Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes

CAN, Günay; Onat, Altan; AYDIN, MESUT; KARAGÖZ, Ahmet; KÖROĞLU, Bayram; Yüksel, Murat

Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes

Bayram KÖROĞLU, (SB Dr Siyami Ersek Göğüs Kalp Damar Cerrahisi Eğitim ve Araştırma Hastanesi, Kardiyoloji Kliniği, İstanbul, Türkiye)

Günay CAN, (İstanbul Üniversitesi, Cerrahpaşa Tıp Fakültesi, İstanbul, Türkiye)

Ahmet KARAGÖZ, (Ankara Numune Eğitim ve Araştırma Hastanesi, Kardiyoloji Kliniği, Ankara, Türkiye)

Murat YÜKSEL, (Dicle Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Diyarbakır Türkiye)

Mesut AYDIN (Dicle Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Diyarbakır Türkiye)

Anadolu Kardiyoloji Dergisi

2 1

Yıl: 2014 Cilt: 14 Sayı: 1 Sayfa Aralığı: 26 - 33 Metin Dili: İngilizce İndeks Tarihi: 29-07-2022

Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes

Öz:

Objective: We investigated the association of serum asymmetric dimethylarginine (ADMA) with metabolic syndrome (MetS), type-2 diabetes and coronary heart disease (CHD) in the general population. Methods: Cross-sectional and, at 2000 person-years’ follow-up, prospective analysis. Adults with measured serum ADMA level (n=848) were analyzed using tertiles or dichotomized values. ADMA concentrations were measured by a validated commercial ELISA kit. Results: Dichotomized subjects of combined sexes with low (≤0.68 μmol/L) ADMA values had significantly higher fasting glucose, total cholesterol, apolipoprotein B and lower diastolic blood pressure. In linear regression analyses comprising age, smoking, triglyceride, HDL-cholesterol, C-reactive protein and waist circumference as well, creatinine was significantly and independently associated with ADMA, further in women glucose (inversely). In logistic regression analyses uniformly adjusted for age, smoking status and waist girth, prevalent MetS tended to positive independent association with ADMA tertiles only in men. Combined prevalent and incident diabetes weakly tended to be associated with the low- est (vs mid- and highest) ADMA tertiles in combined gender; and prevalent and incident CHD was not associated with ADMA tertiles in either sex. Conclusion: Apparently “low” circulating ADMA is independently associated with fasting glucose and tends to be so with type-2 diabetes. The lack of anticipated positive associations of ADMA with cardiometabolic disorders is likely due to autoimmune responses operating against serum ADMA under oxidative stress, rendering partial failure in immunoassay.

Anahtar Kelime:

