Correlation between endothelial dysfunction, inflammatory status, oxidative stress and total (nitrite/ nitrate) in subjects with diabetes mellitus type 2

Authors

  • C. Prabhakar Reddy Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
  • Uday Kumar Chiranjeevi Department of Pharmacology, ASRAM Medical College, Eluru, Andhra Pradesh, India
  • Chandrasekhar N. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
  • Kiran Kishore K. Department of Clinical Pharmacology, Jeevan Scientific Technology Limited, Hyderabad, Telangana, India
  • Kishan P. V. Consultant Clinical Pharmacologist, Bharat Biotech International Limited, Hyderabad, Telangana, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20174157

Keywords:

Augmentation pressure, Augmentation index, Diabetes mellitus, Endothelial dysfunction, Oxidative stress

Abstract

Background: Diabetes Mellitus is a systemic metabolic disorder associated with Endothelial dysfunction and increased systemic inflammatory state with oxidative stress leading to increased Cardiovascular risk. This study planned to correlate the level of Endothelial dysfunction with oxidative stress and inflammatory status.

Methods: Study was conducted in 60 Diabetes Mellitus subjects of both genders with duration of more than two years. Endothelial dysfunction assessed as Augmentation Pressure and Augmentation Index generated from Radial artery waveforms by tonometer using Spygmocor PWA system. Plasma Total Nitrite/ Nitrate, High sensitive C - Reactive Protein, Malondialdehyde and Glutathione were measured.

Results: Out of total 60 Diabetes Mellitus subjects 16 subjects were with Coronary Artery Disease. There was no significant difference in High sensitive C - Reactive Protein, Glutathione, Malondialdehyde and Total Nitrite/ Nitrate between Diabetes Mellitus with Coronary Artery Disease and without Coronary Artery Disease, however significant difference (p=0.02) was observed Augmentation Pressure between Diabetic alone (12.8±5.19 mm of Mercury) and diabetics with Coronary Artery Disease (16.13±33.47 mm of Mercury) and Augmentation Index (p=0.04) between Diabetic alone (29.8±5.68 mm of Mercury) and diabetics with Coronary Artery Disease (40.01±5.74). As endothelial function is age dependent the subjects were divided into three age groups (20-40 years, 40-60 years and more than 60 years). High sensitive C - Reactive Protein, Glutathione, Malondialdehyde, Total Nitrite/ Nitrate and Augmentation Index did not differ in the three age groups while Augmentation Pressure (p=0.0096) showed significant difference between age group 20-40 years (10.59±3.24) and age group more than 60 years (15.83±3.92).

Conclusions: There is significant endothelial dysfunction observed in Diabetes Mellitus subjects and Diabetes Mellitus with coronary artery disease showed greater endothelial dyfunction. Thereby concluding that Diabetes Mellitus subjects were at higher risk for development of coronary artery disease and as endothelial dysfunction is an early event, it may have some prognostic value.

Author Biography

C. Prabhakar Reddy, Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India

 

 

References

World Health Organization, Global Report on Diabetes. Geneva, 2016.

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047-53.

Cho NH. International Diabetes Foundation. Diabetes Atlas. Seventh Edition. Chapter 4.6. South East Asia. Ph:90-93.

Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I, Salvetti A. Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation. 1996;94:1298-303.

Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101:948-54.

Lerman A, Burnett JC. Intact and altered endothelium in regulation of vasomotion. Circulation. 1992;86(3):12-9.

Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance, Circulation. 2007;115(10):1285-95.

Napoli C, Ignarro LJ. Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases, Archives of Pharmacal Research. 2009;32(8):1103-8.

Magenta A, Greco S, Gaetano C. Oxidative stress and microRNAs in vascular diseases, International Journal of Molecular Sciences. 2013;14(9):17319-46.

Muniyappa R, Quon MJ. Insulin action and insulin resistance in vascular endothelium. Current Opinion in Clinical Nutrition & Metabolic Care. 2007 Jul 1;10(4):523-30.

Ware JA, Heistad DD, Flier J, Salzman E, Weller P. Platelet-endothelium interactions. The New England Journal of Medicine. 1993;328(9):628-35.

Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. European heart journal. 2013 May 2;34(31):2436-43.

Keaney JF, Massaro JM, Larson MG, Vasan RS, Wilson PW, Lipinska I, et al. Heritability and correlates of intercellular adhesion molecule-1 in the Framingham Offspring Study. Journal of the American College of Cardiology. 2004 Jul 7;44(1):168-73.

Festa A, D’agostino R, Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome. Circulation. 2000 Jul 4;102(1):42-7.

Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Jama. 2001 Jul 18;286(3):327-34.

Schulze MB, Rimm EB, Li T, Rifai N, Stampfer MJ, Hu FB. C-reactive protein and incident cardiovascular events among men with diabetes. Diabetes care. 2004 Apr 1;27(4):889-94.

Duncan BB, Schmidt MI, Pankow JS, Ballantyne CM, Couper D, Vigo A, Hoogeveen R, Folsom AR, Heiss G. Low-grade systemic inflammation and the development of type 2 diabetes. Diabetes. 2003 Jul 1;52(7):1799-805.

Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascular pharmacology. 2015 Aug 31;71:40-56.

Fox CS, Coady S, Sorlie PD. Trends in cardiovascular complications of diabetes. JAMA, J. Am. Med. Assoc. 2004;292:2495-9.

Fichtlscherer S, Breuer S, Zeiher AM. Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: further evidence for the existence of the “vulnerable” patient. Circulation. 2004;110:1926-32.

