Papers by Spomenka Ljubic
![Research paper thumbnail of [Postprandial hyperglycemia as a risk factor in the development of endothelial dysfunction--how to prevent?]](https://a.academia-assets.com/images/blank-paper.jpg)
[Postprandial hyperglycemia as a risk factor in the development of endothelial dysfunction--how to prevent?]
Lijec̆nic̆ki vjesnik
Diabetes mellitus is characterised by insufficient insulin secretion and/or insufficient utilisat... more Diabetes mellitus is characterised by insufficient insulin secretion and/or insufficient utilisation of glucose. It results in hyperglycemia which is the main reason for the development of late complications of diabetes mellitus. Postprandial hyperglycemia is important in the development of complications because it is accompanied with oxidative stress, inflammation and finally with endothelial dysfunction. Under investigation are superoxide dismutase, catalase, L-propionyl-carnitine, lipoic acid, LY 333351, PJ34, FP15 which is expected to be useful in oxidative stress and early prevention of complications. As opposed to these substances which are still under investigation, drugs like thiazolidinediones, statins and renin-angiotensin system inhibitors have proven, antioxidant effect, aside of their already known clinical indications. Today we have a lot of opportunities to reduce hyperglycemia but also oxidative stress, inflammation and disturbances of coagulation system, and so prev...

Radiology and Oncology, 2009
Background. Massive haemoptysis is a clinical state characterized by the expectoration of blood a... more Background. Massive haemoptysis is a clinical state characterized by the expectoration of blood at a rate of 300-600 mL/24 h, thus causing life-threatening asphyxia. The aim of our study is to review use of transcatheter bronchial artery embolization (BAE) in the treatment of massive haemoptysis. Materials and methods. Series of 11 patients with the clinical picture of massive haemoptysis was referred to our hospital for digital subtraction angiography and BAE within a 33 months period. There were 8 male (aged 43-69, mean age 56) and 3 female patients (aged 63-65, mean age 64). Aortography of thoracic aorta was initially performed in all patients, followed by selective angiography of bronchial and intercostal arteries, and intercostobronchial tree as indicated. A selective arterial embolization was done in 9 patients (9 primary and 3 secondary embolizations). The embolization was performed under fluoroscopy control by manual injection of the mixture of contrast solution (1 ccm) and embolization material, Embosphere (BioSphere Medical Inc., MA, USA), particle size 350-500 µm. Results. Bronchiectasis was the most common cause of bleeding (45.4%), while hypervascularization and intensive parenchymal opacification were the most frequent angiographic indicators of bleeding (100%), followed by tortuous and hypertrophic arteries (72.7%). Primary BAE proved successful in 81.9% and secondary BAE performed within 24 months in 33.3% of patients, whereas the tertiary (operative) treatment was required in 22.2% of patients. In 44.4% of patients, BAE was associated with only mild discomforts, like pain and cough. Conclusions. BAE is a reliable and minimally invasive method in the management of massive haemoptysis. Therefore, it should be considered as the primary method of the treatment or as a procedure for the stabilization the patient before the surgery.

Biomedicines
Background and aims: Diabetic retinopathy (DR) is a microvascular complication of diabetes and re... more Background and aims: Diabetic retinopathy (DR) is a microvascular complication of diabetes and represents the leading cause of blindness in working-age adults. The aim of this study was to investigate the risk factors for DR in patients with type 2 diabetes (T2DM) with and without diabetic nephropathy (DN). Methods: A total of 160 patients with T2DM were included in the study. Photodocumented retinopathy status was determined according to the EURODIAB protocol. Renal function was determined using creatinine-based estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Binary univariate and multiple logistic regression analyses were performed to determine the main predictors of DR. Results: The prevalence of DR in this studied sample was 46.3%. No significant correlation was observed between DR and age, body mass index, serum lipids, and renal function. Binary logistic regression analysis (no DR/DR) showed that longer diabetes duration (p = 0.008), poor gly...

