PRINCIPAL COMPONENT ANALYSIS OF THE OXIDATIVE STRESS, INFLAMMATION, AND DYSLIPIDEMIA INFLUENCE IN PATIENTS WITH DIFFERENT LEVELS OF GLUCOREGULATION
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J Med Biochem 2023; 42 (3) DOI: 10.5937/jomb0-39636
UDK 577.1 : 61 ISSN 1452-8258
J Med Biochem 42: 427–436, 2023 Original paper
Originalni nau~ni rad
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 RAZLI^ITIM NIVOOM GLIKOREGULACIJE
Maja Malenica1, Aleksandra Klisic2, Neven Meseldzic1, Tanja Dujic1,
Tamer Bego1, Jelena Kotur-Stevuljevic3
1Department of Pharmaceutical Biochemistry and Laboratory Diagnostics,
University of Sarajevo, Faculty of Pharmacy, Sarajevo, Bosnia and Herzegovina
2Primary Health Care Center, University of Montenegro – Faculty of Medicine, Podgorica, Montenegro
3Department for Medical Biochemistry, University of Belgrade – Faculty of Pharmacy, Belgrade, Serbia
Summary Kratak sadr`aj
Background: The aim of the study was to explore the mutu- Uvod: Cilj istra`ivanja je bio da se ispita povezanost
al relationship between oxidative stress, inflammation and oksidativnog stresa, inflamacije i metaboli~kih biomarkera
metabolic biomarkers in subjects with prediabetes (PRE), kod pacijenata sa predijabetesom (PRE), de novo dijabe-
newly diagnosed type 2 diabetes patients (NT2D) and overt tesom (NT2D) i ranije dijagnostikovanim dijabetesom
type 2 diabetes (T2D) using principal component analysis (T2D) pomo}u glavne komponentne analize (PCA).
(PCA) as a thorough statistical approach. Metode: Glikozilirani hemoglobin, lipidni status, markeri
Methods: Glycated hemoglobin, lipid parameters, inflam- inflamacije (IL-6, CRP i fibrinogen), parametri oksidativnog
mation (IL-6, CRP and fibrinogen) and oxidative stress stresa [pro-oksidanti (AOPP, PAB, TOS) i antioksidansi
markers [pro-oxidants (AOPP, PAB, TOS) and antioxidants (PON1, tSHG, TAS)] su mereni. PCA je primenjena da bi
(PON1, tSHG, TAS)] were measured. PCA was applied to se ispitali faktori koji najvi{e uti~u na glikoregulaciju.
explore the factors that the most strongly influenced glu- Rezultati: U istra`ivanje je uklju~eno 278 ispitanika: 37
coregulation. PRE, 42 NT2D i 99 T2D, kao i 100 zdravih osoba koji su
Results: A total of 278 subjects were (i.e., 37 PRE, 42 ~inili kontrolnu grupu (CG). PCA je izdvojila 4 razli~ita fak-
NT2D and 99 T2D) were compared with 100 healthy sub- tora obja{njavaju}i 49% varijanse ispitivanih parametara:
jects as a control group (CG). PCA emphasized 4 different oksidativni stres-dislipidemija faktor (sa pozitivnim uticajem
factors explaining 49% of the variance of the tested param- TG i tSHG, i negativnim uticajem HDL-c i TAS), dislipide-
eters: oxidative stress-dyslipidemia related factor (with pos- mija faktor (tj, ukupni holesterol i LDL-c, oba sa pozitivnim
itive loading of TG and tSHG, and with negative loading of uticajem), antropometrijski faktor (tj, obim struka i kukova,
HDL-c and TAS), dyslipidaemia related factor (i.e., total oba sa pozitivnim uticajem) i oksidativni stres-inflamacija
cholesterol and LDL-c, both with positive loading), faktor (tj, PAB, fibrinogen i CRP, svi sa pozitivnim uticajem).
