[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.

[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.

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.

[De Quervain thyroiditis. Corner points of the diagnosis]. / A szubakut de Quervain-thyreoiditis. A kórismézés sarokpontjai négy eset kapcsán.

Inflammatory disorders of the thyroid gland are divided into three groups according to their duration (acute, subacute and chronic). De Quervain's thyroiditis (also termed giant cell or granulomatous thyroiditis) is a subacute inflammation of the thyroid, which accounts for 5% of thyroid disorders. The etiology is unknown, it usually appears two weeks after an upper viral respiratory infection. The clinical feature includes neck pain, which is aggravated during swallowing, and radiates to the ear. On palpation, the thyroid is exquisitely tender. The erythrocyte sedimentation rate is markedly elevated, the leukocyte count, C-reactive protein are normal or slightly elevated. The natural history of granulomatous thyroiditis involves four phases: the destructive inflammation results temporarily in hyperthyroidism followed by euthyroidism. After a transient hypothyroidism the disease becomes inactive and the thyroid function is normalised. Ultrasonographic findings are diffuse hypoechogenic structures, but nodules may also occur. The disease often remains unrecognised, or the first phase of the disease is diagnosed and treated as hyperthyroidism. The diagnosis can be confirmed by the presence of the thyroid autoantibodies, radioiodine uptake and fine needle aspiration cytology. There is no special treatment, non-steroid anti-inflammatory drugs or steroid should be given to relieve the pain. The aim of the authors is to shed light the key points of diagnosis and differential diagnosis by the presentation of four slightly different cases.

[Wernicke encephalopathy accompanying linitis plastica]. / Wernicke-encephalopathia linitis plasticában.

Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke's disease.

[Comparison of the effectiveness of two internationally recommended screening methods for the diagnosis of gestational diabetes]. / A gestatiós diabetes szurésére ajánlott két nemzetközi eljárás hatékonyságának összehasonlítása.

INTRODUCTION: Early diagnosis and adequate care of gestational diabetes is of great importance for both the mother and her fetus. Although several national and international guidelines are known on the methodology for screening gestational diabetes, a not negligible part of the cases remain unrecognized when applying even the most widely used criteria recommended by the World Health Organization (1st recommendation). A connection has been found between the maternal blood glucose values and the prevalence of still-birth, preeclampsia and large for gestational age neonates in several studies, from which the Hyperglycaemia and Adverse Pregnancy Outcomes study has come into prominence. According to conclusions of this study the International Association of Diabetic Pregnancy Study Groups suggested new numeric criteria for the evaluation of the 75-gram oral glucose tolerance test (2nd recommendation), which differs from the evaluation used in the aforementioned screening system. AIMS: The aim of the study was to compare the effectiveness of the two screening systems by evaluation of the pregnancy outcomes. METHODS: By following non-twin pregnancies of 1107 pregnant mothers (831 with normal glucose tolerance, 276 with gestational diabetes based on any of the applied screening methods) the maternal (pre- and post-term birth, caesarean section, toxaemia) and newborns pregnancy outcomes (infants small and large for gestational age, hypoglycaemia) were analysed. RESULTS: With the exception of the prevalence of large for gestational age infants - which was higher among women screened by the new evaluation - no substantial difference in the efficacy of the two investigated methods was found. CONCLUSION: The decision whether the screening of gestational diabetes using the new criteria results in safer recognition of the disturbances of glucose metabolism during pregnancy requires further investigations including a large number of cases.

[Pleiotropic effects of incretins and antidiabetic drugs with incretine mechanism]. / Inkretinek és inkretinhatású vércukorcsökkentok pleiotrop tulajdonságai.

Discovery of physiological and pharmacological characteristics of incretins (glucagon-like peptide-1 and glucose-dependent insulinotrop polypeptide), and the introduction of various products of those into the clinical practice has fundamentally changed blood glucose lowering therapy in type 2 diabetes. In addition to the antidiabetic properties more attention is paid to their favourable pleiotropic effects independent from the blood glucose lowering such as cardio-, vaso- and renoprotectiv, blood pressure lowering effects, as well as beneficial changes on blood lipid values and hepatic steatosis. These preferential changes prevail in slightly different way when incretin mimetics applied and dipeptidyl peptidase-4 inhibitors, furthermore, prolonged action of peptides metabolised by this enzyme may serve additional benefits in this latter mentioned group. The article overviews the currently known most important pleiotropic effects of incretins from the point of view of cardiorenal risk accompanying type 2 diabetes.

