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Parihar V, Ballester R, Ridgway PF, Conlon KC, Gibney J, Ryan BM. Screening for undiagnosed pancreatic exocrine insufficiency (PEI) in a cohort of diabetic patients using faecal elastase testing and PEI scoring system. Acta Diabetol 2024; 61:1301-1307. [PMID: 38796828 PMCID: PMC11486769 DOI: 10.1007/s00592-024-02307-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/15/2024] [Indexed: 05/29/2024]
Abstract
INTRODUCTION Type 1 and type 2 diabetes mellitus (DM) are often accompanied by mild forms of pancreatic exocrine insufficiency (PEI). The prevalence rates of PEI in diabetic patients are unclear and variable depending on the testing modality and the studies published. The clinical consequences of PEI in diabetics are also not well defined. AIM We aimed to determine the prevalence of PEI in a diabetic cohort using the faecal elastase-1 (FE-1) assay as a screening test and to validate a patient-reported symptom-based scoring system, the (PEI-S) for diagnosing PEI within this patient population. METHODS Two hundred and three diabetic patients attending diabetic and gastroenterology outpatients of a university hospital without previously known PEI were recruited for the study. Demographic parameters, PEI score (PEI-S), and glycated hemoglobin (HBA1c) were documented in standardized data sheets, and a stool sample was obtained. A FE-1 value < 200 μg/g and or a PEIS of > 0.6 was used as the screening cut-off for PEI. RESULTS One hundred sixty-six patients returned faecal samples. The prevalence of PEI, as measured by low FE-1, was 12%. Smoking was associated with an increased risk of developing PEI in this diabetic population. No other independent risk factors were identified. The PEI-S system did not differentiate between people with diabetes having a normal and low FE1. CONCLUSION 12% of this mixed, real-life cohort of type 1 and 2 DM patients had undiagnosed PEI, as defined by an FE-1 score of less than 200 μg/g. While this may appear low, given the rising prevalence of type 2 DM worldwide, there is likely an unrecognized burden of PEI, which has long-term health consequences for those affected. The PEI-S, a symptom-scoring system for patients with PEI, did not perform well in this patient group.
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Affiliation(s)
- V Parihar
- Department of Gastroenterology, Tallaght University Hospital, TallaghtDublin 24, Ireland.
- Department of Gastroenterology, Letterkenny University Hospital, Letterkenny, Ireland.
| | - R Ballester
- Department of Gastroenterology, Tallaght University Hospital, TallaghtDublin 24, Ireland
| | - P F Ridgway
- Department of Surgery, Tallaght University Hospital and Trinity College, Dublin, Ireland
| | - K C Conlon
- Department of Surgery, Tallaght University Hospital and Trinity College, Dublin, Ireland
| | - J Gibney
- Department of Endocrinology, Tallaght University Hospital, TallaghtDublin 24, Ireland
| | - B M Ryan
- Department of Gastroenterology, Tallaght University Hospital, TallaghtDublin 24, Ireland
- Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland
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Barkin JA, Delk TB, Powell VJ. Symptoms, burden, and unmet needs of patients living with exocrine pancreatic insufficiency: a narrative review of the patient experience. BMC Gastroenterol 2024; 24:101. [PMID: 38481137 PMCID: PMC10938721 DOI: 10.1186/s12876-024-03188-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 02/26/2024] [Indexed: 03/17/2024] Open
Abstract
Exocrine pancreatic insufficiency (EPI) stems from a deficiency of functional pancreatic enzymes with consequent maldigestion and malnutrition. EPI shares clinical symptoms and manifestations with other disorders and is a considerable burden to individuals affected. In this narrative review, we analyzed the literature to identify relevant publications on living with EPI with the scope of individuating evidence gaps, including those related to symptoms, health-related quality of life (HRQoL), emotional functioning, disease burden, presence of comorbidities, and the use of pancreatic enzyme replacement therapy (PERT). Abdominal pain emerged as one of the most prominent symptoms. HRQoL was affected in EPI, but no articles examined emotional functioning. Comorbidities reported involved other pancreatic disorders, diabetes, gastrointestinal disorders, sarcopenia and osteopenia, cardiovascular disorders, bacterial overgrowth, and nutritional deficiencies. PERT was found to be effective in improving EPI symptoms and was well tolerated by most individuals. Our review revealed a dearth of literature evidence on patients' experience with EPI, such as emotional functioning and disease burden. We also revealed that studies on long-term effects of PERT are missing, as are studies that would help advance the understanding of the disease and its progression, risk/mitigating factors, and comorbidities. Future studies should address these identified gaps.
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Affiliation(s)
- Jodie A Barkin
- University of Miami Miller School of Medicine, 1120 NW 14th St., Clinical Research Building, Suite 1188 (D-49), 33136, Miami, FL, USA.
| | - Trudi B Delk
- Aimmune Therapeutics, a Nestlé Health Science Company, Brisbane, CA, USA
| | - Valerie J Powell
- CorEvitas, LLC, part of Thermo Fisher Scientific, Waltham, MA, USA
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Lewis DM. A Systematic Review of Exocrine Pancreatic Insufficiency Prevalence and Treatment in Type 1 and Type 2 Diabetes. Diabetes Technol Ther 2023; 25:659-672. [PMID: 37440180 DOI: 10.1089/dia.2023.0157] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Type 1 diabetes and type 2 diabetes have high rates of associated exocrine pancreatic insufficiency (EPI). This review evaluated the current evidence on prevalence and treatment of EPI in type 1 and type 2 diabetes and compared general population prevalence rates of EPI and prevalence of other common gastrointestinal conditions such as celiac disease and gastroparesis based on within-diabetes rates of common gastrointestinal (GI) conditions. Prevalence of EPI in type 1 diabetes ranges from 14% to 77.5% (median 33%), while EPI in type 2 diabetes ranges from 16.8% to 49.2% (median 29%), and where type of diabetes is not specified in studies, ranges from 5.4% to 77%. In studies with control groups of the general population, prevalence of EPI overall in those without diabetes ranged from 4.4% to 18%, median 13%, which is comparable with other estimated general population prevalence rates of EPI (10%-20%). Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes (both type 1 and type 2) who present with gastrointestinal symptoms, such as steatorrhea or changes in stool, bloating, and/or abdominal pain, should be screened for EPI. Both diabetes specialists and gastroenterologists and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms.
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Mathew A, Fernandes D, Andreyev HJN. What is the significance of a faecal elastase-1 level between 200 and 500μg/g? Frontline Gastroenterol 2023; 14:371-376. [PMID: 37581180 PMCID: PMC10423608 DOI: 10.1136/flgastro-2022-102271] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 01/26/2023] [Indexed: 08/16/2023] Open
Abstract
Background Pancreatic exocrine insufficiency is a cause of malabsorption. It is generally diagnosed if faecal elastase-1 (FE-1) levels are below 200 µg/g. Pancreatic function is assumed to be normal when faecal elastase levels are >500 µg/g. The significance of faecal elastase levels above 200 µg/g but less than 500 µg/g is unclear. Methods This retrospective study reports the response to treatment in patients who had an FE-1 level between 200 and 500 µg/g. Results Of these 82 patients, 28 were offered pancreatic enzyme replacement therapy (PERT). A clinical response, defined as an improvement in their initial symptoms after commencing PERT, was seen in 20 patients (71%), 7 with potentially predisposing conditions and 13 with functional diarrhoea. PERT particularly abolished or improved diarrhoea, steatorrhoea and flatulence. Conclusion Clinicians should, therefore, be aware that a trial of PERT given to patients with FE-1 levels between 200 and 500 µg/g may lead to improvement in gastrointestinal symptoms.
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Affiliation(s)
| | - Darren Fernandes
- Department of Gastroenterology, United Lincolnshire Hospitals NHS Trust, Lincoln, UK
- School of Health and Social Care, Community and Health Research Unit, University of Lincoln, Lincoln, UK
| | - H Jervoise N Andreyev
- Department of Gastroenterology, United Lincolnshire Hospitals NHS Trust, Lincoln, UK
- The Biomedical Research Centre, Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
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Kaser S, Hofer SE, Kazemi-Shirazi L, Festa A, Winhofer Y, Sourij H, Brath H, Riedl M, Resl M, Clodi M, Stulnig T, Ress C, Luger A. [Other specific types of diabetes and exocrine pancreatic insufficiency (update 2023)]. Wien Klin Wochenschr 2023; 135:18-31. [PMID: 37101022 PMCID: PMC10133035 DOI: 10.1007/s00508-022-02123-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2022] [Indexed: 04/28/2023]
Abstract
The heterogenous category "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e.g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART), checkpoint inhibitors), genetic forms of diabetes (e.g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down‑, Klinefelter- and Turner Syndrome), pancreatogenic diabetes (e.g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.
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Affiliation(s)
- Susanne Kaser
- Universitätsklinik für Innere Medizin 1, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich.
| | - Sabine E Hofer
- Universitätsklinik für Pädiatrie 1, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Lili Kazemi-Shirazi
- Klinische Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Andreas Festa
- Abteilung für Innere Medizin I, LK Stockerau, Stockerau, Österreich
| | - Yvonne Winhofer
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Harald Sourij
- Klinische Abteilung für Endokrinologie und Diabetologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Helmut Brath
- Mein Gesundheitszentrum Favoriten, Österreichische Gesundheitskasse, Wien, Österreich
| | - Michaela Riedl
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Michael Resl
- Abteilung für Innere Medizin, Konventhospital der Barmherzigen Brüder Linz, Linz, Österreich
| | - Martin Clodi
- Abteilung für Innere Medizin, Konventhospital der Barmherzigen Brüder Linz, Linz, Österreich
- ICMR - Institute for Cardiovascular and Metabolic Research, JKU Linz, Linz, Österreich
| | - Thomas Stulnig
- 3. Medizinische Abteilung und Karl Landsteiner Institut für Stoffwechselerkrankungen und Nephrologie, Klinik Hietzing, Wien, Österreich
| | - Claudia Ress
- Universitätsklinik für Innere Medizin 1, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich
| | - Anton Luger
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
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Danioth S, Wiesli P. [CME: Can Slim People Have Type-2 Diabetes?]. PRAXIS 2022; 111:598-602. [PMID: 35975416 DOI: 10.1024/1661-8157/a003915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
CME: Can Slim People Have Type-2 Diabetes? Abstract. Most patients with type-2 diabetes mellitus are obese or overweight. In slim patients with suspected type 2 diabetes mellitus the possibility of other types of diabetes must be considered. In addition to type-1 diabetes in adulthood and genetic forms of diabetes (MODY, mitochondrial diabetes), it could also be diabetes due to a disease of the exocrine pancreas, a condition which is generally underdiagnosed.