Konular: Kalp ve Kalp Damar Sistemi

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Vallance P Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572-5. [CrossRef]
2. Wilson AM, Shin DS, Weatherby C, Harada RK, Ng MK, Nair N, et al. Asymmetric dimethylarginine correlates with measures of disease severity, major adverse cardiovascular events and all- cause mortality in patients with peripheral arterial disease. Vasc Med 2010; 15: 267-74. [CrossRef]
3. Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 2003; 23: 1455-9. [CrossRef]
4. Fard A, Tuck CH, Donis JA, Sciacca R, Di Tullio MR, Wu HD, et al. Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2000; 20: 2039-44. [CrossRef]
5. Mittermayer F, Mayer BX, Meyer A, Winzer C, Pacini G, Wagner OF, et al. Circulating concentrations of asymmetric dimethyl-L-arginine are increased in women with previous gestational diabetes. Diabetologia 2002; 45: 1372-8. [CrossRef]
6. Anderson JL, Carlquist JF, Roberts WL, Horne BD, May HT, Schwarz EL, et al; for the Intermountain Heart Collaborative Study Group. Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: markers for diabetes and cardiovascular risk? Am Heart J 2007; 153: 67-73. [CrossRef]
7. Stühlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin T, Cooke JP et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 2002; 287: 1420-6. [CrossRef]
8. Mittermayer F, Krzyzanowska K, Exner M, Mlekusch W, Amighi J, Sabeti S, et al. Asymmetric dimethylarginine predicts major adverse cardiovascular events in patients with advanced peripheral artery disease. Arterioscler Thromb Vasc Biol 2006; 26: 2536-40. [CrossRef]
9. Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflot I. Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine. Metabolism 2004; 53: 1574-9. [CrossRef]
10. Schulze F, Lenzen H, Hanefeld C, Bartling A, Osterziel KJ, Goudeva L, 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.e1-8.
11. Surdacki A, Martens-Lobenhoffer J, Wloch A, Marewicz E, Rakowski T, Wieczorek-Surdacka E, et al. Elevated plasma asymmetric dimethylarginine levels are linked to endothelial progenitor cell depletion and carotid atherosclerosis in rheumatoid arthritis. Arthritis Rheum 2007; 56: 809-19. [CrossRef]
12. Schnabel R, Blankenberg S, Lubos E, Lackner KJ, Rupprecht HJ, Espinola- Klein C, et al. Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 2005; 97: e53-9. [CrossRef]
13. Zoccali C, Bode-Böger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, et al. Plasma concentration of asymmetric dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 2001; 358: 2113-7. [CrossRef]
14. Maas R, Quitzau K, Schwedhelm E, Spieker L, Rafflenbeul W, Steenpass A, et al. Asymmetrical dimethylarginine (ADMA) and coronary endothelial function in patients with coronary artery disease and mild hypercholesterolemia. Atherosclerosis 2007; 191: 211-9. [CrossRef]
15. Valkonen VP Päivä H, Salonen JT, Lakka TA, Lehtimäki T, Laakso J, et al. Risk of acute coronary events and serum concentration of asymmetric dimethylarginine. Lancet 2001; 358: 2127-8. [CrossRef]
16. Maas R, Schulze F, Baumert J, Lowel H, Hamraz K, Schwedhelm E, et al. Asymmetric dimethylarginine, smoking, and risk of coronary heart disease in apparently healthy men: prospective analysis from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg study and experimental data. Clin Chem 2007; 53: 693-701. [CrossRef]
17. Böger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, et al. Plasma asymmetric dimethylarginine (ADMA) and incidence of cardiovascular disease and death in the community. Circulation 2009; 199: 1592-600. [CrossRef]
18. Schmidt MI, Duncan BB, Sharrett AR, Lindberg G, Savage PJ, Offenbacher S, et al. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study. Lancet 1999; 353: 1649-52. [CrossRef]
19. Onat A, Can G, Yüksel H, Ayhan E, Doğan Y, Hergenç G. An algorithm to predict risk of type 2 diabetes in Turkish adults: contribution of C-reactive protein. J Endocrinol Invest 2011; 34: 580-6.
20. Onat A. Risk factors and cardiovascular disease in Turkey. Atherosclerosis 2001; 156: 1-10. [CrossRef]
21. Onat A, Hergenç G, Can G, Karabulut A. Serum asymmetric dimethylarginine levels among Turks: association with metabolic syndrome in women and tendency to decrease in smokers. Turk Kardiyol Dern Ars 2008; 36: 7-13.
22. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004; 109: 433-8. [CrossRef]
23. Onat A, Uyarel H, Hergenç G, Karabulut A, Albayrak S, Can G. Determinants and definition of abdominal obesity as related to risk of diabetes, metabolic syndrome and coronary disease in Turkish men: a prospective cohort study. Atherosclerosis 2007; 191: 182-90. [CrossRef]
24. Genuth S, Alberti KG, Bennett P Buse J, Defronzo R, Kahn R, et al; Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26: 3160-7. [CrossRef]
25. Rose GA, Blackburn H, Gillum RF, Prineas RJ. Cardiovascular Survey Methods, 2nd ed. Geneva, WHO, 1982.p.124-7.
26. Smith CL, Anthony S, Hubank M, Leiper JM, Vallance P Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA. PLoS Med 2005; 2: 264. [CrossRef]
27. Anderssohn M, Schwedhelm E, Lüneburg N, Vasan RS, Böger RH. Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality. Diab Vasc Dis Res 2010; 7: 105-18. [CrossRef]
28. Bestermann WH Jr. The ADMA-metformin hypothesis: linking the cardiovascular consequences of the metabolic syndrome and type 2 diabetes. Cardiorenal Med 2011; 1: 211-9. [CrossRef]
29. Jacobi J, Tsao PS. Asymmetrical dimethylarginine in renal disease: limits of variation or variation limits? A systematic review. Am J Nephrol 2008; 28: 224-37. [CrossRef]
30. Konukoğlu D, Fırtına S, Serin O. The relationship between plasma asymmetric dimethyl-L-arginine and inflammation and adhesion molecule levels in subjects with normal, impaired, and diabetic glucose tolerance. Metabolism 2008; 57: 110-5. [CrossRef]
31. Zoccali C, Maas R, Cutrupi S, Pizzini P Finocchiaro P Cambareri F, et al. Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections. Nephrol Dial Transplant 2007; 22: 801-6. [CrossRef]
32. Wang JJ, Gong JB, Li HQ, Niu DM, Han AZ, Wu J, et al. Lipoprotein(a) complexes with beta2-glycoprotein I in patients with coronary artery disease. J Atheroscler Thromb 2012; 19: 81-9. [CrossRef]
33. Lopez LR, Bruckner TR, Hurley BL, Kobayashi K, Matsuura E. Determination of oxidized low-density lipoprotein (ox-LDL) versus ox-LDL/beta2GPI complexes for the assessment of autoimmune- mediated atherosclerosis. Ann N Y Acad Sci 2007; 1109:303-10. [CrossRef]
34. Sandoo A, Dimitoulas T, Veldhuizen van Zanten JJ, Smith JP Metsios GS, Nightingale P et al. Lack of association between asymmetric dimethylarginine and in vivo microvascular or macrovascular endothelial function in patients with rheumatoid arthritis. Clin Exp Rheumatol 2012; 30: 388-96.
35. Onat A, Can G, Ademoğlu E, Çelik E, Karagöz A, Örnek E. Coronary disease risk curve of serum creatinine is linear in Turkish men, U-shaped in women. J Investig Med 2013; 61: 27-33.
36. Onat A, Yüksel H, Can G, Köroğlu B, Kaya A, Altay S. Serum creatinine is associated with coronary disease risk even in the absence of metabolic disorders. Scand J Clin Lab Inv 2013; 73: 569-75. [CrossRef]
37. Onat A, Can G, Murat S, Çiçek G, Örnek E, Yüksel H. Aggregation of lipoprotein(a) to apolipoprotein A-I underlying HDL dysfunction as a major coronary risk factor. Anadolu Kardiyol Derg 2013; 13: 543-51.
38. Busch M, Fleck C, Wolf G, Stein G. Asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine as potential risk factors for cardiovascular and renal outcome in chronic kidney disease -possible candidates for paradoxical epidemiology? Amino Acids 2006; 30: 225-32. [CrossRef]
39. Kielstein JT, Böger RH, Bode-Böger SM, Martens-Lobenhoffer J, Lonnemann G, Frölich JC, et al. Low dialysance of asymmetric dimethylarginine (ADMA) –in vivo and in vitro evidence of significant protein binding. Clin Nephrol 2004; 62: 295-300. [CrossRef]

