR = 5.69, 95% CI 2.36-13.74, P < .001) compared to the normal group. Similar results were observed across the various subgroups. As triglyceride levels increased, there was a corresponding increase in ICU admissions. Patients within the 1.7 to 5.65 mmol/L and > 11.3 mmol/L triglyceride groups exhibited higher rates of ICU admissions. Moreover, we observed a higher risk of ICU hospitalization even with mild TG elevation.

Research Progress on the Mechanism of Acute Hypertriglyceridemic Pancreatitis.

The incidence rate of hypertriglyceridemia pancreatitis (HTGP) has experienced a notable increase in recent years, with eclipsing alcohol as the second leading cause of acute pancreatitis (AP). HTGP is often associated with more severe local and systemic complications. Recognized as a metabolic disorder hypertriglyceridemia (HTG), it holds significant relevance in the pathogenesis of HTGP, yet its mechanisms are not fully understood. Both primary (genetic) and secondary (acquired) factors contribute to elevated triglyceride (TG) levels, which concurrently influence the progression of HTGP. This article presents a comprehensive review of the evolving research on HTGP pathogenesis, encompassing lipid synthesis and metabolism, calcium signal transduction, inflammatory mediators, endoplasmic reticulum stress, autophagy, mitochondrial injury by fatty acids, oxidative stress response, genetic factors, and gene mutations. By unraveling the intricate mechanisms underlying HTGP, this article aims to enhance physicians' understanding of the disease and facilitate the development of potential targeted pharmacological interventions for patients.

Liproxstatin-1 attenuates acute hypertriglyceridemic pancreatitis through inhibiting ferroptosis in rats

Ferroptosis is closely associated with inflammatory diseases, including acute pancreatitis (AP); however, the involvement of ferroptosis in hypertriglyceridemic pancreatitis (HTGP) remains unclear. In the present study, we aimed to explore the relationship between lipid metabolism and ferroptosis in HTGP and the alleviating effect of liproxstatin-1 (Lip-1) in vivo. This study represents the first exploration of lipid metabolism and endoplasmic reticulum stress (ERS) in HTGP, targeting ferroptosis as a key factor in HTGP. Hypertriglyceridemia (HTG) was induced under high-fat diet conditions. Cerulein was then injected to establish AP and HTGP models. Lip-1, a specific ferroptosis inhibitor, was administered before the induction of AP and HTGP in rats, respectively. Serum triglyceride, amylase, inflammatory factors, pathological and ultrastructural structures, lipid peroxidation, and iron overload indicators related to ferroptosis were tested. Moreover, the interaction between ferroptosis and ERS was assessed. We found HTG can exacerbate the development of AP, with an increased inflammatory response and intensified ferroptosis process. Lip-1 treatment can attenuate pancreatic injury by inhibiting ferroptosis through lipid metabolism and further resisting activations of ERS-related proteins. Totally, our results proved lipid metabolism can promote ferroptosis in HTGP by regulating ACSL4/LPCAT3 protein levels. Additionally, ERS may participate in ferroptosis via the Bip/p-EIF2α/CHOP pathway, followed by the alleviating effect of Lip-1 in the rat model.

The effect of serum triglyceride levels and different lipid-lowering methods on the prognosis of hypertriglyceridemic acute pancreatitis: a single-center 12-year retrospective study by propensity score matching

