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.

[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.

[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.

[The use of gliclazide in individualized sulfonylurea therapy]. / A gliclazid használata a differenciált szulfanilureaalkalmazás tükrében.

In addition to the common blood glucose lowering effect, sulfonylurea compounds are different in many aspects from each other. Based on earlier findings the second generation gliclazide has special advantages within this group. Although the number of experimental and clinical observations on gliclazide is continuously increasing, these novel findings are not in the focus anymore due to the appearance of new antidiabetics. This article reviews recent experimental (effect on receptors, the absence of Epac2 activation, antioxidant properties, possible incentive of factors participating in beta-cell differentiation) and pharmacogenomic data, and compares them with clinical observations obtained from gliclazide treatment (hypoglycemias, parameters of cardiovascular outcome). The data underline the advantages of gliclazide, the highly pancreas-selective nature, preservation of the ischemic precondition, favourable hemodynamic properties and potential reduction of the beta-cell loss as compared to other compounds of the group. However, gliclazide is not free from disadvantages characteristic to sulfonylureas in general (blood glucose independent insulin stimulation, beta-cell depletion). Comparing gliclazide with other derivatives of the group, the above data indicate individual benefits for the application when sulfonylurea compound is the drug of choice.

[Timely commencement of insulin in type 2 diabetes: benefits and risks]. / Az inzulinkezelés korai megkezdése 2-es típusú cukorbetegségben: haszon és kockázat.

The introduction of insulin in type 2 diabetes is often too late, though the immediate as well as late consequences of inadequate metabolic control are well known. That is the reason, why a special attention is given in recent therapeutic guidelines for the importance of early, at least timely insulinisation. This review article summarizes the advantages (mitigation of the beta-cell dysfunction, long lasting good metabolic control) and potential risks (hypoglycemia, weight gain, possible deteriorating patient compliance) of early or timely insulin therapy. It is pointed out that the introduction of insulin is effective and safe therapeutic option during the whole course of type 2 diabetes, the use of different regimes is suitable to reach and maintain the individual glycemic target and, with a structured patient education, it does not disturb the quality of life and the compliance of patients.

[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.

[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.

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.

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.

[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.

[Difficulties in the differential diagnosis of hyponatremia presenting with severe neuropsychiatric symptoms]. / Súlyos neuropszichiátriai tünetekkel járó hyponatraemia differenciáldiagnosztikai nehézségei.

Hyponatremia is the most frequent eletrolyte imbalance in hospitalized geriatric patient. The accompanying signs and symptoms can run a wide range and, therefore, these patients are usually admitted to various departments, i.e. neurology and/or traumatology first. Directed laboratory investigations demonstrate severe hyponatremia. Differential diagnosis can be very difficult and complex in the clinical settings. Firstly, spurious forms of hyponatremia have to be excluded, then the underlying cause should elucidated based on the patients hydration status and serum osmolarity. Hyponatremia can be divided into hyper-, hypo- and normovolemic forms. Moreover, it can be further classified as hypo-, iso- and hyperosmolar hyponatremias. The differentiation between renal and extrarenal salt wasting forms is hinged on the urine sodium concentration. Syndrome of inappropriate antidiuretic hormone secretion is the most common cause of normovolemic, hypoosmolar forms (named also as Schwartz-Bartter syndrome). The authors aimed to shed light on the often insurmountable difficulties of the diagnosis, differential diagnosis and appropriate treatment of this very frequent electrolyte imbalance by presenting a clinical case report. Their purported aim reflects upon the wide array of ethiopathogenesis of hyponatremia: various endocrine, renal diseases, inappropriateness of antidiuretic hormone secretion as well as the role of different medications (e.g. diuretics). This fine-tuned and intricate physiology of sodium metabolism could fortuitously be overturned by these mechanisms.

[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.

[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.

[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.

[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.

[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.

[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.