5-Fluorouracil-associated severe hypertriglyceridaemia with positive rechallenge.

Chemotherapy-induced hypertriglyceridaemia (HTG) is a potential serious adverse event. Severe HTG with triglycerides (TG) >11.3 mmol/L (1000 mg/dL) can cause acute pancreatitis in addition to cardiovascular diseases such as coronary artery disease. While the association of capecitabine (5-fluorouracil (5-FU) prodrug) with clinically relevant HTG is a well-known adverse reaction, 5-FU is not typically associated with HTG. We here report the case of a patient who developed 5-FU-associated grade 4 HTG with TG level raising up to 37.1 mmol/L (3286 mg/dL) occurring after the ninth cycle of adjuvant FOLFOX (Fluorouracil and Oxaliplatin) chemotherapy. Fenofibrate treatment and diet were started. Chemotherapy was postponed and then resumed for two additional cycles. However, severe HTG recurred shortly after. Chemotherapy was therefore permanently stopped. Approximately 8 weeks after chemotherapy discontinuation, TG fell back to range at 2.1 mmol/L (189 mg/dL) allowing interruption of fenofibrate without HTG recurrence at 3 months.

Medical management of hypertriglyceridemia in pancreatitis.

PURPOSE OF REVIEW: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) should be considered in all cases of acute pancreatitis and triglyceride levels measured early, so that appropriate early and long-term treatment can be initiated. RECENT FINDINGS: In most cases of HTG-AP, conservative management (nothing by mouth, intravenous fluid resuscitation and analgesia) is sufficient to achieve triglyceride levels less than 500 mg/dl. Intravenous insulin and plasmapheresis are sometimes used, although prospective studies showing clinical benefits are lacking. Pharmacological management of hypertriglyceridemia (HTG) should start early and target triglyceride levels of less than 500 mg/dl to reduce the risk or recurrent acute pancreatitis. In addition to currently used fenofibrate and omega-3 fatty acids, several novel agents are being studied for long-term treatment of HTG. These emerging therapies focus mainly on modifying the action of lipoprotein lipase (LPL) through inhibition of apolipoprotein CIII and angiopoietin-like protein 3. Dietary modifications and avoidance of secondary factors that worsen triglyceride levels should also be pursued. In some cases of HTG-AP, genetic testing may help personalize management and improve outcomes. SUMMARY: Patients with HTG-AP require acute and long-term management of HTG with the goal of reducing and maintaining triglyceride levels to less than 500 mg/dl.

Efficacy of Combined Management with Nonsteroidal Anti-inflammatory Drugs for Prevention of Pancreatitis After Endoscopic Retrograde Cholangiography: a Bayesian Network Meta-analysis.

OBJECTIVES: To systematically evaluate the clinical efficacy of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) alone or in combination with other agents for preventing pancreatitis after endoscopic retrograde cholangiopanography. METHODS: We carried out a literature search of random controlled trials (RCTs) on preventing post-operative pancreatitis by administration of the anti-inflammatory drugs, indomethacin and diclofenac, following endoscopic retrograde cholangiopancreatography (ERCP). The databases searched for relevant publications up to July 7, 2021, included PubMed, Cochrane Library, and Embase. We screened the literature according to inclusion criteria and analyzed the extracted data. The overall population and high-risk patient groups were analyzed, with the main outcome being the incidence of PEP. RESULTS: The search identified 32 RCTs that included 15019 patients with post-ERCP pancreatitis and 9 different interventions. The results of the overall population network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs significantly reduced the incidence of PEP compared with placebo. However, compared with placebo, there was no statistically significant difference between the two interventions (NSAIDs + standard hydration and high-dose NSAIDs). In addition, NSAIDs + sublingual nitrates were associated with a lower incidence of PEP compared to that observed with NSAIDs alone. Probability ranking results showed that NSAIDs + sublingual nitrate had the best effect, followed by NSAIDs + standard hydration, NSAIDs + melatonin, NSAIDs + aggressive hydration, NSAIDs + somatostatin, NSAIDs alone, NSAIDs + epinephrine, high-dose NSAIDs, and placebo. In the high-risk subgroup, the results of the network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs showed no statistically significant difference in their ability to reduce the incidence of PEP compared with placebo. Probability ranking results showed that NSAIDs + hydration had the best effect, followed by NSAIDs + sublingual nitroglycerin and NSAIDs + aggressive hydration. CONCLUSION: Of the nine interventions, NSAIDs + sublingual nitrates had considerably better efficacy than the other drugs for reducing the incidence of PEP in the overall population. In high-risk patients, NSAIDs + standard hydration may be the best preventive treatment; however, more randomized, controlled trials are needed to validate our results. TRIAL REGISTRATION: Name of the registry: PROSPERO-International prospective register of systematic reviews. Unique identifying number or registration ID: CRD42021282205.