Targonski PV, Bonetti PO, Pumper GM, Higano ST, Holmes DR, Lerman A. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation. 2003;107:2805-9.

Rahman I, Kode A, Biswas SK. Assay for quantitative determination of Glutathione and disulfide levels using enzymatic recycling method. Nature Protocols. 2008;1:3159-65.

Vidyasagar J, Karunakar N, Reddy MS, Rajnarayana K, Surender T, Krishna DR. Oxidative stress and antioxidant status in acute organophosphorous insecticide poisoning. Indian journal of Pharmacology. 2004 Mar 1;36(2):76.

Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric oxide. 2001 Feb 1;5(1):62-71.

Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao G. Spectrophotometric determination of serum nitrite and nitrate by copper–cadmium alloy. Analytical biochemistry. 2002 Jul 1;306(1):79-82.

Gargiulo P, Marciano C, Savarese G. Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries. April 30, 2013;165(1):67-71.

Reyes-Soffer G, Holleran S, Di Tullio MR, Homma S, Boden-Albala B, Ramakrishnan R, et al. Endothelial function in individuals with coronary artery disease with and without type 2 diabetes mellitus. Metabolism. 2010 Sep 30;59(9):1365-71.

Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium dependent vasodilatation in experimental diabetes. J Clin Invest. 1991;87:432-8.

Zhang L, Zalewski A, Liu Y, Mazurek T, Cowan S, Martin JL, et al. Diabetes-induced oxidative stress and low-grade inflammation in porcine coronary arteries. Circulation. 2003;108:472-8.

Makita Z, Radoff S, Rayfield EJ, Yang Z, Skolnik E, Delaney V, et al. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med. 1991;325:836-42.

Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson DC, et al. Acute hyperglycemia attenuates endothelium-dependent vasodilate on in humans in vivo. Circulation. 1998;97:1695-701.

Muniyappa R, Quon MJ. Insulin action and insulin resistance in vascular endothelium, Current Opinion in Clinical Nutrition and Metabolic Care. 2007;10(4):523-30.

Vicent D, Ilany J, Kondo T, Naruse K, Fisher SJ, Kisanuki YY, et al. The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance J Clin Invest. 2003 May 1;111(9):1373-80.

San Martin A, Du P, Dikalova A, Lassègue B, Aleman M, Góngora MC, et al. Reactive oxygen species-selective regulation of aortic inflammatory gene expression in Type 2 diabetes. American Journal of Physiology-Heart and Circulatory Physiology. 2007 May 1;292(5):H2073-82.

Gao L, Mann GE. Vascular NAD (P) H oxidase activation in diabetes: a double-edged sword in redox signalling. Cardiovascular research. 2009 Jan 29;82(1):9-20.

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circulation research. 2010 Oct 29;107(9):1058-70.

Zhang J, Patel JM, Li YD, Block ER. Proinflammatory cytokines downregulate gene expression and activity of constitutive nitric oxide synthase in porcine pulmonary artery endothelial cells. Research communications in molecular pathology and pharmacology. 1997 Apr;96(1):71-87.

Beckman JA, Paneni F, Cosentino F, Creager MA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. European heart journal. 2013 Apr 26;34(31):2444-52.

Keaney JF, Massaro JM, Larson MG, Vasan RS, Wilson PW, Lipinska I, et al. Heritability and correlates of intercellular adhesion molecule-1 in the Framingham Offspring Study. Journal of the American College of Cardiology. 2004 Jul 7;44(1):168-73.

Festa A, D’agostino R, Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome. Circulation. 2000 Jul 4;102(1):42-7.

Schulze MB, Rimm EB, Li T, Rifai N, Stampfer MJ, Hu FB. C-reactive protein and incident cardiovascular events among men with diabetes. Diabetes care. 2004 Apr 1;27(4):889-94.

Duncan BB, Schmidt MI, Pankow JS, Ballantyne CM, Couper D, Vigo A, et al. Low-grade systemic inflammation and the development of type 2 diabetes. Diabetes. 2003 Jul 1;52(7):1799-805.

Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, et al. Endogenous nitric oxide synthase inhibitor. Circulation. 1999 Mar 9;99(9):1141-6.

Tesfamariam B, Brown ML, Cohen RA. 15-Hydroxyeicosatetraenoic acid and diabetic endothelial dysfunction in rabbit aorta. Journal of cardiovascular pharmacology. 1995 May 1;25(5):748-55.

Valkonen VP, Päivä H, Salonen JT. Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet. 2001;358:2127-8.

Paterson AD, Rutledge BN, Cleary PA, Lachin JM, Crow RS. The effect of intensive diabetes treatment on resting heart rate in type 1 diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Diabetes Care. 2007;30:2107-12.

Hogan P, Dall T, Nikolov P. Economic costs of diabetes in the US in 2002. Diabetes Care. 2003;26:917-32.

Lehto S, Ronnemaa T, Pyorala K, Laakso M. Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes. Stroke. 1996;27:63-8.

Uemura S, Matsushita H, Li W, Glassford AJ, Asagami T, Lee KH, et al. Diabetes mellitus enhances vascular matrix metalloproteinase activity: Role of oxidative stress. Circ Res. 2001;88:1291-8.

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Published

2017-09-23

How to Cite

Reddy, C. P., Chiranjeevi, U. K., N., C., K., K. K., & P. V., K. (2017). Correlation between endothelial dysfunction, inflammatory status, oxidative stress and total (nitrite/ nitrate) in subjects with diabetes mellitus type 2. International Journal of Basic & Clinical Pharmacology, 6(10), 2317–2322. https://doi.org/10.18203/2319-2003.ijbcp20174157

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Original Research Articles