Korelasi Kadar Angiopoietin-2 Plasma dan Petanda Inflamasi Dengan Resistensi Insulin Pada Penderita Obesitas Abdominal

  • Anak Agung Gede Budhitresna Faculty of Medicine and Health Sciences, Warmadewa University, Denpasar

Abstract

Obesitas abdominal (Ob-Ab) merupakan komponen utama resistensi insulin (RI) yaitu kekutan pendorong utama untuk terjadinya diabetes mellitus (DM)  tipe-2. Kadar angiopoietin-2  (Ang-2) plasma dilaporkan mengalami peningkatan pada  penderita Ob-Ab dan diduga bahwa Ang-2 berpengaruh untuk terjadinya RI. Tujuan penelitian ini adalah untuk mengetahui korelasi kadar Ang-2, Inflamasi dan RI pada penderita Ob-Ab. Dilakukan penelitian secara cross-sectional analitik pada 81 penderita dengan Ob-Ab. Kadar  TNF-α, sTNFR1 dan Ang-2 plasma diukur menggunakan metode ELISA. RI diukur menggunakan HOMA-IR. Analisis varian (ANOVA) dipergunakan untuk mengetahui persamaan variabel kontinyu. Analisis multivariat dipergunakan untuk mengetahui peran kadar TNF-α, s-TNFR-1, Ang-2 terhadap RI. Model analisis jalur (path analysis) dipergunakan untuk mengetahui pengaruh faktor risiko terjadinya RI. Hasil penelitian menunjukkan bahwa kadar TNF-α plasma tidak berkorelasi dengan HOMA-IR, sedangkan sTNFR-1 dan  Ang-2 plasma berkorelasi positif bermakna dengan HOMA-IR (masing-masing r=0,323; p=0,003 dan r=0,641; p=<0,001). Pada analisis multivariat ditemukan Ang-2 merupakan faktor bebas berhubungan dengan HOMA-IR (p=<0,001). Kadar Ang-2 plasma yang tinggi merupakan faktor dominan (64,1%, p=<0,001). Simpulan: pada penderita Ob-Ab kadar Ang-2 berkorelasi dengan terjadinya RI dan inflamasi.

Kata kunci: Ang-2, resistensi insulin, inflamasi, obesitas abdominal.

 

[Correlation of Plasma Angiopoietin-2 and Inflammation Marker with Insulin Resistence in Patients with Central Obesity]

Abdominal obesity (Ab-Ob) is a central component of insulin resistance (IR) and it is suggested that IR is a driving factor in the development of type 2 diabetes mellitus (T2DM).  Plasma Ang-2 levels have been reported to increase in the Ab-Ob and it has been hypothesized that Ang-2 plays important role in the occurrence of IR. We assessed the relationship between plasma Ang-2 levels, Inflammation and IR in Ab-Ob. A cross-sectional analytic study on 81 abdominally obese subjects was performed. The concentrations of TNF-α, sTNFR1 and Ang-2 plasma were measured using ELISA method. IR was measured using HOMA-IR. Analysis of variance (ANOVA) was used to test the equality of continuous variables. Multivariate analyses were performed to examine the influence of TNF-α, s-TNFR-1, and Ang-2 on IR. Path analysis models were performed to assess the influence of risk factors on occurrence of IR. Plasma of TNF-α was not correlated with HOMA-IR (r=160; p=0.154) whereasTNFR-1 and Ang-2 were significantly positive correlated with HOMA-IR (r=0.323, p=0.003 and r=0.641, p=<0.001, respectively).  The multivariate analysis showed Ang-2 was independently associated with HOMA-IR (p <0.001). It was found that high Ang-2 level was a dominant risk factor (64.1%, p=<0.001) for influencing IR in the abdominally obese subjects. It is concluded that plasma Ang-2 level is correlated with occurrence of IR and inflammation in abdominally obese subjects.

Keywords: Ang-2, insulin resistance, inflammation, abdominal-obesity.



References

Qatanani M, Lazar MA. Mechanism of obesity-associated insulin resistance: many choices on the menu. Genes & Development 2007; 21: 1443-55.

Schenk S, Saberi M, Olefsky J M.Insulin sensitivity: modulation by nutritients and inflammation. J Clin Invest 2008; 118: 2992-3002.

Liang H, Yin B, Zhang H., Zhang S, Zeng Q, Wang, J, et al. Blockade of TNFR1-mediated TNF-α signaling protected Wistar rats from diet-induced obesity and insulin resistance. Endocrinology 2008; 149: 2943-51.

Shah A. Mehta N, Reilly M P. Adipose Inflammation, Insulin Resistance, and Cardiovascular Disease. Parenter Enteral Nutr 2008; 32: 638-44.

