Faculty of Medicine

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Association of ACEI//D Gene Polymorphism with Diabetic Nephropathy.
(Scientific association of endocrinologists and diabetologists of Macedonia, 2018-05)
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Trajkovska, Ivana
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Doneva, Daniela
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Nedevska Minova, Natasha
Diabetic nephropathy (DN) is considered as a major microvascular complication of type 2 diabetes mellitus (T2DM) and is the leading cause of end-stage renal disease. Genetic susceptibility is a significant risk factor for DN development including the polymorphisms in ACE gene. The aim of this study is to investigate the association of ACE gene I/D polymorphism with DN in T2DM patients. In this prospective, observational, genetic association, case-control study, a demographic, clinical and laboratory data are analyzed from preliminary selected group of 35 patients with T2DM, of which 17 are with DN and 18 without DN. The duration of T2DM is similar to both subgroups. As controls, blood samples from 30 healthy blood donors and volunteers are being collected. Genetic analyses revealed statistically significant (p=0.029) association of genotypes D/D and I/D with occurrence of nephropathy, regarding the homozygous I/I genotype. Carriers of D/D and I/D genotypes has 7.134 folds higher odds and 2.148 folds higher relative risk for developing nephropathy than the carriers of I/I genotype among the patients with T2DM. Although the data and samples from only 35 patients are calculated, preliminary analyses indicates that there is a potential applicable predictive value of determination of this polymorphism during the clinical follow-up, treatment selection and prognosis of diabetic nephropathy.
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Empty Sella Syndrome with Profound Hypopituitarism
(Scientific association of endocrinologists and diabetologists of Macedonia, 2018-05)
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Hasan, Taner
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Doneva, Daniela
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Nedeska Minova, Natasha
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Trajkovska, Ivana
Empty sella (ES) is characterized by herniation of subarachnoid space within the sella caused by various etiopathogenetic mechanisms. Although ES can be presented as benign and asymptomatic condition, it can be also associated with pituitary dysfunction, opthalmologic and neurological abnormalities. Case report: We describe a case of empty sella with profound hypopituitarism. A 36-year-old man was refered to our hospital for evaluation of his obesity. He had complaints of decreased libido, anejaculation, depressive mood and lack of energy for several years. On examination he had body mass index 34kg/m2, waist circumference 108 cm and normal blood pressure. His medical history was unremarkable except for previous head injury. The hormone analysis showed TSH l 9.95 uIU/ml (0.4-4.0), free T4 0.64ng/dl (0.90-1.80), free T3 2.14 pg/ml (1.80-4.20), LH 0.710 mIU/ml(0.80-7.60), FSH 3,25mIU/ml (0.70-11.1), GH 0.05ng/ml (<5ng/ml), prolactin 25ng/ml (2-29) cortisol 3.45ug/dl (5-25) and ACTH 14.3pg/ml (5-48). Other laboratory investigation were significant for hyperinsulinemia, 41 uIU/ml (2-29.1) and atherogenic lipid profile. Furthermore the patient had severe vitamin D deficiency 18.6 nmol/L (75-250). Magnetic resonance imaging of hypotalamic-pituitary area revealed invagination of subarachnoid space to sella, narrow glandular tissue on the left side and pituitary microadneoma of 6 mm within it. Ophtalmological and visual filed examination were insignificant. Replacement hormonal therapy was initiated and patient clinically improved. Conclusion: in our patient ES might be a consequence of previous brain injury. ES syndrome is characterized by variable clinical manifestations. Therefore, patients with ES should be subjected to endocrinological, neurological and ophthalmological evaluation.
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Association of the apoe gene polymorphism with diabetic nephropathy
(SHMSHM - AAMD, 2019-02)
Hasan, Taner
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Pakovski, Kiril
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Josifovska, Slavica
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Baloski, Marjan
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Nedeska Minova, Natasha
The protein isoformes that are products of the Apolipoprotein E (APOB) gene polymorphism have partially altered biological activity and that may lead to greater susceptibility of the patients to microvascular complications including Diabetic nephropathy (DN) in patients with the Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the association between the allele Ԑ2, Ԑ3, and Ԑ4 of the APOE gene, as well as their combination, with the development of DN in patients with T2DM from the North Macedonia. The genotypic and allele frequency of the polymorphisms rs429358 and rs7412 in the APOE gene was determined in a group of patients with T2DM (with and without DN), and in the control group healthy subjects. The study is designed as a case-control genetic association study. The samples from 88 patients with T2DM were analyzed, including 57 patients with DN and 31 without DN and 26 healthy controls. The demographic, clinical and laboratory data were analyzed in addition to the genetic profiling of the patients. Genotyping of the APOE gene polymorphism resulted in determination of the patient’s genotype: Ԑ2/Ԑ2, Ԑ3/Ԑ3, Ԑ4/Ԑ4, Ԑ2/Ԑ3, Ԑ2/Ԑ4 or Ԑ3/Ԑ4, as well as of the alleles: Ԑ2, Ԑ3 or Ԑ4. The results revealed a statistically significant association of the genotype Ԑ2/Ԑ3 (p=0.016) and the allele Ԑ2 (p=0.020) with the occurrence of DN compared to the other genotypes and alleles. The presence of this genotype increases the chances of DN by 4,24 folds and the relative risk by 1,50 folds. In conclusion, the correlation of the APOE gene polymorphism and the development of the DN in patients with T2DM was confirmed indicating that there is a potential applicable value in the prognosis and treatment selection.
