Von Willebrand Factor Levels and Control Glycemic Type 2 Diabetes

Mellitus Patients

Rusdiana

1 *

,Maya Savira

, Sry Suryani Widjaja

,Muhammad Syahputra

Departement of Biochemistry, Medical Faculty, Universitas Sumatera Utara, Jl. dr. Mansur no.5,

Medan, Indonesia.

Departement of Physiology, Medical Faculty, Universitas Sumatera Utara, Jl. dr. Mansur

no.5,Medan, Indonesia.

Keywords: Diabetes mellitus type 2, Fasting Blood Sugar, Von Willebrand Factor

Abstract: Diabetes Mellituswas disorder metabolic syndrome, characterized by hyperglycemia, which was caused by

insulin secretion defect.The chronic hyperglicemia dan insulin resistence caused increasing blood vessel

permeability and endothelial cell damage. Von willebrand factor (vWF) was synthesized by endothelial

cell.The aim of the study was knowingassociation between von Willebrand factor (VWF) levels and control

glycemic base on Fasting Blood Sugar and Haemoglicosylate (Hba1c) at Type 2 diabetes mellituspatients.

The sutudy was cross-sectional design , was conducted on 40 type 2 Diabetes Mellitus patients who

attended Primary Health Care Clinic in Binjai city, Sumatera Utara, Indonesia.The inclusion criteteria of the

samples was patients with age > 40 years old, (both sexes). Body Mass Index, Blood Pressure,disease

history and socioeconomic status were recorded. The laboratory parameters including Hba1c, Fasting Blood

Sugar Levels. Examining Fasting Blood Sugar Levels by using portable measuring instrument, and Hba1c

was examined by Thamrin clinical laboratory. We found there was correlation significant between FBS with

Hba1c and correlation significant FBS and VWF.

1 INTRODUCTION

Diabetes Melitus (DM) was caused by the body’s

inability to produce the insulin as needed or because

of ineffective use of insulinor the both. This is

characterized by increasing blod sugar level or

hyperglycemia and the development of chronic

vascular complications (Perkeni,2011,IDF 5

).There

was an increasing the prevalence the diabetes

mellitus with type 2 the worldwide and it was

association with obesity. The number of diabetics in

Indonesia is 7 th in the world. The prevalence of

diabetes in Indonesia has been diagnosed 1,4%, this

will continue increasing (Rikesdas,2013).The

evidence of diabetes mellitus with a potent

cardiovascular risk factor have annual mean

mortality rate of 5.4% (Rikesdas,2013). Men with

diabetes have two-fold to three-fold increase in

Coronary Artery Disease (CAD) compared with

non-diabetics (Donnelly R,et al, 2000). It affects

between 1% and 10% of most population, although

in some areas of the world up to 50% of the

population has diabetes (Vaccaro O et al,1998).

WHO estimated 21.527.000 Indonesia population

will suffer from diabetes mellitus in 2030

(WHO).As we know for many years that the

complication of diabetes mellitus associated with

cardiovascular, cerebrovascular and peripheral

vascular disease. Because of chronic hyperglycemic

and insulin resitance caused increasing permeability

of blood vessel and disorder endothelial cell. Type 2

diabetes patients have early development of

abnormal endothelial function, it caused

vasocontriction, inflammation cell

accumulated,migration of smooth muscle cell and

increased cytokine production,which results in

plaque development. And then it was caused platelet

hyperactivity, aggressive atherosclerosis,a

propensity for adverse arterial remodeling, enhanced

cellular and matrix proliferation after arterial injury

and impaired fibrinolysis with tendency for

thrombosis and inflammation. The earliest

manifestation of endothelial dysfunction was

profound arteriopathy the result of the diabetic state

(K.G.M.M. Alberti, 2013).

Rusdiana, ., Savira, M., Widjaja, S. and Syahputra, M.

Von Willebrand Factor Levelsand Control glycemic Type 2 Diabetes Mellitus Patients.

