Post-challenge hyperglycaemia, nitric oxide production and endothelial dysfunction: The putative role of asymmetric dimethylarginine (ADMA)

Nutrition, Metabolism and Cardiovascular Diseases

Volumn 21, Issue 1, 2011, Pages 1-10

  Siervo, M ^a   Corander, M ^b   Stranges, S ^c   Bluck, L ^a  

^a MRC HUMAN NUTRITION RESEARCH   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF WARWICK   (United Kingdom)

Author keywords

Inflammation; Insulin resistance; Nitric oxide; Nitric oxide synthase inhibitors; Oxidative stress

Indexed keywords

ARGININE; DIMETHYLARGININE; DRUG DERIVATIVE; GLUCOSE; N,N DIMETHYLARGININE; N,N-DIMETHYLARGININE; NITRIC OXIDE;

ANIMAL; BIOSYNTHESIS; BLOOD; GLUCOSE TOLERANCE TEST; HEART DISEASE; HUMAN; HYPERGLYCEMIA; METABOLIC DISORDER; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; OXIDATIVE STRESS; PATHOLOGY; PHYSIOLOGY; SHORT SURVEY; VASCULAR ENDOTHELIUM;

ANIMALS; ARGININE; DIABETES MELLITUS, TYPE 2; ENDOTHELIUM, VASCULAR; GLUCOSE; GLUCOSE TOLERANCE TEST; HEART DISEASES; HUMANS; HYPERGLYCEMIA; METABOLIC DISEASES; NITRIC OXIDE; OXIDATIVE STRESS;

EID: 78751621726     PISSN: 09394753     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.numecd.2010.10.003     Document Type: Short Survey

References (100)

