Pancreatic enzyme replacement therapy in subjects with exocrine pancreatic insufficiency and diabetes mellitus: a real-life, case-control study.
Diabetes
Exocrine pancreatic insufficiency
Fecal elastase
Pancreatic enzyme replacement therapy
Journal
Diabetology & metabolic syndrome
ISSN: 1758-5996
Titre abrégé: Diabetol Metab Syndr
Pays: England
ID NLM: 101488958
Informations de publication
Date de publication:
09 Feb 2024
09 Feb 2024
Historique:
received:
08
12
2023
accepted:
10
01
2024
medline:
9
2
2024
pubmed:
9
2
2024
entrez:
8
2
2024
Statut:
epublish
Résumé
Exocrine pancreatic insufficiency (EPI) can be associated with all types of diabetes. Pancreatic enzyme replacement therapy (PERT) has short and long-term benefits in subjects with EPI, but its effects on diabetes control are uncertain. We aimed to study the effects of PERT initiation on glycemic control in subjects with diabetes and EPI from any cause. In this retrospective study, we compared subjects with EPI and diabetes who were prescribed PERT with subjects with diabetes who had a fecal elastase-1 concentration dosage, but did not receive PERT. The primary outcome was the effect of PERT on hypoglycemia frequency and severity. The secondary outcomes were the effects of PERT on gastro-intestinal disorders, HbA 48 subjects were included in each group. Overall, PERT did not have any significant effect on hypoglycemia frequency or severity, but hypoglycemia frequency tended to decrease in subjects with chronic pancreatitis. While 19% of subjects experienced mild hyperglycemia after PERT initiation, we did not report any keto-acidosis or any other severe adverse event. Gastro-intestinal disorders improved in 80% of subjects treated with PERT, versus in 20% of control subjects (p = 0.02). Gastro-intestinal disorders improved in 87% of subjects with recommended dosage of PERT, versus in 50% of subjects with underdosage (NS). HbA PERT initiation is safe in subjects with diabetes and EPI. It does not globally decrease hypoglycemia severity of frequency, but is associated with a decrease in gastro-intestinal disorders. Trial registration Retrospectively registered. The database was registered with the Commission Nationale Informatique et Libertés (CNIL), registration number: 2203351v0. The study was approved by the local ethics committee CLEP, registration number: AAA-2023-09047.
Sections du résumé
BACKGROUND
BACKGROUND
Exocrine pancreatic insufficiency (EPI) can be associated with all types of diabetes. Pancreatic enzyme replacement therapy (PERT) has short and long-term benefits in subjects with EPI, but its effects on diabetes control are uncertain. We aimed to study the effects of PERT initiation on glycemic control in subjects with diabetes and EPI from any cause.
METHODS
METHODS
In this retrospective study, we compared subjects with EPI and diabetes who were prescribed PERT with subjects with diabetes who had a fecal elastase-1 concentration dosage, but did not receive PERT. The primary outcome was the effect of PERT on hypoglycemia frequency and severity. The secondary outcomes were the effects of PERT on gastro-intestinal disorders, HbA
RESULTS
RESULTS
48 subjects were included in each group. Overall, PERT did not have any significant effect on hypoglycemia frequency or severity, but hypoglycemia frequency tended to decrease in subjects with chronic pancreatitis. While 19% of subjects experienced mild hyperglycemia after PERT initiation, we did not report any keto-acidosis or any other severe adverse event. Gastro-intestinal disorders improved in 80% of subjects treated with PERT, versus in 20% of control subjects (p = 0.02). Gastro-intestinal disorders improved in 87% of subjects with recommended dosage of PERT, versus in 50% of subjects with underdosage (NS). HbA
CONCLUSIONS
CONCLUSIONS
PERT initiation is safe in subjects with diabetes and EPI. It does not globally decrease hypoglycemia severity of frequency, but is associated with a decrease in gastro-intestinal disorders. Trial registration Retrospectively registered. The database was registered with the Commission Nationale Informatique et Libertés (CNIL), registration number: 2203351v0. The study was approved by the local ethics committee CLEP, registration number: AAA-2023-09047.