Prevalence of undiagnosed abnormal glucose tolerance in adult patients cared for by general practitioners in Hungary. Results of a risk-stratified screening based on FINDRISC questionnaire.

BACKGROUND: The prevalence of type 2 diabetes mellitus is rapidly increasing, worldwide and also in Hungary. Timely diagnosis and early treatment could be aided by targeted screening. Recognizing this, the Hungarian Diabetes Association initiated a risk-stratified screening with the involvement of primary care physicians. MATERIAL/METHODS: In the first phase of screening, the FINDRISC questionnaire was completed, followed by an oral glucose tolerance test (OGTT) for those with a score of ≥12. Between September 1, 2010 and March 31, 2011, 70,432 non-diabetic adults, who visited their general practitioners for any reason, were involved in the screening. Of these, 68,476 questionnaires proved to be suitable for processing. RESULTS: From the questionnaires, 28,077 (41.0%) had a score of ≥12. A valid OGTT was performed in 22,846 cases; of this group 3,217 subjects (14.1%) had elevated fasting glucose levels, 5,663 (24.8%) had impaired glucose tolerance, and 1,750 (7.6%) had manifest, previously undiagnosed, diabetes mellitus. Overall, from the valid OGTT group, 46.5% subjects had some degree of glucose intolerance. CONCLUSIONS: Based on the FINDRISC questionnaire, the risk-stratified screening for diabetes mellitus proved to be simple and cost-effective method for the early detection of carbohydrate metabolism disorders. Using this method, the prevalence rate of previously undiagnosed abnormal glucose tolerance was high in adult patients cared for by general practitioners in Hungary.

[Metabolic effects of bariatric surgery]. / A súlyleadás sebészetének (bariátriai sebészet) anyagcsere-vonatkozásai.

Bariatric surgery managing/preventing complications of severe overweight is nowadays widely accepted as a mainstay in the treatment of morbid obesity. Its role is particularly important in type 2 diabetes developing on the base of long-standing significant overweight. The glycemic control improves within days-weeks after these surgeries, when weight loss and reduction of the visceral fat mass is barely detectable. This short term effect is probably due to an increased secretion of glucagon-like peptide and, as a consequence, an improvement in hepatic insulin sensitivity as well as the whole body glucose uptake. Besides the prolonged glucagon-like peptide effects, the favourable long term effect of these operations - lasting for 10 years even after surgery - is the decrease of visceral fat mass and elimination of harmful influence of cytokines produced by the fatty tissue. The article overviews the metabolic effects of these procedures, their undoubted advantages and potential risks.

[A case of glucose-sensitive insulinoma accompanied by slightly elevated serum insulin levels and persisting convulsions after the surgically removed neuroendocrine tumor]. / Glükózszenzitív insulinoma mérsékelten emelkedett széruminzulinszinttel, eltávolítása után is fennmaradó epilepsziás rohamokkal.

Insul(in)oma is a usually solitary or, in some cases, multifocal tumor of pancreatic beta cells. It may be a component of multiple endocrine neoplasia type 1. or von Hippel-Lindau syndrome. In typical forms the diagnosis - based on the Whipple triad - is simple, however, it may be difficult to recognize in cases with near normal or only slightly elevated serum insulin levels, as well as in patients with known convulsive episodes. With the case presentation of an 81-year-old woman the authors draw attention to the pitfalls of the correct diagnosis. A special feature of the presented case is that convulsions persisted after surgical removal of the pancreatic neuroendocrine tumor verified with functional and imaging methods. Recurrent or residual tumor was not found, and morphological damage of the brain was absent. In the background of the continuing convulsions cerebrovascular alterations as well as the cytotoxic effect of the hypoglycemia-induced excessive glutamate production can be postulated.

[The physiology of incretins]. / Az inkretinek elettana.

