Tímea Varga

Serum Dipeptidyl Peptidase-4 Activity in Insulin Resistant Patients with Non-Alcoholic Fatty Liver Disease: A Novel Liver Disease Biomarker

Background In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4) and the insulin resistance index (HOMA2-IR) in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD) and in healthy controls (CNTRL). Methods and Findings sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs) and 82 type 2 diabetes (F/M:48/34, 62.8 yrs) patients and 26 (F/M:14/12, 35.3 yrs) controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG (“prediabetes”), 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests); NAFLD(NGTonly): 3.23 (p = 0.0013 vs CNTRL); NAFLD(IFG/IGT/type 2 diabetes): 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group). sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L) and abnormal glucose metabolism (30.38U/L) than in CNTRL (25.89U/L, p<0.001 and p = 0.013) or in T2D groups (23.97U/L, p<0.001 and p = 0.004). Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and γGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and γGT: r = 0.4128,p = 0.0210. Conclusions The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among γGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly suggests that serum DPP-4 activity should be considered as a novel liver disease biomarker.

Changes in cognitive function in patients with diabetes mellitus

Patients with diabetes are approximately 1.5 times more likely to experience cognitive decline than individuals without diabetes mellitus. Most of the data suggest that patients with diabetes have reduced performance in numerous domains of cognitive function. In patients with type 1 diabetes, specific and global deficits involving speed of psychomotor efficiency, information processing, mental flexibility, attention, and visual perception seem to be present, while in patients with type 2 diabetes an increase in memory deficits, a reduction in psychomotor speed, and reduced frontal lobe (executive) functions have been found. The complex pathophysiology of changes in the central nervous system in diabetes has not yet been fully elucidated. It is important to consider the patients age at the onset of diabetes, the glycemic control status, and the presence of diabetic complications. Neurological consequences of diabetes appear parallel to those observed in the aging brain. Neuroimaging studies highlight several structural cerebral changes, cortical and subcortical atrophy, beside increased leukoaraiosis that occurs in association with diabetes. There is supporting evidence from many hypotheses to explain the pathophysiology of cognitive decline associated with diabetes. The main hypotheses pointing to the potential, implied mechanisms involve hyperglycemia, hypoglycemia, microvascular disease, insulin resistance, hyperinsulinism, hyperphosphorylation of tau protein, and amyloid-β deposition.

Altered Immune Regulation in Type 1 Diabetes

Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.

[Elevated serum dipeptidyl peptidase-4 activity in type 1 diabetes mellitus: a direct comparison].