Identifiants
pubmed: 38331895
doi: 10.1186/s13098-024-01265-4
pii: 10.1186/s13098-024-01265-4
doi:
Types de publication
Journal Article
Langues
eng
Pagination
39Informations de copyright
© 2024. The Author(s).
Références
Das SLM, Kennedy JIC, Murphy R, Phillips ARJ, Windsor JA, Petrov MS. Relationship between the exocrine and endocrine pancreas after acute pancreatitis. World J Gastroenterol. 2014;20(45):17196–205.
doi: 10.3748/wjg.v20.i45.17196
pubmed: 25493036
pmcid: 4258592
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(4):338–42.
doi: 10.1002/dmrr.2260
pubmed: 22121010
Foster TP, Bruggeman B, Campbell-Thompson M, Atkinson MA, Haller MJ, Schatz DA. Exocrine pancreas dysfunction in type 1 diabetes. Endocr Pract. 2020;26(12):1505–13.
doi: 10.4158/EP-2020-0295
pubmed: 33471743
pmcid: 8697709
Alexandre-Heymann L, Mallone R, Boitard C, Scharfmann R, Larger E. Structure and function of the exocrine pancreas in patients with type 1 diabetes. Rev Endocr Metab Disord. 2019. https://doi.org/10.1007/s11154-019-09501-3 .
doi: 10.1007/s11154-019-09501-3
pubmed: 31077020
Zhang J, Hou J, Liu D, Lv Y, Zhang C, Su X, et al. 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.
doi: 10.1155/2022/7764963
pubmed: 36213198
pmcid: 9536940
Clissold RL, Fulford J, Hudson M, Shields BM, McDonald TJ, Ellard S, et al. Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β-associated renal disease and can be symptomatic. Clin Kidney J. 2018;11(4):453–8.
doi: 10.1093/ckj/sfx150
pubmed: 30094008
pmcid: 6070112
Alexandre-Heymann L, Lemoine AY, Nakib S, Kapel N, Ledoux S, Larger E. Nutritional markers in patients with diabetes and pancreatic exocrine failure. Acta Diabetol. 2019. https://doi.org/10.1007/s00592-019-01294-w .
doi: 10.1007/s00592-019-01294-w
pubmed: 30740639
de la Iglesia D, Vallejo-Senra N, López-López A, Iglesias-Garcia J, Lariño-Noia J, Nieto-García L, et al. Pancreatic exocrine insufficiency and cardiovascular risk in patients with chronic pancreatitis: a prospective, longitudinal cohort study. J Gastroenterol Hepatol. 2019;34(1):277–83.
doi: 10.1111/jgh.14460
pubmed: 30156337
Nakajima K, Oshida H, Muneyuki T, Kakei M. Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency. Core Evid. 2012;7:77–91.
doi: 10.2147/CE.S26705
pubmed: 22936895
pmcid: 3426252
Whitcomb DC, Bodhani A, Beckmann K, Sander-Struckmeier S, Liu S, Fuldeore M, et al. Efficacy and safety of pancrelipase/pancreatin in patients with exocrine pancreatic insufficiency and a medical history of diabetes mellitus. Pancreas. 2016;45(5):679–86.
doi: 10.1097/MPA.0000000000000514
pubmed: 26495784
Gubergrits N, Malecka-Panas E, Lehman GA, Vasileva G, Shen Y, Sander-Struckmeier S, et al. A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery. Aliment Pharmacol Ther. 2011;33(10):1152–61.
doi: 10.1111/j.1365-2036.2011.04631.x
pubmed: 21418260
Safdi M, Bekal PK, Martin S, Saeed ZA, Burton F, Toskes PP. The effects of oral pancreatic enzymes (Creon 10 capsule) on steatorrhea: a multicenter, placebo-controlled, parallel group trial in subjects with chronic pancreatitis. Pancreas. 2006;33(2):156–62.
doi: 10.1097/01.mpa.0000226884.32957.5e
pubmed: 16868481
Whitcomb DC, Lehman GA, Vasileva G, Malecka-Panas E, Gubergrits N, Shen Y, et al. Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: a double-blind randomized trial. Am J Gastroenterol. 2010;105(10):2276–86.
