DOI: https://doi.org/10.30978/MG-2019-2-81

Панкреатогенний цукровий діабет навпаки: зовнішньосекреторна недостатність підшлункової залози на тлі цукрового діабету

N. B. Gubergrits, N. V. Belyayeva, O. Ye. Klochkov, P. G. Fomenko

Анотація


Проаналізовано нормальні фізіологічні взаємозв’язки між екзокринною та ендокринною паренхімою підшлункової залози (ПЗ). Наведено дані літератури щодо патогенезу, особливостей клінічних виявів, лікування панкреатогенного цукрового діабету і зовнішньосекреторної недостатності ПЗ, яка розвинулася внаслідок цукрового діабету. Установлено, що фекальна еластаза-1 є ідеальним біомаркером для ­діагностики екзокринної недостатності ПЗ у пацієнтів з цукровим діабетом 2 типу. Наведено результати досліджень, які свідчать про тісний зв’язок між цукровим діабетом і низьким рівнем фекальної еластази-1, а також про прямо пропорційну кореляцію між вмістом фекальної еластази-1 і рівнями С-пептиду, ліпази, С-реактивного білка, загального 25(ОН) вітаміну D, індексом маси тіла. Представлено дані щодо існування двох інтрапанкреатичних вісей взаємозв’язку: одна бере участь у регуляції виробництва ферментів завдяки інсуліну через інсуліно-ацинарну вісь, інша забезпечує вивільнення інсуліну за рахунок панкреатичних ферментів через ацинарно-інсулярну вісь. Висвітлено концепцію ацинарно-острівцево-ацинарної осі. Таким чином, екзокринну недостатність ПЗ можна розглядати як ускладнення цукрового діабету. Наведено патогенетичне обґрунтування доцільності призначення «Креону» при цукровому діабеті 3 типу і для лікування зовнішньосекреторної недостатності ПЗ у хворих на цукровий діабет. Доведено безпечність терапії панкреатином для пацієнтів із цукровим діабетом та екзокринною дисфункцією ПЗ.


Ключові слова


підшлункова залоза; зовнішньосекреторна та внутрішньосекреторна функції підшлункової залози; взаємозв’язок екзо- та ендокринної панкреатичної недостатності; лікування; замісна ферментна терапія

Повний текст:

PDF (Русский)

Посилання


Gdal V, Morozova Z, Chichulya Yu. Diagnosis of exocrine pancreatic insufficiency in chronic pancreatitis and diabetes. Drugs of Ukraine. 2001;10:52—54.

Almost every second patient with diabetes has pancreatic insufficiency: review / Ed. B. N. Mankovsky. Diabetes and life. 2002;3. Reprint:1-4.

Kagan II, Zheleznov LM. The pancreas: microsurgical and computed tomographic anatomy. Moscow: Medicine, 2004:152.

Kler HU. Chronic pancreatitis: modern aspects of pathophysiology and treatment. Proceedings of the V National school of gastroenterologists, hepatologists of Ukraine. Kyiv, 2003:64-66.

Larin AS, Tkach SM, Yuzvenko TYu. Diagnosis and correction of exocrine pancreatic insufficiency in patients with diabetes mellitus. Modern Gastroenterol. 2006;3:42-45.

Mozheiko LA. Endocrine-exocrine pancreatic interrelations: background. GrSMU Journal. 2007;3:7-11.

Perederiy VG, Tkach SM, Larin AS, Skopichenko SV. Exocrine pancreatic insufficiency. What it is? How often does it occur? How is it diagnosed and treated? In questions and answers of the gastroenterologist to doctors and patients. Kyiv: Tvisa, 2005:193.

Perederiy VG, Tkach SM, Parunyan LM. Frequency and possible causes of exocrine pancreatic insufficiency in diabetes. Ukr. Ther. J. 2004;2:12-16.

Bennett PH. Diabetes in the elderly: diagnosis and epidemiology. Geriatrics. 1984;39:37-41.

