Indian Journal of Medical Biochemistry

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VOLUME 23 , ISSUE 3 ( September-December, 2019 ) > List of Articles


Correlation of Asymmetric Dimethylarginine with Cardiovascular Disease in Prediabetes

Santosh Bidwe, Prashant Hisalkar, Neerja Mallick

Keywords : Asymmetric dimethylarginine, Cardiovascular disease, Nitric oxide, Prediabetes, Type II diabetes

Citation Information : Bidwe S, Hisalkar P, Mallick N. Correlation of Asymmetric Dimethylarginine with Cardiovascular Disease in Prediabetes. Indian J Med Biochem 2019; 23 (3):335-338.

DOI: 10.5005/jp-journals-10054-0114

License: CC BY-NC 4.0

Published Online: 01-06-2018

Copyright Statement:  Copyright © 2019; The Author(s).


Asymmetric dimethylarginine (ADMA) is now well established as a major risk factors for cardiovascular disease (CVD) impact upon endothelial function by decreasing nitric oxide (NO°) bioavailability. Asymmetric dimethylarginine, an endogenous analog of L-arginine, is able to inhibit the activity of endothelial-nitric oxide synthase (eNOS), promoting endothelial dysfunction. Prediabetes is characterized by a reduced endothelium-dependent vasodilation and increased ADMA levels. Asymmetric dimethylarginine is strongly associated with micro- and macrovascular diabetic complications. Asymmetric dimethylarginine activity is strongly correlated with CVD in prediabetes. Materials and methods: This study was a cross-sectional, descriptive type of study. In total, 815 participants were involved in this study, out of which 250 suffered from type II diabetes and 265 were prediabetic patients. 290 controls were involved from hospital OPD. Biochemical parameters including fasting plasma sugar, postprandial plasma sugar (after 2 hours of 75 g oral glucose), fasting lipid profile (serum total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, triglycerides (TG), high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol) were done by enzymatic methods. The quantitative sandwich enzyme immunoassay technique was used to determine plasma ADMA level by using commercially available enzyme-linked immunosorbent assay. Results: The level of ADMA in prediabetes was 0.55 ± 0.11 and of type II diabetes was 0.70 ± 0.14 compared with controls (0.41 ± 0.14). p value was <0.05, which was significant. In the present study, there was a significant increase in serum TC, TG, LDL, VLDL, TG/HDL, and LDL/HDL ratio compared with those of normal healthy subjects, while HDL was significantly decreased in prediabetic as compared to normal healthy subjects. Conclusion: The current study shows that increased ADMA levels can indicate the risk of CVD in prediabetic stage. Prediabetes people are under risk of CVD and type II diabetes. Individuals who are prediabetic are at risk of CVD and type II diabetes. The evaluation of the ADMA levels may improve the early diagnosis of CVD of prediabetes.