The discovery of incretins-glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrop peptide (GIP)-, clarification of their physiological properties as well as therapeutic application of incretin-based blood glucose lowering drugs opened new perspectives in the medical management of type 2 diabetes. New results of basic research investigations led to revaluation of the role of GIP in metabolic processes and a more established use of GLP-1 action. The article overviews the most relevant data of production and effects of incretins, as well as future possibilities of their therapeutic use.

[Multiple hepatic abscesses due to actinomycosis: difficulties of diagnosis]. / Multiplex májtályog képében jelentkezo actinomycosis esete: a kórismézés nehézségei.

Authors present the case of a 65 year-old man without any remarkable previous illness, hospitalized because of having prolonged fever caused probably by an infection due to a tick bite. Tularaemia and bartonellosis based on serological results as well as neoplasm of the sigma with multiple metastases to the liver raised by ultrasonography and abdominal CT could be excluded with detailed investigations. Multiple abscesses of the liver were diagnosed, followed by a percutaneuos ultrasonography directed aspiration of one of the abscesses which resulted in 150 ml buffy pus. Microbiological examination evaluated the presence of Actinomyces meyeri. Instead of neoplasm, diverticulosis and diverticulitis of the sigma could be clarified with perforation of one of the diverticuli causing peridiverticulitis, retroperitoneal abscess and probably abscesses in the liver by haematogenous dissemination. Surgical intervention, resection of the liver and the sigma resulted in recovery of the patient. Difficulties of diagnosis are discussed in the article pointing out the importance of interdisciplinary collaboration, involving also infectologist. Diverticulosis of the sigma as presumably origin of hepatic actinomycosis is a literary curiosity. This was the cause of the case presentation.

[Verrucous carcinoma of the anal margin. The importance of adequate biopsy technique]. / Verrucosus analis carcinoma (Buschke-Löwenstein-tumor): a körültekinto biopsziás mintavétel jelentosége.

Buschke-Löwenstein tumor (verrucous carcinoma, giant condylomata) of the anal margin is a locally invasive, destructively growing carcinoma that does not metastasize. The lesions are rare despite the increased incidence of anal condylomata and anal carcinomas. Authors report a case of a 63-year-old woman suffering from verrucous carcinoma (Buschke-Löwenstein tumor) of the anal margin. The tumor invaded the rectal sphincter and extended beyond the muscle, infiltrating the lower abdomen. Infiltration of the perivesical soft tissue caused bilateral hydronephros. Because both under- and overdiagnosis of anal cancer and precancer may lead to inappropriate treatment, it is important to perform adequate sampling for histology. Non-representative superficial biopsies may result underdiagnosis of the disease.

[Pathomechanism of diabetic neuropathy: background of the pathogenesis-oriented therapy]. / A neuropathia diabetica patomechanizmusa: az oki kezelés elméleti háttere.

The pathomechanism of diabetic neuropathy remains still poorly understood, however, a broad spectrum of novel findings associated with therapeutic consequences emerged during the last decades. Both disturbed function of primary hemostasis and increased activity of coagulation system contribute to the reduced endoneurial blood flow. Increased superoxide anion production induced by hyperglycemia leads to decreased activity of glycerinaldehid-3-phosphate dehydrogenase and to consequential increased activity of alternative pathways, including the polyol-, hexosamine-, diacilglycerol protein kinase-C- and advanced glycation pathways. Advanced glycation endproducts increase the activity of the nuclear-factor kappa-B, as well as the production of vasoactive factors and cytokines (interleukin-1, -6, tumor necrosis factor alpha). The aim of pathogenetic oriented treatment is to slow down, stop or reverse the progression of neuropathy. Components of pathogenetic oriented treatment are glycaemic control, management of risk factors, benfotiamine and alpha-lipoic acid. On one hand, transketolase-activator benfotiamine inhibits alternative pathways induced by hyperglycemia (the polyol-, hexosamine-, diacilglycerol protein kinase-C-, and advanced glycation pathways), while, on the other hand, it increases the activity of the pentose-phosphate-shunt. The clinical effectiveness of benfotiamine has been shown in many international and Hungarian trials. Alpha-lipoic acid as a powerful antioxidant decreases oxidative stress and this way increases the activity of glycerinaldehid-3-phosphate dehydrogenase. Alpha-lipoic acid administered in infusion or oral treatment decreases both symptoms of neuropathy and neuropathic deficit. In conclusion, the case of diabetic neuropathy illustrates well, how widening of our knowledge on pathogenesis might contribute to successful therapy.