Aim To investigate the impact of triglyceride on hypertriglyceridemic acute pancreatitis (HTG-AP) and different lipid-lowering methods on triglyceride-lowering efficiency and HTG-AP. Methods The patients with HTG-AP from January 2012 to December 2023 in Civil Aviation General Hospital were analyzed, retrospectively. Patients were divided and compared according to whether their triglycerides were below 5.56 mmol/L at 48 and 72 h of admission. The patients were divided into control group, insulin group, and low molecular weight heparin (LMWH)+bezafibrate group based on the different methods of lipid-lowering. Propensity score matching (PSM) was employed to balance the baseline characteristics. Results There was no correlation between the severity of HTG-AP and the triglyceride at admission. The incidence of severity, local complications, and persistent organ failure (POF) were significantly decreased in patients with 48-h and 72-h triglyceride attainment. Following PSM, the incidence of infectious pancreatic necrosis (IPN) (3.3% vs. 13.3%) was significantly reduced in insulin group compared with control group (p < .05). Compared with control group, LMWH + bezafibrate group had higher lipid reduction efficiency, and the incidence of IPN (0.9% vs. 10.1%) and POF (8.3% vs. 19.3%) was significantly decreased (p < .05). There was no significant difference in the efficiency of lipid-lowering, complications, and POF between LMWH + bezafibrate group and insulin group (p > .05). Conclusion The severity of HTG-AP is not associated with the triglyceride levels at admission. However, rapid reduction of triglyceride levels can lower the incidence of local complications and respiratory failure. Compared with conservative treatment, insulin and LMWH + bezafibrate can both reduce the incidence of IPN in patients with HTG-AP.

Chaiqin Chengqi Decoction as an adjuvant treatment for mild/moderately severe hypertriglyceridemic acute pancreatitis: A retrospective study.

Hypertriglyceridemia is the third leading cause of acute pancreatitis (AP), and its incidence is increasing. Due to its relatively insidious etiology, it is easy to be ignored in the early stages. In China, Chaiqin Chengqi Decoction (CQCQD) has long been employed for treating AP. To evaluate the effectiveness of CQCQD in patients diagnosed with mild/ moderately severe hypertriglyceridemic AP (HTG-AP). In this study, the clinical data of 39 patients with HTG-AP admitted from January 2019 to November 2022 were collected. The changes of blood lipids, gastrointestinal symptoms, and abdominal pain before and after treatment were analyzed and compared between the two groups. Twenty patients were treated with the conventional HTG-AP regimen, and 19 patients were additionally treated with CQCQD. After receiving treatment, the triglycerides (TG) level of the CQCQD group was lower than that of the CQCQD group (3.14 ± 0.25 mmol/L vs 4.96 ± 0.47 mmol/L, P < 0.01). After 3 d of treatment, the patients in the CQCQD group had more bowel movements than the control group (2.51 ± 0.25 times vs 1.00 ± 0.17 times, P = 0.01). The gastrointestinal function of most patients returned to normal, and the acute gastrointestinal injury score was significantly lower than that of the control group (0.11 ± 0.07 vs 0.42 ± 0.11, P < 0.01). In patients with HTG-AP, CQCQD can significantly reduce the TG level, shorten the recovery time of defecation, significantly improve the gastrointestinal function.

Triglycerides: A Sensitizer but Not a Trigger for Hypertriglyceridemic Acute Pancreatitis.

The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) is increasing. Although the guideline defines the diagnostic criteria as triglyceride (TG) greater than 11.3 mmol/L, there is actually no specific threshold. Many people with hypertriglyceridemia (HTG) or obvious chyloid blood do not develop acute pancreatitis (AP). To explore the role of HTG in the pathogenesis of AP. Thirty-six male SD rats were randomly assigned into normal control, AP, HTG, HTG-AP, low-dose fenofibrate andhigh-dose fenofibrate groups. Serum indices and cytokine levels in serum, and pathological changes in pancreatic tissues were observed. The expression levels of TLR4 and NF-κBp65 in pancreatic tissues were detected by immunohistochemistry and Western blot. In normal rats, HTG alone did not induce AP. However, after establishing the HTG-AP model with Poloxam 407 and L-arginine, serum-free fatty acid and TG levels were positively correlated with the levels of lipase, amylase, IL-1β, IL-6, pancreatic inflammation scores, and the expressions of TLR4 and NF-κBp65 (all P < 0.001). Expressions of TLR4 and NF-κBp65 were significantly increased in the pancreatic tissues of HTG-AP rats. Fenofibrate effectively decreased TG levels in HTG-AP rats and reduced the expression of TLR4 and NF-κBp65 (all P < 0.001). HTG does not directly cause AP, but rather increases the susceptibility to AP or aggravates the inflammatory response. It is more like a sensitizer of inflammation rather than an activator.

