[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.

[Fat tissue as the primary target organ of insulin resistance in diabetes mellitus.] / A zsírszövet mint a 2-es típusú diabetest kíséro inzulinrezisztencia egyik célszerve.

Insulin resistance is a pathological condition in which the effect of endogenous or externally administered (exogenous) insulin to promote tissue glucose uptake and utilization falls short of that observed in metabolically healthy individuals. It affects the entire organism, but the pathogenetic and underlying molecular biological processes of its selected target tissues - the liver, muscle and adipose tissue - are partially different. Recently, knowledge about the role of adipose tissue has expanded significantly, and it increasingly seems that dysfunctional adipose tissue is the central player in these pathological events. The manuscript reviews the structure of adipose tissue, the regulation of adipogenesis and lipolysis, data on the relationship between the microbiome and adipose tissue, the typical differences of the acute and chronic insulin resistance as well as the therapeutic tools currently available to reduce adipose tissue insulin resistance. It may well be that a molecule with a selective adipose tissue attack point and enabling safe long-term use in humans is not yet within the hoped-for proximity, the first animal experimental observations related to the first "adipeuticum" being under development outline the promise of a new treatment option. Orv Hetil. 2023; 164(1): 3-10.

[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.

GLP1 receptor agonists in the therapy of type 2 diabetes / GLP1-receptor-agonisták a 2-es típusú diabetes vércukorcsökkento kezelésében

Glucagon-like peptide receptor-1 agonists have a key place in the hypoglycemic treatment of type 2 diabetes. The possibilities of their administration are now well outlined as well as their use in both the step-up and step-down an-tidiabetic therapy, the advantages and potential disadvantages of the already available oral version over the parenteral formulation, and the possible differentiation options for their basal insulin-combined variants. These issues are re-viewed in the article, but recent research on the drug group, monotherapeutic and combination products being under development are also briefly discussed. Attention is drawn on the importance of the early introduction of any of their long-acting derivates, the cardiorenal protective effect, powerful glycemic effect, weight loss promoting property and low hypoglycemic risk. It is important to keep doctors continuously informed about the latest results of this area as well as the correct patient education.

Real and misinterpretation of insulin resistance in the clinical practice / Az inzulinrezisztencia valós és téves értelmezése a klinikai gyakorlatban

Confirming or ruling out the presence of insulin resistance (IR) is one of the most common reasons for referral to non-diabetics in Hungary for diabetes outpatient units. The article overviews the concept of IR, its importance in pathophysiology, the diagnostic capabilities, and its treatment implications. It emphasizes that the decline in insulin activity is a co-morbidity of many diseases and does not, in itself, require detailed examination without other symptoms. If this occurs, it is sufficient to calculate the HOMA-IR value and determine fasting blood glucose and serum insulin levels for information purposes. If it is confirmed as part of a comorbid condition, complex treatment is required. Orv Hetil. 2020; 161(26): 1088-1093.

[Glucagon-like peptide-1 (GLP1) and the gastrointestinal tract. GLP1 receptor agonists: overemphasized gastric, forgotten intestinal ("ileal brake") effect?] / A glükagonszeru peptid-1 (GLP1) és a gyomor-bél rendszer. GLP1-receptor-agonisták ­ túlértékelt gyomor-, elfelejtodött bél- ("ileal brake") hatás?

Glucagon-like peptide-1 (GLP1) and their receptor agonists - beside their blood glucose lowering and central effects- affect also the gastrointestinal function in many respects. They slow down the stomach emptying, the motility of the small bowel and colon - this is the explanation for the "ileal brake" terminology -, stimulate the function of exocrine pancreatic acinar cells and increase amylase production. GLP1 receptor agonists belong to the defining tools of the blood glucose lowering therapy in type 2 diabetes. Their long- and short-acting derivatives have different influence on the fasting and the postprandial blood glucose, respectively. By introducing the term non-prandial and prandial type analogues - which seems to be forced in light of the newer data - the potential slowdown in gastric emptying is the center of interest, lately, however, especially in the case of long-acting GLP1 variants, at least such attention should be paid to controlling bowel function. The article reviews the physiological effects of GLP1 on the gastrointestinal tract and draws attention to the potential for the prevention of possible side effects through detailed patient information and dietary advises. Orv Hetil. 2019; 160(49): 1927-1934.

Large increase in the prevalence of self-reported diabetes based on a nationally representative survey in Hungary.

AIMS: To estimate and compare the prevalence of self-reported diabetes based on nationally representative surveys of the Hungarian adult population in 2002 (published data - Hungarostudy) and a survey in 2012. METHODS: A cross-sectional computer-assisted telephone interview survey on a stratified representative sample of community-dwelling adults (n=1000) in 2012. To describe self-reported diabetes prevalence and its temporal changes generalized linear models were used and results were compared to figures from Hungarostudy. RESULTS: Age standardized prevalence of self-reported type 2 diabetes was 11.7% (95%CI 10.0-13.8%) without gender or rural-urban differences in 2012. People with self-reported diabetes were older than controls (mean [SE]: 63.9 [0.9] vs. 45.9 [0.3] years, p<0.0001). The prevalence of diabetes sharply increased after 40 years of age and peaked at age 70 (27.7% [2.5], page*age<0.0001). The prevalence of self-reported diabetes increased by 89% (OR 1.89, 95%CI 1.53-2.32) from 6.2 to 11.7% between the two surveys with the most pronounced increase in the age group 55-64 years (from 11.6 to 24.4%). CONCLUSIONS: We reported an alarming increase in the prevalence of self-reported type 2 diabetes in the last decade that mostly affects working age people. If this trend continues, a major public health crisis in Hungary can be envisaged.