Vitamin D and Pancreatitis: A Narrative Review of Current Evidence.

Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.

Prevention and Management of Hypertriglyceridemia-Induced Acute Pancreatitis During Pregnancy: A Systematic Review.

Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2 expert panel recommendations provide guidance on monitoring pregnant women at high risk for hyperlipidemia. We suggest that high-risk women have triglyceride levels checked once every trimester. Fasting triglycerides >250 mg/dL should prompt monthly triglyceride levels, screening for gestational diabetes, and implementing a strict low-carbohydrate, low-fat diet, exercise. Fasting triglycerides >500 mg/dL, despite a strict dietary and lifestyle modifications, should prompt treatment with omega-3-fatty acids and continue a fat-restricted diet (<20 g total fat/d or <15% total calories) under the guidance of a registered dietician. The use of fibrates should be considered as a second-line therapy due to their unclear risk versus benefit and potential teratogenic effects. Plasmapheresis should be considered early in asymptomatic pregnant women with fasting triglyceride levels >1000 mg/dL or in pregnant women with clinical signs and symptoms of pancreatitis and triglyceride levels >500 mg/dL despite maximal lifestyle changes and pharmacologic therapy.

Randomized trial of high-dose rectal diclofenac suppository and epinephrine spray on duodenal papilla for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIMS: High-dose rectal diclofenac suppository and epinephrine spray on duodenal papilla during endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. We performed randomized trial to compare the effect of combination of rectal diclofenac and epinephrine spray on papilla (group A) vs. combination of rectal diclofenac with saline spray (group B) for prevention of post-ERCP pancreatitis. METHODS: We performed a double-blind trial at tertiary care center from April 2018 to May 2020 on 882 patients with naive papilla undergoing ERCP. The patients were randomly assigned to groups, A (n=437) or B (n=445). All patients received a single dose of rectal diclofenac 100 mg within 30 minutes before ERCP; 20 mL of diluted epinephrine 0.02% (group A) or saline (group B) was then sprayed on the duodenal papilla at the end of ERCP. The primary outcome was to compare incidence of post-ERCP pancreatitis (PEP) in two groups. RESULTS: The groups had similar baseline characteristics. PEP developed in 28 patients in group A (6.4%) and 35 patients in group B (7.9%) (relative risk, 1.1; 95% CI, 0.87-1.39; p=0.401). CONCLUSION: Our study showed that addition of epinephrine spray on duodenal papilla did not reduce the risk of post-ERCP pancreatitis. There is need for further studies to evaluate the role of different concentrations of epinephrine spray on papilla for prevention of post-ERCP pancreatitis. TRIAL REGISTRATION: Clinical Trials Registry- India (CTRI/2018/04/013396).

A Comprehensive Update on the Chylomicronemia Syndrome.

