Insulin Resistance, Hypoadiponectinemia and Endothelial Dysfunction Biomarkers Among Type 2 Diabetic Patients

Osama H. Al-Jiffri 1 * , Fadwa M. Al-Sharif 1, Essam H. Al-Jiffri 1
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1 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Saudi Arabia
* Corresponding Author
EUR J BASIC MED SCI, Volume 5, Issue 2, pp. 31-38.
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Type 2 diabetes (T2DM) is a chronic and progressive disease that is strongly associated with all-cause and cardiovascular mortality. The present study aimed to detect the association between insulin resistance , adiponectin and endothelial dysfunction biomarkers among obese T2DM patients. One hundred obese Saudi patients with T2DM (58 males and 42 females). Their age was 44.61 ± 5.32 year, and a control group included one hundred healthy volunteers, who was gender and age matched. Obese T2DM patients showed significantly higher glucose, insulin, Homeostasis Model Assessment-Insulin Resistance (HOMAIR) index, Inter-Cellular Adhesion Molecule (ICAM-1), Vascular Cell Adhesion Molecule (vCAM-1), E-selectin and significantly lower values of the quantitative insulin-sensitivity check index (QUICKI), and adiponectin levels in comparison to controls. Serum levels of adiponectin showed an association with insulin resistance and endothelial dysfunction biomarkers among type 2 diabetic patients. Within the limit of there is an association between insulin resistance and both hypoadiponectinemia and endothelial dysfunction.


Al-Jiffri OH, Al-Sharif FM, Al-Jiffri EH. Insulin Resistance, Hypoadiponectinemia and Endothelial Dysfunction Biomarkers Among Type 2 Diabetic Patients. Eur J Basic Med Sci. 2015;5(2):31-8.


