Prognostic significance of organ failure and infected pancreatic necrosis in acute pancreatitis: An updated systematic review and meta-analysis.

OBJECTIVES: In patients with acute pancreatitis (AP), minimally invasive treatment and the step-up approach have been widely used to deal with infected pancreatic necrosis (IPN) in the last decade. It is unclear whether IPN has become a less important determinant of mortality relative to organ failure (OF). We aimed to statistically aggregate recent evidence from published studies to determine the relative importance of IPN and OF as determinants of mortality in patients with AP (PROSPERO: CRD42020176989). METHODS: Relevant studies were sourced from MEDLINE and EMBASE databases. Relative risk (RR) or weighted mean difference (WMD) was analyzed as outcomes. A two-sided P value of less than 0.05 was regarded as statistical significance. RESULTS: Forty-three studies comprising 11 601 patients with AP were included. The mortality was 28% for OF patients and 24% for those with IPN. Patients with OF without IPN had a significantly higher risk of mortality compared to those with IPN but without OF (RR 3.72, P < 0.0001). However, patients with both OF and IPN faced the highest risk of mortality. Additionally, IPN increased length of stay in hospital for OF patients (WMD 28.75, P = 0.032). CONCLUSION: Though IPN remains a significant concern, which leads to increased morbidity and longer hospital stay, it is a less critical mortality determinant compared to OF in AP.

Intraluminal oxygen mitigates acute mesenteric ischaemia: a systematic review of methods and outcomes in animal studies.

BACKGROUND: Acute Mesenteric Ischaemic (AMI) is a rare condition with significant morbidity and mortality. Many causes of AMI exist, which usually begin with mucosal injury. Onset is insiduous and there is frequent diagnostic delay. Current treatments can only control established injury and prevent propagation, hence new interventions are needed. The prevention and treatment of AMI by intraluminal delivery of oxygen has yet to be investigated in the clinical setting. This article aims to systemically review experimental studies investigating this novel therapy. METHODS: Following the PRISMA guidelines, searches of PubMed and Ovid MEDLINE databases were performed up to June 2022. Two independent investigators extracted the data. RESULTS: There were 20 experimental studies, 16 of which used an occlusive ischaemia reperfusion model. Six different formulations were used to deliver intraluminal oxygen, with perflurocarbon being the most common. Studies consistently showed local and systemic benefits. Intraluminal oxygen therapy improved histological severity of mucosal injury in all studies when oxygen was delivered during the ischaemia phase, but could cause harm if given during the reperfusion phase. Improvement was also demonstrated in endpoints assessing intestinal function, biomarkers of intestinal damage, measures of systemic physiological derangement and mortality. CONCLUSION: Intraluminal oxygenation appears to be an effective treatment for AMI. There remain significant questions regarding optimal timing and delivery formulation before clinical translation of this treatment strategy.

Optimising fluid requirements after initial resuscitation: A pilot study evaluating mini-fluid challenge and passive leg raising test in patients with predicted severe acute pancreatitis.

BACKGROUND: The goals and approaches to fluid therapy vary through different stages of resuscitation. This pilot study was designed to test the safety and feasibility of a fluid therapy protocol for the second or optimisation stage of resuscitation in patients with predicted severe acute pancreatitis (SAP). METHODS: Spontaneously breathing patients with predicted SAP were admitted after initial resuscitation and studied over a 24-h period in a tertiary hospital ward. Objective clinical assessment (OCA; heart rate, mean arterial pressure, urine output, and haematocrit) was done at 0, 4, 8, 12, 18-20, and 24 h. All patients had mini-fluid challenge (MFC; 250 ml intravenous normal saline within 10 min) at 0 h and repeated at 4 and 8 h if OCA score ≥2. Patients who were fluid responsive (>10% change in stroke volume after MFC) received 5-10 ml/kg/h, otherwise 1-3 ml/kg/h until the next time point. Passive leg raising test (PLRT) was done at each time point and compared with OCA for assessing volume status and predicting fluid responsiveness. RESULTS: This fluid therapy protocol based on OCA, MFC, and PLRT and designed for the second stage of resuscitation was safe and feasible in spontaneously breathing predicted SAP patients. The PLRT was superior to OCA (at 0 and 8 h) for predicting fluid responsiveness and guiding fluid therapy. CONCLUSIONS: This pilot study found that a protocol for intravenous fluid therapy specifically for the second stage of resuscitation in patients with predicted SAP was safe, feasible, and warrants further investigation.