Establishment of Prediction Model for Severe Hypertriglyceridemic Acute Pancreatitis Based on Early Laboratory Indicators

Abstract Background Compared with other types of acute pancreatitis (AP), hypertriglyceridemic acute pancreatitis (HTG-AP) is younger, recurrent and more prone to exacerbation. Severe HTG-AP has a high fatality rate. Early and accurate prediction of the severity is crucial. However, there is currently a lack of a specific scoring system for the severity of HTG-AP. Aim/Purpose To construct a risk prediction model that can accurately predict severe HTG-AP in the early stage and evaluate its clinical value. Methods The clinical data of 1768 patients with AP admitted to the Second Affiliated Hospital of Anhui Medical University from January 2020 to May 2023 were analyzed retrospectively, and 136 HTG-AP patients were finally selected. Univariate and multivariate analysis were performed for the early onset indicators to identify the independent risk factors for developing SAP in the patients of HTG-AP. Logistic regression was then utilized to establish a risk prediction model for the severity of HTG-AP, which was subsequently evaluated for its performance through discrimination and calibration analysis. Results Of the 136 patients with HTG-AP, 39 patients (28.7%) progressed to severe acute pancreatitis (SAP). Multivariate analysis revealed that CRP, RDW/SC, and D-dimer were independent risk factors for developing SAP in the patients of HTG-AP. The logistic regression analysis to establish prediction model was: Logit P = − 8.101 + 0.008 × CRP + 0.425 × D-dimer + 0.743 × RDW/SC. The receiver-operating characteristics (ROC) curve showed that area under curve (AUC) value of CRP, RDW/SC, D-dimer, and the prediction model were 0.831, 0.843, 0.874, and 0.915, respectively. Moreover, the AUC value of the prediction model and commonly used scoring systems of AP were compared: prediction model (AUC = 0.915) &gt; Ranson (AUC = 0.900) &gt; SOFA (AUC = 0.899) &gt; CTSI (AUC = 0.889) &gt; BISAP (AUC = 0.887). Conclusion CRP, RDW/SC and D-dimer were independent risk factors for SAP in the patients of HTG-AP. Compared with commonly used scoring systems of AP, the prediction model had good clinical prediction ability, providing reference for early identification of the patients developing severe HTG-AP and active intervention.

Prediction and evaluation of a nomogram model for recurrent acute pancreatitis.

The purpose of this study was to investigate the influencing factors for recurrent acute pancreatitis and construct the nomogram model to predict the risk of recurrent acute pancreatitis. Patients diagnosed with acute pancreatitis in the Affiliated Hospital of Southwest Medical University were enrolled. We collected these patients' basic information, laboratory data, imaging information. Using Logistic regression and least absolute shrinkage and selection operator regression to select risk factor for Cross-Validation Criterion. To create nomogram and validated by receiver operator characteristic curve, calibration curves and decision curve analysis. A total of 533 patients with acute pancreatitis were included, including 99 recurrent acute pancreatitis patients. The average age of recurrent acute pancreatitis patients was 49.69 years old, and 67.7% of them were male. At the same time, in all recurrent acute pancreatitis patients, hypertriglyceridemic pancreatitis is the most important reason (54.5%). Regression analysis and least absolute shrinkage and selection operator regression showed that smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis were identified and entered into the nomogram. The area under the receiver operator characteristic curve of the training set was 0.747. The calibration curve showed the consistency between the nomogram model and the actual probability. In conclusion, some high-risk factors like smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis may predict recurrent pancreatitis and their incorporation into a nomogram has high accuracy in predicting recurrence.

Clinical characteristics and pregnancy outcome analysis of 20 cases of acute pancreatitis during pregnancy.

