Enzyme replacement therapy for pancreatic insufficiency: present and future

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Abstract

Pancreatic enzyme replacement therapy is currently the mainstay of treatment for nutrient malabsorption secondary to pancreatic insufficiency. This treatment is safe and has few side effects. Data demonstrate efficacy in reducing steatorrhea and fat malabsorption. Effective therapy has been limited by the ability to replicate the physiologic process of enzyme delivery to the appropriate site, in general the duodenum, at the appropriate time. The challenges include enzyme destruction in the stomach, lack of adequate mixing with the chyme in the duodenum, and failing to deliver and activate at the appropriate time. Treatment is begun when clinically significant malabsorption occurs resulting in steatorrhea and weight loss. Treatment failure is addressed in a sequential fashion. Current research is aimed at studying new enzymes and delivery systems to improve the efficiency of action in the duodenum along with developing better means to monitor therapy.

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The digestion of dietary triacylglycerols.

H Mu (2004)

Dietary triacylglycerols (TAGs) are the major lipid components in the human diet and they are carriers of energy as well as important fatty acids. Many factors affect the digestion and absorption of TAGs. Evidence is accumulating that, in addition to the overall fatty acid profile, the TAG structure and the species composition are of importance when considering the nutritional effects of a dietary fat. There is good evidence that in addition to its short-term effects in the intestine on absorption of fatty acids the TAG structure also has long-term effects resulting from differences in the profile of absorbed fatty acids. Observations on the different atherogenic potential of dietary fats have given us a clear indication of the importance of the TAG structure for absorption of saturated fatty acids. In this context, one may focus on the effects of the structure of dietary fats as such, or one may speculate additionally on the possibilities of modifying the structure of fats to affect their absorption and the distribution of the fatty acids in the body after digestion and uptake. In this review we will summarize diverse aspects of TAG digestion and absorption, as well as the influences of the fatty acid composition and the intramolecular structure of dietary TAGs on their digestion and absorption.

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The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis.

L Kalthoff, D J Clain, Lori Bakken … (1994)

Compared with alcoholic pancreatitis, little is known about the natural history of idiopathic pancreatitis. Two hundred forty-nine patients with alcoholic pancreatitis and 66 patients with idiopathic chronic pancreatitis seen at our institution between 1976 and 1982 were investigated. Records were analyzed retrospectively from the onset of symptomatic disease, and patients were followed up prospectively until 1985. Patients with early-onset (n = 25) and late-onset (n = 41) idiopathic chronic pancreatitis had a median age at onset of symptoms of 19 and 56 years, respectively. The gender distribution was nearly equal in idiopathic chronic pancreatitis, but 72% of patients with alcoholic pancreatitis were men (P = 0.001 vs. idiopathic). In early-onset idiopathic pancreatitis, calcification and exocrine and endocrine insufficiency developed more slowly than in late-onset idiopathic and alcoholic pancreatitis (P = 0.03). However, in early idiopathic chronic pancreatitis, pain frequently occurred initially (P = 0.003 vs. late and alcoholic) and was more severe (P = 0.04 vs. late and alcoholic). In late-onset idiopathic pancreatitis, pain was absent in nearly 50% of patients. There are two distinct forms of idiopathic chronic pancreatitis. Patients with early-onset pancreatitis have initially and thereafter a long course of severe pain but slowly develop morphological and functional pancreatic damage, whereas patients with late-onset pancreatitis have a mild and often a painless course. Both forms differ from alcoholic pancreatitis in their equal gender distribution and a much slower rate of calcification.

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Lipid digestion and absorption in early life: an update.

Olle Hernell, Susanne Lindquist (2010)

To highlight our understanding of digestion and absorption of dietary lipids in newborn infants, and specifically how these processes differ from those in children and adults. The intestinal concentration of pancreatic triglyceride lipase (PTL) and bile salts is lower in newborns compared to later in life. Instead the PTL-related protein 2 and bile salt-stimulated lipase (BSSL) are the key enzymes secreted from pancreas, which in concerted action with gastric lipase operate to achieve efficient fat absorption during infancy. BSSL is also present in human milk which affects fat absorption and growth in breast-fed preterm infants. Under conditions of low luminal bile salt concentrations fat absorption is likely to occur from liquid crystalline product phases, which may result in absorption from an extended part of the small intestinal mucosal surfaces compared to adults. Chylomicron assembly and secretion also seem to adapt to the specific situation of the newborn. Both fat digestion and product absorption are different in newborn infants compared to adults; other lipases are used for digestion and different physical-chemical phases may be used for product absorption. Why these differences occur is still an unsolved question of considerable importance to neonatal nutrition.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Exp Gastroenterol

Journal ID (publisher-id): Clinical and Experimental Gastroenterology

Title: Clinical and Experimental Gastroenterology

Publisher: Dove Medical Press

ISSN (Electronic): 1178-7023

Publication date Collection: 2011

Publication date (Electronic): 04 May 2011

Volume: 4

Pages: 55-73

Affiliations

[1 ]Division of Digestive Diseases, University of Oklahoma, OKC, OK, USA;

[2 ]INSERM, U476 “Nutrition Humaine et Lipides”, Marseille, F-13385 France; Univ Méditerranée Aix-Marseille 2, Faculté de Médecine, IPHM-IFR 125, Marseille, F-13385 France

Author notes

Correspondence: Martine Armand, INSERM, U476 “Nutrition Humaine et Lipides”, Marseille, F-13385 France; Univ Méditerranée Aix-Marseille 2, Faculté de Médecine, IPHM-IFR 125, Marseille, F-13385 France, Tel +33 4 91 78 21 01, Fax +33 4 91 29 40 93, Email martine.armand@ 123456univmed.fr

Article

Publisher ID: ceg-4-055

DOI: 10.2147/CEG.S17634

PMC ID: 3132852

PubMed ID: 21753892

SO-VID: 81f3db6c-8d57-4d8c-bd17-c5eda8283615

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This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

Enzyme replacement therapy for pancreatic insufficiency: present and future

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Karger: Gastroenterology

Most cited references 197

The digestion of dietary triacylglycerols.

The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis.

Lipid digestion and absorption in early life: an update.

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