The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When due to very rare monogenic mutations in the genes encoding the enzyme, lipoprotein lipase, or its regulators, APOC2, APOA5, GPIHBP1, and LMF1, it is referred to as the familial chylomicronemia syndrome. Much more frequently, the chylomicronemia syndrome results from a cluster of minor genetic variants causing polygenic hypertriglyceridemia, which is exacerbated by conditions or medications which increase triglyceride levels beyond the saturation point of triglyceride removal systems. This situation is termed the multifactorial chylomicronemia syndrome. These aggravating factors include common conditions such as uncontrolled diabetes, overweight and obesity, alcohol excess, chronic kidney disease and pregnancy and several medications, including diuretics, non-selective beta blockers, estrogenic compounds, corticosteroids, protease inhibitors, immunosuppressives, antipsychotics, antidepressants, retinoids, L-asparaginase, and propofol. A third uncommon cause of the chylomicronemia syndrome is familial forms of partial lipodystrophy. Development of pancreatitis is the most feared complication of the chylomicronemia syndrome, but the risk of cardiovascular disease as well as non-alcoholic steatohepatitis is also increased. Treatment consists of dietary fat restriction and weight reduction combined with the use of triglyceride lowering medications such as fibrates, omega 3 fatty acids and niacin. Effective management of aggravating factors such as improving diabetes control, discontinuing alcohol and replacing or reducing the dose of medications that raise triglyceride levels is essential. Importantly, many if not most cases of the chylomicronemia syndrome can be prevented by effective identification of polygenic hypertriglyceridemia in people with conditions that increase its likelihood or before starting medications that may increase triglyceride levels. Several new pharmacotherapeutic agents are being tested that are likely to considerably improve treatment of hypertriglyceridemia in people at risk.

Omega-3 fatty acid exposure with a low-fat diet in patients with past hypertriglyceridemia-induced acute pancreatitis; an exploratory, randomized, open-label crossover study.

BACKGROUND: Omega-3 fatty acids (OM3-FAs) are recommended with a low-fat diet for severe hypertriglyceridemia (SHTG), to reduce triglycerides and acute pancreatitis (AP) risk. A low-fat diet may reduce pancreatic lipase secretion, which is required to absorb OM3-ethyl esters (OM3-EEs), but not OM3-carboxylic acids (OM3-CAs). METHODS: In this exploratory, randomized, open-label, crossover study, 15 patients with SHTG and previous AP were instructed to take OM3-CA (2 g or 4 g) and OM3-EE 4 g once daily for 4 weeks, while adhering to a low-fat diet. On day 28 of each treatment phase, a single dose was administered in the clinic with a liquid low-fat meal, to assess 24-h plasma exposure. Geometric least-squares mean ratios were used for between-treatment comparisons of baseline (day 0)-adjusted area under the plasma concentration versus time curves (AUC0-24) and maximum plasma concentrations (Cmax) for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). RESULTS: Before initiating OM3-FA treatment, mean baseline fasting plasma EPA + DHA concentrations (nmol/mL) were 723 for OM3-CA 2 g, 465 for OM3-CA 4 g and 522 for OM3-EE 4 g. At week 4, mean pre-dose fasting plasma EPA + DHA concentrations increased by similar amounts (+ 735 - + 768 nmol/mL) for each treatment. During the 24-h exposure assessment (day 28), mean plasma EPA + DHA increased from pre-dose to the maximum achieved concentration by + 32.7%, + 45.8% and + 3.1% with single doses of OM3-CA 2 g, OM3-CA 4 g and OM3-EE 4 g, respectively. Baseline-adjusted AUC0-24 was 60% higher for OM3-CA 4 g than for OM3-EE 4 g and baseline-adjusted Cmax was 94% higher (both non-significant). CONCLUSIONS: Greater 24-h exposure of OM3-CA versus OM3-EE was observed for some parameters when administered with a low-fat meal at the clinic on day 28. However, increases in pre-dose fasting plasma EPA + DHA over the preceding 4-week dosing period were similar between treatments, leading overall to non-significant differences in baseline (day 0)-adjusted AUC0-24 and Cmax EPA + DHA values. It is not clear why the greater 24-h exposure of OM3-CA versus OM3-EE observed with a low-fat meal did not translate into significantly higher pre-dose fasting levels of DHA + EPA with longer-term use. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02189252, Registered 23 June 2014.

Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia.

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder of chylomicron metabolism causing severe elevation of triglyceride (TG) levels (>10 mmol L-1 ). This condition is associated with a significant risk of recurrent acute pancreatitis (AP). AP caused by hypertriglyceridaemia (HTG) has been associated with a worse prognosis and higher mortality rates compared to pancreatitis of other aetiology. Despite its association with poor quality of life and increased lifelong risk of HTG-AP, few healthcare providers are familiar with FCS. Because this condition is under-recognized, the majority of FCS patients are diagnosed after age 20 often after consulting several physicians. Although other forms of severe HTG such as multifactorial chylomicronemia have been associated with high atherosclerotic cardiovascular disease (ASCVD) risk and metabolic abnormalities, ASCVD and metabolic syndrome are not usually observed in FCS patients. Because FCS is a genetic condition, the optimal diagnosis strategy remains genetic testing. The presence of bi-allelic pathogenic mutations in LPL, APOC2, GPIHBP1, APOA5 or LMF1 genes confirms the diagnosis. However, some cases of FCS caused by autoantibodies against LPL or GPIHBP1 proteins have also been reported. Furthermore, a clinical score for the diagnosis of FCS has been proposed but needs further validation. Available treatment options to lower triglycerides such as fibrates or omega-3 fatty acids are not efficacious in FCS patients. Currently, the cornerstone of treatment remains a lifelong very low-fat diet, which prevents the formation of chylomicrons. Finally, inhibitors of apo C-III and ANGPTL3 are in development and may eventually constitute additional treatment options for FCS patients.

Factors Associated With Opioid Use in Patients Hospitalized for Acute Pancreatitis.

Importance: Limited guidance exists regarding the optimal approach to management of pain in acute pancreatitis (AP). Objectives: To investigate sources of variability in opioid use for treatment of acute pain in patients hospitalized for AP and to explore a potential association of opioid prescribing patterns with length of stay. Design, Setting, and Participants: This retrospective cohort study included 4307 patients 18 years and older hospitalized for AP in a community-based integrated health care system, from January 1, 2008, to June 30, 2015. Analysis began in November 2017. Exposures: Opioid use was quantified by morphine equivalent dose (MED). Main Outcomes and Measures: Three analyses were performed: (1) factors associated with increased opioid administration during the initial 12 hours of hospitalization (baseline), (2) association of baseline opioid use with length of stay, and (3) frequency of opioid use 90 days after hospital discharge (persistent use). Results: The cohort included 4307 patients (median [interquartile range] age, 57.4 [44.0-70.2] years; 2241 women [52.0%]) with AP. At baseline, 3443 patients (79.9%) received opioids, and 388 patients (9.6%) had persistent opioid use after discharge. After adjusting for pain and other clinical factors, women received less MED than men (adjusted event ratio, 0.83; 95% CI, 0.79-0.86; P < .001). Hispanic and Asian patients received less MED than non-Hispanic white patients (adjusted event ratio, 0.85; 95% CI, 0.81-0.90; P < .001; and adjusted event ratio, 0.79; 95% CI, 0.72-0.86; P < .001, respectively). Alcohol-related AP etiology was associated with increased MED vs gallstone disorders (adjusted event ratio, 1.11; 95% CI, 1.05-1.18; P < .001). Two of 13 hospitals administered significantly less opioids compared with the others. Median (interquartile range) length of stay was independently associated with MED at baseline, with 3.0 (2.1-4.5) days among patients not receiving opioids vs 5.0 (3.2-8.7) days among patients in the highest quintile of MED (P < .001). Conclusions and Relevance: In addition to pain and disease severity, opioid use varied by etiology of AP, sex, race/ethnicity, and institution of treatment. Increased opioid use at baseline was associated with longer hospitalization. These findings suggest opportunities for improved approaches to pain control for patients with AP.