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Angiotensin-converting enzyme gene (I/D) polymorphism in association with diabetic nephropathy
(SHMSHM - AAMD, 2018-03)
Hasan, Taner
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Trajkovska, Ivana
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Balovski, Marjan
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Minova Nedeska, Natasha
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Polymorphisms in the Angiotensin-converting enzyme (ACE) gene have been associated with development of diabetic nephropathy (DN), a major microvascular complication of the type 2 diabetes mellitus (T2DM). Since the genetic predisposition plays an important role in development of DN in patients with T2DM, genetic testing might largely contribute to better assessment of the risk of DN in such patients. The aim of this study is to investigate the association of the ACE gene I/D polymorphism with DN in T2DM patients. The study is designed as a casecontrol genetic association study. The samples from 88 patients with T2DM were analyzed, including 57 patients with DN and 31 without DN. The study includes also 26 healthy controls. The demographic, clinical and laboratory data are analyzed in addition to the genetic profiling of the patients for the ACE gene. Genotyping of the ACE gene I/D polymorphism resulted in determination of the patient’s genotype: D/D, I/D or I/I. The results revealed a statistically significant association of genotypes D/D and I/D with the occurrence of nephropathy compared to the I/I genotype. In the group of patients with T2DM, the carriers of the D/D or I/D genotypes have 6.46 folds higher odds and 1.7 folds higher relative risk for developing nephropathy than the carriers of I/I genotype. The results confirmed the correlation of the genetic polymorphism and the development of the DN in patients with T2DM indicating its potential predictive use in terms of the clinical follow-up, treatment selection and prognosis of DN.
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Is Semaglutide superior than Liraglutide in patients with type 2 diabetes on insulin therapy? - case presentation
(Bioscientifica, 2022-05-07)
Mickovski, Ivana
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Milosheska, Radmila
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Hasan, Taner
Introduction Type 2 diabetes (T2DM) is a chronic and progressive disease associated with microvascular and macrovascular complications leading to increased morbidity and mortality. Insulin remains the cornerstone therapy for longer-duration T2DM and b-cell failure. T2DM is a complex disorder that requires individualized treatment strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of multifactorial T2DM medications that have been shown to improve numerous risk factors for diabetes-related complications, including glycemic control, reduction in body weight and a low risk of hypoglycaemia. Case Presentation A 65-year old obese male presented to the outpatient clinic of Endocrinology, 8th September City General Hospital, Skopje for a regular checkup. He has T2DM for a long time and the last 10-15 years was switch on insulin therapy – at the moment was on premix insulin – Insulin Aspart and OAD. He was complaining of variation of glycaemia (5.0-16.5 mmol/l), felling a little bit thirsty, hungry and without energy. He has arterial hypertension and dyslipidemia (medications was prescribe from cardiologist) but could not tolerated any statins. He is a nonsmoker, with two children and retired. Investigations Initial investigation showed HgA1c 55.2 mmol/mol, FPG 9.1 mmol/l, elevated cholesterol (cho -6.8 mmol/l), low density (LDL – 2.8 mmol/l) triglyceride ( Tg - 2.7 mmol/l). His renal and liver functional test were within normal limits. The tests for thyroid functional were also normal. He was 180centimetar tall, 149kg weight and his body mass index (BMI) was 46.0. Echotomography showed steatotic liver, echocardiography and ophthalmic tests were in normal range for his age. Treatment The patient was overweight, hasn’t achieved the optimal glycemic control even though he was on insulin therapy and one of his biggest concerns was his weight , so the medical team decided to add Liraglutide on his diabetes therapy with gradual titration of the dose ( Liraglutide - was started at 0.6mg daily subcutaneously for 1 week and then increased from 1.2 mg to 1.8mg daily). Also he was educated about titration of the dose of the insulin therapy together with additional lifestyle modifications Because of the positive effect from the therapy with once daily GLP-1 RA, and because we wanted to continue with weight loss, but at the same time reduce the everyday subcutaneous therapy we decide to change Sol Liraglutide 1.8mg per day with Sol Semaglutide starting with 0.25mg once a week for 1 month and then titrating the