DOI: 10.5220/0010067504030406

In Proceedings of the International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches (ICOSTEERR 2018) - Research in Industry 4.0, pages

403-406

ISBN: 978-989-758-449-7

403

Type 2 diabetes mellitus patients have a

higher incidence of thrombotic complications

(Beckman JA, 2002). Many factors that have been

proposed explaining the observed prothrombotic

state. In connection with prothrombotic state,

endothelial activation has been shown to occur in

patients suffering from type 2 diabetes (Frankel DS,

2008). Von Willebrand factor (vWF) is a large

glycoprotein produced by vascular endothelial cells

that mediates platelet adhesion to injured

endothelium, the first step in thrombus formation.

yWF also serves as the carrier protein for

coagulation factor VIII (Natali A, 2006).Given

essential role in thrombosis and is frequently used as

marker for endothelial activation and damage

(Sadler JE, 1991,Ruggeri ZM, 1999)

Recently many researches that was found that

Von Willebrand Factor has been associated with

insulin resistance and type 2 diabetes mellitus

(Blann AD, 2006, Meigs JB et al, 2006).The

previous study in type 2 diabetes mellitus patients it

was found the increased circulating levels of plasma

vWF, it have been attributed to enhanced endothelial

cell release from a potentially greater intracellular

storage pool and to increased endothelial synthesis

(Ostergard T et al, 2006, Porta M, 1982). The aim

of this study was to knowing association von

Willebrand factor levels and glycemic control at

type 2 diabetes mellitus

2 MATERIAL AND METHODS

In the study,a total of 72 patients with type 2

diabetes mellitus were recruited from Primary

Health Care in Binjai city, North Sumatera,

Indonesia. The number of the samples was

calculated using the formula n=N/1 +N (d

). This

was conducted from April to July 2018. In

accordance with the inclusion criteria which

are,aged > 40 years old and cooperative and have a

will to join this research and exclusion criteria which

are, using diuretic and the middle of cancer therapy.

This research was approved by Health Research

Ethical Committee, Medical Faculty of University

Sumatera Utara/H.Adam Malik General Hospital by

number 591/TGL/KEPK FK USU-RSUP HAM

/2018. Patients were informed with the detail of the

study and written consent was obtained from the

patients before they participated in the study.We

measured height and weight with the subjects

standing in light clothes . Body mass index was

calculated as the weight in kilograms divided by

square of the height in meters (kg/m

).We examine

the blood pressure values as mean of two

measurements after the subjects had been seated for

at least five minutes. The patients fasted overnight to

provide a blood specimen. Blood samples were

collected (using syringe) and transferred to Thamrin

clinical laboratory immediately to be conducted

glycosylated haemoglobin test by Alere Afinion as

100 Analyzer . We examined glycosylated

haemoglobin test for patients because of this

examination as gold standard for diabetes mellitus

patients. Fasting blood sugar of samples we

examined by using portable measuring instrument

(Gluco DR).We measured the Von Willebrand

Factor levels with an ELISA assay in laboratory in

Medical Faculty, Universitas Sumatera Utara.

The Examination Von Willebrand Factor levels

in the serum which allow samples to clot for 2 hours

at room temperature or overnight at 4

C before

centrifugation for 15 min at 1000x g g at 2-8

C. We

collect the supernatant to carry out the assay. We

used the blood collection tubes should be disposable

and be non-endotoxin. Average the duplicate

readings for each standard and samples, then

subtract the average zero standard optical density.

Plot a four parameter logistic curve on log-log graph

paper, with standard concentration on the x-axis and

Optical Density (OD) values on the y-axis. If the

samples have been diluted, the concentration

calculated from the standard curve must be

multiplied by dilution factor. If the OD of the

samples surpasses the upper limit of the standard

curve, we must do re-test it with an appropriate

dilution. The actual concentration is calculated

concentration multiplied by dilution factor. The

Optical Density (OD) was determined using a

microplate reader set to 450nm.

3 STASTICAL ANALYSIS

All data were presented by using SPSS software,

version 24.The continuous data was expressed as

mean ±standard deviation (SD). The correlation

were done by Pearson correlation analysis, using

correlation test, p-value < 0.05 was considered to be

statistically significant.