The Chylomicronemia Syndrome Is Most Often Multifactorial: A Narrative Review of Causes and Treatment.

The chylomicronemia syndrome occurs when triglyceride levels are severely elevated (usually >16.95 mmol/L [1500 mg/dL]) and is characterized by such clinical features as abdominal pain, acute pancreatitis, eruptive xanthomas, and lipemia retinalis. It may result from 1 of 3 conditions: the presence of secondary forms of hypertriglyceridemia concurrent with genetic causes of hypertriglyceridemia, termed multifactorial chylomicronemia syndrome (MFCS); a deficiency in the enzyme lipoprotein lipase and some associated proteins, termed familial chylomicronemia syndrome (FCS); or familial partial lipodystrophy. Most chylomicronemia syndrome cases are the result of MFCS; FCS is very rare. In all these conditions, triglyceride-rich lipoproteins accumulate because of impaired plasma clearance. This review describes the 3 major causes of the chylomicronemia syndrome; their consequences; and the approaches to treatment, which differ considerably by group.

Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier.

OBJECTIVE: Qingyi decoction (QYD) has beneficial effects in severe acute pancreatitis (SAP). We assessed the therapeutic effect and mechanisms of QYD in SAP. METHODS: A rat model of SAP was induced by pancreatic ductal injection of sodium taurocholate. QYD was administered intragastrically immediately postoperatively and once every 12 hours. Serum amylase, endotoxin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-lactate levels were measured at 12, 24, and 48 hours. Histological changes in the pancreas and ileum were analyzed. Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. RESULTS: Pancreatic tissue showed extracellular space expansion, inflammatory infiltration, vessels with necrotic walls, and hemorrhage. Ileal tissue showed hemorrhage, inflammatory infiltration, and ileal mucosa destruction. These histological features were dramatically improved by QYD. Increased serum levels of amylase, endotoxin, TNF-α, IL-6, and D-lactic acid were significantly decreased by QYD administration. Increased expression of NF-κB p65 and TLR4 and decreased expression of ZO-1 in the ileal mucosa were also restored to normal levels by QYD treatment. CONCLUSION: QYD alleviates SAP by reducing intestinal barrier dysfunction, inhibiting intestinal bacteria and endotoxin translocation, and preventing NF-κB activation.

Effect of Sheng-jiang powder on multiple-organ inflammatory injury in acute pancreatitis in rats fed a high-fat diet.

BACKGROUND: Obesity worsens inflammatory organ injury in acute pancreatitis (AP), but there is no effective preventive strategy. Sheng-jiang powder (SJP) has been shown to alleviate multiple-organ inflammatory injury in rats with high-fat diet-induced obesity. Hence, SJP is supposed to have an effect on multiple-organ inflammatory injury in AP in rats fed a high-fat diet. AIM: To explore how obesity may contribute to aggravating inflammatory organ injury in AP in rats and observe the effect of SJP on multiple-organ inflammatory injury in AP in rats fed a high-fat diet. METHODS: Rats were randomly assigned to a control group (CG), an obese group (OG), and an SJP treatment group (SG), with eight rats per group. The rats in the OG and SG were fed a high-fat diet. From the third week, the rats in the SG were given oral doses of SJP (5 g/kg of body weight). After 12 wk, AP was induced in the three groups. Serum amylase level, body weight, Lee's index, serum biochemistry parameters, and serum inflammatory cytokine and tissue cytokine levels were assessed, and the tissue histopathological scores were evaluated and compared. RESULTS: Compared with the CG, serum triglyceride, total cholesterol, interleukin-6, and interleukin-10 levels were significantly higher in the OG, and serum high-density lipoprotein cholesterol level was significantly lower in the OG. Moreover, enhanced oxidative damage was observed in the pancreas, heart, spleen, lung, intestine, liver, and kidney. Evidence of an imbalanced antioxidant defense system, especially in the pancreas, spleen, and intestine, was observed in the obese AP rats. Compared with the OG, serum high-density lipoprotein cholesterol, interleukin-10, and superoxide dismutase expression levels in the pancreas, spleen, and intestine were increased in the SG. Additionally, SJP intervention led to a decrease in the following parameters: body weight; Lee's index; serum triglyceride levels; serum total cholesterol levels; malondialdehyde expression levels in the pancreas, heart, spleen, lung, and liver; myeloperoxidase expression levels in the lung; and pathological scores in the liver. CONCLUSION: Obesity may aggravate the inflammatory reaction and pathological multiple-organ injury in AP rats, and SJP may alleviate multiple-organ inflammatory injury in AP in rats fed a high-fat diet.

