TY  - JOUR
AU  - Malenica, Maja
AU  - Klisić, Aleksandra
AU  - Meseldžić, Neven
AU  - Dujić, Tanja
AU  - Bego, Tamer
AU  - Kotur-Stevuljević, Jelena
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4992
AB  - Background: The aim of the study was to explore the mutual relationship between oxidative stress, inflammation and
metabolic biomarkers in subjects with prediabetes (PRE),
newly diagnosed type 2 diabetes patients (NT2D) and overt
type 2 diabetes (T2D) using principal component analysis
(PCA) as a thorough statistical approach.
Methods: Glycated hemoglobin, lipid parameters, inflammation (IL-6, CRP and fibrinogen) and oxidative stress
markers  pro-oxidants (AOPP, PAB, TOS) and antioxidants
(PON1, tSHG, TAS)  were measured. PCA was applied to
explore the factors that the most strongly influenced glucoregulation.
Results: A total of 278 subjects were (i.e., 37 PRE, 42
NT2D and 99 T2D) were compared with 100 healthy subjects as a control group (CG). PCA emphasized 4 different
factors explaining 49% of the variance of the tested parameters: oxidative stress-dyslipidemia related factor (with positive loading of TG and tSHG, and with negative loading of
HDL-c and TAS), dyslipidaemia related factor (i.e., total
cholesterol and LDL-c, both with positive loading),
Anthropometric related factor (i.e., waist and hip circumference, both with positive loading) and oxidative stress-
Inflammation related factor (i.e., PAB, fibrinogen, and CRP, all with positive loading). Out of these 4 factors, only oxidative stress – dyslipidaemia related factor showed a significant predictive capability towards poor glucoregulation. An
increase in this factor by one unit showed a 1.6 times higher probability for poor glucoregulation.
Conclusions: Redox imbalance (determined with lower TAS
and higher tSHG), in addition to higher TG and lower HDL-
c was associated with poor glucoregulation.
AB  - Uvod: Cilj istraživanja je bio da se ispita povezanost oksidativnog stresa, inflamacije i metaboličkih biomarkera kod pacijenata sa predijabetesom (PRE), de novo dijabetesom (NT2D) i ranije dijagnostikovanim dijabetesom (T2D) pomoću glavne komponentne analize (PCA). Metode: Glikozilirani hemoglobin, lipidni status, markeri inflamacije (IL-6, CRP i fibrinogen), parametri oksidativnog stresa pro-oksidanti (AOPP, PAB, TOS) i antioksidansi (PON1, tSHG, TAS) su mereni. PCA je primenjena da bi se ispitali faktori koji najviše utiču na glikoregulaciju. Rezultati: U istraživanje je uključeno 278 ispitanika: 37 PRE, 42 NT2D i 99 T2D, kao i 100 zdravih osoba koji su činili kontrolnu grupu (CG). PCA je izdvojila 4 različita faktora objašnjavajući 49% varijanse ispitivanih parametara: oksidativni stres-dislipidemija faktor (sa pozitivnim uticajem TG i tSHG, i negativnim uticajem HDL-c i TAS), dislipidemija faktor (tj, ukupni holesterol i LDL-c, oba sa pozitivnim uticajem), antropometrijski faktor (tj, obim struka i kukova, oba sa pozitivnim uticajem) i oksidativni stres-inflamacija faktor (tj, PAB, fibrinogen i CRP, svi sa pozitivnim uticajem). Od ova 4 faktora, jedino je oksidativni stres - dislipidemija faktor pokazao značajnu prediktivnu sposobnost za lošu glikoregulaciju. Porast ovog faktora za jednu jedinicu je pokazao 1,6 puta veću verovatnoću za lošu glikoregulaciju. Zaključak: Redoks disbalans (određen nižim vrednostima TAS i višim vrednostima tSHG), kao dodatak većim vrednostima TG i nižim vrednostima HDL-c su povezane sa lošijom glikoregulacijom.
PB  - Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Principal component analysis of the oxidative stress, inflammation, and dyslipidemia influence in patients with different levels of glucoregulation
T1  - Glavna komponentna analiza uticaja oksidativnog stresa, inflamacije i dislipidemije kod pacijenata sa različitim nivoom glikoregulacije
VL  - 42
IS  - 3
SP  - 427
EP  - 436
DO  - 10.5937/jomb0-39636
ER  - 