Anthropometric related factor (i.e., waist and hip circum- Od ova 4 faktora, jedino je oksidativni stres – dislipidemija
ference, both with positive loading) and oxidative stress- faktor pokazao zna~ajnu prediktivnu sposobnost za lo{u
Inflammation related factor (i.e., PAB, fibrinogen, and CRP, glikoregulaciju. Porast ovog faktora za jednu jedinicu je
Address for correspondence:
Aleksandra Klisic, MD PhD
Center for Laboratory Diagnostics, Primary Health Care Center,
University of Montenegro-Faculty of Medicine,
Podgorica, Montenegro
Address: Trg Nikole Kovacevica 6, 81000 Podgorica, Montenegro
Phone and Fax: +382 20 481 999
e-mail: aleksandranklisicªgmail.com428 Malenica et al.: Oxidative stress in (pre)diabetes
all with positive loading). Out of these 4 factors, only oxida- pokazao 1,6 puta ve}u verovatno}u za lo{u glikoregulaciju.
tive stress – dyslipidaemia related factor showed a signifi- Zaklju~ak: Redoks disbalans (odre|en ni`im vrednostima
cant predictive capability towards poor glucoregulation. An TAS i vi{im vrednostima tSHG), kao dodatak ve}im vred-
increase in this factor by one unit showed a 1.6 times high- nostima TG i ni`im vrednostima HDL-c su povezane sa
er probability for poor glucoregulation. lo{ijom glikoregulacijom.
Conclusions: Redox imbalance (determined with lower TAS
and higher tSHG), in addition to higher TG and lower HDL- Klju~ne re~i: antioksidansi, pro-oksidansi, kontrola glike-
c was associated with poor glucoregulation. mije, inflamacija, dislipidemija
Keywords: antioxidants, prooxidants, glycemic control,
inflammation, dyslipidemia
Introduction addition, in an attempt to better explain the complex
pathophysiological processes and to find the best pre-
Oxidative stress is the underlying characteristic dictors of cardiometabolic disorders some recent
of various cardiometabolic disorders (1–5). Type 2 reports included a variety of biomarkers that reflect
diabetes mellitus (T2D) is increasing worldwide, in different signaling pathways of the mentioned disor-
parallel with the increase of individuals with obesity. It ders. In line with this, we have recently shown that a
is well known that enlarged visceral adipose tissue is statistical approach that included principal compo-
a source of a variety of reactive oxygen/nitrogen nent analysis (PCA) of various biomarkers, rather than
species (ROS/RNS) (1, 6, 7). Besides, it secrets dif- each biomarker alone, can be a better determinant of
ferent pro-inflammatory adipokines and cytokines some metabolic disorders (15–17). However, to our
leading to a chronic low-grade inflammation state. As knowledge, there are no studies that applied PCA
a consequence, insulin signaling pathways become including different oxidative stress, inflammation, and
targeted leading to an insulin-resistant state, which cardiometabolic biomarkers in populations with predi-
affects the liver tissue, adipose tissue and skeletal abetes and overt diabetes. Hence, the aim of the cur-
muscles (8). rent project was to find the best diagnostic approach
Insulin resistance (which is a typical finding in to poor glucoregulation, which includes a wide spec-
prediabetes and overt diabetes) favours enhanced trum of prooxidants, antioxidants, as well as inflam-
lipolysis of triglycerides (TG) and causes an increased mation, and metabolic biomarkers.
hepatic flux of free fatty acids (FFA). Moreover,
enhanced lipogenesis [i.e., higher concentration of
very-low density lipoproteins (VLDL) and small dense Materials and Methods
low-density lipoproteins (sdLDL)], as well as a reduc-
Patients
tion in high-density lipoproteins (HDL) and changes
in their composition (the state which is described as A total of 278 subjects were included in the
»atherogenic dyslipidaemia«), is the predictor of study: 37 patients with prediabetes (PRE) (35.2%
atherosclerosis and cardiovascular disease (8, 9). females), 42 newly diagnosed type 2 diabetic patients
(NT2D) (59.5% females), and 99 with type 2 dia-
Prediabetes is an intermediate stage between
betes mellitus (T2D) (52.5% females), who were
normoglycemia and overt T2D and is associated with
compared with 100 healthy subjects as a control
older age and obesity (10). Even though that
group (CG) (60.0% females). All participants were
prediabetes is asymptomatic, subjects with pre-
consecutively recruited in a period between January
diabetes are at risk of progression to T2D, as well as
2016 to January 2017 in the Clinical Centre
cardiovascular disease (11, 12).