Diabetes Research and Clinical Practice, 2000
with unstable angina pectoris, myocardial infarction within three months, mental retardation or r... more with unstable angina pectoris, myocardial infarction within three months, mental retardation or risk for bleeding were excluded from the study. The degree of glomerular pathology and interstitial fibrosis was subdivided into four levels: 0 = normal, 1 = slight, 2 = intermediate, 3 = severe. Results. The histo-pathologicalexamination revealed that ten patients had slight-, eleven moderate-, and four severe degree of diabetic nephropatby. Among the other patients three had normal microscopy findings, three nephrosclerosis, and one patient had glomerulonephritis. Albumin-creatinine clearance ratio correlated to degree of interstitial fibrosis (R= 0.82, p<O.OOl) and to the presence of arteriolar hyalinization (R = 0.51, p-zO.05) but not to the degree of glomerular pathology and sclerosis or to the glomerular filtration rate (GFR). The degree of interstitial fibrosis correlated to GFR (R =-0.42, ~~0.05). systolic blood pressure (R = 0.39, p<O.O5), serum concentration of total cholesterol (R = 0.42, pt0.05) and serum LDL level (R = 0.60, ~~0.05). Blood level of HbAlc was associated with the degree of diabetic nephropathy but not with the degree of interstitial fibrosis. Conclusions. In the study we found that 22% of diabetic patients witbalbuminutia had no sign of diabetes mellitus on routine light microscopy of a kidney biopsy. The degree of interstitial fibrosis, but not the glomerttlar pathology, correlated to albuminuria, GFR, total cholesterol, serum LDL, and systolic blood pressure, while HbAlc levels were associated with the degree of glomerular pathology but not with the interstitial fibrosis.
Insulin therapy with an impact on inflammation can change the risk for cardiovascvular diseases in type 2 diabetes
Endocrine Abstracts, 2017
2018 SCIENTIFIC POSTER SESSION 001. Cardioprotective effect of liraglutide is amplified with anti-inflammatory and decreased brain natriuretic peptide levels, in addition to glycemia and body weight reduction
Purpose Besides an impact on glycemic control and body weight, incretins emerged as important fac... more Purpose Besides an impact on glycemic control and body weight, incretins emerged as important factors in cardiovascular (CV) protection in diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors cleave multiple peptides, which in turn have direct effect on the heart and blood vessels. This distinguishes them in action when compared to GLP-1 agonists. The aim was to compare the impact of DPP-4 inhibitors GLP-1 agonist liraglutide on CV risk factors.

729-P: Decreased Serum Vitamin D Level Implies Increased Cardiovascular Risk in Diabetes
Diabetes, 2020
Increase in homocysteine (HCY) level may increase cardiovascular risk (CVR), partly because of an... more Increase in homocysteine (HCY) level may increase cardiovascular risk (CVR), partly because of an impact on apolipoproteins and inflammation. Absorption of vitamin B12, involved in the regulation of HCY level, decreases with vitamin D deficiency. A possible association of vitamin D with visceral obesity and HCY was studied. HCY, 25-hydroxyvitamin D, vitamin B12, lipids, and other diabetes-related markers, including lipid accumulation product (LAP), were tested in 612 type 2 diabetic patients divided into four groups (1st group: LAP ≤ Q1; 2nd group: Q1 < LAP ≤ Med; 3rd group: Med < LAP ≤ Q3, 4th group: LAP ≥ Q3) according to LAP quartiles (Q1 = 28.5; Med = 50.59; Q3 = 80.64). LAP as an index, combining waist circumference and triglycerides, is related to risk of metabolic syndrome, diabetes and CVR. In all statistical tests: ANOVA, Tukey post-hoc test, and stepwise multivariate linear regression, α=0.05 was considered as statistically significant. Significant difference in vita...

Collegium antropologicum, 2013
The pathogenesis of diabetic retinopathy (DR) is insufficiently understood and presumed to possib... more The pathogenesis of diabetic retinopathy (DR) is insufficiently understood and presumed to possibly involve inflammation and endothelial dysfunction. The aim of the study was to investigate the relationship between inflammation markers, other markers of endothelial dysfunction and anthropometric parameters and their association with DR in patients with type 2 diabetes, divided into three groups: no retinopathy (N = 65), mild/moderate nonproliferative diabetic retinopathy (NPDR; N = 19) and severe NPDR/proliferative diabetic retinopathy (PDR; N = 23). The groups did not differ in the levels of inflammation markers, other markers of endothelial dysfunction and anthropometric parameters. C-reactive protein was correlated with fibrinogen, HbA1c, LDL-cholesterol, BMI, WC, WHR and C index. HbA1c was correlated with cholesterol, LDL-cholesterol, BMI and WC. Logistic regression analysis showed that diabetes duration and HbAlc median were the main predictors of retinopathy. The study demonst...
Male sex, blood pressure and heart rate are associated with the risk of diabetic retinopathy in normoalbuminuric type 1 patients
Diabetologia