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Affiliation(s)
- Simona Danioth
- Medizinische Klinik, Endokrinologie und Diabetologie, Kantonsspital Frauenfeld, Schweiz
| | - Peter Wiesli
- Medizinische Klinik, Endokrinologie und Diabetologie, Kantonsspital Frauenfeld, Schweiz
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Honzlová P, Novosadová Z, Houdek P, Sládek M, Sumová A. Misaligned feeding schedule elicits divergent circadian reorganizations in endo- and exocrine pancreas clocks. Cell Mol Life Sci 2022; 79:318. [PMID: 35622158 PMCID: PMC11072313 DOI: 10.1007/s00018-022-04354-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/05/2022] [Accepted: 05/05/2022] [Indexed: 12/21/2022]
Abstract
Misaligned feeding may lead to pancreatic insufficiency, however, whether and how it affects circadian clock in the exocrine pancreas is not known. We exposed rats to a reversed restricted feeding regimen (rRF) for 10 or 20 days and analyzed locomotor activity, daily profiles of hormone levels (insulin, glucagon, and corticosterone) in plasma, and clock gene expression in the liver and endocrine and exocrine pancreas. In addition, we monitored responses of the exocrine pancreatic clock in organotypic explants of mPer2Luc mice in real time to acetylcholine, insulin, and glucocorticoids. rRF phase-reversed the clock in the endocrine pancreas, similar to the clock in the liver, but completely abolished clock gene rhythmicity and significantly downregulated the expression of Cpb1 and Cel in the exocrine pancreas. rRF desynchronized the rhythms of plasma insulin and corticosterone. Daily profiles of their receptor expression differed in the two parts of the pancreas and responded differently to rRF. Additionally, the pancreatic exocrine clock responded differently to treatments with insulin and the glucocorticoid analog dexamethasone in vitro. Mathematical simulation confirmed that the long-term misalignment between these two hormonal signals, as occurred under rRF, may lead to dampening of the exocrine pancreatic clock. In summary, our data suggest that misaligned meals impair the clock in the exocrine part of the pancreas by uncoupling insulin and corticosterone rhythms. These findings suggest a new mechanism by which adverse dietary habits, often associated with shift work in humans, may impair the clock in the exocrine pancreas and potentially contribute to exocrine pancreatic insufficiency.
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Affiliation(s)
- Petra Honzlová
- Laboratory of Biological Rhythms, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague, Czech Republic
| | - Zuzana Novosadová
- Laboratory of Biological Rhythms, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague, Czech Republic
| | - Pavel Houdek
- Laboratory of Biological Rhythms, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague, Czech Republic
| | - Martin Sládek
- Laboratory of Biological Rhythms, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague, Czech Republic
| | - Alena Sumová
- Laboratory of Biological Rhythms, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague, Czech Republic.
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Zhang J, Hou J, Liu D, Lv Y, Zhang C, Su X, Li L. The Prevalence and Characteristics of Exocrine Pancreatic Insufficiency in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Int J Endocrinol 2022; 2022:7764963. [PMID: 36213198 PMCID: PMC9536940 DOI: 10.1155/2022/7764963] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 05/19/2022] [Accepted: 06/30/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Exocrine pancreatic insufficiency (EPI) is common in patients with type 2 diabetes. However, the prevalence of EPI varies significantly in different studies. Untreated EPI in these patients can adversely affect their nutrition and metabolism. The aim of this study is to estimate the pooled prevalence of EPI in patients with type 2 diabetes and to explore the potential risk factors. METHODS A systematic search was performed in PubMed, Web of Science, and Embase, which included studies meeting inclusion criteria from 1960 to 1 April 2022. Relevant articles were searched using the combination of Medical Subject Heading (MeSH) terms of "Type 2 diabetes" and "pancreatic exocrine insufficiency." The Stata 16.0 software was used for data analyses. The random-effects model was used to estimate the pooled prevalence rates and 95% CI using "metaprop program." RESULTS The pooled prevalence of EPI was 22% (95% CI: 15%-31%) in patients with type 2 diabetes and 8% (95% CI: 4%-14%) of them developed severe pancreatic insufficiency. In the subgroup analyses, the prevalence of EPI in type 2 diabetes was correlated with geographic location. The prevalence in Asian countries (35%, 95% CI: 22%-49%) is higher than in Europe (18%, 95% CI: 10%-29%) and Australia (9%, 95% CI: 4%-16%). Furthermore, patients with higher insulin requirements, who are more likely to be insulin-deficient, have a higher prevalence of EPI. The pooled prevalence was 27% (95% CI: 17%-37%) in type 2 diabetes with higher insulin requirement (1 group) and 15% (95% CI: 1%-40%) in patients with lower insulin requirement (2 group). In addition, the morbidity of severe EPI in the higher insulin requirement group (12%, 95% CI: 7%-19%) was sextuple as much as the lower insulin requirement group (2%, 95% CI: 0%-13%). EPI was more common in subjects younger than 60 compared with elderlies (25% vs. 19%). CONCLUSION The prevalence of EPI in type 2 diabetes may be overestimated. Furthermore, the higher prevalence may be closely related to β-cell function. Endocrine disease therapy would potentially represent a novel therapeutic approach for patients with type 2 diabetes and EPI.
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Affiliation(s)
- Jun Zhang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Jiaying Hou
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Changji Branch, Changji 831100, Xinjiang, China
| | - Dechen Liu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Yingqi Lv
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Chi Zhang
- Department of Endocrinology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan, China
| | - Xianghui Su
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Changji Branch, Changji 831100, Xinjiang, China
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing 210009, Jiangsu, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
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Basturk A, Curek Y, Felek R, Celmeli G, Artan R. Exocrine pancreas functions in children with type 1 diabetes mellitus. Arab J Gastroenterol 2021; 22:236-239. [PMID: 34509389 DOI: 10.1016/j.ajg.2021.05.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 05/08/2021] [Accepted: 05/31/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND AND STUDY AIM We evaluated exocrine pancreas functions using a noninvasive indicator in a case-control study conducted on children and adolescents diagnosed with type 1 diabetes mellitus. PATIENTS AND METHODS Sixty-seven patients who participated in a summer camp were enrolled in this study. Nineteen healthy children in the same age group were assigned to the control group. Fecal pancreatic elastase was assayed using the enzyme-linked immunosorbent assay technique. Values higher than 200 µg/g were considered an indication of sufficient exocrine pancreatic functioning, values between 100 µg/g and 200 µg/g were considered mild exocrine pancreatic insufficiency, and values below 100 µg/g were considered severe exocrine pancreatic insufficiency. RESULTS The mean concentration of fecal elastase was 158.38 ± 59.67 µg/g. The patients were assigned to three groups according to these values. Thirteen patients (22%) had sufficient fecal elastase levels, whereas 36 patients (62%) had mildly insufficient levels, and nine patients (16%) had severely insufficient fecal elastase concentrations. The levels of fecal elastase, amylase, lipase, and zinc were significantly different between the patients and controls (p < 0.001). Only the duration of diabetes was significantly different between patients with different severities of exocrine pancreatic insufficiency (p = 0.037). Additionally, the group with severe pancreatic insufficiency had more frequent hypoglycemic attacks. CONCLUSION Exocrine pancreatic insufficiency may develop in children with diabetes, and hypoglycemia attacks are observed more frequently depending on the severity of pancreatic insufficiency.
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Affiliation(s)
- Ahmet Basturk
- Department of Pediatric Gastroenterology, Faculty of Medicine, Gaziantep University, Üniversite Bulvar P.K. 27310, Şehitkamil/Gaziantep, Turkey.
| | - Yusuf Curek
- Department of Pediatric Endocrinology, Antalya Education and Research Hospital, Kazım Karabekir St. 07100, Antalya, Turkey
| | - Rasih Felek
- Department of Microbiology, Faculty of Medicine, Akdeniz University, Dumlupinar Bulvari-Campus 07059, Antalya, Turkey
| | - Gamze Celmeli
- Department of Pediatric Endocrinology, Antalya Education and Research Hospital, Kazım Karabekir St. 07100, Antalya, Turkey
| | - Reha Artan
- Department of Pediatric Gastroenterology, Faculty of Medicine, Akdeniz University, Dumlupinar Bulvari-Campus 07059, Antalya, Turkey
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Phillips ME, Hopper AD, Leeds JS, Roberts KJ, McGeeney L, Duggan SN, Kumar R. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000643. [PMID: 34140324 PMCID: PMC8212181 DOI: 10.1136/bmjgast-2021-000643] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines.
