Assessment of Cardiovascular Disease Risk in Prediabetes


Download Assessment of Cardiovascular Disease Risk in Prediabetes


Preview text

International Journal of Biochemistry Research & Review
29(2): 1-8, 2020; Article no.IJBCRR.55491 ISSN: 2231-086X, NLM ID: 101654445

Assessment of Cardiovascular Disease Risk in Prediabetes
Ashish Agarwal1, Anupama Hegde2*, Afzal Ahmad1, Charu Yadav3, Poornima A. Manjrekar2 and M. S. Rukmini2
1Department of Biochemistry, GS Medical College and Hospital, Pilkhuwa, U.P., India. 2Department of Biochemistry, Kasturba Medical College, Mangalore, MAHE, Karnataka, India.
3Department of Biochemistry, Lady Harding Medical College, New Delhi, India.
Authors’ contributions
This work was carried out in collaboration among all authors. Authors Ashish Agarwal and AH gave the concept/design and drafted the article. Author Afzal Ahmad did the data acquisition, analysis and interpretation. Authors CY and PAM critically revised the article. Author MSR managed accountability.
All authors finally approved manuscript version to be published.
Article Information
DOI: 10.9734/IJBCRR/2020/v29i230166 Editor(s):
(1) Dr. Chunying li, Georgia State University, USA. Reviewers:
(1) Celestino Sardu, University of Campania Luigi Vanvitelli, Italy. (2) Arthur N. Chuemere, University of Port Harcourt, Nigeria.
Complete Peer review History: http://www.sdiarticle4.com/review-history/55491

Original Research Article

Received 08 January 2020 Accepted 13 March 2020 Published 19 March 2020

ABSTRACT
Introduction: Prediabetes is associated with dysglycemia, endothelial dysfunction, obesity and inflammation, placing them at an increased risk of cardiovascular events. Aims: The present study aimed to investigate the risk of cardiovascular disease associated with prediabetes by estimation of serum interleukin-6, myeloperoxidase and urine microalbumin and their correlation with fasting plasma glucose and anthropometric measurements. Study Design: Cross sectional study. Place and Duration of Study: Study was conducted at Department of Biochemistry, Kasturba Medical College Hospitals, Mangaluru between 2014 and 2015. Methodology: Eighty subjects were categorised into prediabetes and healthy controls based on their fasting plasma glucose values. Anthropometric data (weight, body mass index, waist circumference, hip circumference and waist-to-hip ratio from all subjects were recorded. Interleukin-6 & myeloperoxidase were estimated in serum sample whereas microalbumin was estimated in random urine sample.
_____________________________________________________________________________________________________
*Corresponding author: E-mail: [email protected];

Agarwal et al.; IJBCRR, 29(2): 1-8, 2020; Article no.IJBCRR.55491
Results: The mean anthropometric measurements and cardiovascular disease risk markers (interleukin-6, myeloperoxidase and urine microalbumin) were found to be significantly higher (p < 0.05) in prediabetes group. Myeloperoxidase had significant correlation with fasting plasma glucose (r-0.388) in the prediabetes group. Interleukin-6 and myeloperoxidase also showed a positive correlation with body mass index (r - 0.339, r - 0.327), waist circumference (r - 484, r - 0.493) and waist-to-hip ratio (r - 0.430, r - 0.493) while urine microalbumin did not correlate with fasting plasma glucose and anthropometric measurements in prediabetes group. Conclusion: This study suggests that prediabetes is associated with central adiposity and have an increased risk for cardiovascular disease.

Keywords: Interleukin-6(IL-6); Myeloperoxidase (MPO); Microalbuminuria (MA); cardiovascular risk; prediabetes.

