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.

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.

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.

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 cytokines after an episode of acute pancreatitis: associations with fasting gut hormone profile.

INTRODUCTION: Pro-inflammatory cytokines, such as interleukin (IL)-6, tumour necrosis factor (TNF)α, and monocyte chemoattractant protein (MCP)-1, are often elevated in individuals after acute pancreatitis but what determines their levels is poorly understood. Gut hormones have emerged as possible modulators of inflammatory response. The aim was to investigate the associations between pro-inflammatory cytokines and a comprehensive panel of gut hormones after an episode of acute pancreatitis. MATERIALS AND METHODS: Fasting blood samples were collected to measure cytokines (IL-6, TNFα, and MCP-1) and gut hormones (cholecystokinin, gastric inhibitory peptide (GIP), ghrelin, glicentin, glucagon-like peptide-1, oxyntomodulin, peptide YY, secretin, and vasoactive intestinal peptide). A series of linear regression analyses was conducted and four statistical models were used to adjust for patient- and pancreatitis-related covariates. RESULTS: A total of 83 individuals were recruited. GIP and peptide YY were significantly (p < 0.001) associated with IL-6, TNFα, MCP-1, consistently in all the four models. Every 1 ng/mL change in GIP resulted in a 16.2, 3.2, and 50.8% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. Every 1 ng/mL change in peptide YY resulted in a 7.0, 2.4, and 32.1% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. GIP independently contributed 29.0-36.5% and peptide YY - 17.4-48.9% to circulating levels of the studied pro-inflammatory cytokines. The other seven studied gut hormones did not show consistently significant associations with pro-inflammatory cytokines. CONCLUSIONS: GIP and peptide YY appear to be involved in perpetuation of subclinical inflammation following an episode of acute pancreatitis, which is known to play an important role in the pathogenesis of blood glucose derangements. These findings advance the understanding of mechanisms underlying diabetes of the exocrine pancreas and have translational implications.

Cross-talk between innate cytokines and the pancreatic polypeptide family in acute pancreatitis.

BACKGROUND AND AIM: Low-grade inflammation persists in patients with acute pancreatitis (AP) after hospital discharge, and is linked to metabolic disorders. Neuropeptide Y (NPY) is well recognized as an important mediator of inflammation in these patients but the role of the other two structurally similar peptides, pancreatic polypeptide (PP) and peptide YY (PYY), in inflammation has been sparsely investigated. The aim was to investigate the association between PYY, PP, NPY and circulating levels of innate cytokines in patients after AP. METHODS: Fasting blood samples were collected to measure PYY (ng/mL), PP (ng/mL), NPY (pg/mL), interleukin-6 (IL-6) (ng/mL), monocyte chemoattractant protein (MCP) 1 (ng/mL), and tumour necrosis factor (TNF) α (ng/mL). Modified Poisson regression analysis and linear regression analyses were conducted. Age, sex, ethnicity, obesity, diabetes, aetiology, time from 1st attack of AP, recurrence, severity, physical activity, and smoking were adjusted for in several statistical models. P<0.05 was considered statistically significant. RESULTS: A total of 93 patients were recruited. Peptide YY was significantly associated (p<0.001) with IL-6, MCP-1, and TNFα in the unadjusted and all adjusted models. Pancreatic polypeptide was significantly associated (p<0.001) with IL-6, MCP-1, and TNFα in the unadjusted and at least one adjusted model. Peptide YY and PP together contributed 22.2%, 72.7%, and 34.6% to the variance of IL-6, MCP-1, and TNFα, respectively. Neuropeptide Y was not significantly associated with any of the three cytokines. CONCLUSIONS: Peptide YY and PP are associated with circulating innate pro-inflammatory cytokines in patients after AP and cumulatively contribute to nearly half of the variance of IL-6, MCP-1, and TNFα. Future research is warranted to investigate the signaling pathways that underlie these associations.

Relationship between circulating levels of pancreatic proteolytic enzymes and pancreatic hormones.