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Affiliation(s)
- Mary E Phillips
- Nutrition and Dietetics, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Andrew D Hopper
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - John S Leeds
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, UK
| | - Keith J Roberts
- HPB Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Laura McGeeney
- Nutrition and Dietetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sinead N Duggan
- Department of Surgery, Trinity College Dublin, Dublin, Ireland
| | - Rajesh Kumar
- HPB Surgery, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
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Lam ATN, Aksit MA, Vecchio-Pagan B, Shelton CA, Osorio DL, Anzmann AF, Goff LA, Whitcomb DC, Blackman SM, Cutting GR. Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis. J Clin Invest 2020; 130:272-286. [PMID: 31581148 DOI: 10.1172/jci129833] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 09/25/2019] [Indexed: 12/16/2022] Open
Abstract
Diabetes is a common complication of cystic fibrosis (CF) that affects approximately 20% of adolescents and 40%-50% of adults with CF. The age at onset of CF-related diabetes (CFRD) (marked by clinical diagnosis and treatment initiation) is an important measure of the disease process. DNA variants associated with age at onset of CFRD reside in and near SLC26A9. Deep sequencing of the SLC26A9 gene in 762 individuals with CF revealed that 2 common DNA haplotypes formed by the risk variants account for the association with diabetes. Single-cell RNA sequencing (scRNA-Seq) indicated that SLC26A9 is predominantly expressed in pancreatic ductal cells and frequently coexpressed with CF transmembrane conductance regulator (CFTR) along with transcription factors that have binding sites 5' of SLC26A9. These findings were replicated upon reanalysis of scRNA-Seq data from 4 independent studies. DNA fragments derived from the 5' region of SLC26A9-bearing variants from the low-risk haplotype generated 12%-20% higher levels of expression in PANC-1 and CFPAC-1 cells compared with the high- risk haplotype. Taken together, our findings indicate that an increase in SLC26A9 expression in ductal cells of the pancreas delays the age at onset of diabetes, suggesting a CFTR-agnostic treatment for a major complication of CF.
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Affiliation(s)
- Anh-Thu N Lam
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Melis A Aksit
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Briana Vecchio-Pagan
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Applied Physics Laboratory, Johns Hopkins University, Laurel, Maryland, USA
| | - Celeste A Shelton
- University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Ariel Precision Medicine, Pittsburgh, Pennsylvania, USA
| | - Derek L Osorio
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Arianna F Anzmann
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Loyal A Goff
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Scott M Blackman
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Garry R Cutting
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Lam KW, Leeds J. How to manage: patient with a low faecal elastase. Frontline Gastroenterol 2019; 12:67-73. [PMID: 33489070 PMCID: PMC7802491 DOI: 10.1136/flgastro-2018-101171] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Kwan Wai Lam
- Pancreaticobiliary Medicine, Freeman Hospital, Newcastle upon Tyne, Newcastle upon Tyne, UK
| | - John Leeds
- Pancreaticobiliary Medicine, Freeman Hospital, Newcastle upon Tyne, Newcastle upon Tyne, UK
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13
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[Other specific types of diabetes and exocrine pancreatic insufficiency (Update 2019)]. Wien Klin Wochenschr 2019; 131:16-26. [PMID: 30980164 DOI: 10.1007/s00508-019-1454-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The heterogenous catagory "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e. g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART)), genetic forms of diabetes (e. g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down Syndrome, Klinefelter Syndrome, Turner Syndrome), pancreatogenic diabetes (e. g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.
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14
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Jalal M, Campbell JA, Hopper AD. Practical guide to the management of chronic pancreatitis. Frontline Gastroenterol 2019; 10:253-260. [PMID: 31288255 PMCID: PMC6583580 DOI: 10.1136/flgastro-2018-101071] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 08/19/2018] [Indexed: 02/04/2023] Open
Abstract
Chronic pancreatitis (CP) is an irreversible fibroinflammatory disorder of the pancreas. It presents with relapsing, remitting upper abdominal pain accompanied by features of malabsorption due to pancreatic exocrine insufficiency and endocrine deficiency with the development of diabetes mellitus. The associated increased hospitalisation and high economic burden are related to CP often presenting at advanced stage with irreversible consequences. Diagnosing CP at an early stage is still challenging and therefore CP is believed to be under-reported. Our understanding of this disease has evolved over the last few years with attempts to redesign the definition of CP. Better recognition of the risk factors and conditions associated with CP can lead to an earlier diagnosis and coupled with a multidisciplinary approach to treatment, ultimately reduce complications. This article reviews the epidemiology, risk factors, diagnosis and management of CP.
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Affiliation(s)
- Mustafa Jalal
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | | | - Andrew D Hopper
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
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15
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Zsóri G, Illés D, Terzin V, Ivány E, Czakó L. Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review. Pancreatology 2018; 18:559-565. [PMID: 29779830 DOI: 10.1016/j.pan.2018.05.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Revised: 05/11/2018] [Accepted: 05/12/2018] [Indexed: 12/11/2022]
Abstract
The exocrine and endocrine pancreata are very closely linked both anatomically and physiologically. Abdominal symptoms such as nausea, bloating, diarrhea, steatorrhea, and weight loss can often occur in diabetic patients. Impairments of the exocrine pancreatic function seem to be a frequent complication of diabetes mellitus; however, they are largely overlooked. The aim of this paper is to provide an overview of the current concepts of exocrine pancreatic insufficiency (PEI) in diabetes mellitus. The prevalence and symptoms of PEI in diabetes mellitus, the pathomechanism, and difficulties of diagnosis and therapy of PEI are summarized in this systematic review.
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Affiliation(s)
- Gábor Zsóri
- University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Center, First Department of Medicine, Szeged, Korányi Fasor 8-10, H-6720, Hungary.
| | - Dóra Illés
- University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Center, First Department of Medicine, Szeged, Korányi Fasor 8-10, H-6720, Hungary
| | - Viktória Terzin
- University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Center, First Department of Medicine, Szeged, Korányi Fasor 8-10, H-6720, Hungary
| | - Emese Ivány
- University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Center, First Department of Medicine, Szeged, Korányi Fasor 8-10, H-6720, Hungary
| | - László Czakó
- University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Center, First Department of Medicine, Szeged, Korányi Fasor 8-10, H-6720, Hungary
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16
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Lindkvist B, Nilsson C, Kvarnström M, Oscarsson J. Importance of pancreatic exocrine dysfunction in patients with type 2 diabetes: A randomized crossover study. Pancreatology 2018; 18:550-558. [PMID: 29802077 DOI: 10.1016/j.pan.2018.05.483] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 05/16/2018] [Accepted: 05/18/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Levels of faecal elastase-1 (FE-1), a marker of exocrine pancreatic function, are lower in patients with type 2 diabetes than without diabetes. We aimed to investigate the association between FE-1 and nutritional status, gastrointestinal symptoms, and lipid absorption. METHODS This randomized, open-label, crossover study included 315 patients with type 2 diabetes aged 18-70 years treated with oral antidiabetics, with HbA1c 6.5-9.0% and BMI 18-40 kg/m2. Assessments included levels of FE-1 and blood biomarkers of nutrition, and Bristol Stool Scale and Gastrointestinal Symptom Rating Scale (GSRS) scores. Plasma exposure of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after oral administration of free omega-3 carboxylic acids or ethyl esters with breakfast was investigated in patients with low, intermediate, and normal FE-1 levels. RESULTS The prevalence of low and intermediate FE-1 levels was 5.2% and 4.9%, respectively. Bristol Stool Scale scores and mean values of GSRS Diarrhoea and Indigestion domain symptoms were similar across groups, but patients with low FE-1 were heavier and reported lower stool frequency. FE-1 levels correlated positively with plasma levels of amylase, lipase, 25-hydroxy vitamin D, and albumin. Mean EPA + DHA exposure was similarly higher after intake of free vs. esterified omega-3 fatty acids in all FE-1 groups. CONCLUSIONS The prevalence of low FE-1 (<100 μg/g) as a measure of pancreatic exocrine insufficiency was infrequent in type 2 diabetes. Except for low plasma concentrations of EPA and 25-hydroxy vitamin D, type 2 diabetes patients with low FE-1 had no other signs of malabsorption or gastrointestinal disorders. Plasma levels of EPA and DHA after the intake of esterified versus free EPA and DHA did not correlate with FE-1 levels. TRIAL REGISTRATION ClinicalTrials.gov NCT02370537.
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Affiliation(s)
- Björn Lindkvist
- Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
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17
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Elder PJD, Ramsden DB, Burnett D, Weickert MO, Barber TM. Human amylase gene copy number variation as a determinant of metabolic state. Expert Rev Endocrinol Metab 2018; 13:193-205. [PMID: 30063422 DOI: 10.1080/17446651.2018.1499466] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Humans have multiple genes encoding amylase that are broadly divided into salivary (AMY1) and pancreatic (AMY2) genes. They exhibit some of the greatest copy numbers of any human gene, an expansion possibly driven by increased dietary starch intake. Within the population, amylase gene copy number is highly variable and there is evidence of an inverse association between AMY1 copy number and BMI. AREAS COVERED We examine the evidence for the link between AMY1 and BMI, its potential mechanisms, and the metabolic effects of salivary and pancreatic amylase, both in the gastrointestinal tract and the blood EXPERT COMMENTARY Salivary amylase may influence postprandial 'cephalic phase' insulin release, which improves glucose tolerance, while serum amylase may have insulin-sensitizing properties. This could explain the favorable metabolic status associated with higher AMY1 copy number. The association with BMI is harder to explain and is potentially mediated by increased flux of undigested starch into the ileum, with resultant effects on short-chain fatty acids (SCFAs), changes in gut microbiota and effects on appetite and energy expenditure in those with low copy number. Future research on the role of amylase as a determinant of metabolic health and BMI may lead to novel therapies to target obesity.