International Journal of Endocrinology, 2014
Aim. To investigate whether body mass index (BMI) independently or in correlation with other risk... more Aim. To investigate whether body mass index (BMI) independently or in correlation with other risk factors is associated with diabetic retinopathy (DR) progression.Methods.The study included 176 patients with type 1 diabetes divided into three groups according to DR status: group 1 (no retinopathy;n=86), group 2 (mild/moderate nonproliferative DR;n=33), and group 3 (severe/very severe NPDR or proliferative DR;n=57).Results. A significant deterioration of HbA1c, an increase in total cholesterol, systolic, diastolic blood pressure, and diabetic nephropathy with the progression of retinopathy were found. DR progression was correlated with diabetes duration, HbA1c, hypertension, total cholesterol, and the presence of nephropathy. In patients without nephropathy, statistical analyses showed that progression of retinopathy increased significantly with higher BMI (gr. 1: 24.03 ± 3.52, gr. 2: 25.36 ± 3.44, gr. 3: 26.93 ± 3.24;P<0.01). A positive correlation between BMI and a significant d...

Mediators of Inflammation, 2013
The pathogenesis of diabetic retinopathy (DR) is insufficiently understood but may possibly invol... more The pathogenesis of diabetic retinopathy (DR) is insufficiently understood but may possibly involve chronic, low-grade inflammation. The aim of this cross-sectional study was to investigate the relationship between inflammatory and haemostatic markers, other markers of endothelial dysfunction and anthropometric parameters, and their association with DR in patients with type 2 diabetes. Methods. According to the DR status patients were divided into three groups: no retinopathy, mild/moderate nonproliferative (NPDR), and severe NPDR/proliferative retinopathy (PDR). Results. The groups did not differ in the levels of inflammatory and haemostatic markers, other markers of endothelial dysfunction, and anthropometric parameters. After dividing the patients according to the level of obesity (defined by BMI, WC, and WHR) into three groups ANOVA showed the differences in C-reactive protein according to the WC (= 0.0265) and in fibrinogen according to the WHR (= 0.0102) as well as in total cholesterol (= 0.0109) and triglycerides (= 0.0133) according to the BMI. Logistic regression analyses showed that diabetes duration and prolonged poor glycemic control are the main predictors of retinopathy in patients with type 2 diabetes. Conclusion. Interrelations between obesity, inflammation, haemostatic disturbance, and other risk factors may possibly play an important additional role in endothelial dysfunction involved in the pathogenesis of diabetic retinopathy.

Mediators of Inflammation, 2013
Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is es... more Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been...

Mediators of Inflammation, 2013
The aim of the study was to investigate whether body mass index (BMI) independently or in correla... more The aim of the study was to investigate whether body mass index (BMI) independently or in correlation with other risk factors is associated with diabetic retinopathy (DR) progression. The study included 545 patients with type 2 diabetes. According to DR status, they were divided into three groups: group 1 (no retinopathy;n=296), group 2 (mild/moderate nonproliferative DR;n=118), and group 3 (severe/very severe NPDR or proliferative DR;n=131). Patients without DR were younger than those with signs of retinopathy at time of diabetes onset whilst diabetes duration was longer in groups with severe NPDR and PDR. DR progression was correlated with diabetes duration, BMI, HbA1c, hypertension, and cholesterol. Statistical analyses showed that the progression of retinopathy increased significantly with higher BMI (gr. 1: 26.50 ± 2.70, gr. 2: 28.11 ± 3.00, gr. 3: 28.69 ± 2.50;P<0.01). We observed a significant deterioration of HbA1c and a significant increase in cholesterol and hypertensio...