  • Organization WH. Prevalence of diabetes Worldwide 2010; vol [World Health Organization website].
  • Leiter LA, Fitchett DH, Gilbert RE, et al. Identification and management of cardiometabolic risk in Canada: a position paper by the cardiometabolic risk working group (executive summary). Can J Cardiol 2011;27:124-31.
  • DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 2010;53(7): 1270–87.
  • Seshasai SR, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 2011;364:829-41.
  • Besler C, Luscher TF, Landmesser U. Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease. EMBO Mol Med 2012;4:251e68.
  • Farbstein D, Levy AP. HDL dysfunction in diabetes: causes and possible treatments. Expert Rev Cardiovasc Ther 2012;10:353-61.
  • Chen G, McAlister FA, Walker RL, Hemmelgarn BR, Campbell NR. Cardiovascular outcomes in Framingham participants with diabetes : the importance of blood pressure. Hypertension 57:891–897; 2011.
  • Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83(2):461S–5S.
  • Murdolo G, Smith U. The dysregulated adipose tissue: a connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis. Nutr Metab Cardiovasc Dis 2006;16(Suppl 1):S35–8.
  • Li FY, Cheng KK, Lam KS, Vanhoutte PM, Xu A. Cross-talk between adipose tissue and vasculature: role of adiponectin. Acta Physiol (Oxf) 2010 Nov 10.
  • Zhao l, Fu Z, Liu Z. Adiponectin and insulin cross talk: The microvascular connection. Trends Cardiovascular Med 24(2014) 319–24.
  • Ndumele CE, Pradhan AD, Ridker PM. Interrelationships between inflammation, C-reactive protein, and insulin resistance. J Cardiometab Syndr 2006;1(3):190–6.
  • Misu H, Ishikura K, Kurita S, Takeshita Y, Ota T, Saito Y, Takahashi K, Kaneko S, Takamura T. Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes. PLoS One 2012;7(4):e34952.
  • Gómez JM, Vila R, Catalina P, Soler J, Badimón L, Sahún M. The markers of inflammation and endothelial dysfunction in correlation with glycated haemoglobin are present in type 2 diabetes mellitus patients but not in their relatives. Glycoconj J 2008; 25(6):573-9.
  • Ansar S, Koska J, Reaven PD. Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on in cretins. Cardiovasc Diabetol 2011; 7: 10:61.
  • Cersosimo E, DeFronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev 2006; 22(6):423-36.
  • Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol 2004; 15(8):1983-92.
  • Gómez JM, Sahún M, Vila R, Domènech P, Catalina P, Soler J, Badimón L. Elevation of E-selectin concentrations may correlate with potential endothelial dysfunction in individuals with hypopituitarism during therapy with growth hormone. Curr Neurovasc Res 2007; 4(1):55-62.
  • Lisowska A, Lisowski P, Knapp M, Tycinska A, Sawicki R, Malyszko J, Hirnle T, Musial WJ. Serum adiponectin and markers of endothelial dysfunction in stable angina pectoris patients undergoing coronary artery bypass grafting (CABG). Adv Med Sci 2014;59(2):245-9.
  • Saito T, Saito O, Kawano T, Tamemoto H, Kusano E, Kawakami M, et al. Elevation of serum adiponectin and CD146 levels in diabetic nephropathy. Diabetes Res Clin Pract 2007;78(1):85–92.
  • Lindsay RS, Resnick HE, Zhu J, Tun ML, Howard BV, Zhang Y, et al. Adiponectin and coronary heart disease: the Strong Heart Study. Arterioscler Thromb Vasc Biol 2005;25(March (3)):e15–6.
  • American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33(Suppl. 1):S62–9.
  • Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta cell function from plasma FBS and insulin concentrations in man. Diabetologia 1985;28:412–9.
  • Katz A, Nambi SS, Mather K, Baron DA, Follman DA, Sullivan F, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000;85:2402–2410.
  • Haffner SM,; Lehto S, Ronnemaa T, Pyoral K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339:229–234.
  • Newman A, Siscovick D, Manolio T, Polak J, Fried L, Borhani N, Wolfson S. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study(CHS) Collaborative Research Group. Circulation 1993; 88:837–845.
  • Wannamethee SG, Perry IJ, Shaper AG. Non fasting serum glucose and insulin concentrations and the risk of stroke. Stroke 1999; 30:1780–1786.
  • Almdal T, Scharling H, Jensen JS, Vestergaard H. The independent effect of type 2 diabetes mellitus on ischemic heart disease ,stroke, and death: a population-based study of 13000 men and women with 20 years of follow- up. Arch Intern Med 2004; 164:1422–1426.
  • Kim DH, Vanella L, Inoue K, et al. Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARgamma. Stem Cells Dev 2010;19:1863-73.
  • Shibata R, Sato K, Pimentel DR, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med 2005;11:1096-103.
  • Yki-Ja¨rvinen H. Prediction and prevention of non-insulin-dependent diabetes mellitus. In Williams G & Pickup J (eds) Textbook of Diabetes. Oxford: Blackwell 2001: 83.1–83.13.
  • Steinberg HO, Chaker H, Leaming R et al. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. Journal of Clinical Investigation 1996; 97: 2601–2610.
  • Al Suwaidi J, Higano ST, Holmes DRJ et al. Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries. Journal of the American College of Cardiology 2001; 37: 1523–1528.
  • Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004; 291(16):1978-86.
  • Thorand B, Baumert J, Chambless L, Meisinger C, Kolb H, Döring A, Löwel H, Koenig W. Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population. Arterioscler Thromb Vasc Biol 2006; 26(2):398-405.
  • Song Y, Manson JE, Tinker L, Rifai N, Cook NR, Hu FB, Hotamisligil GS, Ridker PM, Rodriguez BL, Margolis KL, Oberman A, Liu S. Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women. Diabetes 2007; 56(7):1898-904.
  • Laaksonen DE, Niskanen L, Nyyssönen K, Punnonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT. C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 2004; 47(8):1403-10.
  • Ingelsson E, Hulthe J, Lind L. Inflammatory markers in relation to insulin resistance and the metabolic syndrome. Eur J Clin Invest 2008; 38(7):502-9.
  • Hajer GR, van Haeften TW, Visseren FL. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 2008;29(24):2959–71.
  • Matsuzawa Y. Establishment of a concept of visceral fat syndrome and discovery of adiponectin. Proc Jpn Acad B Phys Biol Sci 2010;86(2):131–41.
  • Rui L, Aguirre V, Kim JK, et al. Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest 2001;107(2):181–9.
  • Fernández-Veledo S, Vila-Bedmar R, Nieto-Vazquez I, Lorenzo M. c-Jun N-terminal kinase 1/2 activation by tumor necrosis factor-alpha induces insulin resistance in human visceral but not subcutaneous adipocytes: reversal by liver X receptor agonists. J Clin Endocrinol Metab 2009;94(9):3583–93.
  • Vaverkova H, Karasek D, Novotny D, Kovarova D, Halenka M, Slavik L, Frohlich J. Positive association of adiponectin with soluble thrombomodulin, von Willebrand factor and soluble VCAM-1 in dyslipidemic subjects. Clin Biochem. 2013;46(9):766-71.
  • Vaverkova H, Karasek D, Novotny D, et al. Positive association of adiponectin with soluble vascular cell adhesion molecule sVCAM-1 levels in patients with vascular disease or dyslipidemia. Atherosclerosis 2008;197:725–31.
  • Ran J, Xiong X, Liu W, et al. Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy. Diabetes Res Clin Pract 2010;88:177–83.
  • Shinozaki K, Hirayama A, Nishio Y, Yoshida Y, Ohtani T, Okamura T, Masada M, Kikkawa R, Kodama K, Kashiwagi A. Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress. J Am Coll Cardiol 2001;38:1821–1828.
  • Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin’s vascular effects in humans. J Clin Invest 1994;94: 2511–2515.
  • Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulinmediated skeletal muscle vasodilation is nitric oxide dependent: a novel action of insulin to increase nitric oxide release. J Clin Invest 1994;94:1172–1179.
  • Williams SB, Cusco JA, Roddy MA, Johnstone MT, Creager MA. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 1996;27:567–574.
  • Baron AD, Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J Clin Invest 1995;96:786–792.
  • Malmstrom R, Packard CJ, Caslake M et al. Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 1997; 40: 454–462.
  • Ma¨kimattila S, Liu M-L, Vakkilainen J et al. Impaired endothelium-dependent vasodilatation in NIDDM: relation to LDL size, oxidized LDL and antioxidants. Diabetes Care 1999; 22: 973–981.
  • Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen K, Shulman GI. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 1999; 103: 253−259.
  • Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI. Free fatty acid-induced insulin resistance is associated with activity of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 1999; 48: 1270−1274.
  • Sheng T, Yang K. Adiponectin and its association with insulin resistance and type 2 diabetes. J. Genet. Genomics 2008;5: 321−326.