ABBREVIATIONS

CVD IL-6 MPO MA FPG BMI WC HC WHR R IFG IGT BP ELISA
SPSS
PD H ROS H2O2 NO HOCLRSSDI
MU

: Cardiovascular Disease : Interleukin-6 : Myeloperoxidase : Microalbumin :Fasting Plasma Glucose :Body Mass Index :Waist Circumference :Hip Circumference :Waist-To-Hip Ratio :Pearson’s Correlation :Impaired Fasting Glucose :Impaired Glucose Tolerance :Blood Pressure :Enzyme-Linked Immune Sorbent Assay :Statistical Package For Social Science : Prediabetes Group :Healthy Controls :Reactive Oxygen Species :Hydrogen Peroxide :Nitric Oxide : Hypochlorus Acid :Research Society For Study of Diabetes In India : Manipal University

1. INTRODUCTION

disease (CVD). A major pro-inflammatory cytokine interleukin-6 (IL-6), contributes in the initiation & acceleration of chronic low grade inflammation resulting in endothelial dysfunction and atherosclerotic plaque formation in type 2 diabetes [2]. Myeloperoxidase (MPO) is an enzyme linked to both oxidative stress and inflammation and has been implicated in the pathogenesis of atherosclerosis and is associated with an increased CVD risk in diabetes population [3].
Microalbuminuria (MA) i.e. increased albumin excretion than normal in urine is associated with oxidative stress and endothelial dysfunction. It is a predictor of cardiovascular mortality and an independent risk factor for the development of CVD in the diabetic population [4].
IL-6, MPO and microalbuminuria are associated with endothelial dysfunction, low grade inflammation and oxidative stress which are the mechanisms for the development of CVD in diabetes patients but their role in prediabetes associated CVD is still debatable. Therefore, estimation of IL-6, MPO and microalbuminuria as indicators of CVD risk [3,5,6] in prediabetes and their correlation with fasting glucose and anthropometric measurements forms the basis of this study.

Pre-diabetes is generally defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both. It is associated with dyslipidaemia, endothelial dysfunction, obesity, dysglycemia, pro-coagulant state, insulin resistance, hypertension and inflammation placing individuals with prediabetes at an increased risk of cardiovascular events [1].
Low grade inflammation is one of the major underlying pathophysiologic mechanisms responsible for development of cardiovascular

2. MATERIALS AND METHODS
2.1 Study Design
A cross sectional study was conducted for study subjects who came with requisition for fasting plasma glucose test in a tertiary care hospital, Mangalore. Around 300 patients were screened over a period of one year out of which 80 subjects aged 25-45 years who met the inclusion criteria i.e. FPG of 101-125 mg/dl or 70-100 mg/dl were selected and categorised into prediabetes and

2

Agarwal et al.; IJBCRR, 29(2): 1-8, 2020; Article no.IJBCRR.55491

healthy controls respectively. Subjects with history of diabetes, endocrine disorders, kidney diseases, cardiac diseases, any infectious disease in the past two weeks and pregnant women were excluded.

weight, BMI, WC, HC and WHR were found to be significantly increased in prediabetes group when compared with the healthy controls. The mean age and height were comparable between the groups.

This study was carried out with the approval of the institutional Ethics Committee. After obtaining informed consent, history of the subjects was taken through a structured interview and a thorough physical examination of the subjects was done which included measuring the BP, pulse rate, height, weight, BMI, hip circumference, waist circumference and waist-tohip ratio followed by systemic examination.
2.2 Biochemical Measurements

3.2 CVD Risk Markers
Table 2 shows the central values of cardiovascular disease risk markers (IL-6, MPO and MA) in both the groups. The mean serum IL6, MPO and median urinary MA levels were found to be significantly increased in prediabetes group when compared with healthy controls.
3.3 FPG and CVD Risk Markers Correlation

Along with sample for fasting plasma glucose in fluoride vacutainer, additional blood sample was collected in plain vacutainer for IL-6 & MPO and random urine sample was collected in sterile container for MA estimation. Serum samples for IL-6, MPO and urine for MA were stored at -20°C until further analysis.
Serum IL-6 and MPO were analysed using solid phase enzyme-linked immunosorbent assay (ELISA) based on sandwich principle in ELx 800 by BIO TEK® instruments, Inc. using commercially available kits provided by RayBiotech, Inc. and Immunology Consultants Laboratory, Inc. respectively. Urine MA was analysed by Latex-turbudimetric method in STAR 21 Plus semiautoanalyser using commercially available kit provided by Euro Diagnostic Systems Pvt. Ltd.
2.3 Statistical Analysis
Statistical package SPSS vers.16.0 was used and P < 0.05 was considered significant. Comparison between the groups was done by independent sample ‘t’ test for normal distribution data and for data with skewed distribution MannWhitney U test was used. Correlation was done by Pearson’s correlation for normal distribution data and for data with skewed distribution Spearman’s correlation was used.
3. RESULTS
3.1 Baseline Characteristics
Following the inclusion criteria a total of eighty patients were enrolled in the study. Table 1 shows the baseline characteristics of the patients from both the groups. The mean serum glucose,