The Impact of Pancreatic Enzyme Replacement Therapy on Patients With Advanced Pancreatic Adenocarcinoma: A Systematic Review and Narrative Synthesis.

ABSTRACT: Advanced pancreatic cancer has a poor prognosis globally. Patients often develop pancreatic exocrine insufficiency leading to malabsorption. This systematic literature review explores the impact of pancreatic enzyme replacement therapy (PERT) on patients with advanced pancreatic cancer. Data sources include MEDLINE, CINAHL, Embase, Cochrane (CENTRAL), PsychINFO, and Joanna Briggs Institute databases from inception to January 14, 2022, with reference list checking on Google Scholar. Narrative synthesis was used as the eligible studies were likely to be heterogeneous and hard to compare. This synthesis approach uses 4 steps: theory development, preliminary synthesis, exploration of relationships, and assessment of the robustness of the synthesis. Four themes arose from analyzing the study outcomes including PERT education, efficacy of PERT, the patient experience, and lack of awareness regarding enzyme replacement. The included studies did not use validated tools or standardized measurements, which made it difficult to compare or draw conclusions. Pancreatic enzyme replacement therapy shows the potential to improve symptoms, nutrition, weight loss, and survival, but high-quality studies with standardized outcomes have not been completed. Patient and health professional education is required because there seems to be a general lack of awareness about the use of PERT in pancreatic cancer.Systematic Review Registration: PROSPERO 2020 CRD42020195986.

The Effects of NLRP3 Inflammasome Inhibition in Experimental Acute Pancreatitis: A Systematic Review and Meta-Analysis.

ABSTRACT: Acute pancreatitis (AP) is an inflammatory disease, and NLRP3 inflammasome activation is involved in the pathogenesis of AP. Previous research showed that inhibition of NLRP3 inflammasome may exert protective effects on animal models of AP and reduces disease severity. The aim of this systematic review and meta-analysis is to evaluate the effects of drug treatment of NLRP3 inflammasome on the outcomes of experimental AP. PubMed, Embase, Medline, and Web of Science databases were searched for relevant articles without language restrictions. The main outcomes for this study included local pancreatic injury, the incidence of systemic inflammatory responses, and the incidence of organ failure. Twenty-eight animal studies including 556 animals with AP were included in the meta-analysis. Compared with controls, inhibition of NLRP3 inflammasome significantly reduced the pancreatic histopathological scores, serum amylase, and lipase levels. In addition, inhibition of NLRP3 inflammasome reduced the levels of circulating inflammatory cytokines, as well as mitigating severity of AP-associated acute lung injury and acute intestinal injury. To conclude, inhibition of NLRP3 inflammasome has protective effects on AP by mitigating organ injury and systemic inflammation in animal studies, indicating that NLRP3 inflammasome holds promise as a target for specific AP therapy.

Patient volume and clinical outcome after pancreatic cancer resection: A contemporary systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer remains a highly fatal disease with a 5-year overall survival of less than 10%. In seeking to improve clinical outcomes, there is ongoing debate about the weight that should be given to patient volume in centralization models. The aim of this systematic review is to examine the relationship between patient volume and clinical outcome after pancreatic resection for cancer in the contemporary literature. METHODS: The Google Scholar, PubMed, and Cochrane Library databases were systematically searched from February 2015 until June 2021 for articles reporting patient volume and outcomes after pancreatic cancer resection. RESULTS: There were 46 eligible studies over a 6-year period comprising 526,344 patients. The median defined annual patient volume thresholds varied: low-volume 0 (range 0-9), medium-volume 9 (range 3-29), high-volume 19 (range 9-97), and very-high-volume 28 (range 17-60) patients. The latter 2 were associated with a significantly lower 30-day mortality (P < .001), 90-day mortality (P < .001), overall postoperative morbidity (P = .005), failure to rescue rate (P = .006), and R0 resection rate (P = .008) compared with very-low/low-volume hospitals. Centralization was associated with lower 30-day mortality in 3 out of 5 studies, while postoperative morbidity was similar in 4 out of 4 studies. Median survival was longer in patients traveling greater distance for pancreatic resection in 2 out of 3 studies. Median and 5-year survival did not differ between urban and rural settings. CONCLUSION: The contemporary literature confirms a strong relationship between patient volume and clinical outcome for pancreatic cancer resection despite expected bias toward more complex surgery in high-volume centers. These outcomes include lower mortality, morbidity, failure-to-rescue, and positive resection margin rates.

