-
Journal of Diabetes Investigation Oct 2023It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is...
It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney-pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin-based probe, [ F]FB(ePEG12)12-exendin-4. Following transplantation, PET imaging with [ F]FB(ePEG12)12-exendin-4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [ F]FB(ePEG12)12-exendin-4 whole-body maximum intensity projection and axial PET images. At 1 and 2 h after [ F]FB(ePEG12)12-exendin-4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [ F]FB(ePEG12)12-exendin-4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta-cell mass following simultaneous kidney-pancreas transplantation.
Topics: Humans; Positron Emission Tomography Computed Tomography; Exenatide; Pancrelipase; Peptides; Kidney Transplantation; Pancreas
PubMed: 37377043
DOI: 10.1111/jdi.14045 -
Frontiers in Microbiology 2023The airways of people with cystic fibrosis () often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of...
The airways of people with cystic fibrosis () often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of providing a wealth of insight, this cataloguing tells us little about how the organisms interact with one another in the airways. However, such relationships can be inferred using the theoretical framework of the Lotka-Volterra (LV) model. In the current work, we use a generalized Lotka-Volterra model to interrogate the nationwide data collected and curated by the UK Registry. This longitudinal dataset (covering the period 2008-2020) contains annual depositions that record the presence/absence of microbial taxa in each patient, their medication, and their genotype. Specifically, we wanted to identify trends in ecological relationships between the microbiota at a nationwide level, and whether these are potentially affected by medication. Our results show that some medications have a distinct influence on the microbial interactome, especially those that potentially influence the "gut-lung axis" or mucus viscosity. In particular, we found that patients treated with a combination of antimicrobial agents (targeting the airway microbiota), digestive enzymes (assisting in the assimilation of dietary fats and carbohydrates), and DNase (to reduce mucus viscosity) displayed a distinctly different airway interactome compared with patients treated separately with these medications.
PubMed: 37323900
DOI: 10.3389/fmicb.2023.1178131 -
The Oncologist Dec 2023Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk...
BACKGROUND
Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI.
PATIENTS AND METHODS
A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start.
RESULTS
Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01).
CONCLUSION
ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.
Topics: Humans; Pancrelipase; Immune Checkpoint Inhibitors; Steatorrhea; Retrospective Studies; Case-Control Studies; Acute Disease; Pancreatitis; Exocrine Pancreatic Insufficiency; Hyperglycemia; Weight Loss
PubMed: 37285223
DOI: 10.1093/oncolo/oyad150 -
Journal of Agricultural and Food... Jun 2023Lotus leaf is effective in regulating glycolipid absorption and metabolism, but the roles of small-molecule compounds and polysaccharides are unknown. In this study, the...
Rhamnogalacturonan I-Enriched Pectin, Flavonoids, and Alkaloids from Lotus Leaf Infusion in Regulating Glycolipid Absorption and Metabolism: Isolation, In Vitro Bioactivity Verification, and Structural Characterization.
Lotus leaf is effective in regulating glycolipid absorption and metabolism, but the roles of small-molecule compounds and polysaccharides are unknown. In this study, the small-molecule compounds including flavonoids, alkaloids, and polysaccharides were gradually isolated from lotus leaf infusion by multi-column chromatography and applied to in vitro activity verification and structural characterization. Although flavonoids and alkaloids were effective in inhibiting pancrelipase and α-glucosidase, polysaccharides more effectively bounded bile acids, inhibited cholesterol micelle solubility, and stimulated the growth of than lotus leaf infusion. Polysaccharides, presented as spherical conformation in water, were identified as rhamnogalacturonan I-enriched (93%) low-ester pectin with multiple branches mainly composed of arabinan, arabinogalactan-type II, and galactan formed by →3)-Gal-(1→, →5)-Ara-(1→ and →4)-Gal-(1→ residues. Polysaccharides, which were a key constituent of lotus leaf infusion in regulating glycolipid absorption and metabolism, should be paid more attention and developed as a functional food ingredient.
