Introduction: Tirzepatide is a novel, once-weekly injectable dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, developed for the management of type 2 diabetes mellitus and obesity. Its dual incretin mechanism enhances glucose-dependent insulin secretion, delays gastric emptying, and promotes satiety, resulting in significant improvements in glycemic control and body weight reduction. Obesity is common in people with type 1 diabetes with prevalence similar to the general population, increasing their risk of cardiovascular complications.Case report: A 44 years-old female patient was diagnosed with type 1 diabetes 7 years ago. At the time of the diagnosis her body mass index (BMI) was in the normal range, but during the next 6 years her weight grew continuously, she became overweight, then obese despite the diet and regular physical exercises. Tirzepatide was offered for better weight control, and she started using the medication on the 23rd of May 2025. Her anthropometrics, body composition, glucose and lipid parameters, insulin dosage was followed. The initial once-weekly 2.5 mg tirzepatide effectively decreased her appetite; therefore, she did not elevate the dose further. She also hasn’t experienced any side effects. After 4.5 months of treatment the patient’s weight, BMI and waist circumference have decreased gradually, with 14.3 kg (-18.8%), 5.8 (-18.6%) and 14 cm (-16.3%), respectively. The weight loss mainly affected the adipose tissue (30.7 kg vs. 17.8 kg), while the muscle mass remained unchanged (25 vs. 24.5 kg). Indicators of carbohydrate metabolism also improved, HbA1c decreased with 1.1% (from 7.2% to 6.1%), time in range (TIR) and especially time in tight range (TITR) elevated (80% vs. 89% and 57% vs. 72%, respectively), glucose variability decreased (34.3% vs. 30.7%) while the time spent in hypoglycemia, measured as time below range (TBR) haven’t changed significantly (4% vs. 5%). As a result of the tirzepatide treatment both the total daily insulin dose and insulin requirement per body weight kilogram decreased. No significant side effects were observed, supporting the safety of tirzepatide.Conclusion: Tirzepatide can be used safely to improve carbohydrate metabolism and reduce body weight in patients with type 1 diabetes without severe side effects such as severe hypoglycemia or diabetic ketoacidosis.

Témavezető: Prof. Dr. Gaál Krisztina

Background: Novel transplant biomarkers may complement routine laboratory tests by improving risk stratification during post-transplant follow-up, but their predictive value for patient and graft survival remains unclear.Aims: To assess the association between proteinuria and selected cardiac biomarkers in kidney transplant (KT) recipients with stable graft function, and to compare these biomarkers in heart transplant (HTx) recipients, in whom CKD, acute rejection (AR) and cardiac allograft vasculopathy (CAV) also influence long-term outcomes.Methods: We analyzed 64 transplant patients. Of these, 49 had good graft function (43 had a kidney graft and 6 had a heart transplant). Fifteen patients had a kidney transplant and heart failure. All were followed at the Nephrology Department, University of Debrecen (November 2023–June 2024). In addition to routine parameters, we measured serum IL-33 receptor (sST2), malondialdehyde (MDA), ACE2, neprilysin (NEP) and GDF15, and evaluated their relationships with kidney function (eGFR-EPI), degree of proteinuria, LDH and GGT.Results: Urinary protein excretion showed a moderate but significant correlation with sST2 (SD=7142.893; r = 0.27; p = 0.0448). In the heart failure group anemia was more pronounced (p = 0.0470) and serum iron levels were lower (p = 0.0041) versus KT controls. TAPSE was significantly reduced in HTx recipients compared with KT patients (p = 0.0003). Overall, sST2, NEP and ACE2 were not dependent on renal function, but sST2 correlated with proteinuria, and NEP and ACE2 activity showed strong associations with GGT.Conclusion: Our preliminary data suggest that proteinuria and circulating IL-33/sST2 levels are linked together, supporting a role for this pathway in graft injury among KT recipients. However, larger studies are needed to clarify the significance of the IL33/ST2 signalling. Reduced TAPSE in HTx patients versus KT patients highlights additional cardiac involvement in this population.