This study investigated the clinical characteristics and pregnancy outcomes of acute pancreatitis during pregnancy (APIP). A retrospective analysis was conducted on 20 cases of APIP admitted to Hubei Maternal and Child Health Hospital from January 2017 to September 2021. The etiology, clinical manifestations, and perinatal outcomes of APIP were analyzed using descriptive statistical analysis of the collected data. The incidence of APIP in our hospital was 20 (0.02%) cases, all of which occurred in the late stage of pregnancy. Hypertriglyceridemic acute pancreatitis (HTG-AP) was the primary cause of APIP in 10 (50.0%) patients. A total of 11 (55.0%), seven (35.0%) and two (10.0%) patients had mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), respectively. Pregnant women with HTG-AP had significantly elevated serum triglyceride levels, had higher prepregnancy body mass indices, were more prone to developing diabetes and were more likely to progress to SAP. With a multidisciplinary approach and individualized treatment plans, there were no maternal deaths, and fetal death only occurred in one (5.0%) case. HTG-AP is prone to advancing to more severe states, and it is becoming more common every year. Therefore, blood lipid management during pregnancy should be emphasized. Pregnant women with digestive symptoms or severe hyperlipidaemia should be screened for APIP in a timely manner and receive clinical intervention to improve maternal and fetal outcomes during the perinatal period.

Serum lipase in acute pancreatitis associated with hypertriglyceridaemia.

The incidence of hypertriglyceridaemic pancreatitis is increasing. Hypertriglyceridaemia may be associated with false lowering of serum amylase and lipase in vitro. A retrospective study of serum lipase levels in 26 individuals who had acute pancreatitis diagnosed based on clinical criteria together with changes on computer tomography in the setting of severe hypertriglyceridaemia over a 5-year period from January 2017 to December 2021 was performed. Serum lipase levels were in the normal range in two patients (7.7%) and less than three times the upper end of the reference interval in 11 individuals (42%). Awareness of the potential for normal and nonsignificantly elevated serum lipase levels in the setting of hypertriglyceridaemic pancreatitis is important to avoid a missed diagnosis, to enable appropriate short- and long-term management and to prevent recurrent episodes.

Clinical efficacy of low-molecular-weight heparin combined with insulin in the treatment of hypertriglyceridemic acute pancreatitis

Background: To investigate the clinical effect of low-molecularweight heparin combined with insulin in the treatment of hypertriglyceridemic acute pancreatitis (HTG-AP).

Establishment and validation of early prediction model for hypertriglyceridemic severe acute pancreatitis

BackgroundThe prevalence of hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) is increasing due to improvements in living standards and dietary changes. However, currently, there is no clinical multifactor scoring system specific to HTG-AP. This study aimed to screen the predictors of HTG-SAP and combine several indicators to establish and validate a visual model for the early prediction of HTG-SAP.MethodsThe clinical data of 266 patients with HTG-SAP were analysed. Patients were classified into severe (N = 42) and non-severe (N = 224) groups according to the Atlanta classification criteria. Several statistical analyses, including one-way analysis, least absolute shrinkage with selection operator (LASSO) regression model, and binary logistic regression analysis, were used to evaluate the data.ResultsThe univariate analysis showed that several factors showed no statistically significant differences, including the number of episodes of pancreatitis, abdominal pain score, and several blood diagnostic markers, such as lactate dehydrogenase (LDH), serum calcium (Ca2+), C-reactive protein (CRP), and the incidence of pleural effusion, between the two groups (P < 0.000). LASSO regression analysis identified six candidate predictors: CRP, LDH, Ca2+, procalcitonin (PCT), ascites, and Balthazar computed tomography grade. Binary logistic regression multivariate analysis showed that CRP, LDH, Ca2+, and ascites were independent predictors of HTG-SAP, and the area under the curve (AUC) values were 0.886, 0.893, 0.872, and 0.850, respectively. The AUC of the newly established HTG-SAP model was 0.960 (95% confidence interval: 0.936–0.983), which was higher than that of the bedside index for severity in acute pancreatitis (BISAP) score, modified CT severity index, Ranson score, and Japanese severity score (JSS) CT grade (AUC: 0.794, 0.796, 0.894 and 0.764, respectively). The differences were significant (P < 0.01), except for the JSS prognostic indicators (P = 0.130). The Hosmer–Lemeshow test showed that the predictive results of the model were highly consistent with the actual situation (P > 0.05). The decision curve analysis plot suggested that clinical intervention can benefit patients when the model predicts that they are at risk for developing HTG-SAP.ConclusionsCRP, LDH, Ca2+, and ascites are independent predictors of HTG-SAP. The prediction model constructed based on these indicators has a high accuracy, sensitivity, consistency, and practicability in predicting HTG-SAP.

AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats

GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPLs). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1-/- mice with high hepatic LPL expression did not develop HTG, whereas Gpihbp1-/- rat pups without hepatic LPL expression developed severe HTG. AAV-mediated liver-targeted LPL expression dose-dependently decreased plasma TG levels in Gpihbp1-/- mice and rats, increased post-heparin plasma LPL mass and activity, decreased mortality in Gpihbp1-/- rat pups, and reduced the susceptibility and severity of both Gpihbp1-/- animals to HTG-AP. However, the muscle expression of AAV-LPL had no significant effect on HTG. Targeted expression of LPL in the liver showed no obvious adverse reactions. Thus, liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.

Nonlinear Relationship Between Serum Total Cholesterol Levels and the Severity of Hypertriglyceridemic Acute Pancreatitis: A Cohort Study in China.

The relationship between total cholesterol (TC) levels and the severity of hypertriglyceridemic acute pancreatitis (HTGAP) remains unclear. The aim of this study was to investigate the relationship between the levels of TC at admission with the severity of HTGAP, in order to apply it as a reliable predictor at early stage in clinical practice. We performed a cohort study including 249 patients with AHTGP between November 2012 and April 2022 in XuanWu Hospital. Fasting TC was assayed within 24h of admission, age, gender, body mass index, hypertension, diabetes mellitus, drinking, smoking, neutrophil-lymphocyte ratio, C-reactive protein and glucose were recorded as confounding factors. To evaluate the relationship of TC and the severity of HTGAP, we used smooth curve fitting and a segmented regression model with adjustment of confounding factors to analyze the threshold effect between TC and SAP occurrence risk. 249 Patients were enrolled. The incidence of SAP was 25.3% (63/249). A nonlinear relationship between TC level and the severity of HTGAP. 6.09mmol/L was the optimal TC value associated with the lowest risk of SAP occurrence. Moreover, TC level was negatively correlated with risk of severe HTGAP occurrence for TC < 6.09mmol/L (OR 0.45, 95% CI 0.23-0.85, P = 0.014) and positively correlated for TC > 6.09mmol/L in HTGAP patients (OR 1.14, 95% CI 1.04-1.26, P = 0.006). We found that serum TC level is nonlinearly associated with the severity of HTGAP, and it can be a reliable predictor for early intervention and intensive care.

OR24-03 Triglyceride Clearance In Hypertriglyceridemic Pancreatitis: Time-course And Implications For Management

Abstract Disclosure: S.K. Majumdar: None. Introduction: Uncertainty exists for how to optimally manage severely elevated triglyceride (Tg) levels in patients with hypertriglyceridemic (HTg) pancreatitis. Standard recommendations include NPO (nil per os) status and intravenous (iv) insulin for most patients, yet information is lacking in regards to the natural time-course of Tg lowering, the degree of benefit insulin provides and for whom it may be indicated, and for the Tg level at which transition to feeding would be appropriate. Underlying Questions: (1) What is the natural time-course of triglyceride (Tg) lowering when nutritional intake is held and (2) does it differ according to etiology of hypertriglyceridemia? (3) What is the role of intravenous insulin in acute Tg lowering, and (4) at what threshold of Tg can nutritional intake safely resume? Methods: A retrospective study of patients hospitalized from October 2013 through December of 2018 with a diagnosis of pancreatitis associated with hypertriglyceridemia Tg ≥ 5.65 mM (500 mg/dL), in absence of other causes, was performed by medical record review. The time-course of Tg lowering was assessed for differences in relation to initial Tg values, use of iv insulin, ethanol vs. non ethanol associated causes, and time to Tg values of &amp;lt; 5.65 mM (500 mg/dL) vs &amp;lt; 11.29 (1000 mg/dL). Results: Sixty-six cases were identified and 45 had multiple measurements for time-course evaluation. Those with initial Tg values &amp;lt; 45.16 mM (4000 mg/dL) achieved Tg levels &amp;lt; 11.29 mM in &amp;lt; 3 days, while 18.8% with higher values took 5-9 days. Insulin therapy was associated with a longer duration, and ethanol with a shorter duration, of hypertriglyceridemia. Tg clearance in ethanol associated hypertriglyceridemia appeared independent of insulin treatment. Time to Tg &amp;lt; 5.65 mM vs &amp;lt; 11.29 mM was significantly longer when initial Tg levels were &amp;gt; 22.58 mM (2000 mg/dL). Conclusion: An arbitrary threshold of 45.16 mM (4000 mg/dL) for initial Tg’s in HTg pancreatitis appears to separate those likely to achieve Tg’s &amp;lt; 11.29 mM in &amp;lt; 3 vs. &amp;gt; 3 days, independent of cause or treatment in absence of known genetic defects in Tg clearance. Insulin therapy remains appropriate for hyperglycemic patients but appears unnecessary for isolated ethanol associated hypertriglyceridemia. A threshold Tg of &amp;lt;11.29 mM appears more practical than &amp;lt;5.65 mM for resuming nutritional intake. A randomized trial is necessary to confirm these findings. Presentation: Saturday, June 17, 2023