University in Sarajevo and General Hospital Te{anj,
It is of utmost importance to recognize this Bosnia and Herzegovina. Each examinee completed a
metabolic disorder as early as possible before overt questionnaire that was consisted of questions regard-
diabetes occurs and to delay and/or prevent its ing demographic characteristics, lifestyle habits (e.g.,
further complications, given that clinical symptoms of cigarette smoking, alcohol use and an open question
T2D are often unrecognized. of somatic illnesses).
Hyperglycemia causes increased production of The inclusion criteria for participants with PRE
ROS (13). The moment when antioxidant defense and T2D were taken from the 2020 American Dia-
capacity becomes exhausted signifies the develop- betes Association Standards of Diabetes Care (18).
ment of a toxic milieu, with concomitant structural
Participants were considered to have predia-
and functional changes of deoxyribonucleic acid,
betes if they were not taking any antihyperglycemic
proteins, and lipids, which accelerates tissue damage
therapy, if they exhibited fasting glucose levels
and apoptosis (13).
between 5.6 mmol/L and < 7.0 mmol/L, and/or if
However, the universal biomarker that best they had glycated hemoglobin (HbA1c) levels
reflects oxidative stress is still unrecognized (14). In between 5.7% and 6.4%.J Med Biochem 2023; 42 (3) 429
The control group consisted of diabetes-free Oxidative stress status parameters were deter-
participants who did not use any antihyperglycemic, mined as follows:
antihyperlipidemic and antihypertensive medications,
Total protein sulfhydryl (tSHG) groups were
with HbA1c levels lower than 5.7% and fasting glu- determined spectrophotometrically using 5, 5’-dithio-
cose levels lower than 5.6 mmol/L. bis (2-nitrobenzoic acid) (19, 20). A reaction with
The exclusion criteria were: liver disease (other potassium iodide and glacial acetic acid was applied
than steatosis), kidney disease, chronic pancreatitis, for advanced oxidation protein products (AOPP)
gastrointestinal disease, inflammatory bowel disease, measurement by the method of Witko-Sarsat et al.
endocrine disorders (other than diabetes), infection (21). Total oxidative status (TOS) was determined
and using hormonal therapy. spectrophotometrically using o-dianisidine optimized
by Erel (22). Total antioxidative status (TAS) was
Written informed consent was provided by each obtained spectrophotometrically using ABTS (2,2 -
examinee. The study was conducted in accordance azino-bis-[3-ethyl-benzothiazoline-6-sulfonic acid]) as
with the Helsinki Declaration and was approved by a chromogen (23).
the Ethics Committee of Cantonal Hospital Zenica
The measurement of prooxidant-antioxidant
and the International University of Sarajevo. balance (PAB) was done using 3,3’, 5,5’-tetramethyl-
All patients with T2D used oral antihyper- benzidine as a chromogen (24).
glycemics (metformin and sulfonylureas were used by
86.7% and 43.4 of patients, respectively). There were
no participants in the CG, PRE, and NTD2 group who Calculation of scores
used antihyperglycemic medications, as would be The OXY score was calculated by subtracting
expected based on inclusion/exclusion criteria. the protective score (i.e. obtained as an average of
Antihyperlipidemics (i.e., statins) were used by standardized antioxidant variables (tSHG and TAS,
8%, 19% and 29.3% of participants in the PRE, i.e. ANTIOX score) from the damage score (i.e.
obtained as the average of standardized prooxidant
NT2D and T2D groups, respectively. Antihyper-
factors AOPP, TOS, and PAB, i.e. PROOX score) (25).
tensive drugs were used by 14%, 30% and 60% of
participants in the PRE, NT2D and T2D groups,
respectively. Statistical analysis
Statistical analysis was done using SPSS
Methods Statistics v.26.0 (IBM Corporation, NY). The normal-
ity of the data distribution was evaluated by the
Anthropometric measures were obtained from Shapiro-Wilk and Kolmogorov-Smirnov test, where
each examinee [i.e., body height and weight and appropriate. Shapiro Wilk test was used to test the
waist and hip circumference (WC and HC, respective- normality for the groups 50 participants [i.e. Type
measurements were done by the two licenced 2 diabetic patients (T2D), N = 99 and Control group
researchers who were healthcare workers. The (CG), N= 100].
measurements were performed following the same The significance of differences in clinical mark-
protocol. ers’ concentrations between the groups was estimat-
Blood samples were taken after an overnight ed using the ANOVA test (for the normally distributed
fast (of at least 8 hours). HbA1c was measured in the data) and the Kruskal-Wallis test (for the non-normally
whole blood by the immunoturbidimetry method distributed data). The Tukey’s test was performed for
using the autoanalyzer Dimension Xpand (Siemens, post hoc analysis, as well as the Mann-Whitney test.