When Pearson’s correlation was applied for FPG, versus serum IL-6, MPO and Spearman’s correlation for urinary MA in both the groups as shown in Fig. 1, only MPO had a significant positive correlation (r- 0.388, P-0.013) with FPG in prediabetes group but had no correlation in the healthy controls. IL-6 and Urine MA had no correlation with FPG in both the groups.
3.4 Anthropometric Measurements and CVD Risk Markers Correlation
When Pearson’s correlation was applied for serum IL-6 and MPO and Spearman’s correlation for urinary MA versus anthropometric measurements i.e weight, BMI, WC, HC and WHR in both the groups as shown in Table 3, IL6 were found to be positively correlated with weight, BMI, WC and WHR, MPO was found to be positively correlated with BMI, WC and WHR and Urine MA was not correlated with anthropometric measurements in prediabetes group.
4. DISCUSSION
Prediabetes is associated with microangiopathy and also with more advanced atherosclerotic vascular damage than normoglycemia. Contribution of both glycemic and non-glycemic factors in the development of CVD during prediabetes is supported by the different pathophysiologic pathways leading to vasculopathy [1]. The risk of cardiovascular disease in prediabetes as compared to healthy population was evaluated using serum interleukin-6, myeloperoxidase and urine microalbumin in the current study. At baseline, it was observed that the subjects in prediabetes group had increased weight, BMI, waist

3

Agarwal et al.; IJBCRR, 29(2): 1-8, 2020; Article no.IJBCRR.55491

circumference, hip circumference and waist-tohip ratio in contrast to healthy group (Table 1). We found increased levels of IL-6, MPO and urine MA in prediabetes group as compared to healthy group. Further, we found a correlation of MPO with fasting glucose in prediabetes. We also found correlation of IL-6 and MPO, but not urine MA with anthropometric measurements in prediabetes.

The increase in anthropometric measurements found in prediabetes subjects in the present study is supported by the study conducted by Ferrannini which suggested that prediabetes individuals, aside from having mild hyperglycemia, have a higher BMI as well as more central fat distribution and higher waist-tohip ratio compared with normoglycemic subjects [7].

Table 1. Baseline characteristics of the prediabetes and healthy group

Variable

Prediabetes group (n=40) Healthy controls (n=40)

P -value

Age (years)

37.95 ± 6.08(0.96)

36.05 ± 5.89(0.93)

>0.05

FPG (mg/dl)

109.18 ± 7.51(1.18)

92.98 ± 4.23(0.66)

<0.05*

Height (cm)

158.22 ± 5.80(0.91)

159.72 ± 8.09(1.28)

>0.05

Weight (kg) BMI (kg/m2)

68.55 ± 7.59(1.20) 27.29 ± 1.38(0.21)

58.33 ± 7.06(1.11) 22.81 ± 1.50(0.23)

<0.05* <0.05*

WC (cm)

99.10 ± 4.74(0.75)

87.22 ± 7.44(1.17)

<0.05*

HC (cm)

104.62 ± 3.45(0.54)

102.53 ± 4.55(0.71)

<0.05*

WHR

0.94 ± 0.04(0.006)

0.85 ± 0.05(0.008)

<0.05*

Results are shown as Mean ± SD(SE- standard error of mean), n – number of subjects, FPG-Fasting Plasma Glucose, BMI – Body Mass Index, WC – waist circumference, HC – hip circumference, WHR – waist-to-hip ratio,
* P <0.05 was considered significant

Table 2. Comparison of cardiovascular disease risk markers between the two groups