SAT160 Alcoholic Ketoacidosis : An Endocrine Emergency

Abstract Disclosure: L.E. Tiu: None. T.D. Crisostomo: None. Background: Alcoholic Ketoacidosis is a complex metabolic condition frequently confused with Diabetic Ketoacidosis. Currently, there remains an undefined consensus guideline in the diagnosis and management of this disorder that leads to unreported cases. Clinical Case: A 47-year-old male presented with 2-day history of poor dietary intake due to abdominal pain and vomiting after an alcoholic binge drinking. He is a chronic alcoholic beverage drinker (2 liters of beer per day for 10 years). He has family history of Type 2 Diabetes Mellitus but has no known co-morbidities. Upon admission, vital signs were normal, but he was drowsy and incoherent with signs of dehydration and epigastric tenderness. Initial capillary blood glucose was 52 mg/dL. D50W 50ml intravenously was given with repeat CBG of 222 mg/dL. Arterial blood gas (ABG) showed high anion gap metabolic acidosis (pH 7.0 and anion gap of 42) with undetectable bicarbonate and elevated lactate at 17mmol/L. Serum ketones were elevated at 6mmol/L but Hba1c was normal at 4.6 %. Thus, Alcoholic Ketoacidosis was highly considered. Intravenous hydration with saline solution was instituted then shifted to D10W 125mL/hour to allow insulin infusion therapy at initial rate of 2units/hour. Sodium bicarbonate 100 mEqs was given intravenously with recovery of sensorium thereafter. Oral Vitamin B supplement was started, and two doses of Thiamine 100 mg/IV were given. Other tests showed hyperkalemia (5.28meq/L), hypochloridemia (89.7meq/L), hyperuricemia (12.74mg/dL), and hyperphosphatemia (5.8mg/dL). Serial monitoring and correction of electrolytes were done. Moreover, management integrated simultaneous referrals to other subspecialties to rule out other causes of encephalopathy, to evaluate and manage Hypertriglyceridemic Pancreatitis and Alcoholic Liver Disease, and to facilitate nutritional, psychosocial support and rehabilitation. On 2nd hour, repeat ABG showed improvement of pH to 7.3 and HCO3 to 9.80mmol/L. Lactate decreased to 12.70mmol/L. On the 17th hour, ABG showed metabolic alkalosis with resolution of ketosis hence insulin was discontinued. CBG levels for the next 24-48 hours were within normal limits. Oral feeding was supplemented with parenteral nutrition due to decreased appetite. On 48th hour, he displayed combative behavior with visual hallucinations, but there was no consent for psychiatric referral. On 72nd hour, there was spontaneous marked improvement in his behavior. He was discharged clinically stable. Conclusion: Early recognition of Alcoholic Ketoacidosis is imperative. This is an unrecognized endocrine emergency that portends good outcome with timely diagnosis and management. Treatment includes 1. adequate fluid resuscitation 2. thiamine 3. judicious use of insulin and bicarbonate 4. correction of electrolytes 5. multidisciplinary team management. Presentation: Saturday, June 17, 2023

Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.