doi: 10.1038/ajg.2010.201
pubmed: 20502447
Czakó L, Takács T, Hegyi P, Prónai L, Tulassay Z, Lakner L, et al. Quality of life assessment after pancreatic enzyme replacement therapy in chronic pancreatitis. Can J Gastroenterol. 2003;17(10):597–603.
doi: 10.1155/2003/515848
pubmed: 14571298
D’Haese JG, Ceyhan GO, Demir IE, Layer P, Uhl W, Löhr M, et al. Pancreatic enzyme replacement therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis: a 1-year disease management study on symptom control and quality of life. Pancreas. 2014;43(6):834–41.
doi: 10.1097/MPA.0000000000000131
pubmed: 24717829
Vujasinovic M, Nezirevic Dobrijevic L, Asplund E, Rutkowski W, Dugic A, Kahn M, et al. Low bone mineral density and risk for osteoporotic fractures in patients with chronic pancreatitis. Nutrients. 2021;13(7): 2386.
doi: 10.3390/nu13072386
pubmed: 34371899
pmcid: 8308495
Roberts KJ, Bannister CA, Schrem H. Enzyme replacement improves survival among patients with pancreatic cancer: results of a population based study. Pancreatology. 2019;19(1):114–21.
doi: 10.1016/j.pan.2018.10.010
pubmed: 30385188
Domínguez-Muñoz JE, Nieto-Garcia L, López-Díaz J, Lariño-Noia J, Abdulkader I, Iglesias-Garcia J. Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis. BMC Cancer. 2018;18(1):534.
doi: 10.1186/s12885-018-4439-x
pubmed: 29728096
pmcid: 5935964
Nakamura T, Takebe K, Kudoh K, Ishii M, Imamura K, Kikuchi H, et al. Decreased counterregulatory hormone responses to insulin-induced hypoglycemia in patients with pancreatic diabetes having autonomic neuropathy. Tohoku J Exp Med. 1994;174(4):305–15.
doi: 10.1620/tjem.174.305
pubmed: 7732513
Donowitz M, Hendler R, Spiro HM, Binder HJ, Felig P. Glucagon secretion in acute and chronic pancreatitis. Ann Intern Med. 1975;83(6):778–81.
doi: 10.7326/0003-4819-83-6-778
pubmed: 1200523
Larsen S, Hilsted J, Tronier B, Worning H. Pancreatic hormone secretion in chronic pancreatitis without residual beta-cell function. Acta Endocrinol (Copenh). 1988;118(3):357–64.
pubmed: 2899369
Knop FK, Vilsbøll T, Larsen S, Højberg PV, Vølund A, Madsbad S, et al. Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution. Am J Physiol Endocrinol Metab. 2007;292(1):E324-330.
doi: 10.1152/ajpendo.00059.2006
pubmed: 16954337
Kuo P, Stevens JE, Russo A, Maddox A, Wishart JM, Jones KL, et al. Gastric emptying, incretin hormone secretion, and postprandial glycemia in cystic fibrosis–effects of pancreatic enzyme supplementation. J Clin Endocrinol Metab. 2011;96(5):E851-855.
doi: 10.1210/jc.2010-2460
pubmed: 21389144
Perano SJ, Couper JJ, Horowitz M, Martin AJ, Kritas S, Sullivan T, et al. Pancreatic enzyme supplementation improves the incretin hormone response and attenuates postprandial glycemia in adolescents with cystic fibrosis: a randomized crossover trial. J Clin Endocrinol Metab. 2014;99(7):2486–93.
doi: 10.1210/jc.2013-4417
pubmed: 24670086
Mohan V, Poongothai S, Pitchumoni CS. Oral pancreatic enzyme therapy in the control of diabetes mellitus in tropical calculous pancreatitis. Int J Pancreatol. 1998;24(1):19–22.
doi: 10.1007/BF02787526
pubmed: 9746885
Ebert R, Creutzfeldt W. Reversal of impaired GIP and insulin secretion in patients with pancreatogenic steatorrhea following enzyme substitution. Diabetologia. 1980;19(3):198–204.