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Affiliation(s)
- Patrick J D Elder
- a Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire , Coventry , UK
| | - David B Ramsden
- b Institute of Metabolism and Systems Research, The Medical School, University of Birmingham , Birmingham , UK
| | - David Burnett
- c Micropathology Ltd, University of Warwick Science Park , Coventry , UK
| | - Martin O Weickert
- a Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire , Coventry , UK
- d Division of Biomedical Sciences , Warwick Medical School, University of Warwick , Coventry , UK
- e Centre of Applied Biological & Exercise Sciences, Faculty of Health & Life Sciences , Coventry University , Coventry , UK
| | - Thomas M Barber
- a Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire , Coventry , UK
- d Division of Biomedical Sciences , Warwick Medical School, University of Warwick , Coventry , UK
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18
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Othman MO, Harb D, Barkin JA. Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician. Int J Clin Pract 2018; 72:e13066. [PMID: 29405509 PMCID: PMC5873407 DOI: 10.1111/ijcp.13066] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 01/08/2018] [Indexed: 12/14/2022] Open
Abstract
AIMS In exocrine pancreatic insufficiency (EPI), the quantity and/or activity of pancreatic digestive enzymes are below the levels required for normal digestion, leading to maldigestion and malabsorption. Diagnosis of EPI is often challenging because the characteristic signs and symptoms overlap with those of other gastrointestinal conditions. Additionally, there is no single convenient, or specific diagnostic test for EPI. The aim of this review is to provide a framework for differential diagnosis of EPI vs other malabsorptive conditions. METHODS This is a non-systematic narrative review summarising information pertaining to the aetiology, diagnosis and management of EPI. RESULTS Exocrine pancreatic insufficiency may be caused by pancreatic disorders, including chronic pancreatitis, cystic fibrosis, pancreatic resection and pancreatic cancer. EPI may also result from extra-pancreatic conditions, including coeliac disease, Zollinger-Ellison syndrome and gastric surgery. Timely and accurate diagnosis of EPI is important, as delays in treatment prolong maldigestion and malabsorption, with potentially serious consequences for malnutrition, overall health and quality of life. Symptoms of EPI are non-specific; therefore, a high index of clinical suspicion is required to make a correct diagnosis.
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Affiliation(s)
- Mohamed O. Othman
- Division of GastroenterologyDepartment of MedicineBaylor College of MedicineHoustonTXUSA
| | - Diala Harb
- Global Medical AffairsAbbVie Inc.MettawaILUSA
| | - Jodie A. Barkin
- Division of GastroenterologyDepartment of MedicineLeonard M. Miller School of MedicineUniversity of MiamiMiamiFLUSA
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19
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Prasanna Kumar HR, Gowdappa HB, Hosmani T, Urs T. Exocrine Dysfunction Correlates with Endocrinal Impairment of Pancreas in Type 2 Diabetes Mellitus. Indian J Endocrinol Metab 2018; 22:121-125. [PMID: 29535950 PMCID: PMC5838891 DOI: 10.4103/ijem.ijem_139_17] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Diabetes mellitus (DM) is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1) is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. AIM The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM) by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. METHODOLOGY A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics). Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t-test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. RESULTS Statistically nonsignificant (P = 0.5051) relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation (P = 0.003) between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy (P = 0.001) and peripheral pulses (P = 0.001) with FE-1 levels were found to be statistically significant. CONCLUSION This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.
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Affiliation(s)
- H. R. Prasanna Kumar
- Department of Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India
| | - H. Basavana Gowdappa
- Department of Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India
| | - Tejashwi Hosmani
- Department of Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India
| | - Tejashri Urs
- Department of Microbiology, JSS Medical College, JSS University, Mysore, Karnataka, India
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20
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Singh VK, Haupt ME, Geller DE, Hall JA, Quintana Diez PM. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 2017; 23:7059-7076. [PMID: 29093615 PMCID: PMC5656454 DOI: 10.3748/wjg.v23.i39.7059] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 05/27/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.
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Affiliation(s)
- Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Mark E Haupt
- Medical Affairs, AbbVie Inc., North Chicago, IL 60064, United States
| | - David E Geller
- Cystic Fibrosis Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
| | - Jerry A Hall
- CREON® Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
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21
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Prevalence of exocrine pancreatic insufficiency in patients with chronic pancreatitis without follow-up. PANCR-EVOL Study. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 41:77-86. [PMID: 28935122 DOI: 10.1016/j.gastrohep.2017.08.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 06/20/2017] [Accepted: 08/08/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND/OBJECTIVES Exocrine pancreatic insufficiency (EPI) is an important complication of chronic pancreatitis (CP). Guidelines recommend to rule out EPI in CP, to detect those patients who would benefit from pancreatic enzyme replacement therapy. The aim of this study was to evaluate the prevalence of EPI in patients with CP without follow-up in the last 2 years and to describe their nutritional status and quality of life (QoL). METHODS This was a cross-sectional, multicenter Spanish study. CP patients without follow-up by a gastroenterologist or surgeon in at least 2 years were included. EPI was defined as fecal elastase test <200mcg/g. For nutritional assessment, laboratory and anthropometric data were obtained. QoL was investigated using the EORTC QLQ-C30 questionnaire. RESULTS 64 patients (mean age 58.8±10.3 years, 85.9% men) from 10 centers were included. Median time since diagnosis of CP was 58.7 months [37.7-95.4]. Forty-one patients (64.1%) had EPI. Regarding nutritional status, the following differences were observed (EPI vs. Non-EPI): BMI (23.9±3.5kg/m2 vs. 25.7±2.5, p=0.03); glucose (121 [96-189] mg/dL vs. 98 [90-116], p=0.006); HbA1c 6.6% [6.0-8.4] vs. 5.5 [5.3-6.0], p=0.0005); Vitamin A (0.44mg/L [0.35-0.57] vs. 0.53 [0.47-0.63], p=0.048) and Vitamin E (11.2±5.0μg/ml vs. 14.4±4.3, p=0.03). EPI group showed a worse EORTC QLQ-C30 score on physical (93.3 [66.7-100] vs. 100 [93.3-100], p=0.048) and cognitive function (100 [83.3-100] vs. 100 [100-100], p=0.04). CONCLUSIONS Prevalence of EPI is high in patients with CP without follow-up. EPI group had higher levels of glucose, lower levels of vitamins A and E and worse QoL.
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22
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Pei G, Lv W, Li X, Zhang G, Zhang J. Influence of SPK with Enteric Drainage on the Pancreatic Exocrine Function in Diabetic Patients with Uremia. Int J Endocrinol 2017; 2017:3709306. [PMID: 29138633 PMCID: PMC5613707 DOI: 10.1155/2017/3709306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 06/26/2017] [Accepted: 07/17/2017] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE This study aimed to determine the use of fecal elastase in evaluating the effect of simultaneous pancreas-kidney transplantation with enteric drainage on the pancreatic exocrine function of diabetic patients with uremia. METHODS A total of 19 patients with simultaneous pancreas-kidney transplantation (SPK) with enteric drainage, 31 diabetic patients with uremia (chronic renal failure (CRF)), 22 diabetic patients with uremia who underwent renal transplantation (RT), and 20 normal individuals (CON) were included in the study. Pancreatic exocrine insufficiency was determined using fecal elastase. Results. The fecal pancreatic elastase level in SPK patients with enteric drainage was 479 μg/g, which was significantly higher than 229 μg/g in CRF patients and 197 μg/g in RT patients. Using 200 μg/g as the established threshold, a reduced fecal pancreatic elastase level was found in 14/31 of CRF patients, 12/22 of RT patients, 1/19 of SPK patients with enteric drainage, and 1/20 of CON patients. The correlation analysis revealed a significant association between fecal elastase and glycosylated hemoglobin. CONCLUSIONS The present study indicated that SPK with enteric drainage improves pancreatic endocrine and exocrine functions. Fecal elastase may be a clinically relevant means to determine the therapeutic effects.
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Affiliation(s)
- Guanghui Pei
- Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
- Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Wu Lv
- Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
- Department of General Surgery, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Xiaohang Li
- Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Guoqing Zhang
- Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Jialin Zhang
- Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
- *Jialin Zhang:
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23
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Kangrga RN, Ignjatović SD, Dragašević MM, Jovičić SŽ, Majkić-Singh NT. Pancreatic Elastase Levels in Feces As A Marker of Exocrine Pancreatic Function in Patients With Diabetes Mellitus. Lab Med 2016; 47:140-8. [PMID: 27069032 DOI: 10.1093/labmed/lmw015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE The measurement of pancreatic elastase (PE) in feces is used widely to screen for pancreatic exocrine insufficiency. The aim of our study was to evaluate the relationship of PE with residual beta cell secretion and metabolic control in patients with diabetes mellitus. METHOD We determined the presence of PE in specimens via enzyme-linked immunosorbent assay (ELISA), whereas serum fasting glucose, C-peptide, amylase, lipase, triglycerides, total 25(OH)-vitamin D, C-reactive protein (CRP), and hemoglobin A1c (HbA1c) concentrations were assayed using routine laboratory tests. RESULTS PE values in 48 patients with diabetes were significantly lower than in 24 healthy volunteers (P = 001). In one-third of participants with diabetes mellitus, PE were less than 200 µg per g, indicating pancreatic functional insufficiency. Among the patients in the cohort, PE correlated positively with C-peptide levels (P = 04), lipase (P = 009), CRP (P = 04), sex (P = 03), and BMI (P = 02) but not significantly with duration of diabetes (P = 81) or levels of HbA1c(P = 87), amylase (P = 06), total 25(OH)-vitamin D (P = 16), or triglycerides (P = 52). CONCLUSION Our results demonstrated a strong association of diabetes with low PE levels.