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis.

BACKGROUND/AIMS: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients. METHODS: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared. RESULTS: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone. CONCLUSIONS: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes.

The Challenges and Effects of Ascorbic Acid Treatment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Preclinical and Clinical Studies.

Background: Oxidative stress has been implicated in the pathogenesis of acute pancreatitis (AP), and ascorbic acid (AA), as an important endogenous antioxidant substance, has been shown to reduce AP severity in preclinical studies. However, the effects of AA supplementation in clinical settings remain controversial. Methods: PubMed, EMBASE, MEDLINE, and SCOPUS databases were searched, and both preclinical and clinical studies were included. For clinical trials, the primary outcome was incidence of organ failure, and for preclinical studies, the primary outcome was histopathological scores of pancreatic injuries. Results: Meta-analysis of clinical trials showed that compared with controls, AA administration did not reduce the incidence of organ failure or mortality during hospitalization but was associated with significantly reduced length of hospital stay. Meta-analysis of preclinical studies showed that AA supplementation reduced pancreatic injury, demonstrated as decreased histological scores and serum amylase, lipase levels. Conclusion: AA administration has no effect on survival or organ failure in patients with AP but may reduce the length of hospital stay. However, the evidence to date remains sparse, scattered, and of suboptimal quality, making it difficult to draw any firm conclusion on the clinical benefits of AA in AP.

Forecasting surgical costs: Towards informed financial consent and financial risk reduction.

BACKGROUND: Health care expenditure is increasing around the world and surgery is a major cause of financial hardship to patients and their families. Using pancreatoduodenectomy (PD), one of the most complex, morbid and costly operation as an example, this study aimed to identify the cost drivers of surgery, estimate relative contribution of these drivers, and derive and validate a cohort-specific cost forecasting tool. METHODS: Data on the costs of 1406 patients undergoing PD in three tertiary hospitals in India, Italy and the United States were analysed. Cost drivers were identified and cost models developed using a 4-stage process. RESULTS: There was a significant difference in overall cost of PD between the 3 cohorts. The cost drivers common to the 3 cohorts included duration of hospital stay and the outcome of death (Clavien-Dindo 5). Significant cohort-specific cost drivers included co-morbidities, operating theatre utilisation times and operative blood loss, development of pancreatectomy-specific complications (POPF, DGE, PPH), and need for interventional radiology to manage complications. Based on this, a cost forecasting tool was developed. CONCLUSIONS: Drivers of costs for a surgical procedure (e.g. PD) are different between hospitals. Developing cost models/nomograms to predict the expected cost of surgery and perioperative care will not be applicable between hospitals. However, the approach could be used to develop context-specific data that will provide patients (at the time of the informed financial consent) and funding agencies with a more realistic cost estimate for a given operation. The developed cost forecasting tool warrants future validation.

Associations between ketone bodies and fasting plasma glucose in individuals with post-pancreatitis prediabetes.

Context: Levels of ketone bodies are altered in both acute pancreatitis and type 1 and type 2 diabetes. However, the role of ketone bodies in the pathogenesis of abnormal glucose metabolism after pancreatitis is largely unknown.Objective: To investigate the associations between ketone bodies and glucose homeostasis in individuals with post-pancreatitis prediabetes (PPP) versus normoglycaemia after pancreatitis (NAP).Methods: Fasting blood samples were analysed for acetoacetate, ß-hydroxybutyrate, and markers of glucose metabolism at a median of 26 months after acute pancreatitis. A series of linear regression analyses were conducted adjusting for patient- and pancreatitis-related characteristics.Results: The study included 27 individuals with PPP and 52 with NAP. ß-hydroxybutyrate was significantly associated with fasting plasma glucose (p = .002) and explained 26.2% of its variance in PPP, but not in NAP (p = .814; 0%). Acetoacetate was not significantly associated with fasting plasma glucose in both PPP (p = .681) or NAP (p = .661).Conclusions: An inverse association between ß-hydroxybutyrate and fasting plasma glucose characterises PPP and this may have translational implications.