Topics: Lotus; Flavonoids; Polysaccharides; Pectins; Alkaloids; Plant Leaves
PubMed: 37259824
DOI: 10.1021/acs.jafc.3c02522 -
Histochemistry and Cell Biology Aug 2023Diabetes mellitus is a widespread endocrine disease worldwide, accompanying chronic hyperglycemia. In this study, we investigated the effect of hydroxytyrosol, which...
Diabetes mellitus is a widespread endocrine disease worldwide, accompanying chronic hyperglycemia. In this study, we investigated the effect of hydroxytyrosol, which exerts an antioxidant effect, on the expressions of insulin and peroxiredoxin-6 (Prdx6), which protect cells against oxidative injury in diabetic rat pancreas. This experimental study had four groups with ten animals in each group: control (nondiabetic) group, hydroxytyrosol group [10 mg/kg/day intraperitoneal injection (ip) hydroxytyrosol for 30 days], streptozotocin group (single ip injection of 55 mg/kg streptozotocin), and streptozotocin + hydroxytyrosol group (single ip injection of streptozotocin and ip injection of 10 mg/kg/day hydroxytyrosol for 30 days). During the experiment, blood glucose levels were measured at regular intervals. Insulin expression was determined by immunohistochemistry and Prdx6 expression was determined by immunohistochemistry and western blot. Immunohistochemistry and western blot results were analyzed by one-way ANOVA with applied Holm-Sidak multiple comparison test, and blood glucose results were analyzed by two-way repeated measures ANOVA with applied Tukey's multiple comparison test. Blood glucose levels on days 21 and 28 were significantly lower in the streptozotocin + hydroxytyrosol group compared with the streptozotocin group (day 21, p = 0.049 and day 28, p = 0.003). Expression of both insulin and Prdx6 were lower in the streptozotocin and the streptozotocin + hydroxytyrosol groups compared with the control and hydroxytyrosol groups (p < 0.001). Insulin and Prdx6 expression in the streptozotocin + hydroxytyrosol group were higher compared with the streptozotocin group (p < 0.001). The immunohistochemical findings of Prdx6 and western blot were the same. In conclusion, hydroxytyrosol, which is an antioxidant compound, increased Prdx6 and insulin expression in diabetic rats. Insulin increased by hydroxytyrosol may have been effective in reducing blood glucose levels. Furthermore, hydroxytyrosol may exert its effect on insulin by increasing Prdx6 expression. Thus, hydroxytyrosol may decrease or prevent several hyperglycemia-dependent complications by increasing the expression of these proteins.
Topics: Rats; Animals; Insulin; Blood Glucose; Pancrelipase; Diabetes Mellitus, Experimental; Peroxiredoxin VI; Streptozocin; Hyperglycemia; Antioxidants
PubMed: 37219732
DOI: 10.1007/s00418-023-02207-3 -
PloS One 2023The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess...
INTRODUCTION
The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption.
METHODS
We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase.
RESULTS
The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase.
CONCLUSION
The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.
Topics: Humans; Swine; Animals; Pancrelipase; Lipolysis; Intestinal Absorption; Lipase; Exocrine Pancreatic Insufficiency; Fatty Acids, Omega-3
PubMed: 37155649
DOI: 10.1371/journal.pone.0284651 -
PancreasThis retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated...
A Retrospective Real-World Evidence Evaluation of the Characteristics of Exocrine Pancreatic Insufficiency in Patients With Chronic Pancreatitis and Type 2 Diabetes Treated With Pancrelipase in the United States.
OBJECTIVES
This retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated patients with exocrine pancreatic insufficiency symptoms and chronic pancreatitis (CP) or type 2 diabetes (T2D).
METHODS
Data were from the Decision Resources Group Real-World Evidence Data Repository US database. Patients 18 years and older receiving pancrelipase (Zenpep) between index dates August 2015 and June 2020 were included. Gastrointestinal symptoms were assessed 6, 12, and 18 months post-index versus baseline.