4 RESULT

Among 72 known type 2 Diabetes Mellitus patients

30 people were male (41.7%) and 42 people were

female (58.3%). The characteristic of the subjects of

ICOSTEERR 2018 - International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches

404

this study are shown in the table 1. Subjects in this

study were not bellow 40 years old. Maximum age

of the samples were 79 years old and minimum age

were 40 years old. Maximum of Body Mass Index of

the samples were 32.86 kg/m

and minimum were

16.02 kg/m

. Maximum of waist size of the samples

were 107 cm and minimum were 73 cm. Maximum

of the Fasting Blood Sugar (FBS) of the patients

were 600 mg/dL and Minimum were 85 mg/dL.

Maximum of the Hba1c of patients were 14% and

minimum were 6% and Maximum of the Von

Willebrand Factor Level of the patients were 35.10

ng/mL and minimum were 2.16 ng/mL. The range of

fasting plasma levels of vWF at baseline was from

0.64 to 5.35 U/ml.

The Pearson’s correlation coefficient for the

correlation between von Willebrand Factor levels

and and Hba1c showed a negative correlation but a

positive correlation between von Willebrand Factor

levels and fasting blood sugar levels and showed a

positive correlation between Fasting Blood Sugar

Levels and Hba1c (p<0.005.)

Table 1: Baseline characteristic of 72 patients type 2

diabetes mellitus

Minimum Maximum Mean SD

Age

(y.o)

BMI

(kg/m

)

Waist

size (cm)

FBS

(mg/dL)

Hba1C

(%)

VWF

(mg/dL)

16.02

2.16

32.86

107

600

35.10

58.31

24.33

91.32

243.0

9.501

11.14

8.82

3.34

8.18

102.

1.90

6.84

Table 2 : Pearson Correlation vWF and glycemic control

(Hba1c,FBS)

Hba1c

vWF FBS

Hba1c Pearson Correlation 1 0.002

389**

Sig.(2-tailed) 0.985

0.001

N 72 72

vWF Pearson Correlation 0.002 1

0.250*

Sig.(2-tailed) 985**

034

N 72 72

FBS Pearson Correlation 389**

250* 1

Sig.(2-tailed) 001 034

N 72 72

**.Correlation is significant at the 0.01 level (2-tailed).

*. Correlation is significant at the 0.05 level (2-tailed).

5 DISCUSSION

The aim of study was to knowing association

between von Willebrand factor levels and glycemic

control at type 2 diabetes mellitus. As we know that

von Willebrand factor was one of the marker for

endothelial dysfunction (Porta M, 2006).The

primary physiologic function of von Willebrand

factor is to maintain haemostatic balance in the

vasculature, but because the endothelium is a

primary source of von Willebrand factor elevated

levels reflect stimulation or injury to endothelial

cells (Goldberg RB et al, 2012).This research

showed that there was significant correlation

between vWF level with fasting blood sugar as

glycemic control, as we know that vWF were

significantly higher in patients with type 2 diabetes

mellitus. Another study by Umadevi B et al showed

that a significant increase in plasma levels of von

Willebrand factor (vWF) in patients with type 2 DM

compared to normal, which suggests that there is

significant endothelial injury in type 2 diabetes

mellitus patients (Tian J et al, 2012).And the present

study shows that type 2 diabetes mellitus patients

have significant endothelial injury as assessed by

increased levels of plasma von Willebrand Factor

(vWF) and these are probably at risk of developing

cardiovascular complications in the future.

6 CONCLUSION

There was significant correlation between vWF level

with fasting blood sugar at type 2 diabetes mellitus

patients.

ACKNOWLEDGMENTS

The authors gratefully acknowledge that the present

research is supported by Ministry of Research and

Technology and Higher Education Republic

Indonesia. The support is under the research grant

TALENTA USU of Year 2018.