@article{
author = "Malenica, Maja and Klisić, Aleksandra and Meseldžić, Neven and Dujić, Tanja and Bego, Tamer and Kotur-Stevuljević, Jelena",
year = "2023",
abstract = "Background: The aim of the study was to explore the mutual relationship between oxidative stress, inflammation and
metabolic biomarkers in subjects with prediabetes (PRE),
newly diagnosed type 2 diabetes patients (NT2D) and overt
type 2 diabetes (T2D) using principal component analysis
(PCA) as a thorough statistical approach.
Methods: Glycated hemoglobin, lipid parameters, inflammation (IL-6, CRP and fibrinogen) and oxidative stress
markers  pro-oxidants (AOPP, PAB, TOS) and antioxidants
(PON1, tSHG, TAS)  were measured. PCA was applied to
explore the factors that the most strongly influenced glucoregulation.
Results: A total of 278 subjects were (i.e., 37 PRE, 42
NT2D and 99 T2D) were compared with 100 healthy subjects as a control group (CG). PCA emphasized 4 different
factors explaining 49% of the variance of the tested parameters: oxidative stress-dyslipidemia related factor (with positive loading of TG and tSHG, and with negative loading of
HDL-c and TAS), dyslipidaemia related factor (i.e., total
cholesterol and LDL-c, both with positive loading),
Anthropometric related factor (i.e., waist and hip circumference, both with positive loading) and oxidative stress-
Inflammation related factor (i.e., PAB, fibrinogen, and CRP, all with positive loading). Out of these 4 factors, only oxidative stress – dyslipidaemia related factor showed a significant predictive capability towards poor glucoregulation. An
increase in this factor by one unit showed a 1.6 times higher probability for poor glucoregulation.
Conclusions: Redox imbalance (determined with lower TAS
and higher tSHG), in addition to higher TG and lower HDL-
c was associated with poor glucoregulation., Uvod: Cilj istraživanja je bio da se ispita povezanost oksidativnog stresa, inflamacije i metaboličkih biomarkera kod pacijenata sa predijabetesom (PRE), de novo dijabetesom (NT2D) i ranije dijagnostikovanim dijabetesom (T2D) pomoću glavne komponentne analize (PCA). Metode: Glikozilirani hemoglobin, lipidni status, markeri inflamacije (IL-6, CRP i fibrinogen), parametri oksidativnog stresa pro-oksidanti (AOPP, PAB, TOS) i antioksidansi (PON1, tSHG, TAS) su mereni. PCA je primenjena da bi se ispitali faktori koji najviše utiču na glikoregulaciju. Rezultati: U istraživanje je uključeno 278 ispitanika: 37 PRE, 42 NT2D i 99 T2D, kao i 100 zdravih osoba koji su činili kontrolnu grupu (CG). PCA je izdvojila 4 različita faktora objašnjavajući 49% varijanse ispitivanih parametara: oksidativni stres-dislipidemija faktor (sa pozitivnim uticajem TG i tSHG, i negativnim uticajem HDL-c i TAS), dislipidemija faktor (tj, ukupni holesterol i LDL-c, oba sa pozitivnim uticajem), antropometrijski faktor (tj, obim struka i kukova, oba sa pozitivnim uticajem) i oksidativni stres-inflamacija faktor (tj, PAB, fibrinogen i CRP, svi sa pozitivnim uticajem). Od ova 4 faktora, jedino je oksidativni stres - dislipidemija faktor pokazao značajnu prediktivnu sposobnost za lošu glikoregulaciju. Porast ovog faktora za jednu jedinicu je pokazao 1,6 puta veću verovatnoću za lošu glikoregulaciju. Zaključak: Redoks disbalans (određen nižim vrednostima TAS i višim vrednostima tSHG), kao dodatak većim vrednostima TG i nižim vrednostima HDL-c su povezane sa lošijom glikoregulacijom.",
publisher = "Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Principal component analysis of the oxidative stress, inflammation, and dyslipidemia influence in patients with different levels of glucoregulation, Glavna komponentna analiza uticaja oksidativnog stresa, inflamacije i dislipidemije kod pacijenata sa različitim nivoom glikoregulacije",
volume = "42",
number = "3",
pages = "427-436",
doi = "10.5937/jomb0-39636"
}