Pancreatic Hormone Responses to Mixed Meal Test in New-onset Prediabetes/Diabetes After Non-necrotizing Acute Pancreatitis.

AIM: To investigate the pancreatic hormone responses to mixed meal test, in particular changes in insulin secretion, insulin sensitivity, and their interrelationship, in individuals with new-onset prediabetes or diabetes after non-necrotizing acute pancreatitis (NODAP) compared with healthy controls. METHODS: Twenty-nine individuals with NODAP and 29 age-and sex-matched healthy controls were recruited. All participants (after fasting for at least 8 h) were given 12 oz. of BOOST drink and blood samples were collected before and after stimulation to measure insulin, C-peptide, glucagon, and pancreatic polypeptide. Indices of insulin sensitivity (HOMA-IS, 1/fasting insulin, Raynaud, and Matsuda) and insulin secretion (HOMA-ß, Stumvoll, insulinogenic index 30' and 60') were calculated. Repeated measures analyses were conducted in the unadjusted and adjusted models. RESULTS: Insulin and C-peptide levels were significantly higher in individuals with NODAP compared with controls during mixed meal test in both the unadjusted (P=0.001 for both) and adjusted (P=0.004 and P=0.006, respectively) models. HOMA-IS (P=0.005), 1/fasting insulin (P=0.018), Raynaud index (P=0.018), and Matsuda index (P=0.021) were significantly lower in individuals with NODAP, whereas HOMA-ß (P=0.028) and Stumvoll index (P=0.013) were significantly higher. Glucagon and pancreatic polypeptide levels did not differ significantly between NODAP and controls during mixed meal test in both the unadjusted (P=0.345 and P=0.206, respectively) and adjusted (P=0.359 and P=0.158, respectively) models. CONCLUSIONS: Decreased insulin sensitivity, ß-cell compensation, and no significant change in postprandial levels of glucagon and pancreatic polypeptide characterize NODAP. The above findings may help develop an evidence-based protocol with a view to optimize control of glucose homeostasis in NODAP.

Glucose Counter-regulation After Acute Pancreatitis.

OBJECTIVES: Persistent hyperglycemia is a common sequela of acute pancreatitis (AP). The role of counter-regulatory hormones in maintaining glucose homeostasis has been largely studied during the course of AP, but not after clinical resolution of the disease. The objectives of this study were to investigate the associations between circulating levels of glucagon, cortisol, and human growth hormone and glucose homeostasis after AP as well as their associations with a comprehensive panel of pancreatic hormones, gut peptides, and proinflammatory cytokines. METHODS: Participants with no history of pre-existing prediabetes or diabetes were categorized into hyperglycemia and normoglycemia after AP groups. Binary logistic regression and linear regression analyses were conducted. RESULTS: Eighty-three individuals were included, of whom 19 had hyperglycemia. Glucagon, cortisol, and human growth hormone did not differ significantly between the groups. Glucagon explained up to 86% of the variance in glucagon-like peptide 1, whereas cortisol explained up to 89% of the variance in interleukin 6 in hyperglycemia after AP. CONCLUSIONS: Counter-regulatory hormones do not appear to play a direct role in the mechanisms underlying hyperglycemia after AP. However, significant associations between glucagon and glucagon-like peptide 1, as well as between cortisol and interleukin 6, suggest that that these hormones may be involved indirectly in the pathophysiology of hyperglycemia after AP.

Associations between gastrointestinal humoral factors and pancreatic proteolytic enzymes in alcohol-related versus non-alcohol-related pancreatitis.