Témavezető: Dr. P.Szabo Reka

Introduction and aims:The cardiovascular (CV) diseases represent the leading cause of death in developed Westerncountries. In the 2025 ESC/EAS guidelines, within the SCORE2 recommendations,lipoprotein(a) (Lp(a) appears as a risk-modifying factor. Therefore, we aimed to assesswhether this recommendation is applied in the therapeutic algorithm for patients with elevatedLp(a) levels. We examined what proportion of individuals with very high CV risk achieve thelow-density lipoprotein cholesterol (LDL-C) target values defined in the guidelines, andwhether high Lp(a) levels influence therapy or the attainment of LDL-C targets amongpatients treated in a Cardiology Department and in primary care.Methods:We carried out an observational, retrospective cohort study from 2022-2025 based on medicaldatabase. 141 patients were enrolled into this study at Cardiology Centre, Jósa AndrásMember Hospital, Szabolcs-Szatmár-Bereg County Teaching Hospital, Nyíregyháza and 92patients at a general practitioner (GP), Nyíregyháza, as well. The study population wasstratified according to their CV risk. Lipid parameters were examined over a one-year follow-up period.Results:Patients with very high risk from Cardiology Centre were significantly older (p<0.001); alsocoronary artery disease (p<0.001) and smoking (p=0.036) were more common compared tolow-risk patients. Baseline lipid-lowering therapy (LLT) and lipid levels including Lp(a) weresimilar among different CV risk categories. During the one-year follow-up, total cholesterol,LDL-C and high-density lipoprotein cholesterol (HDL-C) improved in very high risk group(all p<0.05). 23.6 % of high risk patients reached the LDL-C target (<1.4 mmol/l) and all ofthese had low Lp(a) level (<50 mg/dl). Patients with very high risk in the GP weresignificantly older (p<0.001) with higher prevalence of type 2 diabetes (44.7 %) compared topatients with low or moderate risk (p=0.003). Lp(a) increased with the severity of CV risk(p=0.039). After one-year follow-up, lipid levels were unchanged. After one year, 12.0 % ofhigh risk patients reached the LDL-C target and all of these had low Lp(a) level (<50 mg/dl). Conclusion:This study confirmed that only a limited number of high‑risk patients reached the LDL‑Ctarget. Therefore, effective and long‑term LLT management is highly recommended in thispopulation. Our data also suggest reconsidering the modification of cardiovascular risk stratification and intensifying LLT.

Témavezető: Prof. Dr. György Paragh

Background: Acute myocardial infarction (AMI) is associated with a prominent inflammatory response and is implicated in maladaptive cardiac remodeling as well as poor long-term outcome. Previous studies indicated the significant role of circulating biomarkers like galectin-3 (Gal-3), which reflect myocardial fibrosis; interleukin-6 (IL-6), a pro-inflammatory cytokine; and growth differentiation factor 15 (GDF-15) indicating generalized cellular stress and cardiometabolic disease. Indeed, the impact of standard high-intensity statin treatment on these biomarkers has not been studied.Aim: The main goal of the present investigation was to assess the changes in the specific inflammatory (IL-6), fibrotic (Gal-3) and stress (GDF-15) markers in statin-naive AMI patients after three months of high-intensity statin treatment. Methods: We included 37 AMI patients (25m/12f; 48.4±11.7 years; body mass index (BMI): 27.9±5.1 kg/m2) who had no past history of statin use and 12 age-, gender- and BMI-matched healthy controls (7m/5f; 49.3±11.7 years; BMI: 25.9±2.9 kg/m2). Plasma biomarker levels were assessed at baseline (immediately following AMI) and 3 months after statin therapy by an ultra-sensitive Olink® Proximity Extension Assay platform (Part of Thermo Fisher Scientific, Inc., Uppsala, Sweden). Results: Baseline normalized protein expression (NPX) value of GDF-15, IL-6 and Gal-3 were significantly higher in the AMI cohort compared to the control group (all P < 0.001). After 3-month statin treatment, the NPX of GDF-15 and IL-6 markedly reduced (P < 0.001 and P < 0.001, respectively) but did not reach the controls’ NPX value. Nevertheless, the NPX of Gal-3 were found to be unchanged (P = 0.141) in patients with AMI during the statin treatment. There were strong positive correlations between IL-6 (r = 0.585; p <0.001), Gal-3 (r = 0.637; P < 0.001), NT-proBNP and GDF-15 (r = 0.488; p < 0.001) in patients with AMI before the statin use and controls.Conclusion: This study confirms that the 3-month statin therapy has a beneficial effect to reduce cellular stress and the degree of inflammation in patients with AMI. The persistently elevated Gal-3 may suggest that short-term statin therapy might be unable to eliminate the prolonged fibrosis in AMI. Our results indicate the favorable effects of long-term lipid-lowering therapy to reduce residual cardiovascular risk in this vulnerable patient population.