  1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2004;27:5–10. DOI: 10.2337/diacare.27.2007.S5.
  2. Romeo JH, Seftel AD, Madhun ZT, et al. Sexual function in men with diabetes type II: association with glycemic control. J Urol 2000;163:788–791. DOI: 10.1016/S0022-5347(05)67805-6.
  3. Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 2008;88:1322–1335. DOI: 10.2522/ptj.20080008.
  4. Rahman S, Rahman T, Ismail AA-S, et al. Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis. Diabetes Obes Metab 2007;9:767–780. DOI: 10.1111/j.1463-1326.2006.00655.x.
  5. Tabák AG, Herder C, Rathmann W, et al. Prediabetes: Ahigh-risk state for diabetes development. Lancet 2012;379:2279–2290. DOI: 10.1016/S0140-6736(12)60283-9.
  6. Anderson JL, Carlquist JF, Roberts WL, et al. Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: markers for diabetes and cardiovascular risk? Am Heart J 2007;153:67–73. DOI: 10.1016/j.ahj.2006.10.014.
  7. Wilson AM, Shin DS, Weatherby C, et al. Asymmetric dimethylarginine correlates with measures of disease severity, major adverse cardiovascular events and allcause mortality in patients with peripheral arterial disease. Vasc Med 2010;15:267–274. DOI: 10.1177/1358863X10364552.
  8. Achan V, Broadhead M, Malaki M, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 2003;23:1455–1459. DOI: 10.1161/01.ATV.0000081742.92006.59.
  9. Schulze F, Lenzen H, Hanefeld C, et al. Asymmetric dimethylarginine is an independent risk factor for CHD: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study. Am Heart J 2006;152:493–498. DOI: 10.1016/j.ahj.2006.06.005.
  10. Bal UA, Yıldırır A, Aydinalp A, et al. Could plasma asymmetric dimethylarginine level be a novel predictor beyond the classic predictors of stent restenosis? Anadolu Kardiyol Derg 2014;14: 491–497. DOI: 10.5152/akd.2014.4922.
  11. Patel VB, Robbins MA, Topol EJ. C-reactive protein: a “golden marker” for inflammation and coronary artery disease. Cleve Clin J Med 2001;68:521–534. DOI: 10.3949/ccjm.68.6.521.
  12. Kaplan LA. Carbohydrates and metabolite. In Clinical Chemistry: theory, Analysis and co-relation, Kaplan LA, Pesce AJ. ed., Toronto: C.V. Obsy; 1984. pp. 1032–1040.
  13. Allain CC, Poon L, Chan CS, et al. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20(4):470–475.
  14. Rifal N, Bachorik PS, Albers JJ. Lipoproteins and apolipoproteins. In: Burtie CA, Ashwood ER. Tietz Textbook of Clinical Chemistry, 3rd ed., Philadelphia: W.B. Saunders Company; 1999. pp. 809–861.
  15. Williams P, Robinson D, Bailey A. High density of lipoprotein and coronary risk factor in normal man. Lancet 1979;1:72. DOI: 10.1016/S0140-6736(79)90063-1.
  16. Japan Diabetes Society. ed., Treatment Guide for Diabetes, vol. 9. Bunkodo; 2010.
  17. Schulze F, Wesemann R, Schwedhelm E, et al. Determination of ADMA using a novel ELISA assay. Clin Chem Lab Med 2004;42:1377–1383. DOI: 10.1515/CCLM.2004.257.
  18. Schulze F, Maas R, Freese R, et al. Determination of a reference value for N,N-dimethyl-L-arginine in 500 subjects. Eur J Clin Invest 2005;35:622–626. DOI: 10.1111/j.1365-2362.2005.01561.x.
  19. Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci 2005;109: 143–159. DOI: 10.1042/CS20050025.
  20. Steinberg HO, Brechtel G, Johnson A, et al. 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. DOI: 10.1172/JCI117433.
  21. Vincent MA, Clerk LH, Lindner JR, et al. Microvascular recruitment is an early insulin effect that regulates skeletal muscle glucose uptake in vivo. Diabetes 2004;53:1418–1423. DOI: 10.2337/diabetes. 53.6.1418.
  22. Hamed S, Brenner B, Aharon A, et al. Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type II diabetes mellitus. Cardiovasc Diabetol 2009;8:56. DOI: 10.1186/1475-2840-8-56.
  23. Böger RH, Bode-Böger SM, Tsao PS, et al. An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. J Am Coll Cardiol 2000;36:2287–2295. DOI: 10.1016/S0735-1097(00)01013-5.
  24. Stühlinger MC, Abbasi F, Chu JW, et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 2002;287:1420–1426. DOI: 10.1001/jama.287.11.1420.
  25. Mclaughlin T, Stühlinger M, Lamendola C, et al. Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss. J Clin Endocrine Metab 2006;91:1896–1900. DOI: 10.1210/jc.2005-1441.
  26. Sydow K, Mondon CE, Schrader J, et al. Dimethylarginine dimethylaminohydrolase overexpression enhances insulin sensitivity. Arterioscler Thromb Vasc Biol 2008;28:692–697. DOI: 10.1161/ATVBAHA.108.162073.
  27. Deftereos S, Bouras G, Tsounis D, et al. Association of asymmetric dimethylarginine levels with treadmill-stress-test-derived prognosticators. Clin Biochem 2014;47:593–598. DOI: 10.1016/j.clinbiochem.2014.01.031.
  28. Riccioni G, Scotti L, D'Orazio N, et al. ADMA/SDMA in elderly subjects with asymptomatic carotid atherosclerosis: values and site-specific association. Int J Mol Sci 2014;15:6391–6398. DOI: 10.3390/ijms15046391.
  29. Protopsaltis I, Foussas S, Angelidi A, et al. Impact of ADMA, endothelial progenitor cells and traditional cardiovascular risk factors on pulse wave velocity among prediabetic individuals. Cardiovasc Diabetol 2012;11:141. DOI: 10.1186/1475-2840-11-141.
  30. Kawano H, Motoyama T, Hirashima O, et al. Hyperglycemia rapidly suppresses flow-mediated endothelium dependent vasodilation of brachial artery. J Am Coll Cardiol 1999;34(1):146–154. DOI: 10.1016/S0735-1097(99)00168-0.
  31. Cosentino F, Hishikawa K, Katusic ZS, et al. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 1997;96(1):25–28. DOI: 10.1161/01.CIR.96.1.25.
  32. Jawalekar SL, Karnik A, Bhutey A. Risk of cardiovascular diseases in diabetes mellitus and serum concentration of asymmetrical dimethylarginine. Biochem Res Int 2013;2013:189430. DOI: 10.1155/2013/189430.
  33. Surdacki A, Stochmal E, Szurkowska M, et al. Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance. Metabolism 2007;56(1):77–86. DOI: 10.1016/j.metabol.2006.08.023.
  34. Eliana F, Suwondo P, Makmun LH, et al. AADMA as a marker of endothelial dysfunction in prediabetic women. Acta Med Indones 2011;43(2):92–98.
  35. Kathiresan S, Otvos JD, Sullivan LM, et al. Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation 2006;113(1):20–29. DOI: 10.1161/CIRCULATIONAHA.105.567107.
  36. Zhang WZ, Venardos K, Finch S, et al. Detrimental effect of oxidized LDL on endothelial arginine metabolism and transportation. Int J Biochem Cell Biol 2008;40:920–928. DOI: 10.1016/j.biocel.2007.10.027.
  37. Yoshino G, Hirano T, Kazumi T. Atherogenic lipoproteins and diabetes mellitus. J Diabetes Complications 2002;16(1):29–34. DOI: 10.1016/S1056-8727(01)00199-4.
  38. Nakano S, Kuboki K, Matsumoto T, et al. Small, dense LDL and high-sensitivity C-reactive protein (hsCRP) in metabolic syndrome with type II diabetes mellitus. J Atheroscler Thromb 2010;17(4):410–415. DOI: 10.5551/jat.1891.
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