[Screening for type 2 diabetes and prediabetes--methodological concerns and feasibility in Hungary]. / A 2-es típusú diabetes és elôállapotainak szûrése--módszertani megfontolások, hazai lehetôségek.

It is well documented that type 2 diabetes often has a long and latent pathogenetic process before its manifestation; even patients with short duration of diabetes can be asymptomatic. At these stages, patients with type 2 diabetes or prediabetes can be identified by screening. Several screening procedures have been developed; however, risk-stratified screening method is the most accepted worldwide. Risk-stratified screening implies two stages, starting with the selection of people at higher risk. At the second stage, blood glucose measurement should be carried out. For selection of subjects at higher risk, the FINDRISC (Finnish Diabetes Risk Score) questionnaire proved to be useful in different settings. Based upon the results of a screening procedure, early treatment of patients with type 2 diabetes and primary prevention of diabetes in subjects with prediabetes can be performed. All these activities can lead to a decrease of prevalence rate of type 2 diabetes. Similarly to other countries, all these concerns should be addressed within a frame of a new National Diabetes Programme in Hungary.

[Risk-stratified screening for diabetes in adults: results of the first investigation in Hungary]. / Kockázatalapú diabetesszûrés felnôttek körében: az elsô hazai vizsgálat eredményei.

Prevalence rate of diabetes mellitus, especially of type 2 diabetes, has been increasing worldwide; this is the case in Hungary as well. The early diagnosis of diabetes should be considered as one of the most important factors improving the late prognosis of the disease. Due to cost-effectiveness, screening should primarily be implemented in subjects at high risk to glucose intolerance. A risk-stratified nationwide screening procedure was performed by the Hungarian Diabetes Association in collaboration with general practitioners (GPs) in adult subjects without known diabetes. The screening procedure, which was sponsored by the 77 Elektronika Ltd (Budapest), was performed in a two steps manner. At first step, the Hungarian version of the internationally validated FINDRISC questionnaire (maximal score 26) was filled out by subjects while waiting for GP. At second step, blood glucose value in venous sample was locally measured by standard laboratory methods in subjects with a score value of > or = 12. The further diagnostic steps were carried out by WHO guidelines. As a total, 8921 subjects (59.7% women, 40.3% men) were screened between 01, April 2008 and 31, March 2009. Out of 4286 subjects with a score of > or = 12 (age 53.4 +/- 11.4 years; BMI: 29.9 +/- 4.8 kg/m2; waist circumference: 101.7 +/- 12.7 cm) 3733 (87.1%) had normal fasting blood glucose values, while 283 subjects (6.6%) had IFG, 122 (2.85%) had IGT and 19 participants (0.44%) had isolated IGT. Unknown diabetes was found in 129 subjects (3.01%). If the score value requiring laboratory confirmation was set at higher level (> or = 15 or > or = 20), the proportion of subjects with any degree of glucose intolerance increased. Among anthropometric parameters, BMI had the strongest association with the risk of glucose intolerance: 1 kg/m 2 increase in BMI value increased the risk of abnormal score category (> or = 12) by 24.7% (95% confidence interval: 23.3-26.2%). The risk-stratified screening procedure proved to be simple and effective for detecting early impairment of the carbohydrate metabolism, therefore, its wider implementation should be considered advisable.

[Molecular mechanisms and correlations of insulin resistance, obesity, and type 2 diabetes mellitus]. / Molekuláris tényezôk szerepe az inzulinrezisztencia-elhízás-2-es típusú diabetes patogenetikai kapcsolatban.

Adipose tissue cells express and secrete numerous proteins influencing the signal transduction pathways of insulin receptor by auto-, para- and endocrine manner. Several cytokines, tumor necrosis factor-alpha and its soluble receptor forms, sTNFR1 and sTNFR2, resistin, retinol-binding protein 4, plasminogen activator inhibitor, lipocain 1 inhibit the signalization of insulin receptor causing insulin resistance in target tissues, mainly in adipose, liver and muscle, brain, endothelial as well as in pancreatic beta-cells. However, many other proteins produced by the fat tissue, such as adiponectin, visfatin, vaspin, apelin, omentin and chemerin enhance the signal transmission of the receptor. Recently discovered common mechanisms leading to insulin and cytokine resistance in obesity and type 2 diabetes mellitus, e.g. protein family of suppressor of cytokine signaling (SOCS) are also discussed.