München, Germany). C-reactive protein (CRP) was The results are presented as mean ± standard devia-
measured nephelometrically on the same analyzer. tion (SD) and median (25th–75th percentile).
Fibrinogen levels were measured on an automatic Principal component analysis (PCA) (26) with
coagulation analyzer (Sysmex CA-600, Cobe, Japan). varimax-normalized rotation was used to determine
For the determination of interleukin-6 (IL-6) flow all variables that significantly affected T2D, grouped
cytometry was used. For the assay for IL-6 particles into several factors. The basic criteria for the vari-
with defined fluorescence intensity were used for the ables’ inclusion into the distinct factors were: factor
detection of soluble cytokine at very low concentra- extraction based on eigenvalues higher than 1 and for
tions (10–2500 pg/mL) (Human IL-6 Flex Set, BDTM factor, influence coefficient higher than 0.5. Finally,
Cytometric Bead Array). the number of factors was fixed at 4.430 Malenica et al.: Oxidative stress in (pre)diabetes
Binary logistic regression analysis was used to Results
test the possible predictive capability of 4 PCA-select-
ed factors which were transformed into 4 separate Table I shows the descriptive statistics of demo-
scores – quantitative variables. The dependent graphic and anthropometric characteristics of the
variable in binary logistic regression analysis was subjects included in the study. Participants with PRE,
glucoregulation status (0-good, 1-poor) and NT2D, and T2D were older and displayed higher
independent variables were 4 new factors created by anthropometric indices (i.e., BMI, WC, HC, WHR),
PCA analysis and presented as their numerical values SBP, and DBP vs. CG.
– scores. Multicollinearity was checked by VIF Also, more individuals with T2D used anti-
parameters calculation and all VIFs = 1, which hyperlipidemic agents (statins) and antihypertensives,
denied multicollinearity between the tested variables. as compared with NTD2 and PRE group.
P-values less than 0.05 were considered statistically
significant. The levels of clinical markers in the examined
groups are shown in Table II.
Table I Demographic and anthropometric characteristics of control (CG), prediabetes (PRE), newly diagnosed Type 2 diabetes
mellitus (NT2D), and Type 2 diabetes mellitus (T2D) individuals.
Patients with newly
Patients with Patients with type 2
Control group (CG) diagnosed type 2
Variables prediabetes (PRE) diabetes (T2D) P
N= 100 diabetes (NT2D)
N = 37 N = 99
N = 42
Age, years 48±7 55±11aaa 57±7aaa 56±6aaaJ Med Biochem 2023; 42 (3) 431
Table II Clinical markers of tested population groups.
Patients with newly
Patients with Patients with type 2
Control group (CG) diagnosed type 2
Variables prediabetes (PRE) diabetes (T2D) P
N=100 diabetes (NT2D)
N = 37 N = 99
N = 42
5.0 6.6 8.5 8.1
Glucose, mmol/L432 Malenica et al.: Oxidative stress in (pre)diabetes Figure 1 The values of ANTIOX, PROOX and OXY score in examined groups. P- Kruskal-Wallis test; aaa p
J Med Biochem 2023; 42 (3) 433
Table IV Binary logistic regression analysis of poor glycaemic control (HbA1c > 7.0%) predictors.
-2 Log Negelkerke OR
Predictors of HbA1c > 7.0% c2, p# Precision p
likelihood R2 (95% C.I.)