Marker

Prediabetes group

Healthy controls

P value

IL-6 (pg/ml)

66.29 ± 15.39( 2.43 )

12.59 ± 2.69( 0.42 )

<0.05

MPO (ng/ml)

67.46 ± 13.77( 2.17)

46.78 ± 9.93( 1.57 )

<0.05

MA (mg/L)

19.07(14.75,28.96)*

12.60(9.64, 15.81)*

<0.05

Results are shown as Mean ± SD (SE-standard error of mean),* median (interquartile range), IL-6 - Interleukin 6,

MPO –Myeloperoxidase, MA-microalbumin, P <0.05 was considered significant

Table 3. Correlation of serum IL-6, MPO and urinary MA with anthropometric measurements between the groups

Parameter

IL6 (pg/ml)

MPO (ng/ml)

Urine MA (mg/L) #

Weight (Kg)

PD

H BMI (Kg/m2) PD

H

WC (cm)

PD

H

HC (cm)

PD

H

WHR

PD

H

r value (p value) 0.341 (<0.05*) 0.113 (>0.05) 0.339 (<0.05*) -0.044 (>0.05) 0.484 (<0.05*) 0.225 (>0.05) 0.141 (>0.05) 0.240 (>0.05) 0.430 (<0.05*) 0.145 (>0.05)

r value (p value) 0.274 (>0.05) 0.033 (>0.05) 0.327 (<0.05*) 0.121 (>0.05) 0.493 (<0.05*) -0.083 (>0.05) 0.074 (>0.05) 0.175 (>0.05) 0.493 (<0.05*) -0.249 (>0.05)

r value (p value) 0.178# (>0.05) -0.217# (>0.05) 0.214# (>0.05) -0.048# (>0.05) -0.116# (>0.05) 0.161# (>0.05) -0.110# (>0.05) 0.147# (>0.05) -0.076# (>0.05) 0.100# (>0.05)

BMI – Body Mass Index, WC – waist circumference, HC – hip circumference, WHR – waist-to-hip ratio, PD –

Prediabetes group, H – Healthy controls, IL-6 – Interleukin-6, MPO- Myeloperoxidase, MA- microalbumin, r value – Pearson’s correlation, # - Spearman’s correlation, *P<0.05 considered significant

4

Agarwal et al.; IJBCRR, 29(2): 1-8, 2020; Article no.IJBCRR.55491
r-0.227, p-0.158
105

Serum IL-6

85

65

45 100
105

110

120

130

FPG

r-0.388, p-0.013*

Serum MPO

85

65

45

100

110

120

130

FPG

100 r- -0.059,p-0.716

80

Urinary MA

60

40

20

0

100

110

120

130

FPG

Fig. 1. Scatter plot showing correlation between serum IL-6, MPO and urinary MA with FPG in prediabetes group
FPG-Fasting Plasma Glucose, IL-6 - Interleukin 6, MPO –Myeloperoxidase, MA-microalbumin, r- correlation coefficient, * P <0.05 was considered significant

5

Agarwal et al.; IJBCRR, 29(2): 1-8, 2020; Article no.IJBCRR.55491

Chronic inflammation could be one of the reasons of endothelial dysfunction and atherosclerotic plaque formation, processes which contribute to the development of vascular complications in patients with diabetes [8]. Elevated serum IL-6 concentration in the prediabetes group (Table 2) indicates the presence of chronic ongoing inflammatory process in this group [9], which has been confirmed by the results of a study conducted by Sommer et al., where it has been found that hyperglycemia induces IL-6 production [10]. This can be attributed to the formation of advanced glycation end products by persistent hyperglycemia, contributing in the development of chronic inflammation [11]. No correlation could be established between IFG and IL-6 concentration in the present study (Table 2). Hossain et al. [12] reported correlation of IL-6 with IGT but not with IFG. In present study only IFG subjects were enrolled which could be a reason for this result.