Von Willebrand Factor Levelsand Control glycemic Type 2 Diabetes Mellitus Patients

405

REFFERENCES

Beckman JA, Creager MA, Libby P, Diabetes and

atherosclerosis epidemiology, pathophysiology, and

management. JAMA 2002;287 (19):2570- 81.

Blann AD,Plasma von Willebrand factor, thrombosis, and

the endothelium: the first 30 years. Thromb

Haemost,2006;95:49-55.

Donnelly R, Emslie-Smith AM, Gardner ID, et al.

Vascular complication of diabetes. BMJ

2000;320:1062-6.

Frankel DS, Meigs JB, Massaro JM, Wilson PW,

O’Donnell CJ, D’Agostino RB, Tofler GH, Von

Willebrand Factor, type 2 diabetes mellitus, and risk

of cardiovascular disease: the Framingham offspring

study. Circuation.2008;118:2533-2539.doi:

10.1161/CIRCULATIONAHA.108.792986.[PMC

free article] [Pubmed] [Cross Ref].

Goldberg RB. Cytokine and cytokine-like inflammation

markers, endothelial dysfunction and imbalanced

coagulation in development of diabetes and its

complications. J.Cin Endocrinol Metab

2009;(9):3171-82.

International diabetes Federation (IDF) atlas 5th edition.

Available from:

http://www.idf.org/diabetesatlas/5e/the-global-

burden

K.G.M.M. Alberti and P.Zimmet, “Epidemiology: global

burden of disease-where does diabetes mellitus fit

in?” Nature Reviews Endocrinology, vol.9,

no.5,pp.258-260,2013.View at Publisher . View at

Google Scholar . View at Scopus

Meigs JB, O’Donnell CJ, Tofler GH, Benjamin EJ, Fox

CS, Lipinska I, Nathan DM , Sullivan LM,

D’AGostino RB, Wilson PW. Haemostatic markers

of endothelial dysfunction and risk of incident type 2

diabetes , the Framingham Offspring

Study.Metabolism , 2006;55:1133-1140.

Natali A, Toschi E, Baldeweg S,et al. Clustering of insulin

resistance with vascular dysfunction and low-grade

inflammation in type 2 diabetes . Diabetes,

2006;55:1133-1140.

Ostergard T, Nyhol B, Hansen TK,Rasmussen LM,

Ingerslev J,Sorensen KE, Botker HE, Saltin B,

Schmitz O. Endothelial function and biochemical

vascular markers in first- degree relatives of type

diabetic patients: the effect of exercise training .

Metabolism, 2006;55:530-537.

PERKENI 2011. Konsensus pengelolaan dan pencegahan

diabetes melitus tipe 2.di indonesia, PB. PERKENI

Porta M. Availability of endothelial von Willebrand factor

and platelet function in diabetic patients infused with

a vasopressin analogue. Diabetologia.1982;23:452-

455.

Prevention of diabetes mellitus.Report of WHO study

group. World Health Organ Tech Rep Ser

1994;844:1-100.

Riskesdas 2013. Riset kesehatan dasar Riskesdas 2013.

Ruggeri ZM. Structure and function of von Willebrand

factor. Thromb Haemost 1999;82:576-84.

[PubMed:10605754].

Sadler JE, Von Willebrand factor. J Biol Chem.

1991;266:22777-22780

Tian J, Wangf J, Li Y, et al. Endothelial function in

patients with newly diagnosed type 2 diabetes

receiving eary intensive insulin therapy . American

Journal of Hipertension 2012;25 (12):1242-8.

Umadevi B, Roopakala M.S, Wilma Delphine Silvia C.R,

Prasanna Kumar K.M. Role of Von Willebrand Factor In

Type 2 Diabetes Mellitus Patients. J.Evolution

Med.Dent.Sci 2016;5: 81.DOI:10.14260/jemds/20161372

Vaccaro O, Stamler J, Neaton JD. Sixteen- year coronary

mortality in black and white men with diabetes screened

for the multiple risk factor intervention trial (MRFIT).

Int.J.Epidemiol 1998;27 (4):636-41.

ICOSTEERR 2018 - International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches

406