WeisbergSP, McCann D, DesaiM, Rossenbaun M, Leibel RL, Ferrante A W.Obesity is associated with macrophage accumulation in adiposa tissue. J Clin Invest 2003; 112: 1796-1808.

Lijnen H R. Angiogenesis and obesity. Cardio.Res 2010; 78: 286-93.

Tahergorabi Z, Khazaei M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA Atheroscler 2013; 9(4): 247-53.

Imhof B A., Aurrand-Lions M. Angiogenesis and inflammation face off. Nat. Med 2006; 12: 171-72.

Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G. Angiopoietin-2 sensitizes endothelial cells to TNF-Alpha and has a crucial role in the induction of inflammation. Nat Med 2006; 12(2): 235-39.

Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, et al. Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance. Cell Metab 2009; 10: 178-88.

Rasul S, Reiter M H, Ilhan A, Lampchler K, Wegner L, Kautzky-Willer A. Circulating angiopoietin-2 and soluble Tie-2 in type 2 Diabetes mellitus: a cross-sectional study. Cardivascular Diabet 2011; 10: 55-61.

World Health Organization (WHO) Western Pacific Region. 2000. The Asia-Pacific perspective: Redifining Obesity and its treatment.

Chobanian A V, Bakris G L, Black H, Cushman W C, Green L A., Izzo J L, et al. National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003; 289: 2560-2572.

Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assesment: Insulin resistance and beta-cell function from plasma glucose and insulin concentration in man. Diabetologia 1985; 28: 412-19.

Guilherme A, Virbasius JV, Puri V, Czech P. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Mol Cel Biol 2008; 9: 367-77.

Ruan H, LodishH F. Insulin resistance in adiposa tissue: direct and indirect effects of tumor necrosis factor-α. Cytokine & Growth Factor 2003; 14: 447-55.

Després J P, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, et al. Abdominal Obesity and Metabolic syndrome: Contribution to Global Cardiometabolic Risk. Arterioscler ThrombVasc Biol 2008; 28: 1039-49.

Swaroop J J Rajarajeswari D, Naidu J N. Association of TNF-α with insulin resistance in type 2 diabetes mellitus. Indian J Med Res 2012; 135(1): 127-30.

Cawthorn W P, Sethi J K. TNF-α and adipocyte biology. FEBS Lett 2008; 582: 117-131

Zahorska-Markiewicz B. Metabolic effects associated with adipose tissue distribution. Adv Med Sci 2006; 51: 111-14.

Uysal K, Wiesbrock M., Marino N W, Hotamisligil G S. Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature 1997; 389: 610-14.

Sethi J K, Xu H., Uysal K T., Wiesbrock S M, Scheja L, Hotamisligil GS. Characterisation of receptor-spesific TNF-alpha functions in adipocyte cell lines lacking type 1 and 2 TNF-α receptors. FEBS Lett 2000; 469: 77-82.

Shoelson S E, Lee J, Goldfine A B. Inflammation and insulin resistance. J Clin Invest 2006; 116: 1793-1801

Muramoto A, Tsushita K, Kato A, Ozaki N, Tabata M, Endo M, et al. Angiopoietin-like protein 2 sensitively respond to wight reduction induced by lifestyle intervention on overweight Japanese men. Nutrition and Diabetes 2011; 16: 1038-48.

Silha J V, Krisek M, Sucharda P, Murphy L J. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes 2005; 29: 1308-14.

Ye J. Adipose Tissue Vascularization: Its Role in Chronic Inflammation. Curr Diab Rep. 2011; 11(3); 203-210.

Rasul S, Reiter M H, Ilhan A, Lampchler K., Wegner L, Kautzky-Willer A. Circulating angiopoietin-2 and soluble Tie-2 in type 2 Diabetes mellitus: a cross-sectional study. Cardivascular Diabet 2011; 10: 55-61.

Kota S K, Meher L K, Jammula S, Kota S K, Khrismna S V S, Modi K D. Abberant angiogenesis: The gateway to diabetic complication. IJEM 2014; 16: 918-30.

Doi Y, Ninomiya T, Hirakaya Y, Takahashi Y, Naoko M, Hata J, et al. Angiopoietin-Like Protein-2 and Risk of Type2 Diabetes in a General Japanese Population.The Hisayama Study. Diabetes Care 2013; 36: 98-100.

Published
2017-02-18
How to Cite
Budhitresna, A. A. G. (2017). Korelasi Kadar Angiopoietin-2 Plasma dan Petanda Inflamasi Dengan Resistensi Insulin Pada Penderita Obesitas Abdominal. WMJ (Warmadewa Medical Journal), 1(1), 10-16. https://doi.org/10.22225/wmj.1.1.5.10-16
Section
Articles
Abstract viewed = 308 times
PDF (Bahasa Indonesia) downloaded = 279 times