DOI: 10.
18585/inabj.
Correlation between HOMA-IR with ADMA in Prehypertension (Novianti ME) Indones Biomed J.
: 169-72
RESEARCH ARTICLE
Correlation between Homeostatic Model Assessment-estimated Insulin Resistance (HOMA-IR) with Asymmetric Dimethylarginine (ADMA) in Prehypertension Maria Evi Novianti1,2.
Syakib Bakri2.
Mansyur Arief2.
Ferry Sandra1,3,E Prodia Clinical Laboratory.
Jl.
Kramat Raya No.
Jakarta.
Indonesia Postgraduate Program in Clinical Biochemistry.
Hasanuddin University.
Jl.
Perintis Kemerdekaan Km.
Makassar.
Indonesia Department of Biochemistry and Molecular Biology.
Faculty of Dentistry.
Trisakti University.
Jl.
Kyai Tapa No.
Jakarta.
Indonesia Corresponding author.
E-mail: ferrysandra@gmail.
Abstract ACKGROUND: Not only hypertension, prehypertension has been reported to be linked with increased cardiovascular morbidity and mortality risks as well.
Prehypertension has three-fold hypertension and two-fold cardiovascular risks.
Pathomechanism that links hypertension with cardiovascular is related with endothelial dysfunction and insulin resistance.
Endothelial dysfunction occurs when nitric oxide (NO) biological function was impaired, whereas shown by asymmetric dimethylarginine (ADMA).
Subjects with prehypertension had higher insulin resistance events than normotension, whereas shown by homeostatic model assessment-estimated insulin resistance (HOMA-IR).
This research was conducted to investigate the correlation of HOMA-IR with ADMA in prehyper- and normo-tension.
METHODS: A cross-sectional comparative research was designed.
Subjects were recruited and divided into prehyper- and normo-tensive groups.
ADMA was measured using ELISA method, while HOMA-IR was calculated by the ratio of fasting insulin and glucose.
Spearman 1-tail and Mann Whitney statistical analyses were performed.
RESULTS: Comparing to normotensive group, elevated levels of HOMA-IR and ADMA in prehypertensive group were shown, but not significant.
In prehypertensive group, we found significant correlation between HOMA-IR and ADMA.
CONCLUSION: Insulin resistance and endothelial dysfunction was elevated in prehyper-compared to normotension.
Abstrak
ATAR
BELAKANG:
Selain prehipertensi juga telah dilaporkan berkaitan dengan peningkatan resiko morbiditas dan mortalitas yang berkaitan dengan kardiovaskuler.
Prehipertensi memiliki resiko tiga kali lipat mengalami hipertensi dan dua kali lipat mengalami kardiovaskular.
Patomekanisme yang menghubungkan hipertensi dengan kardiovaskular berhubungan dengan disfungsi endotel dan resistensi insulin.
Disfungsi endotel terjadi apabila fungsi biologis NO terganggu, dan parameter yang menggambarkan kondisi tersebut adalah asymmetric dimethylarginine (ADMA).
Subyek dengan prehipertensi lebih resistensi insulin dibandingkan normotensi, dan parameter yang menggambarkan kondisi tersebut adalah homeostatic model assessment-estimated insulin resistance (HOMA-IR).
Penelitian ini dilakukan untuk mengetahui korelasi ADMA dengan HOMA-IR pada prehiper- dan normo-tensi.
METODE: Dilakukan penelitian komparasi dengan rancangan potong lintang.
Subyek direkrut dan dibagi menjadi grup hiper- dan normo-tensif.
ADMA diukur dengan menggunakan metode ELISA, dan HOMA-IR dihitung dengan menggunakan rasio insulin dan gula puasa.
Kemudian analisa statistik Spearman 1-tail and Mann Whitney dilakukan.
HASIL: Hasil penelitian menunjukkan terdapat peningkatan kadar HOMA-IR dan ADMA pada kelompok prehipertensi dibandingkan normotensi, namun tidak bermakna.
Pada kelompok prehipertensi terdapat hubungan yang bermakna antara HOMA-IR dengan ADMA.
The Indonesian Biomedical Journal.
Vol.
No.
December 2013, p.
KEYWORDS: prehypertension, insulin endothelial dysfunction.
HOMA-IR.
ADMA Indones Biomed J.
: 169-72
Introduction Hypertension is an important public health issue, not only because of high prevalence, but also the cause of morbidity and mortality.
In the world, the prevalence reached 1 billion, and hypertension-related death reached 7.
1 million per year .
, due to increasing cardiovascular risk.