Büchler MW, Uhl W, Malfertheiner P, Sarr MG. Diseases of the pancreas. Basel; Freiburg; Paris et al. Karger, 2004:212.

Bytzer P, Talley NJ, Leemon M et al. Prevalence of the gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med. 2001;161:1989-1996.

Chey WY, Shay H, Shuman CR. External pancreatic secretion in diabetes mellitus. Ann Intern Med. 1963;59:812-821.

Clinical Pancreatology for practicing gastroenterologists and surgeons / Ed. by J. E. Dominguez-Munoz. Magdeburg: A Blackwell Publ. Co, 2005. 535 р.

Dyck WP, Texter EC.J., Lasater JM et al. Influence of glucagons on pancreatic exocrine secretion in man. Gastroenterology. 1970;58:532-539.

El Newihi H, Dooley CP, Saad C et al. Impaired exocrine pancreatic function in diabetes with diarrhea and peripheral neuropathy. Dig Dis Sci. 1988;33:705-710.

Emoto T, Miyata M, Izukura M et al. Simultaneous observation of endocrine and exocrine functions of the pancreas responding to somatostatin in man. Regul Pept. 1997;68:1-8.

Ewald N, Bretzel R, Fantus I 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;23:386-391. DOI: 10.1002/dmrr.708

Ewald N, Hardt P, Andersen D. Pancreatogenic diabetes: peculiarities in diagnosis and treatment. Pancreatology. 2018;18, N 4 (suppl.). P. S39–S40.

Ewald N, Raspe A, Kaufmann C et al. Determinants of exocrine pancreatic function as measured by fecal elastase-1 concentrations (FEC) in patients with diabetes mellitus. Eur J Med Res. 2009;14 (3):118-122.

Ferrer R, Medrano J, Diego M et al. Effect of exogenous insulin and glucagon on exocrine pancreatic secretion in rats in vivo. Int J Pancreatol. 2000;28:67-75.

Foulis AK. Histology of the islet in insulin-dependent diabetes mellitus: a positive sequence of events. Textbook of diabetes / J. C. Pickup, G. Williams, eds. 2nd ed. Oxford, 1997;15:24-29.

Frier BM, Saunders JH.B., Wormsley KG, Bouchier IA.D. Exocrine pancreatic function in juvenile-onset diabetes mellitus. Gut. 1976;17:685-691.

Gepts W. Pathology of the pancreas in juvenile diabetes. Diabetes. 1965;14:619-633.

Gilbeau JP, Poncelet V, Libon E et al. The density, contour, and thickness of the pancreas in diabetics: CT findings in 57 patients. Am J Roentgenol. 1992;159:527-531.

Grandt D, Bein S, Beglinger C et al. Peptide YY inhibits interdigestive pancreatic enzyme secretion in humans. Pancreas. 1995;11:430.

Gröger G, Keller J, Bertram C et al. Pancreatic enzyme responses are altered in patients with insulin dependent diabetes mellitus. Digestion. 1999;60:378.

Hardt P, Kloer H. Diabetes mellitus and exocrine pancreatic disease. Pancreatic disease: towards the year 2000 / Ed. by C. D. Johnson, C. W. Imrie. London. et al., 1999:33-39.

Hardt PD, Krauss A, Bretz L et al. Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus. Acta Diabetol. 2000;37:105-110.

Hirota M, Hashimoto M, Hiratsuka M.et al. Alterations of plasma immunoreactive glucagons-like peptide-1 behavior in non-insulin-dependent diabetics. Diabetes Res Clin Pract. 1990;9:179-185.

Icks A, Haastert B, Giani G, Rathmann W. Low fecal elastase-1 in type 1 diabetes mellitus. Z Gastroenterol. 2001;39:823-830.

Kangrga R, Ignjatovic S, Dragasevic М et al. Pancreatic elastase levels in feces as a marker of exocrine pancreatic function in patients with diabetes mellitus. Laboratory Medicine. 2016;47(2):140-148. DOI: 10.1093/labmed/lmw015

Keller J, Conrads H, Goebell H et al. Differential responses of human pancreatic and biliary secretion to graded ileal lipid perfusion. Digestion. 1998;59:206.