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Affiliation(s)
- Ranka N Kangrga
- Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia
| | - Svetlana D Ignjatović
- Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia, Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia
| | - Mirjana M Dragašević
- Clinic for Endocrinology, Clinical Center of Serbia, Belgrade, Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, and
| | - Snežana Ž Jovičić
- Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia, Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia,
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Abstract
OBJECTIVE Abnormalities in exocrine pancreatic function have been reported in diabetes mellitus (DM). We reviewed published literature to determine the nature of structural and functional alterations in the exocrine pancreas in DM. METHODS We identified and abstracted data from original studies (n = 50) describing morphological, structural, and functional changes in the exocrine pancreas in types 1 and 2 DM. RESULTS Pancreatic weight and volume are markedly lower in type 1 DM (P < 0.005) with insignificant decrease in type 2 DM compared with age-, sex-, and body mass index-matched controls. Pancreatic histopathological changes seen in most subjects with DM at autopsy (n = 7 studies, 1272 autopsies) include mild-to-marked interacinar fibrosis, scant inflammatory infiltrate, no pancreatic ductal changes, and hyalinization of arteries. In subjects with DM, pooled prevalence of decreased fecal elastase 1 (<200 μg/g) is higher, coefficient of fat absorption is near normal (mean, 91%-94%), and pancreatic exocrine dysfunction is nonprogressive over time. Diabetes mellitus is asymptomatic in regard to the exocrine pancreas. CONCLUSIONS In types 1 and 2 DM, moderate-to-severe subclinical pancreatic fibrosis and modest exocrine dysfunction occurs in the absence of clinical or histopathological evidence of chronic pancreatitis. We call this novel entity "diabetic exocrine pancreatopathy."
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25
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Exokrine Pankreasinsuffizienz und Diabetes mellitus. Wien Klin Wochenschr 2016; 128 Suppl 2:S163-6. [DOI: 10.1007/s00508-015-0934-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Li BR, Pan J, Du TT, Liao Z, Ye B, Zou WB, Chen H, Ji JT, Zheng ZH, Wang D, Lin JH, Ning SB, Hu LH, Li ZS. Risk Factors for Steatorrhea in Chronic Pancreatitis: A Cohort of 2,153 Patients. Sci Rep 2016; 6:21381. [PMID: 26877248 PMCID: PMC4753434 DOI: 10.1038/srep21381] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 01/22/2016] [Indexed: 02/08/2023] Open
Abstract
This study aimed to investigate the occurrence of and determine the risk factors for steatorrhea in chronic pancreatitis (CP). It was based on analysis of both retrospectively and prospectively acquired database for CP patients admitted to our center from January 2000 to December 2013. Demographic data, course of disease, medical history, and follow-up evaluations of patients were documented in detail. Cumulative rate of steatorrhea was calculated by using the Kaplan-Meier method. For risk factor analysis, multivariate analysis by Cox proportional hazards regression model was performed. A total of 2,153 CP patients were included with a mean follow-up duration of 9.3 years. Approximately 14% (291/2,153) of CP patients presented with steatorrhea at diagnosis of CP. Cumulative rates of steatorrhea at 1, 5, 10, and 20 years after diagnosis of CP were 4.27% (95% CI: 3.42%-5.34%), 12.53% (95% CI: 10.74%-14.59%), 20.44% (95% CI: 17.37%-23.98%) and 30.82% (95% CI: 20.20%-45.21%), respectively. Male gender (HR = 1.771, p = 0.004), diabetes (HR = 1.923, p < .001), alcohol abuse (HR = 1.503, p = 0.025) and pancreaticoduodenectomy (HR = 2.901, p < 0.001) were independent risk factors for steatorrhea while CP in adolescents (HR = 0.433, p = 0.009) was a protective factor. In conclusion, male gender, adult, diabetes, alcohol abuse and pancreaticoduodenectomy lead to increased risk of steatorrhea in CP patients.
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Affiliation(s)
- Bai-Rong Li
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China.,Department of Gastroenterology, Air Force General Hospital, Beijing, China
| | - Jun Pan
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Ting-Ting Du
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Zhuan Liao
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Bo Ye
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Wen-Bin Zou
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Hui Chen
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Jun-Tao Ji
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Zhao-Hong Zheng
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Dan Wang
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Jin-Huan Lin
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Shou-Bin Ning
- Department of Gastroenterology, Air Force General Hospital, Beijing, China
| | - Liang-Hao Hu
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology &Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China
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Rathmann W, Haastert B, Oscarsson J, Berglind N, Lindkvist B, Wareham NJ. Association of faecal elastase 1 with non-fasting triglycerides in type 2 diabetes. Pancreatology 2016; 16:563-9. [PMID: 27086060 PMCID: PMC6215701 DOI: 10.1016/j.pan.2016.03.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 02/22/2016] [Accepted: 03/21/2016] [Indexed: 12/11/2022]
Abstract
AIMS Intestinal absorption of esterified fatty acids depends on exocrine pancreatic function and influences plasma triglycerides levels. The aim was to investigate the association of reduced exocrine pancreatic function (low fecal elastase-1; FE1) with plasma triglycerides in type 2 diabetes and controls without diabetes. METHODS FE1 (μg/g stool) and non-fasting plasma triglyceride measurements were undertaken in 544 type 2 diabetes patients (age: 63 ± 8 years) randomly selected from diabetes registers in Cambridgeshire (UK), and 544 matched controls (age, sex, practice) without diabetes. Linear regression models were fitted using FE1 as dependent and log-triglycerides as independent variable adjusting for sex, age, body mass index, alcohol consumption, serum lipase, HbA1c, and smoking. RESULTS FE1 concentrations were lower (mean ± SD: 337 ± 204 vs. 437 ± 216 μg/g, p < 0.05) and plasma triglycerides were higher (geometric mean */: standard deviation factor: 2.2*/:1.9 vs. 1.6*/:1.8 mmol/l, p < 0.05) in type 2 diabetes compared to controls, respectively. Within the category of type 2 diabetes and controls separately, a 10% increase in plasma triglycerides was associated with 4.5 μg/g higher FE1 concentrations (p < 0.01) after adjusting for confounders. In contrast, in diabetes patients and controls with pathological FE1 (<100 μg/g), low FE1 levels were associated with high plasma triglycerides (significant only in controls). CONCLUSIONS Non-fasting triglycerides were positively related to FE1 in both type 2 diabetes and controls suggesting that impairment of exocrine pancreas function is influencing plasma triglycerides. Marked loss of exocrine pancreatic function had the opposite effect, resulting in higher levels of plasma triglycerides.
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Affiliation(s)
- Wolfgang Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf, Germany
| | | | | | | | - Björn Lindkvist
- Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Shivaprasad C, Pulikkal AA, Kumar KMP. Pancreatic exocrine insufficiency in type 1 and type 2 diabetics of Indian origin. Pancreatology 2015; 15:616-9. [PMID: 26549275 DOI: 10.1016/j.pan.2015.09.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 08/22/2015] [Accepted: 09/21/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency has been frequently described in both type 1 and type 2 diabetes. Fecal elastase test has been demonstrated to have good correlation with direct tests for exocrine function, especially in moderate to severe cases. There are no data on the prevalence of pancreatic exocrine insufficiency in Indian patients with diabetes utilizing FEC concentrations. The objective of our study is to evaluate the prevalence of pancreatic exocrine insufficiency (PEI) in type 1 and type 2 diabetes and study the impact of PEI on glycemic control and metabolic parameters in diabetes. METHODS AND MATERIALS We conducted a cross sectional study on 89 T1D, 95 T2D patients and 90 healthy controls. Biochemical parameters including FBS, HbA1c, serum albumin and serum calcium were estimated. Fecal elastase concentrations (FEC) were estimated by ELISA. Patients with FEC <200 μg/g were considered to have pancreatic exocrine insufficiency. RESULTS The prevalence of PEI was 31.4% in T1D, 29.4% in T2D and 4.4% in controls (P < 0.01). A significant negative correlation was observed between FEC levels and, both FBS and HbA1c in diabetic patients. There was also a significant positive correlation between BMI and FEC. There was no significant association between low FEC and other biochemical parameters. CONCLUSION Nearly one third of patients with both T1D and T2D showed evidence of impaired exocrine function utilizing FEC test. Presence of PEI correlated with lower BMI and higher HbA1c.
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Affiliation(s)
- C Shivaprasad
- Department of Endocrinology & Metabolism, Vydehi Institute of Medical Sciences, Bangalore, India.
| | - Annie A Pulikkal
- Department of Endocrinology & Metabolism, Vydehi Institute of Medical Sciences, Bangalore, India
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Piciucchi M, Capurso G, Archibugi L, Delle Fave MM, Capasso M, Delle Fave G. Exocrine pancreatic insufficiency in diabetic patients: prevalence, mechanisms, and treatment. Int J Endocrinol 2015; 2015:595649. [PMID: 25892991 PMCID: PMC4393909 DOI: 10.1155/2015/595649] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 02/28/2015] [Accepted: 03/09/2015] [Indexed: 02/07/2023] Open
Abstract
Pancreas is a doubled-entity organ, with both an exocrine and an endocrine component, reciprocally interacting in a composed system whose function is relevant for digestion, absorption, and homeostasis of nutrients. Thus, it is not surprising that disorders of the exocrine pancreas also affect the endocrine system and vice versa. It is well-known that patients with chronic pancreatitis develop a peculiar form of diabetes (type III), caused by destruction and fibrotic injury of islet cells. However, less is known on the influence of diabetes on pancreatic exocrine function. Pancreatic exocrine insufficiency (PEI) has been reported to be common in diabetics, with a prevalence widely ranging, in different studies, in both type I (25-74%) and type II (28-54%) diabetes. A long disease duration, high insulin requirement, and poor glycemic control seem to be risk factors for PEI occurrence. The impact of pancreatic exocrine replacement therapy on glycemic, insulin, and incretins profiles has not been fully elucidated. The present paper is aimed at reviewing published studies investigating the prevalence of PEI in diabetic patients and factors associated with its occurrence.