2461-PUB: Increased Apolipoprotein A1 Can Suggest the Presence of Latent Autoimmune Diabetes and a Lower Cardiovascular Risk Compared with Type 2 Diabetes
Diabetes, 2019
Latent autoimmune diabetes (LADA) could be misdiagnosed as type 2 diabetes (DM2). Lipids, apolipo... more Latent autoimmune diabetes (LADA) could be misdiagnosed as type 2 diabetes (DM2). Lipids, apolipoproteins, adiponectin (APN), interleukin-6 (IL-6), homocysteine (HCY), other markers of DM, including antibodies, were tested in 276 patients with DM1, DM2 and LADA. Quartiles of lipid accumulation product (LAP) (Q1:≤21.23, Q2:(21.23, 40.69], Q3:(40.69, 92.02], Q4:>92.02) were calculated as: [waist (cm) - 65 for men/58 for women] x triglycerides (mmol/L)]. In all statistical tests: ANOVA and Tukey post hoc test, and stepwise multivariate regression, α=0.05 was considered statistically significant. ANOVA revealed significant differences in HCY, APN, IL-6 and apolipoprotein A1 (Apo A1) among DM types. Patients with DM1 (1.73±0.33) and LADA (1.66±0.38) had significantly higher values of HDL compared to DM2 (1.33±0.31). IL-6 was statistically increased in DM2 compared to DM1; Apo A1 was statistically increased in LADA (1.7±0.36) compared to DM2 (1.4±0.22), whereas HCY was decreased (LADA:...

International Journal of Endocrinology, 2015
Aims.To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabeti... more Aims.To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabetic nephropathy.Methods.ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER), and creatinine clearance (CrCl) categories in 219 type 1 and type 2 diabetic patients.Results.Significant differences among ApN levels according to AER were found in both types of diabetes (F=8.45,df=2,P<0.001). With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (F=12.7,df=1,P<0.001). The best model for ApN (R2=0.9002) obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes (R2=0.2882) it included ppPG, LDL, and UA.Conclusion.ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabe...
Adiponectin has different mechanisms in type 1 and type 2 diabetes with

Clinical & Investigative …, 2009
Purpose: Adiponectin (ApN) is considered to be responsible for reduction of inflammation and is k... more Purpose: Adiponectin (ApN) is considered to be responsible for reduction of inflammation and is known to be included in lipid metabolism. This study was designed to assess the role of adiponectin in patients with type 1 and type 2 diabetes and to determine parameters important in the prediction of adiponectin. Methods: Adiponectin, high sensitive C-reactive protein, fibrinogen, homocysteine, C-peptide, and lipid panel in addition to clinical and laboratory parameters important for the definition of diabetes, obesity and the metabolic syndrome were measured in 118 patients. Results: The best model (R 2 =0.989) for predicting adiponectin in type 1 diabetes included fibrinogen, white blood cell count, uric acid and triglycerides. In type 2 diabetes the best model (R 2 =0.751) included C-peptide, white blood cell count, systolic blood pressure, fasting blood glucose, glycated hemoglobin and high-density lipoprotein cholesterol. ANOVA showed among-group differences in adiponectin (P=0.028), body mass index (P <0.001), fasting blood glucose (P <0.001) and high-density lipoprotein cholesterol (P =0.012) according to the type of diabetes. Between-group differences were also observed in adiponectin (P =0.033) and high-density lipoprotein cholesterol (P =0.009) according to sex. Adiponectin correlated (P <0.05) with body mass index, C-peptide, pulse pressure and high-density lipoprotein cholesterol. Conclusion: Adiponectin levels were higher in type 1 diabetes. The association between C-peptide and adiponectin is probably one of the reasons for their different respective levels in different types of diabetes. Interrelations between adiponectin and inflammation, dyslipidemia, C-peptide levels and sex appear to be important for complex adiponectin modulation and action. Adiponectin (ApN) is considered to be responsible for reduction in inflammation, stimulation of nitric oxide production and consequently modulation of endothelial cell function. 1-3 Dyslipidemia in the metabolic syndrome, an important risk factor for endothelial dysfunction and atherosclerosis, is characterized by increased serum triglycerides and decreased highdensity lipoprotein cholesterol (HDL-C), the latter correlating with low ApN levels. 4 Because of their impact on dyslipidemia and inflammation, low ApN ORIGINAL RESEARCH
Uploads
Papers by Spomenka Ljubic