A corrrelation between IL-6 concentration with

weight and BMI in prediabetes subjects indicates

that increased weight strongly contributes to the

development of chronic inflammation (Table 3)

[13]. The results of an in vitro study has

demonstrated that after adding the extract of

adipocytes to human umbilical venous

endothelial cells, there is increased production

of IL-6 by these cells [14]. A strong corrrelation

between IL-6 concentration and abdominal

obesity (suggested by waist circumference (WC)

and waist-hip ratio (WHR) was observed in our

study. Previously documented findings [8,15]

indicate that IL-6 is produced by adipose tissue

macrophages, which may have an important role

in the development of obesity and insulin

resistance.

IL-6

reduces

tyrosine

phosphorylation, impairing insulin sensitivity and

increases serine phosphorylation leading to

insulin resistance in target tissues, increasing

lipolysis and decreasing glucose uptake in the

adipose tissue [16].

Recent advances in diabetic research suggest that hyperglycemia-mediated endothelial dysfunction and micro and macrovascular complications can be attributed to reactive oxygen species (ROS). Positive correlation was observed between MPO with FPG only in the prediabetes group (Fig. 1). Earlier studies have demonstrated a similar correlation in diabetes [17] and higher levels of MPO with poor glycemic control [18]. There are two proposed mechanisms that may be involved in endothelial dysfunction by MPO. Firstly, H2O2 mediated

consumption of NO by MPO [19] and secondly production of HOCl- and its chlorinating species by reaction with high-glucose–stimulated H2O2 [20] resulting in reduced NO bioavailability. Elevated serum MPO concentration in the prediabetes group (Table 2) indicate the presence of chronic inflammation and endothelial dysfunct ion in them [19]. MPO levels also correlates with anthropometric measures like BMI, WC and WHR in prediabetes group (Table 3) Increased BMI is related to inflammation and oxide tive stress [21]. Similarly abdominal obesity as suggested by increased WC and WHR is also associated with systemic oxidative stress [22]. Thus it can be deduced that prediabetes group had raised levels of MPO as a marker of oxidative stress and signs of central obesity seen in this group predisposes them to dyslipidemia and cardiovascular diseases.
Proteinuria is a sign of more advanced renal disease and is a precursor to renal failure. Importantly, albuminuria is a strong and independent predictor of cardiovascular and all cause mortality [23]. In the present study Urinary Albumin concentration was significantly increased in prediabetes group (Table 2) suggesting that hyperglycemia of prediabetes also leads to renal damage [24]. A recent study of the Korean general population also showed that subjects with urine albumin in microalbuminuria range had a higher fasting plasma glucose than subjects without microalbuminuria [25]. Bahar et al. reported a significant correlation between FPG and urine albumin excretion (r - 0.32, p < 0.001) in prediabetes patients, where the prevalence of MA was 18% in IFG group. In the current study though 30% of prediabetes group were found to have MA. No correlation was observed between FPG and MA in this group (Fig. 1). In the AusDiab Study, [26] the prevalence of albuminuria increased significantly with increasing glycaemia, particularly postprandial glycaemia [27]. Current study had enrolled people with IFG only, hence there was no correlation observed between FPG and MA.
Urinary Albumin concentration has been linked to obesity in earlier studies [28,29]. The prediabetes group had higher BMI, WC, WHR and increased MA level. But MA did not correlate with anthropometric measures of this group because of low prevalence in prediabetes subjects.
Therefore, our data suggest that prediabetes may play a role in the development and

6

Agarwal et al.; IJBCRR, 29(2): 1-8, 2020; Article no.IJBCRR.55491

progression of cardiovascular disease. This is 3. Schindhelm RK, Zwan LP, Teerlink T,

important because, screening for diabetes in

Scheffer P. Myeloperoxidase: A useful

prediabetes stage may have an importance for

biomarker for cardiovascular disease risk

CVD in the future.

stratification? Clin Chem. 2009;55(8):

1462–70.

5. CONCLUSION

4. Chowta NK, Pant P, Chowta MK.

Microalbuminuria in diabetes mellitus:

In view of MPO and IL-6 being markers of

Association with age, sex, weight and

oxidative stress and CVD risk their elevation in

creatinine clearance. Indian J Nephrol.

IFG predisposes these people to increased CVD

2009;19(2):53–6.

and mandates preventive measures to be taken 5. Rothenbacher D, Kleiner A, Koenig W,

at the initial level of hyperglycemia.