Témavezető: Dr. Hajnalka Lőrincz

Background:Rituximab (RTX) has become an important targeted therapy not only for immune-mediated glomerular diseases, particularly PLA2R-positive membranous nephropathy (PMN), but also in some cases of podocytopathies. However, long-term real-world outcome data from Central Europe remains limited. This study provides a seven-year overview of RTX use at the University of Debrecen, including the first Hungarian implementation of ELISA-based PLA2R antibody measurement.Aims:To evaluate the long-term efficacy and safety of RTX in PMN and podocytopathies, using detailed biochemical, immunological, and renal function parameters.Methods:Between 2019 and 2025, 34 patients were followed: 27 with biopsy-proven PMN and 7 with podocytopathies. From 2024 onward, anti-PLA2R titers were measured by ELISA, allowing more accurate tracking of immunological response. Efficacy assessments included PLA2R titers, urinary protein-to-creatinine ratio (uTP/CR), serum albumin, cholesterol, serum creatinine, and eGFR. Safety outcomes included infusion reactions, infections, malignancies, and mortality. No statistical analysis was performed in the podocytopathy group due to a small number of cases.Results:In the PMN group, with a median follow-up of 34 months, 6 patients achieved complete remission (CR), 18 partial remission (PR) without other maintenance immunosuppressants, and remission did not occur in one patient. RTX led to significant reductions in PLA2R titers (p = 0.0225), cholesterol levels (p = 0.0005), and uTP/CR ratio (p = <0.0001), alongside a significant increase in serum albumin (p = <0.0001). Serum creatinine and eGFR remained stable, indicating preserved renal function. Safety outcomes were favorable: RTX stopped permanently due to allergic reaction in 1 patient, one elderly male patient died from infection following RTX, another developed prostate cancer, and two deaths were unrelated to treatment. In the podocytopathy group, after a median follow-up of 12 months, 4 out of 7 cases achieved CR, 2 PR, and in 1 patient, end-stage kidney disease developed. An infusion-related allergic reaction occurred in 1 patient; another required filgrastim due to leukopenia.Conclusion:RTX demonstrated strong efficacy in improving nephrotic parameters and inducing immunological remission in PMN, with stable kidney function and generally acceptable safety. These findings support RTX as an effective and well-tolerated therapeutic option for autoimmune podocytopathies.

Témavezető: Dr. Markóth Csilla

ssociation of serum chemerin and advanced glycation end products in patients with Hashimoto’s thyroiditisMazvita Shamiso Maxine TakuvaSupervisor: Eszter Berta, MD, PhDDepartment of Pharmaceutical Clinical Basics Background: Autoimmune thyroiditis is a chronic condition characterized by lymphocytic infiltration of the thyroid gland, which leads to hypothyroidism in most of the cases in Hashimoto’s thyroiditis. Hashimoto’s thyroiditis has a known bidirectional relationship with obesity. Recent evidence suggests that inflammatory mediators and metabolic by-products, such as chemerin and serum advanced glycation end products (AGEs), may contribute to the pathogenesis and progression of autoimmune thyroid disorders. Chemerin is an adipokine involved in the pathogenesis of metabolic syndrome and immune signaling, while AGEs are known to induce oxidative stress and immune dysregulation.Objective: In our study we investigated the association between thyroid hormone levels, thyroid antibodies, the components of lipid metabolism, renal and liver functions as well as anthropometrical parameters, serum chemerin and AGEs.Methods: We enrolled one hundred and ten patients (9 men, 101 women, mean age 49.3±16.7 years, mean BMI 27.5±5.8 kg/m2) from the outpatient clinic of Endocrine Department of University of Debrecen, Faculty of Medicine. All patients had Hashimoto’s thyroiditis with various thyroid hormone status from hypothyroidism to hyperthyroidism. We determined serum AGEs concentrations by autofluorescence. Thyroid hormone levels, anti-thyroperoxidase concentration and lipid levels were measured by routine laboratory methods. Chemerin levels were measured by ELISA method.Results: We found that median serum AGEs level was 10.4 (9.4 – 11.8) AU/μg protein, median chemerin level was 91.2 (79.8 – 104.8) ng/ml, while mean total cholesterol level was 5.3±1.1 mmol/l. Mean fT3and fT4 were 4.56±0.76 and 17.8±3.7 pmol/l, respectively. We found significant negative correlation between fT3 and log AGEs/total protein levels. There was a significant correlation between log chemerin, total cholesterol, log creatinine, log ApoB100 and log AGEs/total protein levels. However, we could not find correlation between log AGEs/total protein levels and aTPO levels.Conclusion: The significant negative correlation between log AGEs/total protein levels and fT3 levels suggests that T3 might have a regulatory effect on metabolism. However, further clinical investigations are needed to clarify

