[From GLP1 receptor agonists to triple hormone receptor activation supplemented with glucagon receptor agonism.] / A GLP1-receptor-agonistáktól a glükagonreceptor-agonizmussal kiegészített hármashormonreceptor-aktiválásig.

Following the introduction of mono- and then dual hormone (incretin) receptor agonists into therapy, attention was turned to multiple receptor stimulation, with the additional activation of the glucagon receptor, as a new option for the pharmaceutical treatment of type 2 diabetes and obesity. In addition to its role in carbohydrate metabolism, the article reviews the other important physiological tasks of glucagon, especially its participation in intrainsular paracrine regulation, energy expenditure and the shaping of appetite and food consumption. It covers the potential benefits of the triple combination and briefly touches data on the efficacy and safety of the first triple receptor agonist drug, retatrutide, in preclinical human studies. Further confirmation of the promising results may represent progress in the treatment of these forms of disease and their accompanying conditions, such as steatosis hepatis. Orv Hetil. 2023; 164(42): 1656-1664.

[Diabetes mellitus and the intestinal microbiome]. / A diabetes mellitus és a bélmikrobiom.

The intestinal microbiome plays an important role in the body's physiological processes. One of its most decisive roles is the production of short-chain fatty acids, which has crucial importance in the maintenance of an intact intestinal barrier and immune homeostasis. Dysbiosis in the microbiome caused by dietary habits, regular medication use, and other factors can result in damage to the barrier function, which triggers the translocation of lipopolysaccharides into the portal circulation. By maintaining subclinical inflammation, these can lead to the development of obesity, insulin resistance, and fatty liver. The entry of pathogenic bacteria into the portal circulation can cause beta cell destruction through molecular mimicry and consequent autoimmunity. Both mechanisms can lead to diabetes mellitus. The paper reviews the changes in the intestinal microbiome in type 1 and type 2 diabetes mellitus, detailing experimental and clinical data. It points out that even though our knowledge is not yet sufficient to help daily clinical practice, the expansion of data can help the prognostic use of some results. All this, however, requires further investigations and observations. Orv Hetil. 2023; 164(25): 981-987.

[The "other" incretin - the therapeutic rediscovery of the glucose-dependent insulinotropic polypeptide]. / A "másik" inkretin ­ a glükózdependens insulinotrop polipeptid terápiás újrafelfedezése.

Among the two incretins that strongly stimulate insulin secretion and are also involved in its physiological regulation in type 2 diabetes, glucagon-like peptide-1 (GLP1) has been the focus of interest for a long time, due to its retained - although reduced - secretagogue nature also in type 2 diabetes. Its receptor agonists were also included in the antidiabetic treatment toolkit. In the light of more recent studies, however, the "other" incretin, the glucose-dependent insulinotropic polypeptide (GIP) has also come into a different light. It turned out that by regulating glucagon and insulin production according to blood sugar levels, it acts as a bifunctional blood sugar stabilizing factor in type 2 diabetes as well. The article reviews new data on the physiology of GIP, its verifiable effects in type 2 diabetes and obesity, the so-called "twincretin" effect as well as the benefits of the double stimulation of the GIP and the GLP1 receptor. It describes the pharmacology of the first dual receptor agonist, tirzepatide, already incorporated in therapeutic recommendations, and the first clinical trials related to its use. In the light of the data so far, the molecule may open new horizons in the treatment of type 2 diabetes and obesity. Orv Hetil. 2023; 164(6): 210-218.

[Is there a need for a revised classification in diabetes mellitus?] / Indokolt-e a klasszifikáció módosítása diabetesben?

Diabetes mellitus is a cluster of diseases with heterogeneous etiopathogenesis and clinical nature. The exact classification of certain cases is of decisive importance in terms of the optimal choice of treatment. However, the classification is still not completely resolved, despite the available, ever-expanding tool park and rapidly expanding knowledge. Therefore, new recommendations are made to clarify the grouping. This article reviews the classification guidelines created between 1965 and 2019 based on international consensus, with the coordination of the World Health Organization (WHO), as well as the proposals made based on recent tests and observations. It states that for daily practice, the present WHO guideline is still the most orienting. In addition, in cases of uncertain classification, it is essential to follow up the patients and repeat the examinations as necessary, until the nature of the specific form of the disease is clarified. Orv Hetil. 2022; 163(48): 1909-1916.

Lower prevalence of Helicobacter pylori infection in patients with inflammatory bowel disease but not with chronic obstructive pulmonary disease - antibiotic use in the history does not play a significant role.

BACKGROUND: Patients with inflammatory bowel disease have lower prevalence of Helicobacter pylori infection, but the exact reason for this is not yet clear. AIM: To examine whether the antibiotics frequently used in inflammatory bowel disease are responsible for the lower prevalence of H. pylori infection. Patients with chronic obstructive pulmonary disease on prolonged previous antibiotic therapy were used for comparison. METHODS: Presence/absence of H. pylori infection was detected by a (13)C-urea breath test in 133 patients with inflammatory bowel disease (82 ulcerative colitis, and 51 Crohn's disease) and compared with that of 135 patients with chronic obstructive pulmonary disease and with two age-matched control groups (200 patients each). Primary disease location, duration of disease and detailed analysis of previous and current medication (dose and duration of antibiotics, steroids, 5-aminosalicylic acid) were analysed in each cases. RESULTS: Seventeen of the 133 patients with inflammatory bowel disease [12.2% (10/82) of ulcerative colitis and 13.7% (7/51) of Crohn's disease] and 90/135 patients with chronic obstructive pulmonary disease (66.7%) were positive for H. pylori. A total of 78/200 (39%) for the inflammatory-bowel-disease-group-matched controls and 110/210 (55%) for the chronic-obstructive-pulmonary-disease-matched controls were positive for H. pylori. The history of any antibiotic or steroid therapy had no influence on H. pylori status of patients with inflammatory bowel disease. CONCLUSION: The prevalence of H. pylori compared to the age-matched controls is significantly lower in patients with inflammatory bowel disease but not in those with chronic obstructive pulmonary disease. Antibiotic use is not responsible for the lower prevalence of H. pylori infection in patients with inflammatory bowel disease.

Helicobacter pylori infection and molecular changes in gastric carcinogenesis.

In recent years there has been much progress in understanding the pathogenesis of gastric cancer. The role of individual factors in gastric carcinogenesis continues to be debated and is also subject to further analysis. In addition to the activation of oncogenes and the inactivation of tumor suppressor genes, alteration of adhesion molecules seems to be critical for the development of gastric cancer. Helicobacter pylori has been linked to an increased risk of developing gastric cancer, and the molecular changes induced by H. pylori are currently being investigated. Recent studies indicate that H. pylori induces cell proliferation and apoptosis during the early phase of chronic inflammation of the gastric mucosa, whereas in the malignant transformation of the gastric mucosa apoptosis is inhibited and adhesion of gastric epithelial cells is impaired. This review focuses on the role of H. pylori in the development of molecular changes in gastric cancer and its preneoplastic lesions.