doi: 10.1007/BF00275269
pubmed: 6997121
Riceman MD, Bound M, Grivell J, Hatzinikolas S, Piotto S, Nguyen NQ, et al. The prevalence and impact of low faecal elastase-1 in community-based patients with type 2 diabetes. Diabetes Res Clin Pract. 2019;156: 107822.
doi: 10.1016/j.diabres.2019.107822
pubmed: 31446113
Glasbrenner B, Malfertheiner P, Kerner W, Scherbaum WA, Ditschuneit H. Effect of pancreatin on diabetes mellitus in chronic pancreatitis. Z Gastroenterol. 1990;28(6):275–9.
pubmed: 2238755
O’Keefe SJ, Cariem AK, Levy M. The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis. J Clin Gastroenterol. 2001;32(4):319–23.
doi: 10.1097/00004836-200104000-00008
pubmed: 11276275
Ewald N, Bretzel RG, Fantus IG, Hollenhorst M, Kloer HU, Hardt PD, et al. Pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase 1 concentrations. Results of a prospective multi-centre trial. Diabetes Metab Res Rev. 2007;23(5):386–91.
doi: 10.1002/dmrr.708
pubmed: 17103488
Dominguez-Munoz JE, Drewes AM, Lindkvist B, Ewald N, Czakó L, Rosendahl J, et al. Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis. Pancreatology. 2018;18(8):847–54.
doi: 10.1016/j.pan.2018.09.016
pubmed: 30344091
Phillips ME, Hopper AD, Leeds JS, Roberts KJ, McGeeney L, Duggan SN, et al. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol. 2021;8(1): e000643.
doi: 10.1136/bmjgast-2021-000643
pubmed: 34140324
pmcid: 8212181
Layer P, Kashirskaya N, Gubergrits N. Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency. World J Gastroenterol. 2019;25(20):2430–41.
doi: 10.3748/wjg.v25.i20.2430
pubmed: 31171887
pmcid: 6543241
Shafiq N, Rana S, Bhasin D, Pandhi P, Srivastava P, Sehmby SS, et al. Pancreatic enzymes for chronic pancreatitis. Cochrane Database Syst Rev. 2009;4: CD006302.
Erchinger F, Tjora E, Nordaas IK, Dimcevski G, Olesen SS, Jensen N, et al. Pancreatic enzyme treatment in chronic pancreatitis: quality of management and adherence to guidelines-a cross-sectional observational study. United Eur Gastroenterol J. 2022;10(8):844–53.
doi: 10.1002/ueg2.12276
Sikkens ECM, Cahen DL, van Eijck C, Kuipers EJ, Bruno MJ. Patients with exocrine insufficiency due to chronic pancreatitis are undertreated: a Dutch national survey. Pancreatology. 2012;12(1):71–3.
doi: 10.1016/j.pan.2011.12.010
pubmed: 22487479
Barkin JA, Westermann A, Hoos W, Moravek C, Matrisian L, Wang H, et al. Frequency of appropriate use of pancreatic enzyme replacement therapy and symptomatic response in pancreatic cancer patients. Pancreas. 2019;48(6):780–6.
doi: 10.1097/MPA.0000000000001330
pubmed: 31210656
pmcid: 6749961
Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman MO. Diagnostic performance of measurement of fecal Elastase-1 in detection of exocrine pancreatic insufficiency: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018;16(8):1220-1228e4.
doi: 10.1016/j.cgh.2018.01.027
pubmed: 29374614
pmcid: 6402774
Hahn JU, Kerner W, Maisonneuve P, Lowenfels AB, Lankisch PG. Low fecal elastase 1 levels do not indicate exocrine pancreatic insufficiency in type-1 diabetes mellitus. Pancreas. 2008;36(3):274–8.
doi: 10.1097/MPA.0b013e3181656f8
pubmed: 18362841
Hardt PD, Hauenschild A, Nalop J, Marzeion AM, Jaeger C, Teichmann J, et al. High prevalence of exocrine pancreatic insufficiency in diabetes mellitus. A multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients. Pancreatology. 2003;3(5):395–402.
doi: 10.1159/000073655
pubmed: 14526149