Keller J, Conrads H, Holst JJ et al. The ratios between pancreatic secretory enzymes are modulated by physiologic ileal lipid concentrations. Pancreas. 1998;17:442.

Keller J, Layer P. Acinar-islet interactions: Pancreatic exocrine insufficiency in diabetes mellitus: Pancreatic disease: Basic science and clinical management. London et al., 2004. 21:267-278.

Knop FK, Vilsboll T, Larsen S et al. Increased postpran.dial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution. Am J Physiol Endocrinol Metab. 2007;292. P. E324-E330.

Kobayashi T, Nakanishi K, Kajio H et al. Pancreatic cytoceratin: an antigen of pancreatic exocrine cell autoantibodies in type-1 (insulin-dependent) diabetes mellitus. Diabetologia. 1990;33:363-370.

Kobayashi T, Nakanishi K, Sugimoto T et al. Histopathological changes of the pancreas in islet cell antibodies (ICA)-positive subjects before and after the clinical onset of insulin-dependent diabetes mellitus. Diabetes. 1988;37:24A.

Kondrashova A, Nurminen N, Lehtonen J et al. Exocrine pancreas function decreases during the progression of the beta-cell damaging process in young prediabetic children. Pediatric Diabetes. 2018;19(3):398-402.

Konturek SJ, Tasler J, Obulowicz W. Characteristics of inhibition of pancreatic secretion by glucagons. Digestion. 1974;10:138-149.

Lankisch PG, Manthey G, Otto J et al. Exocrine pancreatic function in insulin-dependent diabetes mellitus. Digestion. 1982;25:210-216.

Layer P, Keller J. Pancreatic enzymes: secretion and luminal nutrient digestin in health and disease. J Clin Gastroenterol. 1999;28:3-10.

Layer P, Ohe M, Groeger G et al. Luminal availability and digestive efficacy of substituted enzymes in pancreatic insufficiency. Pancreas. 1992;7:745.

Layer P, Peschel S, Schlesinger T et al. Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion. Am J Physiol. 1990;258. P. G196–G201.

Layer P, von der Ohe MR, Holst JJ et al. Altered postprandial motility in chronic pancreatitis: role of malabsorption. Gastroenterology. 1997;112:1624-1634.

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;Pii: S1424-3903 (18)30589-1. doi: 10.1016/j.pan.2018.05.483.

Lohr M, Kloppel G. Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy. Diabetologia. 1987;30:757-762.

Lozinska L et al. Decreased insulin secretion and glucose clearance in exocrine pancreas-insufficient pigs. Exp Physiol. 2016;101:100-112.

Mally M, Cirulli V, Hayek A, Otonkosky T. ICA 69 is expressed equally in the human endocrine and exocrine pancreas. Diabetologica. 1996;39:474-480.

Mandel AL, Breslin PA. High endogenous salivary amylase activity is associated with improved glycemic homeostasis following starch ingestion in adults. J Nutr. 2012;142:853-858.

Mohapatra S, Majumder S, Smyrk TC et al. Exocrine pancreatopathy: Conclusions from a review of literature. Pancreas. 2016;45 (8):1104-1110. doi: 10.1097/MPA.0000000000000609.

Morgenroth K, Kozuschek W. Pancreatitis. Berlin; New York: Walter de Gruyter, 1991:120.

Murakami Т. Pancreatic insulo-acinar portal systems in humans, rats, and some other mammals: Scanning electron microscopy of vascular casts. Microscopy research and technique. 1997;37:478-488. https://doi.org/10.1002/ (SICI)1097-0029 (19970601)37 : 5/6 < 478. P.:AID-JEMT10 > 3.0.CO;2-N

Nakajima K et al. Low serum amylase in association with metabolic syndrome and diabetes: a community-based study. Cardiovasc Diabetol. 2011;N 10:34.

