Abstract
After an attack of pancreatitis, individuals may develop metabolic sequelae (eg, new-onset
diabetes) and/or pancreatic cancer. These new-onset morbidities are, at least in part,
driven by low-grade inflammation. The aim was to study the profiles of cytokines/chemokines
in individuals after an attack of pancreatitis. A commercially available panel including
31 cytokines/chemokines was investigated. Random forest classifier and unsupervised
hierarchical clustering were applied to study participants (who had no persistent
organ failure and did not require ICU admission) according to their cytokine/chemokine
profiles. Pancreatitis-related characteristics, detailed body composition (determined
using 3.0 T magnetic resonance imaging), markers of glucose, lipid, and iron metabolism,
gut and pancreatic hormones, as well as liver and pancreatic enzymes, were compared
between clusters. Bootstrap validation was employed. A total of 160 participants,
including 107 postpancreatitis individuals (investigated at a median of 18 months
after the last attack of pancreatitis) and 53 healthy volunteers, were studied. Twenty-two
cytokines/chemokines were significantly different between postpancreatitis and health.
Two distinct endotypes of individuals after an attack of pancreatitis were identified–‟inflammatory”
and ‟noninflammatory.” Sixteen cytokines/chemokines were significantly higher in the
inflammatory endotype compared with the noninflammatory endotype. No cytokine/chemokine
was significantly higher in the noninflammatory endotype. The inflammatory endotype
was characterized by significantly elevated insulin (P= 0.001), glucose-dependent insulinotropic peptide (P = 0.001), peptide YY (P = 0.017), and ghrelin (P = 0.014). The noninflammatory endotype was characterized by significantly elevated
hepcidin (P= 0.016). Pancreatitis-related factors, body composition, and other studied parameters
did not differ significantly between the 2 endotypes. Individuals with a similar phenotype
and clinical course of pancreatitis have differing cytokine/chemokine profiles after
clinical resolution of the disease. People with the inflammatory endotype have distinct
changes in the pancreatic and gut hormones known to be involved in the pathogenesis
of new-onset morbidities after an attack of pancreatitis.
Abbreviations:
ARIES (Analytic moRphomics In pancrEatic diseaSes), BMI (Body mass index), COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatic diseaseS), GIP (Glucose dependent insulinotropic peptide), GLP-1 (Glucagon-like peptide 1), HbA1c (Glycated hemoglobin), HDL (High density lipoprotein), HOMA-β (Homeostasis model of assessment of β cell function), HOMA-IR (Homeostasis model assessment of insulin resistance), ICU (Intensive care unit), IHFD (Intra-hepatic fat deposition), LDL (Low density lipoprotein), ROC (Receiver operation curve), SMFD (Skeletal muscle fat deposition)To read this article in full you will need to make a payment
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References
- Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies.Lancet Gastroenterol Hepatol. 2016; 1: 45-55
- Global incidence of acute pancreatitis is increasing over time: a systematic review and meta-analysis.Gastroenterology. 2022; 162: 122-134
- Global epidemiology and holistic prevention of pancreatitis.Nat Rev Gastroenterol Hepatol. 2019; 16: 175-184
- Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis.Gastroenterology. 2015; 149: 1490-1500
- Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis.Sci Rep. 2019; 9: 7318
- Panorama of mediators in postpancreatitis diabetes mellitus.Curr Opin Gastroenterol. 2020; 36: 443-451
- Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.Pancreatology. 2016; 16: 748-755
- Complications of chronic pancreatitis.Dig Dis Sci. 2017; 62: 1745-1750
- Trajectories of glycaemia following acute pancreatitis: a prospective longitudinal cohort study with 24 months follow-up.J Gastroenterol. 2020; 55: 775-788
- Relationship between the exocrine and endocrine pancreas after acute pancreatitis.World J Gastroenterol. 2014; 20: 17196-17205
- Effect of acute pancreatitis on the risk of developing osteoporosis: a nationwide cohort study.PLoS One. 2017; 12: e0179358
- High prevalence of osteoporosis in patients with chronic pancreatitis: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2014; 12: 219-228
- Cross-talk between innate cytokines and the pancreatic polypeptide family in acute pancreatitis.Cytokine. 2017; 90: 161-168