[Effectiveness of cardiometabolic risk reduction in patients with type 1 diabetes mellitus]. / A kardiometabolikus kockázati tényezôk kezelésének eredményessége 1-es típusú diabetesben szenvedôk körében.

UNLABELLED: The attainment and maintenance of therapeutic goal of cardiovascular risk factors are of great clinical importance. The effectiveness of cardiovascular risk management is not well characterized during regular care of patients with type 1 diabetes mellitus. AIM: The aim of the study was to estimate the effectiveness of cardiovascular risk management in type 1 diabetic patients. METHODS: Adult patients with type 1 diabetes mellitus (n = 533; 256 men, 277 women; age: 35.6 +/- 11.6 years; duration of diabetes: 18.0 +/- 11.1 years; x +/- SD) were consecutively enrolled from 11 diabetes outpatient departments. Data on medical history, actual treatment, anthropometric and laboratory parameters as well as actual blood pressure were registered, while eating and smoking habits, education level and physical activity were evaluated by standardized questionnaires. The treating goal was set according to the national guideline which corresponds to the current international task force. RESULTS: Of 533 patients, the body mass index target level (< 25 kg/m 2 ) was achieved by 295 (55.5%) patients. Ideal waist circumference (< 80 cm for women and < 94 cm for men) was measured in 140 (50.5%) and in 165 (63.7%) patients, respectively. Optimal glycaemic control (HbA 1c level < 6.5%) was documented in 45 (8.4%) patients. Lipid lowering drugs (statins, fibrates or ezetimibe) were used by 130 patients, among which 53.1% reached the target triglyceride level, 71.5% the target HDL-cholesterol and 27.8% the target LDL-cholesterol levels. Taking the lipid target values together, only 23 (17.7%) patients were at goal. Antihypertensive drugs were used by 173 patients among which 29.5% reached the systolic and 34.8% the diastolic target values (< 130/80 mmHg). Regarding smoking habits, 94 (17.7%) patients were current smokers and 102 (19.2%) ex-smokers. CONCLUSIONS: The attainment of therapeutic goal of cardiovascular risk factors proved to be difficult in a substantial part of patients. Further efforts are needed for attaining and maintaining the established goal of cardiovascular risk management during regular care of adult patients with type 1 diabetes mellitus.

[Incretin enhancers, incretin mimetics: from therapeutic concept to clinical application]. / Inkretin hatáserosítok, inkretin mimetikumok - a terápiás alkalmazás kigondolásától a gyakorlati megvalósításig.

The incretins are peptide hormones produced by special cell types of the intestines, which are secreted following ingestion of foods, indirectly, through a complex mechanism, by decreasing postprandial blood glucose levels participate in the regulation of the glucose homeostasis. The article beside of summarizing the physiological aspects of the two most important incretins, the glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrope polypeptide (GIP), gives a detailed overview of multifaceted effects of GLP-1 and their potential application in the therapy of type 2 diabetes mellitus. The human GLP-1 because of its very short half-life is not suitable for therapeutic use. However, by inhibition its degradation, by suppression of activity of the serine peptidase type enzyme dipeptidyl peptidase (DPP) IV, its effect can be prolonged. Compounds with this effect have been synthetised, as well as drugs resistant to DPP IV, not being identical with the structure of the human GLP-1, but having agonist effect on its receptor could also be manufactured. Members of the first group are called incretin (GLP-1) enhancers, while of the second one incretin mimetics. Two of the enhancers, the sita- and vildagliptin, and one representative of the incretin mimetics, the exenatide after encouraging preclinical and human experiences have also been registered and introduced in the clinical practice. Their potential place in the treatment of type 2 diabetes is not exactly outlined at present. Though there are arguments underlining their early use in the glucose lowering drug treatment of type 2 diabetes, their application as part of a combination therapy seems to be a real indication.