RESULTS
A total of 10,656 pancrelipase-treated patients with CP (n = 3215) or T2D (n = 7441) were identified. Significant/sustained reductions in gastrointestinal symptoms were observed in both cohorts after pancrelipase treatment (P < 0.001) versus baseline. Significantly fewer patients with CP compliant with treatment for more than 270 days (n = 1553) reported abdominal pain (P < 0.001) and nausea/vomiting (P < 0.05) versus those compliant for less than 90 days (n = 1115). Significantly fewer patients with T2D compliant with treatment for more than 270 days (n = 2964) reported abdominal pain (P < 0.001) and diarrhea/steatorrhea (P < 0.05) versus those compliant for less than 90 days (n = 2959).
CONCLUSIONS
Pancrelipase reduced exocrine pancreatic insufficiency symptoms in patients with CP or T2D, with greater treatment compliance associated with improved gastrointestinal symptom profiles.
Topics: Humans; United States; Pancrelipase; Gastrointestinal Agents; Diabetes Mellitus, Type 2; Retrospective Studies; Exocrine Pancreatic Insufficiency; Pancreatitis, Chronic; Abdominal Pain
PubMed: 37099771
DOI: 10.1097/MPA.0000000000002203 -
Internal Medicine (Tokyo, Japan) Sep 2023We herein report two cases of rapidly progressive fatty liver (FL) disease due to pancreatic exocrine insufficiency (PEI) without a surgical history. Two women, 59 and...
We herein report two cases of rapidly progressive fatty liver (FL) disease due to pancreatic exocrine insufficiency (PEI) without a surgical history. Two women, 59 and 72 years old, with no history of abdominal surgery presented to our hospital with severe anorexia and nausea persisting for one week. Examinations revealed progressive, marked FL disease with hepatomegaly and PEI, for which pancreatic enzyme replacement therapy was effective. Commonly known causes of PEI include chronic pancreatitis, abdominal surgery (e.g. pancreaticoduodenectomy), pancreatic cancer, and obstruction of the pancreatic duct, none of which were present in either of these two cases.
Topics: Humans; Female; Middle Aged; Aged; Exocrine Pancreatic Insufficiency; Pancreas; Non-alcoholic Fatty Liver Disease; Pancreatitis, Chronic; Pancreatic Neoplasms; Enzyme Replacement Therapy
PubMed: 36754408
DOI: 10.2169/internalmedicine.0775-22 -
Frontiers in Medicine 2022Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to...
BACKGROUND
Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to treat non-responsive celiac disease (NRCD) in clinical practice, clinical outcomes are variable and there is limited and low quality evidence to support this practice. The aim of this study was to assess the efficacy of pancreatic enzyme supplements (PES) for improvement of gastrointestinal symptoms in NRCD.
METHODS
Prospective, randomized, placebo-controlled, double-blind, cross-over trial in adults with NRCD examining Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores on PES (pancrelipase co-administered with omeprazole) versus placebo (omeprazole only) during a 10-day treatment period. The study was registered under the clinical trials registry (https://clinicaltrials.gov/ number, NCT02475369) on 18 Jun 2015.
RESULTS
Twelve participants (nine female) were included in the per-protocol analysis; one participant had low fecal elastase-1. Pancrelipase was not associated with significant change in CeD-GSRS compared to placebo (-0.03 versus -0.26; = 0.366). There was a significant decrease in mean values of total CeD-GSRS scores (3.58 versus 2.90, = 0.004), abdominal pain (2.92 versus 2.42, = 0.009), and diarrhea sub-scores (3.44 versus 2.92, = 0.037) during the run-in period with omeprazole.
CONCLUSION
In this prospective, cross-over randomized, placebo-controlled study, PES did not improve symptoms in patients with NRCD. It is unclear whether this is a trial effect or related to administration of omeprazole.
PubMed: 36687454
DOI: 10.3389/fmed.2022.1001879