Hypertension and cardiovascular disease pathomechanism is related with interrelated and interacted endothelial dysfunction and insulin resistance, generating the complex mechanisms.
Endothelial dysfunction occurs when nitric oxide (NO) biological function was impaired, whereas asymmetric dimethylarginine (ADMA) is one of the parameters to assess the incidence of endothelial dysfunction.
ADMA,
an L-arginine analogue, is a natural product of metabolism.
ADMA will inhibit synthesis of NO, leading to endothelial .
Hypertension has been reported to have relation with increase in insulin resistance, in which vascular inflammation is the core of their relationships.
Pathomechanism linking hypertension with insulin resistance is not fully understood.
Insulin was suggested to stimulate sympathetic nervous system, increase kidney sodium retention, modulate cation and induce vascular smooth muscle hypertrophy.
Insulin has several functions, the most important one is the regulation of glucose, and others such as vasodilatation, anti-apoptosis, anti-inflammation and anti-oxidation as defense mechanism for cardiovascular.
Insulin resistance is a condition in which cells become resistant to the effects of insulin, resulting normal response to insulin is Therefore higher levels of insulin are needed for optimal insulin function.
According to the Joint National Committee, prehypertension was designated whereas systolic blood pressure (SBP) 120-139 mm Hg or diastolic blood pressure (DBP) 80-89 mmHg.
Subject with prehypertension had incidence increase of cardiovascular disease.
Moreover, compared with normo-, the prehyper-tensive group had three-fold risk of hypertension and two-fold risk of .
Role of endothelial dysfunction and insulin resistance in elevating blood pressure was proven experimentally ISSN: 2085-3297 KESIMPULAN: Terjadi peningkatan resistensi insulin dan disfungsi endotel pada prehiper- dibandingkan normo-tensi.
KATA KUNCI: prehipertensi, resistensi insulin, disfungsi endotel.
HOMA-IR.
ADMA and clinically, however the mechanisms and dynamics of endothelial dysfunction and insulin resistance have not been elucidated.
It was reported that prehypertension was correlated with insulin resistance in Japanese.
Indian and American, but not in African American.
In our current interest, we conducted a study to investigate the correlation of homeostatic model assessmentestimated insulin resistance (HOMA-IR) with ADMA in prehyper- and normo-tension.
As insulin resistance marker, both HOMA-IR and euglycaemic clamp method were correlated with insulin resistance.
Meanwhile ADMA was used as endothelial dysfunction marker, since ADMA inhibit NO synthesis and endothelial function, leading to incidence of atherosclerosis.
ADMA levels were increased in subjects with hypertension, hypercholesterolemia, chronic heart failure, diabetes mellitus and chronic kidney Methods A cross-sectional study was designed.
Subjects were recruited and selected based on blood pressure measurement (SBP & DBP) according to the Joint National Committee .
Briefly, subjects with liver or kidney diseases, acute infections, anti-inflammatory or anti-oxidant drugs intake for 3 months, pregnant, were all excluded.
Subjects were measured/tested for waist circumference (WC).
SBP and DBP, which later divided into 2 groups: prehyper- and normo-tensive groups.
All subjects were further tested for fasting plasma glucose (FPG), triglyceride, high density lipoprotein (HDL), low density lipoprotein (LDL), insulin, and ADMA.
Blood Collection and Biochemical Analyses Blood were collected intravenously from all subjects.
Serum was generated, stored and tested for all parameters.
FPG,
HDL and LDL were tested based on method routinely applied in clinical laboratory.
For insulin test, we used 1 ReadyPack (Cat.
No.
: 02230141.
Siemens Healthcare Diagnostics Inc.
Tarrytown.
NY).
Briefly, 1 ReadyPack, named as The ADVIA Centaur Insulin assay, is a two-site sandwich immunoassay using direct chemiluminescent technology, which uses constant amounts of two antibodies.
DOI: 10.
18585/inabj.
Correlation between HOMA-IR with ADMA in Prehypertension (Novianti ME) Indones Biomed J.
: 169-72
The first antibody is a monoclonal mouse anti-insulin antibody labeled with acridinium ester.
The second antibody is a monoclonal mouse anti-insulin antibody, which is covalently coupled to paramagnetic particles.
Later on.
HOMA-IR was calculated using formula: fasting insulin x fasting glucose / 22.
To analyze ADMA.
We used Enzyme Immunoassay for the Quantitative Determination of Endogenous Asymmetric Dimethylarginine (ADMA) in Serum or Plasma (Cat.
No.
: 17-EA201/96.
DLD
Gesellschaft fyr Diagnostika und medizinische GmbH.