Enhanced Neutrophil Extracellular Trap Formation in Acute Pancreatitis Contributes to Disease Severity and Is Reduced by Chloroquine.

Background: Neutrophil extracellular traps (NETs) are generated when activated neutrophils, driven by PAD4, release their DNA, histones, HMGB1, and other intracellular granule components. NETs play a role in acute pancreatitis, worsening pancreatic inflammation, and promoting pancreatic duct obstruction. The autophagy inhibitor chloroquine (CQ) inhibits NET formation; therefore, we investigated the impact of CQ mediated NET inhibition in murine models of pancreatitis and human correlative studies. Methods: L-arginine and choline deficient ethionine supplemented (CDE) diet models of acute pancreatitis were studied in wild type and PAD4-/- mice, incapable of forming NETs. Isolated neutrophils were stimulated to induce NET formation and visualized with fluorescence microscopy. CQ treatment (0.5 mg/ml PO) was initiated after induction of pancreatitis. Biomarkers of NET formation, including cell-free DNA, citrullinated histone H3 (CitH3), and MPO-DNA conjugates were measured in murine serum and correlative human patient serum samples. Results: We first confirmed the role of NETs in the pathophysiology of acute pancreatitis by demonstrating that PAD4-/- mice had decreased pancreatitis severity and improved survival compared to wild-type controls. Furthermore, patients with severe acute pancreatitis had elevated levels of cell-free DNA and MPO-DNA conjugates, consistent with NET formation. Neutrophils from mice with pancreatitis were more prone to NET formation and CQ decreased this propensity to form NETs. CQ significantly reduced serum cell-free DNA and citrullinated histone H3 in murine models of pancreatitis, increasing survival in both models. Conclusions: Inhibition of NETs with CQ decreases the severity of acute pancreatitis and improves survival. Translating these findings into clinical trials of acute pancreatitis is warranted.

GPR120 protects lipotoxicity-induced pancreatic ß-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation.

G-protein coupled receptor 120 (GPR120) has been shown to act as an omega-3 unsaturated fatty acid sensor and is involved in insulin secretion. However, the underlying mechanism in pancreatic ß cells remains unclear. To explore the potential link between GPR120 and ß-cell function, its agonists docosahexaenoic acid (DHA) and GSK137647A were used in palmitic acid (PA)-induced pancreatic ß-cell dysfunction, coupled with GPR120 knockdown (KD) in MIN6 cells and GPR120 knockout (KO) mice to identify the underlying signaling pathways. In vitro and ex vivo treatments of MIN6 cells and islets isolated from wild-type (WT) mice with DHA and GSK137647A restored pancreatic duodenal homeobox-1 (PDX1) expression levels and ß-cell function via inhibiting PA-induced elevation of proinflammatory chemokines and activation of nuclear factor κB, c-Jun amino (N)-terminal kinases1/2 and p38MAPK signaling pathways. On the contrary, these GPR120 agonism-mediated protective effects were abolished in GPR120 KD cells and islets isolated from GPR120 KO mice. Furthermore, GPR120 KO mice displayed glucose intolerance and insulin resistance relative to WT littermates, and ß-cell functional related genes were decreased while inflammation was exacerbated in islets with increased macrophages in pancreas from GPR120 KO mice. DHA and GSK137647A supplementation ameliorated glucose tolerance and insulin sensitivity, as well as improved Pdx1 expression and islet inflammation in diet-induced obese WT mice, but not in GPR120 KO mice. These findings indicate that GPR120 activation is protective against lipotoxicity-induced pancreatic ß-cell dysfunction, via the mediation of PDX1 expression and inhibition of islet inflammation, and that GPR120 activation may serve as a preventative and therapeutic target for obesity and diabetes.