Oxidative stress-Dyslipidemia
4.9, 0.026 88.1 0.076 86.2 1.639 (1.075–2.498) 0.022
related factor
Dyslipidemia related factor 12.0, 0.001 81.1 0.178 87.1 0.719 (0.484-1.067) 0.101
Anthropometric related factor 3.1, 0.078 90.0 0.048 86.2 0.777 (0.522–1.158) 0.215
Oxidative stress-Inflammation
2.1, 0.146 91.0 0.033 87.1 0.948 (0.641–1.401) 0.788
related factor
OR- odds ratio; C.I. – confidence interval; # from Omnibus test
We performed binary logistic regression analysis Fluctuations in glucose level are related to
to test the possible predictive capability of 4 PCA- oxidative stress (13). ROS production is directly
selected factors on glucoregulation. These factors were induced by the severity and the length of hyper-
then transformed into 4 separate scores. Univariate glycemia. ROS affect multiple signalling pathways
analysis showed the significant predictive capability of (e.g., activation of the protein kinase C isoform,
factor 1 (oxidative stress – dyslipidaemia (HDL-c) relat- higher hexosamine pathway flow and higher polyols
ed factor). On the other hand, factor 2 (dyslipidaemia formation) (13).
(LDL-c) related factor), factor 3 (anthropometric relat-
A significant difference in tSHG values (which
ed factor), and factor 4 (oxidative stress-inflammation
represents the major part of antioxidants in the
related factor) did not show significant predictive
human body) was observed in PRE, NT2D and T2D,
potency towards glycaemic control assessed by HbA1c
respectively, compared to controls (Table II).
values. This analysis revealed that an increase in oxida-
Significantly lower tSHG levels were also observed in
tive stress – dyslipidaemia (TG, HDL-c) related factor
PRE compared with NT2D and T2D patients.
(redox disbalance + higher TG and lower HDL-c) by
one unit has a 1.6 times higher chance for poor glu- This may be explained by increased antioxida-
coregulation (Table IV). tive defense capacity when hyperglycemia occurs in
an attempt to cope with the increased generation of
ROS (1, 6). Our results are in line with a previous
Discussion study (27) that reported higher tSHG levels (i.e. total
thiols) in patients with diabetes mellitus, as well as in
As far as we are aware, this is the first research patients with pre-diabetes, when compared with a
that used PCA of different biomarkers in order to control group. This suggests that a higher level of
investigate complex pathophysiological processes in antioxidants may represent a compensatory mecha-
prediabetes and overt diabetes. Also, this study is nism for the increased production of ROS due to
unique since it explored a wide spectrum of bio- prolonged hyperglycemia. One of the possible
markers that reflects redox homeostasis (i.e., explanations related to higher levels of several pro-
prooxidants such as PAB, AOPP, TOS and PROOX oxidants and lower levels of several antioxidants in
score and antioxidants such as PON1, TAS, tSHG and NT2D as compared to T2D may lie in the fact that
ANTIOX score, as well as its comprehensive OXY participants with T2D used antihyperglycemic and
score) and inflammation status (CRP, IL-6, fibrinogen) antihyperlipidemic medications that might diminish
in diabetes. To better enlighten the mentioned oxidative stress and inflammation (28). Moreover, the
processes we included participants with different possibility that some of them may also have used
glucoregulation status such as prediabetes and NT2D antioxidant supplements which might modulate the
(both groups without antihyperglycemic medication level of oxidative stress, cannot be ruled out (29).
use) and T2D, compared with the healthy control However, based on the results of the current study,
group. compared with healthy counterparts, participants with
As it would be expected, the control group of prediabetes had higher levels of prooxidants (i.e.,
healthy participants displayed significantly lower levels AOPP, TOS, PROOX score, and OXY score) and
of oxidative stress and inflammation as reflected by lower levels of antioxidants (i.e., PON1, and TAS)
the levels of AOPP, PAB, TOS (Table II), ANTIOX (Table II, Figure 1). This is supported by the notion
score, PROOX score and OXY score (Figure 1), and that hyperglycemia even in prediabetes is reflected by
the higher level of PON1 and TAS (Table II) as increased production of ROS and concomitant insulin
compared with NT2D and T2D. resistance is tightly connected with increased434 Malenica et al.: Oxidative stress in (pre)diabetes
oxidative stress (8). Prolonged hyperglycemia leads to Taking into account all these complex processes
depletion of antioxidant enzymes activity, favoring the and different pathways of cardiometabolic conse-
increase in ROS, prooxidants and overt diabetes (1, quences of the insulin resistance state, we aimed to
6, 8). Once the diagnosis of T2D is confirmed, find the best diagnostic approach for the mentioned
antihyperglycemic medications that patients use may disorder. The different level of glucoregulation, i.e.