Primatesta P, Breitling LP, Brenner H.

Relationship between inflammatory

CONSENT

cytokines and uric acid levels with adverse

All authors declare that written informed consent

was obtained from the patient for publication as

per international and university standards.

6.

cardiovascular outcomes in patients with stable coronary heart disease. PLoS One. 2012;7(9):1-8. Naidoo DP. The link between

microalbuminuria, endothelial dysfunction

ETHICAL APPROVAL

and cardiovascular disease in diabetes.

All authors hereby declare that all experiments 7. have been examined and approved by the
appropriate ethics committee and have therefore
been performed in accordance with the ethical 8. standards laid down in the 1964 Declaration of
Helsinki.

Cardiovas J. SA. 2002;13:194-9. Ferrannini E. Definition of intervention points in prediabetes. Lancet Diabetes Endocrinol. 2014;2(8):667-75. Hartge MM, Unger T, Kintscher U. The endothelium and vascular inflammation in diabetes. Diab Vasc Dis Res. 2007;4(2):

ACKNOWLEDGEMENT

84–8. 9. Fisman EZ, Tenenbaum A. The ubiquitous

interleukin-6: A time for reappraisal. We acknowledge gratefully the financial support
Cardiovasc Diabetol. 2010;9:62-8. received by Research Society for the Study of
10. Marcovecchio ML, Dalton RN, Prevost AT, Diabetes in India (RSSDI) and Manipal University
Acerini CL, Barrett TG, Cooper JD, et al. (MU) in the form of research grant. The authors
Prevalence of abnormal lipid profiles and approve that the funders had no impact over the
the relationship with the development of content, study design or selection of the article
microalbuminuria in adolescents with type for this journal.
1 diabetes. Diabetes Care. 2009;32:658–

COMPETING INTERESTS

63. 11. Nevado, J, Peiró C, Vallejo S, El-Assar M,

Authors have declared that no competing interests exist.

Lafuente N, Matesanz N, et al. Amadori adducts activate nuclear factor-kappaBrelated proinflammatory genes in cultured

REFERENCES

human peritoneal mesothelial cells. Br J Pharmacol 2005;146:268–79.

1. De Fronzo RA, Abdul-Ghani M. 12. Hossain M, Faruque MO, Kabir G, Hassan

Assessment and treatment of

N, Sikdar D, Nahar Q, et al. Association of

cardiovascular risk in prediabetes:

serum TNF-α and IL-6 with insulin

Impaired glucose tolerance and impaired

secretion and insulin resistance in IFG and

fasting glucose. Am J Cardiol. 2011;

IGT subjects in a Bangladeshi population.

108(3):3-24.

Int J Diabetes Mellit. 2010;2:165-8.

2. Wegner M, Araszkiewicz A, Stolzmann 13. Illán-Gómez F, Gonzálvez-Ortega M,

MP, Wysocka BW, Ziolkiewicz DZ.

Orea-Soler I, Alcaraz-Tafalla MS, Aragón-

Association between IL-6 concentration

Alonso A, Pascual-Díaz M, et al. Obesity

and diabetes-related variables in DM1

and inflammation: Change in adiponectin,

patients with and without microvascular

C-reactive protein, tumour necrosis factor-

complications. Inflammation. 2013;36(3):

alpha and interleukin-6 after bariatric

723-8.

surgery. Obes Surg. 2012;22:950–5.

7

Agarwal et al.; IJBCRR, 29(2): 1-8, 2020; Article no.IJBCRR.55491

14. Sommer G, Kralisch S, Stangl V, Vietzke

myeloperoxidase and blood pressure.

A, Köhler U, Stepan H, et al. Secretory

Hypertension. 2010;55(6):1366-72.

products from human adipocytes stimulate 22. Fujita K, Nishizawa H, Funahashi T,

proinflammatory cytokine secretion from

Shimomura I, Shimabukuro M. Systemic

human endothelial cells. J Cell Biochem.

oxidative stress is associated with visceral

2009;106:729–37.

fat accumulation and the metabolic

15. Wilkinson CP, Ferris FL 3rd, Klein RE, Lee

syndrome. Circ J. 2006;70(11):1437-42.