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Affiliation(s)
- Matteo Piciucchi
- Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Gabriele Capurso
- Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Livia Archibugi
- Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Martina Maria Delle Fave
- Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Marina Capasso
- Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
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Pezzilli R, Andriulli A, Bassi C, Balzano G, Cantore M, Fave GD, Falconi M, Group LFTEPIC(EPI. Exocrine pancreatic insufficiency in adults: A shared position statement of the Italian association for the study of the pancreas. World J Gastroenterol 2013; 19:7930-7946. [PMID: 24307787 PMCID: PMC3848141 DOI: 10.3748/wjg.v19.i44.7930] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 08/18/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas (AISP). We covered the main diseases associated with exocrine pancreatic insufficiency (EPI) which are of common interest to internists/gastroenterologists, oncologists and surgeons, fully aware that EPI may also occur together with many other diseases, but less frequently. A preliminary manuscript based on an extended literature search (Medline/PubMed, Cochrane Library and Google Scholar) of published reports was prepared, and key recommendations were proposed. The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012. Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached. The final draft of the manuscript was then sent to the AISP Council for approval and/or modification. All concerned parties approved the final version of the manuscript in June 2013.
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Weitgasser R, Abrahamian H, Clodi M, Fortunat W, Hammer H. [Position paper: Exocrine pancreatic insufficiency and diabetes mellitus]. Wien Klin Wochenschr 2013; 124 Suppl 2:100-3. [PMID: 23250472 DOI: 10.1007/s00508-012-0290-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Exocrine pancreatic insufficiency in diabetic patients is frequent. Studies based on fecal elastase-1 measurement give prevalence rates of about 50 % in type 1 and 33 % in type 2 diabetic patients. Nevertheless, not all patients report typical symptoms like diarrhea, steatorrhea and weight loss. For indirect testing the determination of fecal elastase-1 has the highest sensitivity and specificity. This test should be performed at least in all symptomatic patients. For differential diagnosis celiac disease (with a prevalence of about 3-5 % of type 1 diabetic patients), autonomic neuropathy, but also diseases like irritable colon and gastrointestinal tumors have to be taken into account. Patients with symptoms and a fecal elastase-1 < 100 µg/g should be treated with pancreas enzymes in adequate daily doses administered at main meals. Treatment improves symptoms significantly, supply with fat soluble vitamins is normalised, risk for osteoporosis is reduced. An improvement of glucose metabolism is but not seen in all studies. A pancreatogenic diabetes, also termed as type 3c diabetes, has not primarily to be treated with insulin, often-at least initially-treatment with oral antidiabetic drugs is possible and sufficient.
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Affiliation(s)
- Raimund Weitgasser
- Abteilung für Innere Medizin, Diakonissen-Krankenhaus, Salzburg, Österreich.
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Vujasinovic M, Zaletel J, Tepes B, Popic B, Makuc J, Epsek Lenart M, Predikaka M, Rudolf S. Low prevalence of exocrine pancreatic insufficiency in patients with diabetes mellitus. Pancreatology 2013; 13:343-346. [PMID: 23890131 DOI: 10.1016/j.pan.2013.05.010] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2013] [Revised: 05/30/2013] [Accepted: 05/31/2013] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Exocrine pancreatic insufficiency (EPI) can occur in patients with diabetes mellitus (DM). Incidence of EPI and its clinical significance remain poorly defined. The aim of our study was to determine whether exocrine pancreatic function is impaired in patients with DM. PATIENTS AND METHODS One hundred and fifty consecutive patients, mean age 59.0 (± 12.0 years), with DM lasting at least 5 years were included in the study. We included 50 patients with type 1 DM (DM1), 50 insulin-treated patients DM type 2 (DM2-insulin) and 50 non-insulin treated patients with DM type 2 (DM2 no-insulin). Diagnosis of DM was established from health records, lasting 15.0 ± 9.9 years on average. EPI was diagnosed with a fecal elastase-1 concentration (FE1) of less than 200 μg/g (ELISA). RESULTS FE1 was reduced in 8 (5.4%) patients: mildly reduced (100-200 μg/g) in 4 patients (2.7%) and markedly reduced (<100 μg/g) in 4 patients (2.7%). Frequency of EPI was 3 in DM1, 5 in DM2(insulin) and none in DM2 (no-insulin) groups. CONCLUSIONS EPI in DM occurred less frequently than in previous studies, probably due to our strict exclusion criteria (age, alcohol intake).
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Affiliation(s)
- Miroslav Vujasinovic
- Department of Internal Medicine, Slovenj Gradec General Hospital, Gosposvetska 1, 2380 Slovenj Gradec, Slovenia.
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Ewald N, Bretzel RG. Diabetes mellitus secondary to pancreatic diseases (Type 3c)--are we neglecting an important disease? Eur J Intern Med 2013; 24:203-6. [PMID: 23375619 DOI: 10.1016/j.ejim.2012.12.017] [Citation(s) in RCA: 105] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 12/22/2012] [Indexed: 12/29/2022]
Abstract
Type 3c diabetes mellitus (T3cDM) is a clinically relevant condition with a prevalence of 5-10% among all diabetic subjects in Western populations. Its prevalence and clinical importance have been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes, the endocrinopathy in T3cDM is very complex and complicated by additional present comorbidities such as maldigestion and concommitant qualitative malnutrition. The failure to correctly diagnose T3cDM leads to failure to implement an appropriate medical therapy of these patients. Physicians should screen for important and easily reversable pathological conditions such as exocrine insufficiency, lack of fat-soluble vitamins (especially vitamin D) and impairment of fat hydrolysis and incretin secretion which are found very commonly in T3cDM. Since most patients with T3cDM suffer from chronic pancreatitis, physicians must additionally be aware of the elevated risk of pancreatic cancer in this subset of patients.
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Affiliation(s)
- Nils Ewald
- Third Medical Department, University Hospital Giessen and Marburg, Giessen Site, Klinikstrasse 33, Giessen, Germany.
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Nakajima K, Oshida H, Muneyuki T, Kakei M. Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency. CORE EVIDENCE 2012; 7:77-91. [PMID: 22936895 PMCID: PMC3426252 DOI: 10.2147/ce.s26705] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type 2), and among elderly subjects. Finally, although there is currently limited clinical evidence, numerous extrapancreatic diseases and conditions that are highly prevalent in the general population may also be considered potential targets for PERT and related treatments.
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Affiliation(s)
- Kei Nakajima
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado
| | - Haruki Oshida
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado
| | - Toshitaka Muneyuki
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Amanuma, Omiya, Saitama, Japan
| | - Masafumi Kakei
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Amanuma, Omiya, Saitama, Japan
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Muneyuki T, Nakajima K, Aoki A, Yoshida M, Fuchigami H, Munakata H, Ishikawa SE, Sugawara H, Kawakami M, Momomura SI, Kakei M. Latent associations of low serum amylase with decreased plasma insulin levels and insulin resistance in asymptomatic middle-aged adults. Cardiovasc Diabetol 2012; 11:80. [PMID: 22748134 PMCID: PMC3439247 DOI: 10.1186/1475-2840-11-80] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2012] [Accepted: 06/15/2012] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Low serum amylase is likely to be associated with obesity and metabolic abnormalities, which are often accompanied by impaired insulin action. However, it is unclear whether low serum amylase is associated with impaired insulin action in clinical settings. Therefore, we investigated the associations of low serum amylase with plasma insulin levels, and obesity-related parameters, including leptin. RESEARCH DESIGN AND METHODS We measured serum amylase, plasma insulin, obesity-related parameters such as leptin, cardiometabolic risk factors, and anthropometric parameters in a cross-sectional study of 54 asymptomatic subjects (mean age 48.6 ± 7.6 years) who were not being treated for diabetes. RESULTS Body mass index (BMI) and plasma glucose at 120 min after a 75-g oral glucose tolerance test (OGTT) were significantly higher in subjects with low serum amylase (< 60 IU/l, n = 21) than in those with normal-to-high serum amylase (n = 33) (P = 0.04 and P = 0.004, respectively). In univariate correlation analysis, serum amylase was significantly correlated with BMI alone (r = -0.39, P = 0.004). By contrast, multivariate logistic analysis showed that each 1-SD increase in quantitative insulin sensitivity check index, and each 1-SD decrease in plasma insulin OGTT at 0 and 60 min, homeostasis model assessment of insulin resistance (HOMA)-R, and HOMA-β were significantly associated with low serum amylase, particularly after adjusting for BMI. When subjects were divided into three groups according to HOMA-R, serum amylase levels were significantly lower in subjects with HOMA-R > 2.5 (n = 23) compared with subjects with HOMA-R 1.6-2.5 (n = 10) (61.1 ± 13.6 U/ml versus 76.9 ± 20.5 U/ml, Bonferroni test, P = 0.02), but not compared with subjects with HOMA-R<1.6 (n = 21; 62.7 ± 17.6 U/ml). Similar trends were observed when subjects were divided according to plasma leptin and fasting plasma insulin levels. CONCLUSIONS These results suggest that after adjusting for BMI, low serum amylase is associated with decreased basal insulin levels and insulin secretion, as well as high insulin resistance. The nature of these associations remains to be elucidated in further studies.
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Affiliation(s)
- Toshitaka Muneyuki
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
| | - Kei Nakajima
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
- Department of Internal Medicine, Social Insurance Omiya General Hospital, 453, Bonsai, Kit, Japan
| | - Atsushi Aoki
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
| | - Masashi Yoshida
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
| | - Hiroshi Fuchigami
- Department of Health Care Center, Social Insurance Omiya General Hospital, 453 Bonsai, Kita, Saitama, 331-0805, Japan
| | - Hiromi Munakata
- Department of Internal Medicine, Social Insurance Omiya General Hospital, 453, Bonsai, Kit, Japan
| | - San-e Ishikawa
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
| | - Hitoshi Sugawara
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
| | - Masanobu Kawakami
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
| | - Shin-ichi Momomura
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
| | - Masafumi Kakei
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan
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Affiliation(s)
- Philip D Hardt
- Medizinische Klinik und Poliklinik III, Universitätsklinikum Giessen und Marburg GmbH Standort Giessen.