further modulate/decrease the level of oxidative insulin-resistant state in subgroups of examined par-
stress (30). This might in part explain the results ticipants, is one of the strengths of the current study
obtained in the current study. Also, our results might since we included participants with prediabetes,
support the notion that timely diagnosis of NT2D (both groups without antidiabetic therapy),
prediabetes is of great importance and use of and T2D (on antidiabetic therapy). Also, as previously
antihyperglycemic medications in prediabetes might stated, a variety of redox homeostasis and inflamma-
reduce oxidative stress and prevent overt T2D. tion biomarkers were explored, as well as factorial
Binary logistic regression analysis showed signif- analysis/PCA as a reliable statistical approach to
icant predictive capability of only oxidative stress – investigate the joint effect of oxidative stress, dyslipi-
dyslipidaemia (HDL-c) related factor, whereas the daemia, and inflammation on T2D.
other factors did not show significant predictive The limitations of this study include its cross-
potency towards glycaemic control assessed by sectional design, which restricts our ability to define
HbA1c values. An increase in oxidative stress – dys- causality between examined variables. Although a
lipidaemia (HDL-c) related factor (i.e., redox disbal- pattern of non-specific marker levels can result in a
ance + higher TG and lower HDL-c) showed a 1.6 «score” that can be more specific than the individual
times higher possibility for poor glycaemic control marker, it is worth mentioning that the data used in
(Table IV). In a previous study (5), we have shown that PCA represent a collection of more or less non-spe-
the comprehensive DOI score (that represented the cific markers, that can be increased due to more than
summary involvement of dyslipidemia, oxidative one mechanism, which suggests that the PCA analy-
stress and inflammation) is an independent predictor sis may not always be reliable. Moreover, there is a
of HbA1c level, although the study did not include possibility that some of the participants may also have
newly diagnosed patients with T2D and despite the used antioxidant supplements, which might modulate
fact that all studied patients with T2D used the level of oxidative stress and this cannot be ruled
antihyperglycemic medications. In this study we
out. Other limitations include the relatively small
showed that as the DOI score rose by 1 unit, the
number of participants included in the study. Also,
probability for higher HbA1c levels increased by 9%.
due to the lack of diversity within the study groups the
This appears to confirm the complex relationship
data cannot be readily applied to non-Caucasians.
between all of these pathophysiological processes.
Longitudinal studies with different ethnic groups are
As previously stated, visceral adipose tissue (in needed to further elucidate this issue.
routine practice most often determined by WC)
secretes proinflammatory adipokines and cytokines
which are shown to have an adverse impact on insulin Conclusions
signalling pathways (1, 6). Indeed, we have shown
higher levels of IL-6 and fibrinogen in NT2D and T2D As far as we know, this is the first study that used
compared to prediabetes, as well as higher levels of factorial analysis of different factors consisted of car-
CRP in prediabetes, NT2D and T2D compared to diometabolic biomarkers, markers of oxidative stress
healthy controls. In parallel with the extent and dura- and inflammation in participants with different levels
tion of obesity, insulin resistance favours the increase of glucoregulation. In line with this, we have shown
in lipolysis of TG and consequently the increase of that oxidative stress – dyslipidaemia (HDL-c) related
free fatty acids (FFA) secretion from adipose tissue. factor showed a significant predictive capability
These processes precede oxidative phosphorylation, towards poor glycaemic control. An increase in oxida-
peroxidation of lipoproteins in the liver and free radi- tive stress – dyslipidaemia (HDL-c) related factor (i.e.,
cal production (1). The increased hepatic production redox imbalance, in addition to higher TG and lower
of VLDL which are enriched with TG and are HDL-c) by one unit showed a 1.6 times higher prob-
assumed to be very lipotoxic are the consequences of ability for poor glucoregulation.
an insulin-resistant state, also. The transformation of
HDL particles into the smaller HDL3 particles and the
increased production of small dense LDL (9), both of Conflict of interest statement
which are shown to be prone to oxidative modifica-
All the authors declare that they have no conflict
tions, is another consequence of the insulin-resistant
of interest in this work.
state, thus enabling the beginning and the progres-
sion of atherosclerotic alterations (30).J Med Biochem 2023; 42 (3) 435
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Received: June 27, 2022
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