doses till 1mg per week, together with reducing the insulin therapy, metformin 2000mg daily, balance food and physical activity (Table 1). Discussion The objective of this case report was to demonstrate the efficacy and safety of onceweekly semaglutide vs once daily GLP-1 RAs in patient with T2DM inadequately controlled on insulin therapy (± OADs). In our case report, we observed that once-weekly semaglutide 1 mg was dominant compared with once-daily liraglutide 1.8 mg. In this case report, once-weekly semaglutide 1.0 mg was the most clinically effective GLP-1 RA for achieving glycemic targets and reducing HbA1c, FPG, and body weight in patient who is receiving insulin therapy. In patients with T2DM inadequately controlled with insulin therapy, semaglutide provided superior improvements in mean HbA1c, FPG, and superior weight loss compared with liraglutide. Conclusion Semaglutide, administered subcutaneously once weekly, provided superior glycemic control and body weight reductions compared with other GLP-1 RA in patient with T2DM receiving insulin therapy. Therefore, it is likely that once-weekly semaglutide will not increase the risk of hypoglycemia when added to insulin therapy. The reasons for switching to semaglutide from liraglutide included a need to reduce HbA1c or weight further, decreased frequency of administration and cardiovascular protection. In addition, significant weight loss was observed with both doses of semaglutide vs liraglutide.
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Graft-versus-host disease in patients treated with allogenic hematopoetic cell transplantation: experience from North Macedonia
(VM Media SP. zo.o VM Group SK, 2021-10-28)
Mickovski, Ivana
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Hasan, Taner
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Nedeska Minova, Natasha
Introduction: Graft-versus-host disease (GvHD) is the major complication arising after allogeneic hematopoietic cell transplantation (allo-HCT). It can be presented as acute and/or chronic GvHD. The purpose of this study was describe the incidence of acute and chronic GvHD in patients treated with allo-HCT. Materials and methods: This study was designed as a retrospective study, which included 65 patients treated with allogeneic transplantation from human leukocyte antigen identical donor at University Clinic of Hematology in Skopje, North Macedonia. Results: Acute GvHD (aGvHD) was observed in 28 patients, with the most common localization on the skin (75%). Post-transplant phase had significant effect on the frequency of skin aGvHD (p =0.038). Also statistically significant difference was confirmed between patients with and without acute skin GvHD in terms of conditioning regimen (p =0.034). Chronic GvHD (cGvHD) was diagnosed in 10 patients, mostly progressing from the previous acute GvHD (9.23%). Post-transplant phase had also significant effect on the frequency of skin cGvHD (p =0.018). Patients with higher European Society for Blood and Marrow Transplantation risk score had significantly more frequent skin cGvHD than the others. Conclusions: Acute and chronic GvHD were one of the main causes of morbidity and mortality of patients after aloo-HCT. GvHD remains a major risk for patients with allo-HCT regardless of diagnosis and type of transplantation.
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DEEP VEIN THROMBOSIS AND RECURENT PULMONARY EMBOLISM IN A PATIENT WITH THROMBOPHILIC MUTATIONS AND GENERALIZED PSORIASIS: A CASE REPORT
(Association of medical doctors "Sanamed" Novi Pazar, 2020-07-29)
Baloski, Marjan
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Brishkoska Boshkovski, Vesna
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Hasan, Taner
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Nedeska Minova, Natasha
Introduction: Genetic risk factors that increase venous thromboembolism risk are disorders in the synthesis or activity of coagulation factors. Fac- tor V Leiden, prothrombin (20210-A), antithrombin deficiency, protein C and protein S deficiency, and hyperhomocysteinaemia are the most common venous thromboembolism-related gene mutations. When ge- netic factors are combined with non-provoking risk factors (obesity, psoriasis, smoking and previous veno- us thromboembolism) the result is increased venous thromboembolism risk for each factor individually. Previous venous thromboembolism is one of the stron- gest risk factors, even in patients actively treated with anticoagulant. Patients are more likely to have recur- rent venous thromboembolism with longer duration. Psoriasis is a complex immune–mediated disease, as- sociated with cardiovascular risk, hypercoagulability markers and elevated homocysteine. Lots of observati- onal reports suggest increased incidence of venous trombembolic events in patient with psoriasis

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