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Ewald N, Kaufmann C, Raspe A, Kloer HU, Bretzel RG, Hardt PD. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c). Diabetes Metab Res Rev 2012; 28:338-42. [PMID: 22121010 DOI: 10.1002/dmrr.2260] [Citation(s) in RCA: 183] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Diabetes mellitus secondary to pancreatic diseases is a condition seldom thought of in clinical practice. Yet, a high percentage of exocrine pancreatic insufficiency has been reported for the general population and especially for diabetic subjects. Thus, we investigated the prevalence of diabetes mellitus due to pancreatic diseases. METHODS In this study, we investigated 1868 patients diagnosed with diabetes mellitus who had been admitted to our hospital during the last 24 months. Patient data were diligently studied, and patients were reclassified according to the diabetes classification as proposed by the American Diabetes Association. RESULTS Among 1868 subjects, 172 patients could be classified as type 3c diabetes mellitus (9.2%). Among these were 135 diagnosed with chronic pancreatitis (78.5%), 12 with hereditary haemochromatosis, 14 with pancreatic cancer and 7 with cystic fibrosis. Thus, diabetes mellitus due to chronic pancreatitis occurred in this collective in 7.2% of all diabetic subjects. Misclassification of these patients was very common. Only 51.2% (88/172) were initially classified correctly. Most type 3 diabetes patients were initially misclassified as type 2 diabetes (69/84). CONCLUSIONS Diabetes mellitus secondary to pancreatic diseases (especially chronic pancreatitis) seems more common than generally believed with a prevalence of 9.2% among the subjects studied here. Because the awareness of this diabetes type is poor, misclassification is quite frequent. A common problem seems to be the differentiation between type 2 and type 3. Yet, the right classification of diabetes mellitus is important, because there are special therapeutic options and problems in patients with diabetes secondary to pancreatic diseases.
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Affiliation(s)
- N Ewald
- Third Medical Department and Policlinic, University Hospital Giessen and Marburg, Giessen Site, Klinikstrasse 33, Giessen, Germany.
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Teichmann J, Riemann JF, Lange U. Prevalence of exocrine pancreatic insufficiency in women with obesity syndrome: assessment by pancreatic fecal elastase 1. ISRN GASTROENTEROLOGY 2011; 2011:951686. [PMID: 22111014 PMCID: PMC3216381 DOI: 10.5402/2011/951686] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/04/2011] [Accepted: 09/13/2011] [Indexed: 12/12/2022]
Abstract
Background. Previous research on the combined association of 25-hydroxyvitamin D [25(OH)D] and exocrine pancreas insufficiency may have been limited by restricted age variability and a lack of representation of both body weight and body mass index. There are still too few conclusive reports about conspicuous vitamin D metabolism according to pancreatic fecal elastase 1 (FE1) in obese patients. Methods. Between May 2004 and July 2008, we investigated in 125 female patients with obesity syndrome at an average age of approximately 52.9 years as well as in age-matched 80 healthy female controls the prevalence of pancreas insufficiency. Serum levels of PTH, total calcium, and D3 vitamins calcitriol and calcifediol, as well as the concentration of fecal elastase 1 (FE1) were determined in patients and controls. Results. In 75 female nondiabetic patients with obesity syndrome (BMI 35 ≤ 40 kg/m2), calcifediol was markedly decreased (25.0 ± 4.9 ng/mL) compared to controls (50.2 ± 14.7 nmol/L; P < 0.01). FE1 level was significantly decreased in obese subjects compared to controls ( P < 0.01). Calcifediol was significantly lower in patients with morbid obesity (for calcifediol, P < 0.05). Conclusion. In obese females, pancreatic FE1 in feces confirms the extent of vitamin D supply, and thus shows a vitamin D3 deficiency, depending on the loss of stool content. There seems to be a connection between the loss of exocrine function and the increasing body mass index. Pancreas insufficiency, as detected by low FE1 concentrations, is frequent in obese patients. However, the BMI is an additional factor for lowered fecal excretion of FE1.
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Affiliation(s)
- J Teichmann
- Department of Gastroenterology, Endocrinology, and Diabetology, Klinikum Lüdenscheid, 58515 Lüdenscheid, Germany
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Abstract
PURPOSE OF REVIEW We review important new clinical observations in chronic pancreatitis made in the past year. RECENT FINDINGS Tropical pancreatitis associates with SPINK1 and/or CFTR gene mutations in approximately 50% of patients, similar to the frequency in idiopathic chronic pancreatitis. Corticosteroids increase secretin-stimulated pancreatic bicarbonate concentrations in autoimmune pancreatitis (AIP) by restoring mislocalized CFTR protein to the apical ductal membrane. Most patients with asymptomatic hyperenzymemia have pancreatic lesions of unclear significance or no pancreatic lesions. Common pitfalls in the use of diagnostic tests for exocrine pancreatic insufficiency (EPI) confound interpretation of findings in irritable bowel syndrome and severe renal insufficiency. Further study is needed to improve the accuracy of endoscopic ultrasonography (EUS) to diagnose chronic pancreatitis. Celiac plexus block provides short-term pain relief in a subset of patients. SUMMARY Results of this year's investigations further elucidated the genetic associations of tropical pancreatitis, a reversible mislocalization of ductal CFTR in AIP, the association of asymptomatic pancreatic hyperenzymemia with pancreatic disorders, limitations of diagnostic tests for EPI, diagnosis of chronic pancreatitis by EUS and endoscopic pancreatic function testing and treatment of pain.
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Affiliation(s)
- Matthew J DiMagno
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0682, USA.
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Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes? EXPERIMENTAL DIABETES RESEARCH 2011; 2011:761950. [PMID: 21822421 PMCID: PMC3148449 DOI: 10.1155/2011/761950] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/27/2011] [Accepted: 05/25/2011] [Indexed: 02/08/2023]
Abstract
Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis). Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus.
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Abstract
Exocrine pancreatic disease is thought to be uncommon in clinical practice and usually secondary to excess alcohol intake. Although excess alcohol intake does account for many cases of exocrine pancreatic disease, other conditions are associated with exocrine pancreatic insufficiency and such dysfunction perhaps occurs more frequently than conventionally expected. A reliable, patient-friendly, cheap and easy to use test for exocrine pancreatic disease is yet to be established; however, in many countries the main (and often only available) method of assessment of exocrine pancreatic function is the fecal-elastase-1 test. This Review examines the role of fecal-elastase-1 testing in detecting exocrine pancreatic insufficiency in a number of gastrointestinal and nongastrointestinal conditions and determines the value of pancreatic enzyme supplementation in these settings.
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Han J, Liu YQ. Suppressed glucose metabolism in acinar cells might contribute to the development of exocrine pancreatic insufficiency in streptozotocin-induced diabetic mice. Metabolism 2010; 59:1257-67. [PMID: 20051281 DOI: 10.1016/j.metabol.2009.11.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2009] [Revised: 11/13/2009] [Accepted: 11/23/2009] [Indexed: 01/30/2023]
Abstract
High prevalence of exocrine pancreatic insufficiency has been observed in diabetic patients. However, the underlying mechanisms are not well known. Reduced cytosolic Ca(2+) signals in pancreatic acinar cells may contribute to lower digestive enzyme secretion. It is well known that adenosine triphosphate (ATP) regulates cytosolic Ca(2+) signals in acinar cells; however, little is known as to whether diabetes impairs glucose metabolism that produces ATP in acinar cells. Streptozotocin (STZ)-induced diabetic C57BL/6 mouse model was used. Four weeks after being diabetic, pancreatic acinar cells were isolated; and amylase secretion and contents, glucose utilization and oxidation, the activities of several key enzymes for glucose metabolism, and ATP and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) contents were determined. Compared with controls, diabetic mice had lower body weight. Cholecystokinin-8- and acetylcholine-stimulated amylase secretion was significantly impaired, and total amylase activity in acinar cells of STZ-diabetic mice was markedly reduced. Glucose utilization and oxidation were suppressed; measured enzyme activities for glucose metabolism and the ATP and NADPH contents were significantly reduced. These data indicate that glucose metabolism and ATP and NADPH productions are very important for maintaining acinar cell normal function. Reduction of ATP (reduces cytosolic Ca(2+) signals) and NADPH (reduces cell capability for antioxidative stress) productions may contribute to the development of exocrine pancreatic insufficiency in STZ-diabetic mice.
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Affiliation(s)
- Junying Han
- The Research Institute for Children, Children's Hospital, New Orleans, Louisiana 70118, USA
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Abstract
Diabetic patients with diarrhea may present clinical challenges in diagnosis and treatment. Particular diagnoses are more prevalent in diabetic patients than in the general population. Medications are often a culprit for chronic diarrhea, and the medication list should always be carefully scrutinized for those with diarrhea as a side effect. In diabetic patients, metformin is a common cause of diarrhea. Diabetic patients are more likely to have associated diseases (eg, celiac sprue and microscopic colitis) that present with diarrhea as the sole complaint. Ingested sugar-free foods that may contain sorbitol or other agents can cause diarrhea in diabetic patients. Finally, diabetic enteropathy can itself cause diarrhea. The various etiologies can be diagnosed with a thorough history and appropriate diagnostic tests. This article focuses on the etiologies of diarrhea that are seen with higher incidence in diabetic patients.
