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Abstract
Following current European recommendations for the diagnosis and treatment of exocrine pancreatic insufficiency (EPI), its definition has been changed. EPI is a decrease in exocrine secretion of the pancreas and/or intraluminal activity of pancreatic enzymes below the level that ensures normal digestion of nutrients. EPI is associated with malabsorption of these substances and can lead to intestinal symptoms and/or nutrient deficiencies.
The pathogenesis of EPI in diabetes mellitus (DM) is multifactorial. Thanks to the vessels that supply the exocrine acini with hormones from the endocrine islets, the acinar cells are under endocrine control, both in the short term for well-regulated activation of pancreatic enzyme secretion and in the long term for trophic control of both acinar cells and ductal cells. In general, and subsequently, the pancreas in patients with type 1 and 2 DM decreases in volume due to atrophy processes; therefore, not only endocrine but also exocrine functions are reduced. Microcirculation in the islets may be impaired as a result of diabetic microangiopathy, and it is also discussed that diabetic neuropathy also affects this islet-acinar axis. Infiltration by immune cells and autoantibodies targeting the exocrine parenchyma is often found in both type 1 and type 2 DM. Increased collagen deposition and loss of extracellular matrix remodelling, promoted by activated pancreatic stellate cells, lead to increased degree of pancreatic fibrosis in patients with DM. In addition, it is discussed that ectopic fat accumulation in the pancreas may contribute to the development of EPI, but the literature data are contradictory.
In a systematic review analysing data from 41 publications, it was concluded that the prevalence of EPI is 33% (14–78%) in type 1 diabetes and 29% (17–49%) in type 2 diabetes. According to the authors, such a high frequency indicates that there may be a significant number of patients with diabetes and EPI who have not been diagnosed.
Type 3 diabetes, according to the classification of the World Health Organization, the American Diabetes Association, and the Diabetes UK, is associated with diseases of the exocrine part of the pancreas — various conditions that affect the pancreas and can cause hyperglycaemia (trauma, tumours, inflammation, haemochromatosis, cystic fibrosis. Type 3c diabetes can also develop if a patient has had his pancreas removed due to any other disease. Pancreatic DM involves both structural and functional loss of glucose-normalising insulin secretion in the context of exocrine pancreatic dysfunction and is often misdiagnosed as type 2 DM. Distinctive features of type 3c DM are concomitant EPI (according to faecal elastase test or direct functional tests), pathological results of pancreatic imaging (endoscopic ultrasound, magnetic resonance imaging, computed tomography) and the absence of type 1 DM-related autoimmunity.
Enzyme replacement therapy does not significantly affect carbohydrate metabolism in patients with DM, but it does have some positive effect on the number of episodes of mild and moderate hypoglycaemia when treated with Creon up to the 16th week of therapy.
Enzyme replacement therapy significantly reduces the frequency and severity of gastrointestinal symptoms of DM.
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