Témavezető: Dr. Berta Eszter

BevezetésA familiáris hiperkoleszterinémia (FH) a koleszterin anyagcsere autoszomális domináns módon öröklődő zavara, mely jelentősen emelkedett össz- és LDL-koleszterinszinttel és a szív- és érrendszeri megbetegedések korai megjelenésével jár. Kialakulásáért elsősorban az LDLR és APOB gének funkcióvesztő mutációi felelősek. A gyakoribb, heterozigóta formában (HeFH) egy, míg a ritka, homozigóta (HoFH) esetekben két patogén mutáció jelenléte igazolható. A genetikai eltérések és a klinikai kép között azonban nem minden esetben van szoros kapcsolat. Ugyanakkor a genetikai vizsgálat eredménye fontos támpontot nyújt a diagnózis és a kezelés szempontjából is.CélkitűzésCélul tűztük ki a Debreceni Egyetem Belgyógyászati Klinika Lipid szakrendelésén gondozott genetikai vizsgálattal igazolt FH betegek klinikai jellemzőinek elemzését, ezen belül a lipid paraméterek, a kardiovaszkuláris szövődmények, a társbetegségek, valamint az alkalmazott kezelés vizsgálatát. Betegek és módszerekA vizsgálatba összesen 60 beteg került bevonásra (39 nő, 21 ffi). 6 esetben HoFH (1 valódi, 1 kettős és 4 összetett heterozigóta), és 54 beteg esetén HeFH igazolódott a genetikai vizsgálat során. EredményekA HoFH betegek átlagos össz- és LDL-koleszterinszintje szignifikánsan magasabb volt a HeFH betegekhez viszonyítva (13,48±7,4 vs. 9,13±1,9, ill. 10,89±6,6 vs. 6,6±1,8 mmol/L, p<0,05), de a két csoport között átfedés észlelhető. Mindkét csoportban a leggyakoribb kardiovaszkuláris szövődmény az iszkémiás szívbetegség (16,7 vs. 18,5 %), de a két csoport között az érrendszeri szövődmények elfordulási arányát tekintve nem volt szignifikáns különbség. A társbetegségek közül mindkét csoportban a magasvérnyomás betegség volt a leggyakoribb (33,3 vs 20,4 %). A genetikai eltérések közül a missense mutációk kevésbé jelentős, míg a deléciók, splicing variánsok és korai stop kodonok igen jelentős lipidszint eltérésekkel és súlyosabb klinikai képpel társultak. A kezelés során mindkét csoportban gyakori volt a nem megfelelő betegegyüttműködés. A statin és ezetimib kezelés mellett gyakran PCSK9 gátló kezelés alkalmazása is szükséges volt, a HoFH betegek esetén emellett LDL-aferezis kezelést és lomitapid terápiát alkalmaztunk.KövetkeztetésekEredményeink alapján a genetikai vizsgálat elvégzése kiemelt fontosságú FH betegek esetén a HoFH és HeFH esetek elkülönítése, a súlyosabb klinikai megjelenés okának tisztázása, valamint az alkalmazott lipidcsökkentő kezelési stratégia kiválasztása szempontjából.

Témavezető: Prof. Dr. Harangi Mariann

Bevezető: A kallistatin antioxidáns, anti-atherogén és anti-inflammatorikus protein, melynek szintje krónikus gyulladásos állapotokban emelkedett, ami feltehetően kompenzatórikus védekező mechanizmust jelez. Az inkretin tengelyen ható készítmények bizonyítottan javítják a glikémiás kontrollt T2DM-ben, és kedvezően befolyásolják a lipidprofilt és a gyulladásos paramétereket, azonban kevés adat áll rendelkezésre hatásukról a kallistatinra. Célkitűzés:Vizsgálatunk célja az 52 hetes semaglutid- és sitagliptin-kezelés hatásának értékelése volt a szérum kallistatin szintjére, a lipid szubfrakciókra és a gyulladásos markerekre elhízott, T2DM-es és nem diabeteses betegekben. Módszerek:A vizsgálatban 34 T2DM-es beteg vett részt (18 fő semaglutid, 16 fő sitagliptin), valamint 31 korban és nemben illesztett elhízott, nem diabeteses kontroll. Mintavétel a kezelés előtt, a 6. és 12. hónapban történt. A kallistatin és oxidált LDL szintjét ELISA-val, a lipid szubfrakciókat Lipoprint® módszerrel határoztuk meg. Eredmények:A kiindulási kallistatin szint nem különbözött a T2DM-es és kontrollcsoport között (p=0.557). A kallistatin numerikusan csökkent semaglutid kezelés mellett, de nem volt szignifikáns (p=0.763). A sitagliptin szignifikáns csökkenést eredményezett (p=0.033). Az életkor negatív korrelációt mutatott a kallistatinnal (p=0.0097). Pozitív korrelációt találtunk a HDL-C szinttel (p=0.028), a kis HDL arányával (p=0.019) és az oxidált LDL-lel (p=0.028), míg a közepes HDL frakció aránya negatív összefüggést mutatott (p=0.035). Következtetések:Az inkretin alapú terápiák kedvező hatással lehetnek az oxidatív stressz folyamatokra, melyet a kompenzatórikusan emelkedett kallistatin szint csökkenése is jelezhet. Eredményeink felvetik, hogy a kallistatin kiegészítő biomarkerként szolgálhat a sitagliptin terápia hatékonyságának követésére, azonban megerősítéshez nagyobb prospektív vizsgálatok szükségesek.

Témavezető: Dr. Sztanek Ferenc és Dr. Lőrincz Hajnalka