A dipeptidil-peptidaz-4 enzim – amely azonos a T-lymphocyta membranfelszinhez kotott CD26 molekulaval – az inkretin hormonok bontasaval jelentős szerepet jatszik a szenhidrat-anyagcsere szabalyozasaban. Celkitűzes: Vizsgalatunk celja az volt, hogy meghatarozzuk az ehomi es postprandialis szerum-DPP-4 enzimaktivitasat 41 1-es, 87 2-es tipusu cukorbetegben, valamint 25 egeszseges szemelyben. Modszer: A szerum-DPP-4-enzimaktivitas meghatarozasa microplate-alapu kinetikus eljarassal tortent ehomi, majd etkezest kovetően 60 es 120 perces időszakokban. Eredmenyek: A DPP-4-enzimaktivitas mind ehomi, mind postprandialis allapotban szignifi kansan magasabb volt az 1-es tipusu diabetesben szenvedőknel, mint a 2-es tipusu diabeteses vagy a kontrollszemelyekben. Nem talaltunk valtozast az enzimaktivitasban egyik csoporton belul sem a postprandialis es az ehomi allapot kozott. Nem volt korrelacio sem az ehomi plazmaglukoz- es a szerum-DPP-4-enzimaktivitas, sem a HbA1c es a szerum-DPP-4-enzimaktivitas kozott. Kovetkeztetes: Eredmenyeink felvetik annak a valoszinűseget, hogy a DPP-4-gyel kapcsolatba hozhato vercukorszint-valtozas nem a szerumban merhető DPP-4-aktivitas-valtozas kovetkezmenye, hanem parakrin modon hato DPP-4-hataskent jelentkezik. Az 1-es tipusu diabetesben eszlelhető emelkedett DPP-4-enzimaktivitas ugyanakkor a pancreas autoimmun folyamatara utalhat, de hormonalis feed-back mechanizmust, esetleg celszervkarosodast is jelezhet. Kulcsszavak: dipeptidil-peptidaz-4, glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, 1-es tipusu cukorbetegseg, 2-es tipusu cukorbetegseg, autoimmunitas Elevated serum dipeptidyl peptidase-4 activity in type 1 diabetes mellitus: a direct comparison Dipeptidyl peptidase-4 (DPP-4) has an important role in the carbohydrate metabolism with the degradation of incretin hormones. Aim: We assessed the serum DPP-4 activity both in fasting and postprandial condition in patients with type 1-, type 2 diabetes and healthy controls. Methods: Serum DPP-4 activities were determined at fasting sate and at 60 and 180 minutes after test meal. DPP4 activity was measured by microplate-based kinetic assay in 41 type 1-, and in 87 type 2 diabetic patients and in 25 healthy volunteers. Results: Serum DPP-4 activities were found signifi cantly higher both in fasting and postprandial state in patients with type 1 diabetes than in type 2 and control subjects. No change in the enzyme activities was found after test meal. Correlation was neither detected between the fasting plasma glucose nor between the HbA1C and the DPP-4 values in any of the groups studied. Conclusions: Results suggest that it is not the hyperglycemia, rather the type of diabetes which determinates the serum DPP-4 enzymatic activity. The exact background of this phenomenon is not yet clear, however, increased serum DPP-4 enzyme activity in type 1 diabetes mellitus may refer to pancreatic autoimmune process, concomitant autoimmune diseases, hormonal feed back mechanism, or even target organ damage.UNLABELLED Dipeptidyl peptidase-4 (DPP-4) has an important role in the carbohydrate metabolism with the degradation of incretin hormones. AIM We assessed the serum DPP-4 activity both in fasting and postprandial condition in patients with type 1-, type 2 diabetes and healthy controls. METHODS Serum DPP-4 activities were determined at fasting sate and at 60 and 180 minutes after test meal. DPP-4 activity was measured by microplate-based kinetic assay in 41 type 1-, and in 87 type 2 diabetic patients and in 25 healthy volunteers. RESULTS Serum DPP-4 activities were found significantly higher both in fasting and postprandial state in patients with type 1 diabetes than in type 2 and control subjects. No change in the enzyme activities was found after test meal. Correlation was neither detected between the fasting plasma glucose nor between the HbA(1C) and the DPP-4 values in any of the groups studied. CONCLUSIONS RESULTS suggest that it is not the hyperglycemia, rather the type of diabetes which determinates the serum DPP-4 enzymatic activity. The exact background of this phenomenon is not yet clear, however, increased serum DPP-4 enzyme activity in type 1 diabetes mellitus may refer to pancreatic autoimmune process, concomitant autoimmune diseases, hormonal feed back mechanism, or even target organ damage.

Evolution and predictors of morphological and functional arterial changes in the course of type 1 diabetes mellitus

Diabetes mellitus results in accelerated atherosclerosis. We evaluated preclinical, morphological and functional vascular changes in type 1 diabetes mellitus.