Malenica, M., Klisić, A., Meseldžić, N., Dujić, T., Bego, T.,& Kotur-Stevuljević, J.. (2023). Principal component analysis of the oxidative stress, inflammation, and dyslipidemia influence in patients with different levels of glucoregulation. in Journal of Medical Biochemistry
Society of Medical Biochemists of Serbia., 42(3), 427-436.
https://doi.org/10.5937/jomb0-39636

Malenica M, Klisić A, Meseldžić N, Dujić T, Bego T, Kotur-Stevuljević J. Principal component analysis of the oxidative stress, inflammation, and dyslipidemia influence in patients with different levels of glucoregulation. in Journal of Medical Biochemistry. 2023;42(3):427-436.
doi:10.5937/jomb0-39636 .

Malenica, Maja, Klisić, Aleksandra, Meseldžić, Neven, Dujić, Tanja, Bego, Tamer, Kotur-Stevuljević, Jelena, "Principal component analysis of the oxidative stress, inflammation, and dyslipidemia influence in patients with different levels of glucoregulation" in Journal of Medical Biochemistry, 42, no. 3 (2023):427-436,
https://doi.org/10.5937/jomb0-39636 . .

TY  - JOUR
AU  - Dujić, Tanja
AU  - Cvijić, Sandra
AU  - Elezović, Amar
AU  - Bego, Tamer
AU  - Imamović Kadrić, Selma
AU  - Malenica, Maja
AU  - Elezović, Alisa
AU  - Pearson, Ewan R.
AU  - Kulo, Aida
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4087
AB  - The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4–1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6-and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.
PB  - MDPI
T2  - Journal of Personalized Medicine
T1  - Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype
VL  - 11
IS  - 5
DO  - 10.3390/jpm11050367
ER  - 

@article{
author = "Dujić, Tanja and Cvijić, Sandra and Elezović, Amar and Bego, Tamer and Imamović Kadrić, Selma and Malenica, Maja and Elezović, Alisa and Pearson, Ewan R. and Kulo, Aida",
year = "2021",
abstract = "The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4–1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6-and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.",
publisher = "MDPI",
journal = "Journal of Personalized Medicine",
title = "Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype",
volume = "11",
number = "5",
doi = "10.3390/jpm11050367"
}

Dujić, T., Cvijić, S., Elezović, A., Bego, T., Imamović Kadrić, S., Malenica, M., Elezović, A., Pearson, E. R.,& Kulo, A.. (2021). Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype. in Journal of Personalized Medicine
MDPI., 11(5).
https://doi.org/10.3390/jpm11050367

Dujić T, Cvijić S, Elezović A, Bego T, Imamović Kadrić S, Malenica M, Elezović A, Pearson ER, Kulo A. Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype. in Journal of Personalized Medicine. 2021;11(5).
doi:10.3390/jpm11050367 .

Dujić, Tanja, Cvijić, Sandra, Elezović, Amar, Bego, Tamer, Imamović Kadrić, Selma, Malenica, Maja, Elezović, Alisa, Pearson, Ewan R., Kulo, Aida, "Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype" in Journal of Personalized Medicine, 11, no. 5 (2021),
https://doi.org/10.3390/jpm11050367 . .