Hamburg.
Germa.
The substrate reaction was monitored at 450 nm.
We found that DBP.
SBP.
FPG, triglyceride of prehyper- and normo-tension and were significantly different.
HOMA-IR
and ADMA of prehypertension were higher the ones of normotension, but not significant.
Based on Spearman 1-tail correlation analysis, we found HOMA-IR was negatively correlated with ADMA .
=-0.
p=0.
in normotensive group.
Meanwhile HOMA-IR was significantly correlated with ADMA .
=0.
330, p=0.
in prehypertensive group.
Discussion In our current results.
HOMA-IR and ADMA of prehypertensive group were higher than the ones of normotensive group.
This might be related to the fact that hypertension is interrelated and interacted with endothelial dysfunction and insulin resistance.
ADMA is an endogenous inhibitor of endothelial NO synthesis .
NOS), was used as endothelial dysfunction parameter for this ADMA is synthesized from arginine residues and metabolized by dimethylarginine-dimethylaminohydrolase (DDAH) to citrulline.
Increased concentration of ADMA Results was reported to have an association with endothelial .
Meanwhile.
HOMA-IR values was used Sixty-two subjects consisting of 43 prehyper- and 19 normoas insulin resistance parameter for this study.
Insulin has tensive subjects, were selected according to inclusion and vasodilatory function through Phosphatidylinositol 3 exclusion criteria.
The study was approved by the Ethics Kinase (PI3K) pathway whereby insulin increases eNOS, committee of the University of Hasanuddin (UH09060.
which will then produce NO.
In insulin resistance condition.
All subject characteristics including WC, age.
DBP.
SBP, the insulin does not function optimally, causing lower NO FPG, triglyceride.
HDL and LDL, were obtained (Table .
Meanwhile ADMA acts as an inhibitor of HOMA-IR and ADMA results were also obtained (Table .
eNOS activity, which can also lower down production of NO.
These two mechanisms in turn will cause Table 1.
Subject characteristics.
HOMA-IR and ADMA analyses in increased vasoconstriction.
prehyper- and normo-tensive and groups.
It was reported previously that endothelial Normotension .
Prehypertension .
and insulin resistance were Test p value Average A SD Average A SD correlated in elevating blood pressure.
Many cross-sectional studies have examined WC .
4 A 9.
3 A 9.
the relationship between insulin resistance/ Age .
4 A 7.
9 A 9.
sensitivity and endothelial function.
In DBP .
3 A 6.
6 A 4.
these studies, endothelial function was evaluated SBP .
8 A 7.
9 A 5.
by high resolution brachial artery ultrasound.
FPG .
g/dL) 8 A 8.
2 A 8.
venous occlusion plethysmography, and laser doppler imaging techniques.
Insulin sensitivity Triglyceride .
g/dL) 7 A 39.
4 A 91.
was assessed by euglycemic hyperinsulinemic HDL .
g/dL) 0 A 7.
8 A 9.
clamps and HOMA-IR.
These studies LDL .
g/dL) 7 A 28.
9 A 25.
suggest that insulin resistance may only partly Insulin .
lU/mL) 2 A 4.
4 A 6.
explain the impaired endothelial function.
It is also possible that other manifestations of insulin
HOMA-IR
547 A 1.
930 A 1.
resistance such as hyperglycemia, dyslipidemia.
ADMA .
ol/mL) 656 A 0.
678 A 0.
inflammation, and obesity may be intermediary Statistical Analysis Statistical analyses were performed using SPSS for Windows version 15.
0 (USA.
SPSS Inc.
To measure the difference significance of each parameter between prehyperand normo-tensive groups, we used Mann Whitney analysis.
Meanwhile, to measure the correlation significance of HOMA-IR with ADMA in each group, we used Spearman 1-tail analysis.
* Mann Whitney test.
Significant p value <0.
SD: Standard Deviation The Indonesian Biomedical Journal.
Vol.
No.
December 2013, p.
mediators that act in concert with insulin resistance to mediate endothelial dysfunction.
Therefore, although we found HOMA-IR and ADMA of prehypertensive group were higher than the ones of normotensive group, we suggest that further study should be pursued in order to correlate other factors that might playing role in endothelial dysfunction and insulin resistance in prehyper- and normotensive subjects.
Conclusion In the prehypertension group had an increase in endothelial dysfunction which is a risk for cardiovascular disease events in which the mechanisms of endothelial dysfunction in the prehypertension group affected by insulin resistance.
Acknowledgement This study was supported by the Prodia Education and Research Institute.
References