Development of silent gastric carcinoid in a type 1 diabetic patient with primer hypothyreosis

Type 1 diabetes is usually associated with other autoimmune diseases. Parietal cell antibodies (PCA) are found in 20% of type 1 diabetic patients which might be an early sign of autoimmune gastritis and pernicious anemia. PCA destroy the gastric H+/K+ ATP-ase. The chronic auto-destruction of the proton pump leads to hypo/achlorhydria and hypergastrinemia which leads to the hyper/dysplasia of enterochromaffin-like cells (ECL). ECL hyper/dysplasia is known to increase the likelihood of gastric carcinoid tumor development in affected patients. Gastric carcinoid tumors forming from the hyperplasia of ECL cells are found in 4-9% of patients having autoimmune gastritis or pernicious anemia. The 29-years-old type 1 diabetic patient, having primer hyperthyroidism was admitted to our clinic because of gastric pain. Results of endoscopy and biopsy showed multiple small polyps in the fundus with non-antral hypergastrinemic (type A) atrophic gastritis. The parietal cell antibody test was positive, the serum chromogranin A level was 289,7 ng/ml (normal value

Verrucous carcinoma of the anal margin. The importance of adequate biopsy technique

98 ng/ml), TSH level was 9,93 mIU/L. The histological examination indicated carcinoid tumor. Sandostatin therapy was started then partial gastrectomy was done. After the operation the plasma chromogranin level normalized. Non-antral, multiple polyps could cover silent neuroendocrine tumors, which are slowly growing benign endocrine tumors, however, they also might be high malignity endocrine carcinomas. These tumors could be easily recognized in the clinical practice by measuring the serum or tissue chromogranin A level and other markers of tumor growth. Thus screening of gastric endocrine tumors in type 1 diabetic patients with co-morbid autoimmune diseases is recommended.

[Mechanical circulatory support saves lives -- three years' experience of the newly established assist device program at Semmelweis University, Budapest, Hungary].

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.

A mechanikus keringéstámogatás életet ment-A muszívprogram elso három évének tapasztalata a Semmelweis Egyetemen

INTRODUCTION Since the celebration of the 20th anniversary of the first heart transplantation in Hungary in 2012 the emerging need for modern heart failure management via mechanical circulatory support has evolved. In May 2012 the opening of a new heart failure and transplant unit with 9 beds together with the procurement of necessary devices at Semmelweis University accomplished this need. AIM The aim of the authors was to report their initial experience obtained in this new cardiac assist device program. METHOD Since May, 2012, mechanical circulatory support system was applied in 89 cases in 72 patients. Indication for support were end stage heart failure refractory to medical treatment and acute left or right heart failure. RESULTS Treatment was initiated for acute graft failure after heart transplantation in 27 cases, for end stage heart failure in 24 cases, for acute myocardial infarction in 21 cases, for acute postcardiotomy heart failure in 14 cases, for severe respiratory insufficiency in 2 cases and for drug intoxication in one case. Among the 30 survivor of the whole program 13 patients were successfully transplanted. CONCLUSIONS The available devices can cover all modalities of current bridge therapy from short term support through medium support to heart transplantation or long term support and destination therapy. These conditions made possible the successful start of a new cardiac assist device program.

[2012 -- the year of success in the 20 year-old adult heart transplant program of Hungary].

INTRODUCTION Since the celebration of the 20th anniversary of the first heart transplantation in Hungary in 2012 the emerging need for modern heart failure management via mechanical circulatory support has evolved. In May 2012 the opening of a new heart failure and transplant unit with 9 beds together with the procurement of necessary devices at Semmelweis University accomplished this need. AIM The aim of the authors was to report their initial experience obtained in this new cardiac assist device program. METHOD Since May, 2012, mechanical circulatory support system was applied in 89 cases in 72 patients. Indication for support were end stage heart failure refractory to medical treatment and acute left or right heart failure. RESULTS Treatment was initiated for acute graft failure after heart transplantation in 27 cases, for end stage heart failure in 24 cases, for acute myocardial infarction in 21 cases, for acute postcardiotomy heart failure in 14 cases, for severe respiratory insufficiency in 2 cases and for drug intoxication in one case. Among the 30 survivor of the whole program 13 patients were successfully transplanted. CONCLUSIONS The available devices can cover all modalities of current bridge therapy from short term support through medium support to heart transplantation or long term support and destination therapy. These conditions made possible the successful start of a new cardiac assist device program.