Type 3 diabetes mellitus: is there a chance to become famous?

DOI: https://dx.doi.org/10.18565/pharmateca.2022.4.18-25

L.Yu. Morgunov

Medical Institute, Peoples’ Friendship University of Russia, Moscow, Russia
Diabetes mellitus type 3c (DM3c) develops as a result of a number of exocrine diseases of the pancreas: chronic pancreatitis, pancreatic ductal adenocarcinoma of the, hemochromatosis, cystic fibrosis, and previous pancreatic surgery Inflammation and fibrosis in the pancreatic tissue cause damage to both endocrine and exocrine functions, resulting in decreased levels of insulin, glucagon, and exocrine function. The prevalence of DM3c reaches 5-10% among diabetic patients in developed countries. In 1.8% of adults with newly diagnosed diabetes, diabetes can be classified as type 3 diabetes, and individuals with this disease have varying degrees of exocrine and endocrine dysfunction. DM3c, or impaired glucose tolerance, develops in 25-75% of adults with chronic pancreatitis. After acute pancreatitis DM3c develops in a year in 15% of patients, and an even in greater proportion of patients - in 5 years. Pancreatitis increases the risk of pancreatic cancer in diabetic patients, and the highest risk of this cancer occurs in DM3c patients. The incidence of newly diagnosed DM varied depending on the type of surgical intervention: from 9 to 24% after pancreatoduodenal resection (PDR), 3-40% after distal and 0-14% after central pancreatectomy. The type of resection, high preoperative HbA1c and fasting glucose levels, and low pancreatic residual volume after surgery had the strongest associations with new onset DM. Three mandatory criteria for diagnosing DM3c have been identified: the presence of exocrine pancreatic insufficiency, pathological changes during its visualization (endoscopic ultrasound and other instrumental methods), and the absence of autoantibodies to DM1. Minor criteria include impaired в-cell function, low levels of fat-soluble vitamins (A, D, E, and K), lack of insulin resistance, and impaired secretion of incretins and pancreatic polypeptide. It is assumed that the gut microbiome of DM3c patients differs from that of patients with type 1 and type 2 diabetes mellitus. Early recognition of DM3c associated with pancreatic ductal adenocarcinoma improves patient survival. In the presence of unexpressed hyperglycemia and insulin resistance, the appointment of metformin should be considered, since side effects in the form of weight loss and disorders of the gastrointestinal tract are undesirable in DM3c. The main defect in DM3c is insulin deficiency; insulin which is prescribed when oral hypoglycemic therapy has failed, but it may increase the risk of malignancy in addition to weight gain and hypoglycemia. In progressive DM3c, a basal-bolus insulin regimen should be used, with attention paid to education, continuous glycemic monitoring, and the possible use of insulin pumps. Derivatives of oxyntomodulin, an incretin mimetic with an optimal ratio of the effects of activation of glucagon-like peptide-1 and the glucagon receptor, may be promising for the treatment of DM3c. With exocrine insufficiency, replacement therapy with pancreatic enzymes is recommended; treatment with a pancreatic polypeptide appears promising. Islet transplantation has become an established approach to в-cell replacement therapy for the treatment of insulin-deficient diabetes. As an alternative approach, human pluripotent stem cells can provide an unlimited number of cells with the ability to secrete insulin in response to high blood glucose levels. Beta cells, progenitors of pluripotent stem cells, are the best candidate given the availability of encapsulation technology.

About the Autors

Corresponding author: Leonid Yu. Morgunov, Dr. Sci. (Med.), Professor, Professor at the Department of Hospital Therapy with the Course of Endocrinology, Hematology and Clinical Laboratory Diagnostics, Medical Institute, Peoples’ Friendship University of Russia, Moscow, Russia; morgunov.l.y@mail.ru, https://orcid.org/0000-0002-6608-2825

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