PP, Agardh CD, Davis M, et al. Global 23. Zacharias JM, Young TK, Riediger ND,

Diabetic Retinopathy Project Group.

Roulette J, Bruce SG. Prevalence, risk

Proposed international clinical diabetic

factors and awareness of albuminuria on a

retinopathy and diabetic macular edema

Canadian First Nation: A community-based

disease severity scales. Ophthalmology

screening study. BMC Public Health.

2003;110:1677–82.

2012;12:290-8.

16. Jialal I, Kaur H. The role of toll-like 24. Garg JP, Bakris GL. Microalbuminuria:

receptors in diabetes-induced inflamma-

Marker of vascular dysfunction, risk factor

tion: Implications for vascular complica-

for cardiovascular disease. Vascular

tions. Curr Diab Rep. 2012;12(2):172-9.

Medicine. 2002;7:35-43.

17. Bandeira SM, Guedes GS, da Fonseca LJ, 25. Palaniappan L, Carnethon M, Fortmann

Pires AS, Gelain DP, Moreira JC, et al.

SP. Association between microalbuminuria

Characterization of blood oxidative stress

and the metabolic syndrome: Nhanes III.

in type 2 diabetes mellitus patients:

AJH. 2003;16:952–8.

increase in lipid peroxidation and SOD 26. Tapp RJ, Shaw JE, Zimmet PZ Balkau B,

activity. Oxid Med Cell Longev. 2012;

Chadban SJ, Tonkin AM, et al. Albuminuria

2012:13.

is evident in the early stages of diabetes

onset: Results from the Australian 18. Shetty S, Kumari SN, Madhu LN.
Diabetes, Obesity, and Lifestyle Study Variations in serum myeloperoxidase
(AusDiab). Am J Kidney Dis. 2004;44:792– levels with respect to hyperglycemia,
8. duration of diabetes, BMI, sex and aging in
27. Ritz E, Viberti GC, Ruilope LM, Rabelink type 2 Diabetes mellitus. IJRPBS. 2012;
AJ, Izzo Jr JL, Katayama S, et al. 3(2):652-5.
Determinants of urinary albumin excretion

19. Eiserich JP, Baldus S, Brennan ML, Ma W,

within the normal range in patients with

Zhang C, Tousson A, et al.

type 2 diabetes: The randomised

Myeloperoxidase, a leukocyte-derived

Olmesartan and Diabetes Microal-

vascular no oxidase. Science. 2002;296:

buminuria Prevention (ROADMAP) study.

2391–4.

Diabetologia 2010;53:49–57.

20. Nuszkowski A, Grabner R, Marsche G, 28. Cirillo M, Senigalliesi L, Laurenzi M, Alfieri

Unbehaun A, Malle E, Heller R.

R, Stamler J, Stamler R, et al.

Hypochlorite modified low density

Microalbuminuria in nondiabetic adults

lipoprotein inhibits nitric oxide synthesis in

relation of blood pressure, body mass

endothelial cells via an intracellular

index, plasma cholesterol levels and

dislocalization of endothelial nitric-oxide

smoking: The Gubbio population study.

synthase. J Biol Chem. 2001;276:14212–

Arch Intern Med. 1998;158(17):1933-9.

21.

29. Chang Y, Yoo T, Ryu S, Huh BY, Cho BL,

21. Van der Zwan LP, Scheffer PG, Dekker

Sung E, et al. Abdominal obesity, systolic

JM, Stehouwer CD, Heine RJ, Teerlink T.

blood pressure and microalbuminuria in

Hyperglycemia and oxidative stress

normotensive and euglycemic Korean

strengthen the association between

men. Int J Obes. 2006;30:800–4.

_________________________________________________________________________________

© 2020 Agarwal et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License

(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,

provided the original work is properly cited.

Peer-review history: The peer review history for this paper can be accessed here:
http://www.sdiarticle4.com/review-history/55491

8

Preparing to load PDF file. please wait...

0 of 0
100%
Assessment of Cardiovascular Disease Risk in Prediabetes