BACKGROUND: Alcohol-related pancreatitis is common and the gastrointestinal tract plays an important role in the regulation of pancreatic exocrine function. While the relationship between pancreatic proteolytic enzymes and insulin (as well as other pancreatic hormones) has been investigated in detail, little is known about the relationship between pancreatic proteolytic enzymes and gastrointestinal humoral factors. The aim of this study was to study the associations between trypsin, chymotrypsin, and a panel of gastrointestinal humoral factors in patients after an episode of alcohol-related versus non-alcohol-related pancreatitis. METHODS: Fasting venous blood samples were analyzed for trypsin, chymotrypsin, cholecystokinin, gastrin, ghrelin, gastrin-related peptide, neuropeptide Y, peptide YY, secretin, and vasoactive intestinal peptide. Linear regression analysis was used in three statistical models, adjusting for covariates (age, sex, ethnicity, smoking, exercise, body mass index, dysglycemia, recurrence of pancreatitis, duration of pancreatitis, and severity of pancreatitis). RESULTS: The study included 21 patients with alcohol-related pancreatitis and 72 with non-alcohol-related pancreatitis. Gastrin, cholecystokinin, and vasoactive intestinal peptide were significantly associated with chymotrypsin in all three statistical models and resulted in a 1.06, 1.98, and 2.74 times higher chymotrypsin level in alcohol-related pancreatitis, respectively. Ghrelin was significantly associated with trypsin in all three statistical models and resulted in a 2.64 times higher trypsin level in alcohol-related pancreatitis. Other associations did not demonstrate a consistent significant pattern. CONCLUSION: In alcohol-related pancreatitis, several gut-related peptides are significantly associated with pancreatic exocrine function. Further studies to investigate the effect of alcohol on the interaction between cholecystokinin (as well as gastrin, ghrelin, and vasoactive intestinal peptide) and pancreatic exocrine function are warranted.

Comprehensive analysis of body composition and insulin traits associated with intra-pancreatic fat deposition in healthy individuals and people with new-onset prediabetes/diabetes after acute pancreatitis.

Current knowledge of biomarkers of intra-pancreatic fat deposition (IFD) is limited. We aimed to analyse comprehensively body composition and insulin traits as biomarkers of IFD in healthy normoglycaemic individuals as well as in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP). A total of 29 healthy individuals and 34 individuals with NODAP took part in this cross-sectional study. The studied biomarkers belonged to the following domains: body composition (anthropometric and MRI-derived variables); indices of insulin secretion; indices of insulin sensitivity; incretins and related peptides; and pancreatitis-related factors. All MRI-derived variables (including IFD) were measured using ImageJ software. Univariate and step-wise regression analyses were conducted to determine variables that best explained variance in IFD. Visceral fat volume and oxyntomodulin were the best biomarkers of IFD in normoglycaemic healthy individuals, contributing to 64% variance. The Raynaud index was the best biomarker of IFD in individuals with NODAP, contributing to 20% variance. Longitudinal studies are warranted to investigate the cause and effect relationship between oxyntomodulin and IFD in healthy individuals, as well as insulin sensitivity and IFD in individuals with NODAP.

Frequency and risk factors for liver disease following pancreatitis: A population-based cohort study.

BACKGROUND & AIMS: Both liver disease (LD) and pancreatitis pose substantial burdens. There have been no general population-based studies on frequency of LD after an episode of pancreatitis. The aim of this study was to investigate the occurrence of LD in a population-based cohort of patients following pancreatitis. METHODS: Nationwide data on the general population of nearly 3 million people were used to identify retrospectively diagnoses of acute pancreatitis, chronic pancreatitis (CP), LD and cirrhosis from 1998 to 2016. Acute pancreatitis was categorised as first (FAP) or recurrent (RAP) episode. Number of pancreatitis recurrences prior to LD diagnosis was determined. RESULTS: A total of 20,931 pancreatitis patients were included, of which 874 developed LD following pancreatitis. The incidence of LD in FAP was 115.59 (95% confidence interval 102.19-128.98), in RAP - 217.63 (95% confidence interval 173.31-261.94), and in CP - 539.43 (95% confidence interval 494.72-584.13) patients per 100,000 pancreatitis patients per year. There was a significant increase in the probability of LD with increasing number of pancreatitis recurrences and, for the same number of pancreatitis recurrences, LD was significantly more frequent after CP than RAP (hazard ratio 1.666 (95% confidence interval 1.322-2.098; p = <0.001)). CONCLUSIONS: The frequency of LD increases from FAP to RAP to CP. While number of pancreatitis recurrences is a significant risk factor for development of LD, there is a higher probability of LD following CP than RAP even for the same number of recurrences. Interventions preventing pancreatitis and its progression may lower the burden of LD.

Gut Hormone Responses to Mixed Meal Test in New-Onset Prediabetes/Diabetes After Acute Pancreatitis.