Nakanishi K, Kobayashi T, Miyashita H et al. Exocrine pancreatic ductograms in insulin-dependent diabetes mellitus. Am J Gastroenterol. 1994;89:762-766.

Panicot L, Mas E, Thi-Volet C et al. Circulating antibodies against an exocrine pancreatic enzyme in type 1 diabetes. Diabetes. 1999;48:2316-2323.

Pierzynowski SG, Goncharova K, Gregory PC et al. Experiments suggesting extra-digestive effects of enteral pancreatic amylase and its peptides on glucose homeostasis in a pig model. Sci Rep. 2017;8628.

Pierzynowski SG, Gregory PC, Filip R et al. Glucose homeostasis dependency on acini-islet-acinar (AIA) axis communication: a new possible pathophysiological hypothesis regarding diabetes mellitus. Nutr Diabetes. 2018;8 (1):55. doi: 10.1038/s41387-018-0062-9.

Pollard H, Miller L, Brewer W. External secretion of the pancreas and diabetes (study of secretin test). Am J Dig Dis. 1943;10:20.

Prasanna Kumar HR, Gowdappa HB, Hosmani T, Urs T. Exocrine dysfunction correlates with endocrinal impairment of pancreas in Type 2 diabetes mellitus. Indian J Endocr Metab. 2018;22:121-125.

Rathmann W, Haastert B, Icks A et al. Low fecal elastase 1 concentration in type 2 diabetes mellitus. Scand J Gastroenterol. 2001;36:1056-1061.

Ross JJ, Wasserfall C, Perry DJ et al. Exocrine pancreatic function as a novel biomarker in pre-T1D. Diabetes. 2018;67 (suppl.). P. A412–A413.

Schäfer E, Fekete Á, Gasparics R et al. A comparatives study of diabetic complications in patients with pancreatic diabetes mellitus and chronic pancreatitis. Pancreatology. 2006;6:375.

Semakula C, Vandewalle CL, Van Schravendijk CF et al. Abnormal circulating pancreatic enzyme activities in more than twenty-five percent of recent-onset insulin-dependent diabetic patients: association of hyperlipasemia with high-titer islet cell antibodies. Belgian Diabetes Registry Pancreas. 1996;12:321-333.

Suarez F, Fevitt MD, Adshead J et al. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Dig Dis Sci. 1999;44:1317-1321.

Talley SJ, Bytzer P, Hammer J et al. Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol. 2001;96:1033-1038.

Talukdar R, Reddy DN. Pancreatic exocrine insufficiency in type 1 and 2 diabetes: therapeutic implications. J Assoc Physicians India. 2017;65 (9):64-70.

The pancreas: An integrated textbook of basic science, medicine and surgery / Ed. by H. G. Beger, A. L. Warshaw, R. H. Hruban. et al. Oxford: Willey Blackwell, 2018:1173.

Tully GT, Lowenthal JJ. The diabetic coma of acute pancreatitis. Ann Intern Med. 1958;48:310.

Van der Layer OP, Wollny C et al. Somatostatin 28 and coupling of human interdigestive intestinal motility and pancreatic secretion. Gastroenterology. 1992;103:974-982.

Waguri M, Hanafusa T, Itoh N et al. Histopathologic study of the pancreas shows a characteristic lymphocytic infiltration in Japanese patients with IDDM. Endocr J. 1997;44 (1):23-33.

Whitcomb DC, Bodhani A, Beckmann K et al. Effcacy and safety of pancrealipase/ pancreatin in patients with exocrine pancreatic insufficiency and a medical history of diabetes mellitus. Pancreas. 2016;45:676-686.

Zsóri G, Illés D, Terzin V et al. Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review. Pancreatology. 2018;ii: S1424-3903 (18)30111-X. doi: 10.1016/j.pan.2018.05.006.




© Сучасна гастроентерологія, 2019
© ТОВ «ВІТ-А-ПОЛ», 2019