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Affiliation(s)
- Milena Gould
- Section of Gastroenterology, Baylor College of Medicine, Suite 8.36, Houston, TX 77030, USA
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Bilgin M, Balci NC, Momtahen AJ, Bilgin Y, Klör HU, Rau WS. MRI and MRCP findings of the pancreas in patients with diabetes mellitus: compared analysis with pancreatic exocrine function determined by fecal elastase 1. J Clin Gastroenterol 2009; 43:165-70. [PMID: 18797409 DOI: 10.1097/mcg.0b013e3181587912] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
GOALS To review magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRCP) findings in patients with diabetes mellitus (DM), with pancreatic exocrine insufficiency, and with combined pancreatic exocrine insufficiency and DM. STUDY MRI/MRCP findings of 82 consecutive patients with DM (n=28), pancreatic exocrine insufficiency (n=25), and combination of both (n=29) were evaluated and compared with MRI/MRCP findings of 21 healthy volunteers with normal pancreatic exocrine function. Pancreatic exocrine function was determined by fecal elastase 1. MRCP images were evaluated according to the Cambridge classification. MRI of the pancreas was assessed for pancreatic size, signal intensity ratio (SIR), and arterial/venous enhancement ratio (A/V). RESULTS On MRI, significant difference was present in terms of mean values of pancreatic size (P<0.0001), A/V (P<0.02), and SIR (P<0.005) between the control group and groups of patients with DM, pancreatic exocrine insufficiency, and combined DM and pancreatic exocrine insufficiency. No significant difference was observed between groups of patients with DM and pancreatic exocrine function alone in terms of pancreatic size, A/V, and SIR. Chronic pancreatitis MRCP findings were present with increasing frequency in groups of DM, pancreatic exocrine insufficiency, and combination of both. CONCLUSIONS MRI/MRCP findings suggesting chronic pancreatitis may exist in patients with DM comparable to patients with pancreatic exocrine insufficiency. The frequency and severity of MRI/MRCP findings increase when the patients have combined DM and pancreatic exocrine insufficiency.
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Affiliation(s)
- Mehmet Bilgin
- Department of Radiology, University Hospital Giessen and Marburg, Giessen, Germany
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Zhang WY, Zhang JQ, Wang Q, Li GL, Wang XC, Zhang CY, Yang D, Cheng J. Screening of proteins binding to hepatitis B core antigen from human pancreas cDNA library by yeast two-hybrid system. Shijie Huaren Xiaohua Zazhi 2008; 16:1746-1750. [DOI: 10.11569/wcjd.v16.i16.1746] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To screen proteins in human pancreas cDNA library interacting with hepatitis B core antigen (HbcAg) by yeast two-hybrid system.
METHODS: After amplification, purification, and identification, the human pancreas cDNA library plasmid was transformed into yeast Y187. Thereafter, the reconstructed bait plasmid (pGBKT7-HBcAg) was transformed into yeast cells AH109. Then, the transformed AH109 was mated with Y187 that contained the library plasmid. The diploid yeast cells were plated on nutrient deficiency medium SD/-Trp/-Leu/-His/-Ade and SD/-Trp/-Leu/-His/-Ade containing X-α-gal for selecting. The plasmids in diploid yeast cells were extracted and electrotransformed into E.coli DH5α. The plasmids in DH5α were extracted, sequenced and analyzed by bioinformatic methods.
RESULTS: The human pancreas cDNA library was constructed successfully. The reconstructed bait plasmid (pGBKT7-HBcAg) was transformed into yeast cells AH109 successfully. Nine proteins interacting with HBcAg were screened, and their sequences were homologous with human pancreatic lipase (PNLIP), CEL, CTRC, trypsinogen, carboxypeptidase 1 (CPB1), human complete mitochondrial genome, human pancreatic elastinase 2A, human complement lipase (CLPS) and human ribosomal protein (RPL10A).
CONCLUSION: HBcAg protein may be related with the exocrine pancreatic function and metabolism of glucose or lipid. HBV infection probably leads to metabolic abnormality or metabolic diseases through interacting with pancreatic enzymes.
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Weksler-Zangen S, Raz I, Lenzen S, Jörns A, Ehrenfeld S, Amir G, Oprescu A, Yagil Y, Yagil C, Zangen DH, Kaiser N. Impaired glucose-stimulated insulin secretion is coupled with exocrine pancreatic lesions in the Cohen diabetic rat. Diabetes 2008; 57:279-87. [PMID: 17977959 DOI: 10.2337/db07-0520] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE The Cohen diabetes-sensitive rat develops postprandial hyperglycemia when fed a high-sucrose, copper-poor diet, whereas the Cohen diabetes-resistant rat maintains normoglycemia. The pathophysiological basis of diabetes was studied in the Cohen diabetic rat centering on the interplay between the exocrine and endocrine compartments of the pancreas. RESEARCH DESIGN AND METHODS Studies used male Cohen diabetes-sensitive and Cohen diabetes-resistant rats fed 1-month high-sucrose, copper-poor diet. Serum insulin and glucose levels were measured during glucose and insulin tolerance tests. The pancreas was evaluated for weight, insulin content, macrophage, and fat infiltration. Glucose-stimulated insulin secretion (GSIS) was determined in isolated perfused pancreas and in islets. RESULTS Hyperglycemic Cohen diabetes-sensitive rats exhibited reduced pancreatic weight with lipid deposits and interleukin-1beta-positive macrophage infiltration in the exocrine pancreas. Islet morphology was preserved, and total pancreatic insulin content did not differ from that of Cohen diabetes-resistant rats. Lipids did not accumulate in skeletal muscle, nor was insulin resistance observed in hyperglycemic Cohen diabetes-sensitive rats. Intravenous glucose-tolerance test revealed markedly elevated glucose levels associated with diminished insulin output. Insulin release was induced in vivo by the non-nutrient secretagogues arginine and tolbutamide, suggesting a selective unresponsiveness to glucose. Decreased GSIS was observed in the isolated perfused pancreas of the hyperglycemic Cohen diabetes-sensitive rat, whereas islets isolated from these rats exhibited glucose-dependent insulin secretion and proinsulin biosynthesis. CONCLUSIONS The association of the in vivo insulin secretory defect with lipid accumulation and activated macrophage infiltration in the exocrine pancreas suggests that changes in the islet microenvironment are the culprit in the insulin secretory malfunction observed in vivo.
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Affiliation(s)
- Sarah Weksler-Zangen
- The Diabetes Unit, Hadassah-Hebrew University Medical Center, Jerusalem 1200, Israel.
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Hardt PD, Brendel MD, Kloer HU, Bretzel RG. Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed? Diabetes Care 2008; 31 Suppl 2:S165-9. [PMID: 18227480 DOI: 10.2337/dc08-s244] [Citation(s) in RCA: 123] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Exocrine pancreatic insufficiency is frequently associated with diabetes, with high prevalence in both insulin-dependent or insulin-independent patients. Exocrine pancreatic failure has often been perceived as a complication of diabetes. In contrast, recent clinical observations lead to the notion that nonendocrine pancreatic disease is a critical factor for development rather than a sequel to diabetes. The incidence of diabetes caused by exocrine pancreatic disease appears to be underestimated and may comprise 8% or more of the general diabetic patient population. Nonendocrine pancreas disease can cause diabetes by multiple mechanisms. Genetic defects have been characterized, resulting in a syndrome of both exocrine and endocrine failure. Regulation of beta-cell mass and physiological incretin secretion are directly dependent on normal exocrine function. Algorithms for diagnosis and therapy of diabetes should therefore address both endocrine and exocrine pancreatic function.
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Affiliation(s)
- Philip D Hardt
- Third Medical Department and Policlinic, University Hospital Giessen and Marburg, Giessen, Rodthohl 6, D-35385 Giessen, Germany.
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Vesterhus M, Raeder H, Johansson S, Molven A, Njølstad PR. Pancreatic exocrine dysfunction in maturity-onset diabetes of the young type 3. Diabetes Care 2008; 31:306-10. [PMID: 17989309 DOI: 10.2337/dc07-1002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Exocrine pancreas dysfunction is seen in 10-30% of patients with type 1 and 2 diabetes. We have recently identified a syndrome of diabetes and exocrine pancreas dysfunction attributable to mutations in the carboxyl ester lipase (CEL) gene. We wanted to investigate the prevalence of pancreatic exocrine dysfunction in patients with maturity-onset diabetes of the young type 3 (MODY3). RESEARCH DESIGN AND METHODS All 119 patients with MODY3 in the Norwegian MODY Registry were invited to participate, and 70 (60.5%) responded, among whom 63 were adults. Control groups included 140 subjects with type 1 diabetes and 78 nondiabetic control subjects. Pancreatic dysfunction was defined by fecal elastase deficiency. Fecal fat excretion was measured in 25 patients with fecal elastase deficiency. CEL was investigated for sequence changes. RESULTS We found a prevalence of fecal elastase deficiency of 12.7% in adult patients with MODY3, compared with 18.6% in patients with type 1 diabetes and 3.8% in nondiabetic control subjects. The six patients with MODY3 with fecal elastase deficiency available for analysis all had increased fecal fat excretion. Fecal elastase decreased with age. Controlled for age, patients with MODY3 still had decreased fecal elastase compared with control subjects. Twelve of 70 patients (17%) had single-base insertions in CEL exon 11. Two of these had fecal elastase deficiency. CONCLUSIONS The prevalence of pancreatic exocrine dysfunction was 12.7% in a cohort of 63 adult patients with MODY3, similar to the prevalence among type 1 diabetic patients. Fecal fat excretion was increased in all patients with MODY3 with fecal elastase deficiency who were investigated, underscoring the potential clinical importance of the exocrine dysfunction.
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Affiliation(s)
- Mette Vesterhus
- Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
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