Influence of Ambulatory Triglyceride Levels on Risk of Recurrence in Patients with Hypertriglyceridemic Pancreatitis.

BACKGROUND AND AIMS: To evaluate impact of ambulatory triglyceride levels on risk of recurrent pancreatitis in patients with hypertriglyceridemic pancreatitis. METHODS: We conducted a longitudinal retrospective cohort study of patients with serum triglyceride level ≥ 500 mg/dL during index hospitalization for acute pancreatitis within a regional integrated healthcare system between 2006 and 2013 (follow-up through 2015). Cases were identified based on combination of diagnosis codes and serum amylase/lipase. We used multivariable robust Poisson regression to determine independent effect of baseline (first outpatient) triglyceride measurement on risk of recurrent pancreatitis. Ambulatory triglyceride levels were categorized as normal (0-200 mg/dL), moderately elevated (201-500 mg/dL), and highly elevated (> 500 mg/dL). We further assessed factors related to likelihood of normalization of serum triglycerides (< 200 mg/dL) in the outpatient setting. RESULTS: One hundred and fifty-one patients met study inclusion criteria with median follow-up of 3 years. Overall, 45 (29.8%) patients experienced at least 1 recurrent attack with 25 (16.6%) experiencing multiple episodes. In multivariable analysis, patients that continued to have moderately elevated ((adjusted rate ratio RR 5.47 (95% CL 1.80, 16.65)) as well as highly elevated (RR 8.45 (2.55, 27.96)) triglycerides were at increased risk of disease recurrence compared to patients that achieved normalization. Patients with triglyceride measurement performed within 30 days from discharge were more likely to achieve normalization, 40 versus 26%, p = 0.03. CONCLUSIONS: For patients with hypertriglyceridemic pancreatitis, even modest elevation in subsequent triglyceride levels was associated with increased risk of recurrence. Future efforts should focus on ensuring timely care in the outpatient setting with a goal of normalizing triglycerides.

Treatment of Pegylated Asparaginase-Induced Hypertriglyceridemia with Continuous Intravenous Infusion of Insulin and Heparin: A Case Report.

BACKGROUND: Pegylated asparaginase may induce prolonged hypertriglyceridemia. To date, there is no standard management of this complication. Here, we present a case report of pegylated asparaginase-induced hypertriglyceridemia and hepatotoxicity successfully treated with continuous intravenous infusion of insulin and heparin. CASE PRESENTATION: A 51-year-old male patient with lymphoid blast crisis of chronic myelogenous leukemia was treated with pegylated asparaginase. The patient developed severe hypertriglyceridemia. Supportive therapy with low-fat diet, fibric acids, and omega-3 fatty acids was not successful, and later, the patient developed high-grade hepatotoxicity. Like hypertriglyceridemia-induced pancreatitis, continuous intravenous infusion of insulin and heparin was initiated. The level of triglyceride and cholesterol decreased rapidly within 4 days. CONCLUSION: In case of severe pegylated asparaginase-induced hypertriglyceridemia, continuous intravenous infusion of insulin and heparin can reduce rapidly and safely the triglyceride level. Controlled trials are needed to address this important issue.