[Metformin - new data for an "old", but efficient, safe and reliable antidiabetic drug]. / Metformin - újabb adatok egy megbízható és hatékony "régi" vércukorcsökkento készítményrol.

Metformin is the basic drug of antihyperglycemic therapy in type 2 diabetes: according to actual therapeutic guidelines, it should be given in the absence of contraindications or intolerance during the whole course of the disease even after the initiation of insulin therapy. Recently more and more details have been explored regarding the molecular background of its effects, however, in parallel with the enormous growing knowledge, the number of questions still waiting to be answered has also grown. This review article deals with data already crystallized as well as with details not definitely cleared up. Genetic polymorphisms as well as potential drug interactions influencing the effects of metformin are also briefly summarized.

Cost-effectiveness of a risk-based secondary screening programme of type 2 diabetes.

OBJECTIVE: The objective of this study was to develop a long-term economic model for type 2 diabetes to describe the entire spectrum of the disease over a wide range of healthcare programmes. The model evaluates a public health, risk-based screening programme in a country specific setting. METHODS: The lifespan of persons and important phases of the disease and related interventions are recorded in a Markov model, which first simulates the effect of screening, then replicates important complications of diabetes, follows the progression of individuals through physiological variables and finally calculates outcomes in monetary and naturalistic units. RESULTS: The introduction of the screening programme nearly doubled the proportion of diagnosed patients at the age of 50 and prolonged life expectancy. Three-yearly screening gained 0.0229 quality adjusted life years for an additional €83 per person compared with no screening and resulted an incremental cost-effectiveness ratio of €3630/quality adjusted life years. CONCLUSION: From the economic perspective introduction of the 3-yearly screening programme is justifiable and it provides a good value for money. Copyright © 2016 John Wiley & Sons, Ltd.

[Sulfonylureas in today's blood glucose lowering therapy. New data on advantages and potential barriers of an "old" antidiabetic group]. / Szulfanilureák napjaink vércukorcsökkento kezelésében. Újabb adatok egy régi gyógyszercsoport elonyeirol és korlátairól.

Sulfonylurea compounds have been basic elements of antidiabetic treatment in type 2 diabetes for a long time. However, with the introduction of incretin type insulin secretagogues it is often arises, whether is still there a place for sulfonylureas in the today's therapy. To answer this question the author overviews general pharmaceutical characteristics of the sulfonylurea compounds as well as individual particularities of the second generation derivatives used at present in Hungary. The author details also the most important differences between incretin type drugs - first of all dipeptidyl peptidase-4 inhibitors - and sulfonylureas. On the basis of available data it can be concluded in accordance with the latest international guidelines, that sulfonylureas have still role in the blood glucose lowering therapy of type 2 diabetes, though they became somewhat pushed back among insulin secretagogue type drugs. If a sulfonylurea compound is the drug of choice, it is important to select the appropriate molecule (in case of normal renal function gliclazide or glimepiride). It is also important to re-educate the patient, as well as to apply the minimal dose providing the desired glycaemic effect.

Anti glutamate-decarboxylase antibodies: a liaison between localisation related epilepsy, stiff-person syndrome and type-1 diabetes mellitus.

We present two patients with partial epilepsy, type-1 diabetes and stiff person syndrome associated with high serum auto-antibody levels to glutamate-decarboxylase (anti-GAD). Both patients were or have suffered from additional autoimmune conditions. The presence of stiff person syndrome and elevated anti-GAD levels have to make clinicians look for additional autoimmune conditions including type-1 diabetes. On the other hand, the co-morbidity of partial epilepsy with autoimmune conditions in patients with elevated serum anti-GAD suggests an autoimmune mechanism of partial epilepsy in these cases.

LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.

[Is there any progress in the blood glucose lowering therapy of type 2 diabetes?]. / Van-e elorelépés a 2-es típusú diabetes vércukorcsökkento kezelésében?

Principles of glycemic treatment of type 2 diabetes are well outlined for a long time, however, emphasis of therapeutic strategies and treatment guidelines are continuously changing partially due to the continuous expansion of the available antihyperglycemic drugs. This article overviews the modifications of the drug selection arising from the broadening of the pathogenetic knowledge and recent therapeutic guidelines. It presents the role of the patient-centered approach in the therapeutic choice, highlights occasional contradictions between recent international and national guidelines and financing rules in Hungary. While consideration of the different antidiabetics by the same criteria and the choice of the most appropriate drug characterize international practice, prescription of certain compounds is often restricted by financial rules in Hungary.