The study was aimed to investigate gut hormone responses to mixed meal test in individuals with new-onset prediabetes or diabetes after acute pancreatitis (cases) compared with healthy controls, and the effect of body fat parameters. A total of 29 cases and 29 age- and sex-matched healthy controls were recruited. All participants were given standard mixed meal drink and blood samples were collected to measure dipeptidyl peptidase IV, gastric inhibitory peptide, glucagon like peptide-1, insulin, oxyntomodulin, and peptide YY. Body fat parameters were measured using magnetic resonance imaging. Repeated measures and linear regression analyses were conducted in unadjusted and adjusted models. Gastric inhibitory peptide levels were significantly higher whereas oxyntomodulin levels were significantly lower in cases compared with controls in both the unadjusted (p<0.001 and p<0.001, respectively) and adjusted (p<0.001 and p<0.001, respectively) models. In cases, liver fat % contributed up to 13.4% (vs. 2.9% in controls) to variance in circulating levels of gastric inhibitory peptide whereas body mass index - up to 20.8% (vs. 9.9% in controls) in circulating levels of oxyntomodulin. New-onset prediabetes/diabetes after acute pancreatitis is characterised by increased levels of gastric inhibitory peptide and decreased levels of oxyntomodulin. Further, liver fat % and body mass index appear to be the body fat parameters that contribute most significantly to gastric inhibitory peptide and oxyntomodulin levels, respectively.

Profile of Gut Hormones, Pancreatic Hormones and Pro-inflammatory Cytokines in New Zealand Maori.

BACKGROUND: Maori, indigenous people of New Zealand, have at least two times higher prevalence of obesity and diabetes in comparison with the general population in the country. Gut and pancreatic hormone profile differences as well as pro-inflammatory milieu may contribute to this disparity. The aim was to investigate the differences in gut hormones, pancreatic hormones and pro-inflammatory cytokines between Maori and non-Maori individuals. METHODS: This was a cross-sectional study. Fasting blood samples were collected to measure cholecystokinin, ghrelin, gastric inhibitory peptide, glicentin, glucagon-like peptide-1 and -2, oxyntomodulin, secretin, amylin, C-peptide, glucagon, insulin, pancreatic polypeptide, somatostatin, interleukin-6, monocyte chemoattractant protein-1 and tumour necrosis factor-α. Binary logistic regression analysis was conducted in one unadjusted and four adjusted statistical models adjusting for patient-, metabolic- and pancreatitis-related factors. RESULTS: A total of 8 Maori and 85 non-Maori individuals were included. Circulating levels of ghrelin, pancreatic polypeptide and interleukin-6 levels were significantly higher in Maori (P = 0.005, P = 0.003 and P = 0.011, respectively) in both unadjusted and all the four adjusted analyses. Other signaling molecules did not show consistently significant associations with ethnicity. CONCLUSION: Profile of gut hormones, pancreatic hormones and pro-inflammatory cytokines appears to differ between Maori and non-Maori individuals, independent of obesity, diabetes and other covariates. This may go some way to explain the increased propensity to obesity and diabetes in the Maori population.

Abdominal obesity and insulin resistance after an episode of acute pancreatitis.

BACKGROUND: Emerging evidence indicates that individuals after an episode of acute pancreatitis (AP) are at an increased risk of developing metabolic derangements. While the link between general obesity and insulin resistance (IR) is well established, only a few studies have investigated the association between abdominal obesity and IR. The aim of this study was to investigate the associations between abdominal obesity and several indices of IR in individuals after an episode of AP. METHODS: Patients were eligible for this cross-sectional study if they were previously admitted with a primary diagnosis of AP based on the recent international guidelines. Fasting venous bloods were collected to measure glucose, insulin, free fatty acids, glycerol, adiponectin (AD), omentin (OM), and vaspin (VAS). The IR indices - HOMA-IR, Adipo-IR, insulin*glycerol (IG) index, HOMA-AD, HOMA-OM, and HOMA-VAS were calculated. Modified Poisson regression was conducted, with statistical model adjusting for patient-, metabolic-, and pancreatitis-related risk factors. Areas under ROC curve were calculated and Bland-Altman plots were created. RESULTS: Of the 92 individuals recruited, 41 had abdominal obesity. HOMA-IR, IG index, HOMA-OM, and HOMA-VAS were significantly associated with abdominal obesity, both in unadjusted and adjusted models. Area under ROC curves for HOMA-IR, IG index, HOMA-OM, and HOMA-VAS were 0.698, 0.695, 0.756, and 0.735, respectively. There was a good agreement between observed HOMA-IR values and values obtained from HOMA-OM (P = 0.733) and HOMA-VAS (P = 0.595). CONCLUSION: Individuals with abdominal obesity after AP have a significantly higher IR, independent of diabetes and other covariates. Visceral adipose tissue specific adipokines, omentin and vaspin, hold promise for future clinical investigation of tissue-specific IR.