APA	Onat A, KÖROĞLU B, CAN G, KARAGÖZ A, Yüksel M, AYDIN M (2014). Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. , 26 - 33.
Chicago	Onat Altan,KÖROĞLU Bayram,CAN Günay,KARAGÖZ Ahmet,Yüksel Murat,AYDIN MESUT Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. (2014): 26 - 33.
MLA	Onat Altan,KÖROĞLU Bayram,CAN Günay,KARAGÖZ Ahmet,Yüksel Murat,AYDIN MESUT Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. , 2014, ss.26 - 33.
AMA	Onat A,KÖROĞLU B,CAN G,KARAGÖZ A,Yüksel M,AYDIN M Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. . 2014; 26 - 33.
Vancouver	Onat A,KÖROĞLU B,CAN G,KARAGÖZ A,Yüksel M,AYDIN M Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. . 2014; 26 - 33.
IEEE	Onat A,KÖROĞLU B,CAN G,KARAGÖZ A,Yüksel M,AYDIN M "Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes." , ss.26 - 33, 2014.
ISNAD	Onat, Altan vd. "Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes". (2014), 26-33.

APA	Onat A, KÖROĞLU B, CAN G, KARAGÖZ A, Yüksel M, AYDIN M (2014). Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. Anadolu Kardiyoloji Dergisi, 14(1), 26 - 33.
Chicago	Onat Altan,KÖROĞLU Bayram,CAN Günay,KARAGÖZ Ahmet,Yüksel Murat,AYDIN MESUT Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. Anadolu Kardiyoloji Dergisi 14, no.1 (2014): 26 - 33.
MLA	Onat Altan,KÖROĞLU Bayram,CAN Günay,KARAGÖZ Ahmet,Yüksel Murat,AYDIN MESUT Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. Anadolu Kardiyoloji Dergisi, vol.14, no.1, 2014, ss.26 - 33.
AMA	Onat A,KÖROĞLU B,CAN G,KARAGÖZ A,Yüksel M,AYDIN M Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. Anadolu Kardiyoloji Dergisi. 2014; 14(1): 26 - 33.
Vancouver	Onat A,KÖROĞLU B,CAN G,KARAGÖZ A,Yüksel M,AYDIN M Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes. Anadolu Kardiyoloji Dergisi. 2014; 14(1): 26 - 33.
IEEE	Onat A,KÖROĞLU B,CAN G,KARAGÖZ A,Yüksel M,AYDIN M "Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes." Anadolu Kardiyoloji Dergisi, 14, ss.26 - 33, 2014.
ISNAD	Onat, Altan vd. "Apparently “low” serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes". Anadolu Kardiyoloji Dergisi 14/1 (2014), 26-33.