- Associations between circulating levels of adipocytokines and abdominal adiposity in patients after acute pancreatitis.Clin Exp Med. 2017; 17: 477-487
- Fasting levels of insulin and amylin after acute pancreatitis are associated with pro-inflammatory cytokines.Arch Physiol Biochem. 2017; 123: 238-248
- Gastrin-releasing peptide and glucose metabolism following pancreatitis.Gastroenterol Res. 2017; 10: 224-234
- Interplay between innate immunity and iron metabolism after acute pancreatitis.Cytokine. 2018; 103: 90-98
- Pro-inflammatory cytokines after an episode of acute pancreatitis: associations with fasting gut hormone profile.Inflamm Res. 2018; 67: 339-350
- Pro-inflammatory cytokine-induced lipolysis after an episode of acute pancreatitis.Arch Physiol Biochem. 2018; 124: 401-409
- Associations between intra-pancreatic fat deposition and circulating levels of cytokines.Cytokine. 2019; 120: 107-114
- Unique circulating immune signatures for recurrent acute pancreatitis, chronic pancreatitis and pancreatic cancer: a pilot study of these conditions with and without diabetes.Pancreatology. 2020; 20: 51-59
- Systematic investigation of cytokine signaling activity at the tissue and single-cell levels.Nat Methods. 2021; 18: 1181-1191
- Random forests.Mach Learn. 2001; 45: 5-32
- Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome.Gut. 2021; 70: 1287-1298
- Inadequate rectal pressure and insufficient relaxation and abdominopelvic coordination in defecatory disorders.Gastroenterology. 2022; 162: 1111-1122
- Machine learning prediction model for inflammatory bowel disease based on laboratory markers. Working model in a discovery cohort study.J Clin Med. 2021; 10: 4745
- 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.Diabetes, Obes Metab. 2019; 21: 417-423
- Pancreatic enzymes and abdominal adipose tissue distribution in new-onset prediabetes/diabetes after acute pancreatitis.World J Gastroenterol. 2021; 27: 3357-3371
- Using random forest to learn imbalanced data.Univiversity of California, Berkeley 110, 242004: 1-12
- An empirical study of learning from imbalanced data using random forest.in: 19th IEEE International Conference on Tools with Artificial Intelligence (ICTAI 2007). IEEE, 2007: 310-317
- Progressive statistics for studies in sports medicine and exercise science.Med Sci Sport Exerc. 2009; 41: 3-12
- Silhouettes: a graphical aid to the interpretation and validation of cluster analysis.J Comput Appl Math. 1987; 20: 53-65
- Natural history of organ failure in acute pancreatitis.Pancreatology. 2003; 3: 111-114
- Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α, and IL-6.Diabetes Res Clin Pract. 2005; 69: 29-35
- The relation of body fat mass and distribution to markers of chronic inflammation.Int J Obes. 2001; 25: 1407-1415
- Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses.J Clin Endocrinol Metab. 1986; 63: 492-498
- Functional GIP receptors are present on adipocytes.Endocrinology. 1998; 139: 4004-4007
- Glucose-dependent insulinotropic peptide impairs insulin signaling via inducing adipocyte inflammation in glucose-dependent insulinotropic peptide receptor-overexpressing adipocytes.FASEB J. 2012; 26: 2383-2393
- Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation.J Immunol. 2014; 193: 4002-4009
- Gut hormone responses to mixed meal test in new-onset prediabetes/diabetes after acute pancreatitis.Horm Metab Res. 2019; 51: 191-199
- Cytokine signature for predicting new-onset prediabetes after acute pancreatitis: a prospective longitudinal cohort study.Cytokine. 2022; 150155768
- Pancreatic hormone responses to mixed meal test in new-onset prediabetes/diabetes after non-necrotizing acute pancreatitis.J Clin Gastroenterol. 2020; 54: e11-e20
- Hepcidin and iron homeostasis.Biochim Biophys Acta - Mol Cell Res. 2012; 1823: 1434-1443
- Iron metabolism and the exocrine pancreas.Clin Chim Acta. 2020; 511: 167-176
- Iron: a strong element in the pathogenesis of chronic hyperglycaemia after acute pancreatitis.Biol Trace Elem Res. 2018; 183: 71-79
- Association between habitual dietary iron intake and glucose metabolism in individuals after acute pancreatitis.Nutrients. 2020; 12: 3579
- Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study.Artif Organs. 2022; 46: 1019-1026
Article info
Publication history
Published online: July 17, 2022
Accepted:
July 8,
2022
Received in revised form:
June 30,
2022
Received:
May 3,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.