Interplay between innate immunity and iron metabolism after acute pancreatitis.

Emerging evidence shows that chronic low-grade inflammation and changes in markers of innate immunity are implicated in a range of metabolic abnormalities following an episode of acute pancreatitis. Also, deranged iron metabolism has been linked to type 2 diabetes mellitus, gestational diabetes, and new-onset diabetes after pancreatitis - the conditions characterized by high haemoglobin glycation index (HGI). This study aimed to investigate the associations between markers of innate immunity and iron metabolism in individuals after acute pancreatitis. Fasting blood samples were collected to analyse lipopolysaccharide binding protein (LBP), interleukin (IL)-6, tumor necrosis factor-α, hepcidin, ferritin, soluble transferrin receptor, HbA1c, and glucose. Participants were categorized into two groups: low HGI and high HGI. Linear regression analyses were conducted, and potential confounders (age, sex, ethnicity, body mass index, diabetes mellitus status, smoking status, aetiology of pancreatitis, duration, recurrence, and severity of pancreatitis) were adjusted for in 5 statistical models. A total of 93 patients following an episode of acute pancreatitis were included, of who 40 (43%) had high HGI. In the overall cohort, LBP was significantly associated with hepcidin and ferritin, and IL-6 was significantly associated with hepcidin, consistently in all the models. Further, LBP contributed to 7.7% and 9.5% of variance in hepcidin and ferritin levels, respectively, whereas IL-6 contributed to 5.3% of hepcidin variance. Upon subgroup analysis, the observed LBP associations were maintained in the high HGI subgroup only and the IL-6 association in the low HGI subgroup only. No consistently significant associations were found between any of the other markers. The interplay between LBP, IL-6, hepcidin, and ferritin characterizes metabolic derangements after acute pancreatitis and may play a role in the pathogenesis of new-onset diabetes after pancreatitis.

Pro-inflammatory cytokine-induced lipolysis after an episode of acute pancreatitis.

CONTEXT: Pro-inflammatory cytokine-stimulated lipolysis is one of the mechanisms underlying the pathogenesis of type 2 diabetes. However, whether it plays a role in the pathogenesis of post-pancreatitis diabetes mellitus (PPDM) remains unknown. OBJECTIVE: To investigate the associations between markers of lipid metabolism and pro-inflammatory cytokines in individuals after acute pancreatitis (AP) in general, and in individuals with abnormal glucose metabolism (AGM) following AP in particular. METHODS: Fasting blood samples were collected to measure markers of lipid metabolism (apolipoprotein-B, cholesterol, free fatty acids (FFA), glycerol, high and low-density lipoproteins, triglycerides) and cytokines (interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and tumour necrosis factor (TNF) α). Linear regression analysis was conducted. Four statistical models were used to adjust for patient- and pancreatitis-related characteristics. RESULTS: A total of 83 patients were recruited. IL-6 was significantly associated with glycerol in all models (p < .05), with glycerol levels increasing by 106% in individuals with AGM after AP (p <.05) compared to a 30.3% increase in individuals with normal glucose metabolism (NGM) (p >.05). TNFα was significantly associated with FFA (p = .015) in individuals with AGM after AP in the most adjusted model, with FFA levels increasing by 314% in these individuals compared to a 162% decrease in individuals with NGM after AP (p >.05). CONCLUSIONS: Lipolysis appears to be an important pathogenetic mechanism in glucose derangements after diseases of the exocrine pancreas. IL-6 and TNFα are the driving forces behind lipolysis in individuals with AGM after AP. Modulation of lipolysis may be a promising therapeutic modality.