BACKGROUND: While the close morphological relationship between the exocrine and endocrine pancreas is well established, their functional interaction remains poorly understood. The aim of this study was to investigate the associations between circulating levels of pancreatic proteolytic enzymes and insulin, as well as other pancreatic hormones. METHODS: Fasting venous blood samples were collected and analyzed for trypsin, chymotrypsin, insulin, glucagon, somatostatin, and pancreatic polypeptide. Linear regression analysis was used in unadjusted and two adjusted (accounting for prediabetes/diabetes, body mass index, smoking, and other covariates) statistical models. RESULTS: A total of 93 individuals with a history of acute pancreatitis were included in this cross-sectional study. Chymotrypsin was significantly associated with insulin in the two adjusted models (p = 0.005; p = 0.003) and just missed statistical significance in the unadjusted model (p = 0.066). Chymotrypsin was significantly associated with glucagon in both unadjusted (p = 0.025) and adjusted models (p = 0.014; p = 0.015); as well as with somatostatin - in both unadjusted (p = 0.001) and adjusted models (p = 0.001; p = 0.002). Trypsin was not significantly associated with insulin in any of the models but was significantly associated with glucagon in both unadjusted (p < 0.001) and adjusted models (p < 0.001), and pancreatic polypeptide in both unadjusted (p < 0.001) and adjusted (p < 0.001) models. CONCLUSION: The state of hyperinsulinemia is characterized by a dysfunction of the exocrine pancreas. In particular, chymotrypsin is increased in the state of hyperinsulinemia and trypsin is significantly associated with glucagon and pancreatic polypeptide.

Glucose Variability Measures as Predictors of Oral Feeding Intolerance in Acute Pancreatitis: A Prospective Pilot Study.

BACKGROUND: Oral feeding intolerance (OFI) is a common complication in patients with acute pancreatitis (AP). Variations in blood glucose are associated with impaired gastrointestinal function but, to date, measures of glucose variability have not been investigated to predict OFI in patients with AP. AIM: To investigate the usefulness of several glucose variability measures in predicting the occurrence of OFI early in the course of AP. METHODS: In this prospective cohort study, six measures of glucose variability were calculated prior to the occurrence of OFI. Multivariate binary logistic regression analyses were conducted, and the diagnostic performance and accuracy of glucose variability measures were assessed. RESULTS: Of the 95 prospectively enrolled patients, 21 (22%) developed OFI. After adjusting for confounders, admission blood glucose concentration and mean blood glucose concentration were significantly associated with OFI [odds ratio 1.49 (95% confidence interval 1.01-2.20) and odds ratio 1.67 (95% confidence interval 1.07-2.61), respectively]. Both admission blood glucose and mean blood glucose had an area under the curve of 0.83 and positive likelihood ratios of 6.45 and 10.19, respectively. Blood glucose concentration before refeeding, standard deviation of blood glucose concentration, coefficient of variation, and mean amplitude of glycemic excursions were not significantly associated with OFI. CONCLUSION: In-hospital blood glucose concentrations are associated with subsequent development of OFI in patients with AP. In particular, admission blood glucose and mean blood glucose could be useful predictors of OFI in this setting.

Relationship between pancreatic hormones and glucose metabolism: A cross-sectional study in patients after acute pancreatitis.

Abnormal glucose metabolism is present in almost 40% of patients after acute pancreatitis, but its pathophysiology has been poorly investigated. Pancreatic hormone derangements have been sparingly studied to date, and their relationship with abnormal glucose metabolism is largely unknown. The aim was to investigate the associations between pancreatic hormones and glucose metabolism after acute pancreatitis, including the effect of potential confounders. This was a cross-sectional study of 83 adult patients after acute pancreatitis. Fasting venous blood was collected from all patients and used for analysis of insulin, glucagon, pancreatic polypeptide, amylin, somatostatin, C-peptide, glucose, and hemoglobin A1c. Statistical analyses were conducted using the modified Poisson regression, multivariable linear regression, and Spearman's correlation. Age, sex, body mass index, recurrence of acute pancreatitis, duration from first attack, severity, and etiology were adjusted for. Increased insulin was significantly associated with abnormal glucose metabolism after acute pancreatitis, in both unadjusted (P = 0.038) and adjusted (P = 0.001) analyses. Patients with abnormal glucose metabolism also had significantly decreased pancreatic polypeptide (P = 0.001) and increased amylin (P = 0.047) in adjusted analyses. Somatostatin, C-peptide, and glucagon were not changed significantly in both unadjusted and adjusted analyses. Increased insulin resistance and reduced insulin clearance may be important components of hyperinsulinemic compensation in patients after acute pancreatitis. Increased amylin and reduced pancreatic polypeptide fasting levels characterize impaired glucose homeostasis. Clinical studies investigating islet-cell hormonal responses to mixed-nutrient meal testing and euglycemic-hyperinsulinemic clamps are now warranted for further insights into the role of pancreatic hormones in glucose metabolism derangements secondary to pancreatic diseases.

Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.

BACKGROUND: Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. METHODS: This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. RESULTS: A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. CONCLUSION: Interleukin-6 appears to be implicated in the development of chronic hyperglycemia and insulin resistance in patients after acute pancreatitis. It may become a potential target in the prevention and early treatment of diabetes after diseases of the exocrine pancreas.

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.

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.

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.

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.

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.

Iron: a Strong Element in the Pathogenesis of Chronic Hyperglycaemia After Acute Pancreatitis.

Evidence shows an association between markers of iron metabolism and glucose metabolism in type 2 diabetes mellitus. Acute pancreatitis is the largest contributor to diabetes of the exocrine pancreas. However, the pathogenesis of new-onset pre-diabetes or diabetes after pancreatitis remains unclear. This study aimed to investigate associations between markers of iron metabolism and glucose metabolism following acute pancreatitis. Fasting blood samples were collected to analyse markers of glucose metabolism (haemoglobin A1c) and iron metabolism (hepcidin, ferritin, and soluble transferrin receptor). Participants were categorised into two groups: normoglycaemia after acute pancreatitis and chronic hyperglycaemia after acute pancreatitis. Binary logistic and linear regression analyses were conducted, and potential confounders were adjusted for in multivariable analyses. A total of 83 individuals following an episode of acute pancreatitis were included, of whom 19 developed chronic hyperglycaemia. Hepcidin was significantly increased in individuals with chronic hyperglycaemia after acute pancreatitis in two adjusted models (p = 0.045 and p = 0.048). Ferritin was significantly decreased in individuals with chronic hyperglycaemia after acute pancreatitis in three adjusted models (p = 0.016, p = 0.009, and p = 0.011). Soluble transferrin receptor was not significantly associated with chronic hyperglycaemia after acute pancreatitis. These findings suggest that iron metabolism is significantly altered in individuals with chronic hyperglycaemia after acute pancreatitis and may provide better insights into the pathogenesis of new-onset diabetes after pancreatitis.

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.

Age- and sex-specific prevalence of diabetes associated with diseases of the exocrine pancreas: A population-based study.

BACKGROUND AND AIMS: Diabetes associated with diseases of the exocrine pancreas (DP) is a recognized clinical condition but data on its prevalence are limited to a few single centre studies. Relative contribution of the three major diseases of the exocrine pancreas (acute pancreatitis, chronic pancreatitis, pancreatic cancer) to prevalence of DP as well as the effect of age and sex is largely unknown. The study aimed to determine age- and sex-specific prevalence of DP overall and after acute pancreatitis, chronic pancreatitis, and pancreatic cancer alone at the population level. METHODS: Nationwide population database covering nearly 3 million residents in New Zealand over a 10-year study period was used. DP was identified based on International Classification of Diseases-10 codes. Data were reported as prevalence per 1000 population and corresponding 95% confidence intervals. RESULTS: The crude prevalence of DP was 1.13 [1.12, 1.14] per 1000, with 70-79 years age group having the highest prevalence at 3.94 [3.92, 3.97] per 1000. Men had an overall prevalence of 1.32 [1.31, 1.33] per 1000 and women-0.93 [0.92, 0.94] (p<0.05). Acute pancreatitis contributed 61% to overall prevalence of DP. CONCLUSIONS: Prevalence of DP in the general population is close to that of type 1 diabetes. Three out of five DP cases develop after acute pancreatitis. There is a variation in age of onset of DP, with the working and ageing population most affected. Men have a 40% higher risk of developing DP than women.

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

BACKGROUND: Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. METHODS: Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. RESULTS: A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. CONCLUSION: GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro-inflammatory cytokines, as well as certain pancreatic and gut hormones. Detailed mechanistic studies are now warranted to investigate the exact role of GRP in derangements of glucose homeostasis following pancreatitis.