1. Turner R.C., Millns H., Neil H.A., Stratton I.M., Manley S.E., Matthews D.R., et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ 1998, 316:823-828.
2. Rijkelijkhuizen J.M., Nijpels G., Heine R.J., Bouter L.M., Stehouwer C.D., Dekker J.M. High risk of cardiovascular mortality in individuals with impaired fasting glucose is explained by conversion to diabetes: the hoorn study. Diabetes Care 2007, 30:332-336.
3. Temelkova-Kurktschiev T.S., Koehler C., Leonhardt W., Schaper F., Henkel E., Siegert G., et al. Increased intimal-medial thickness in newly detected type 2 diabetes: risk factors. Diabetes Care 1999, 22:333-338.
4. Wajchenberg B.L. {beta}-Cell failure in diabetes and preservation by clinical treatment. Endocr Rev 2007, 28:187-218.
5. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414:813-820.
6. Zierler K. Whole body glucose metabolism. Am J Phys 1999, 276:E409-E426.
7. Kahn S.E., Hull R.L., Utzschneider K.M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006, 444:840-846.
8. Eriksson J., Franssila-Kallunki A., Ekstrand A., Saloranta C., Widen E., Schalin C., et al. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med 1989, 321:337-343.
9. Tripathy D., Carlsson A.L., Lehto M., Isomaa B., Tuomi T., Groop L. Insulin secretion and insulin sensitivity in diabetic subgroups: studies in the prediabetic and diabetic state. Diabetologia 2000, 43:1476-1483.
10. Taylor R. Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia 2008, 51:1781-1789.
11. Diagnosis and Classification of Diabetes Mellitus Diabetes Care 2009, 33:S62-S69.
12. Balkau B., Shipley M., Jarrett R.J., Pyorala K., Pyorala M., Forhan A., et al. High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. 20-year follow-up in the whitehall Study, the Paris prospective study, and the helsinki policemen study. Diabetes Care 1998, 21:360-367.
13. Hanefeld M., Fischer S., Julius U., Schulze J., Schwanebeck U., Schmechel H., et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia 1996, 39:1577-1583.
14. Cavalot F., Petrelli A., Traversa M., Bonomo K., Fiora E., Conti M., et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J Clin Endocrinol Metab 2006, 91:813-819.
15. Ceriello A., Esposito K., Piconi L., Ihnat M., Thorpe J., Testa R., et al. Glucose ″ peak″ and glucose ″ spike″: impact on endothelial function and oxidative stress. Diabetes Res Clin Pract 2008, 82:262-267.
16. Marfella R., Esposito K., Giunta R., Coppola G., De Angelis L., Farzati B., et al. Circulating adhesion molecules in humans: role of hyperglycemia and hyperinsulinemia. Circulation 2000, 101:2247-2251.
17. Makimattila S., Virkamaki A., Groop P.H., Cockcroft J., Utriainen T., Fagerudd J., et al. Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus. Circulation 1996, 94:1276-1282.
18. Monnier L., Mas E., Ginet C., Michel F., Villon L., Cristol J.P., et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006, 295:1681-1687.
19. Ceriello A., Quagliaro L., Catone B., Pascon R., Piazzola M., Bais B., et al. Role of hyperglycemia in nitrotyrosine postprandial generation. Diabetes Care 2002, 25:1439-1443.
20. Lapolla A., Traldi P., Fedele D. Importance of measuring products of non-enzymatic glycation of proteins. Clin Biochem 2005, 38:103-115.
21. Esposito K., Ciotola M., Carleo D., Schisano B., Sardelli L., Di Tommaso D., et al. Post-meal glucose peaks at home associate with carotid intima-media thickness in type 2 diabetes. J Clin Endocrinol Metab 2008, 93:1345-1350.
22. Temelkova-Kurktschiev T.S., Koehler C., Henkel E., Leonhardt W., Fuecker K., Hanefeld M. Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care 2000, 23:1830-1834.
23. Monnier L., Colette C. Target for glycemic control. Diabetes Care 2009, 32:S199-S204.
24. Ceriello A., Colagiuri S., Gerich J., Tuomilehto J. Guideline for management of postmeal glucose. Nutr Metab Cardiovasc Dis 2008, 18:S17-S33.
25. Monnier L., Colette C. Glycemic variability: should we and can we prevent it?. Diabetes Care 2008, 31(Suppl. 2):S150-S154.
26. Alssema M., Schindhelm R.K., Dekker J.M., Diamant M., Kostense P.J., Teerlink T., et al. Postprandial glucose and not triglyceride concentrations are associated with carotid intima media thickness in women with normal glucose metabolism: the hoorn prandial study. Atherosclerosis 2008, 196:712-719.
27. Hanefeld M., Koehler C., Henkel E., Fuecker K., Schaper F., Temelkova-Kurktschiev T. Post-challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima-media thickness: the RIAD Study. Risk Factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes. Diabet Med 2000, 17:835-840.
28. Donahue R.P., Abbott R.D., Reed D.M., Yano K. Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program. Diabetes 1987, 36:689-692.
29. de Vegt F., Dekker J.M., Ruhe H.G., Stehouwer C.D., Nijpels G., Bouter L.M., et al. Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia 1999, 42:926-931.
30. Ceriello A., Esposito K., Piconi L., Ihnat M.A., Thorpe J.E., Testa R., et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 2008, 57:1349-1354.
31. Barrett-Connor E., Ferrara A. Isolated postchallenge hyperglycemia and the risk of fatal cardiovascular disease in older women and men. The Rancho Bernardo Study. Diabetes Care 1998, 21:1236-1239.
32. Marfella R., Nappo F., De Angelis L., Paolisso G., Tagliamonte M.R., Giugliano D. Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients. Diabetes Care 2000, 23:658-663.
33. Dickinson S., Colagiuri S., Faramus E., Petocz P., Brand-Miller J.C. Postprandial hyperglycemia and insulin sensitivity differ among lean young adults of different ethnicities. J Nutr 2002, 132:2574-2579.
34. Bonora E., Corrao G., Bagnardi V., Ceriello A., Comaschi M., Montanari P., et al. Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus. Diabetologia 2006, 49:846-854.
35. Marfella R., Quagliaro L., Nappo F., Ceriello A., Giugliano D. Acute hyperglycemia induces an oxidative stress in healthy subjects. J Clin Invest 2001, 108:635-636.
36. Glucose tolerance and mortality Comparison of WHO and American diabetes association diagnostic criteria. The DECODE study group. European diabetes Epidemiology group. Diabetes Epidemiology: collaborative analysis of diagnostic criteria in Europe. Lancet 1999, 354:617-621.
37. Coutinho M., Gerstein H.C., Wang Y., Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 1999, 22:233-240.
38. O'Keefe J.H., Bell D.S. Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol 2007, 100:899-904.
39. Henry R.M., Paulus W.J., Kamp O., Kostense P.J., Spijkerman A.M., Dekker J.M., et al. Deteriorating glucose tolerance status is associated with left ventricular dysfunction-the Hoorn Study. Neth J Med 2008, 66:110-117.
40. Wolever T.M., Chiasson J.L., Csima A., Hunt J.A., Palmason C., Ross S.A., et al. Variation of postprandial plasma glucose, palatability, and symptoms associated with a standardized mixed test meal versus 75 g oral glucose. Diabetes Care 1998, 21:336-340.
41. Wentholt I.M., Kulik W., Michels R.P., Hoekstra J.B., DeVries J.H. Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes. Diabetologia 2008, 51:183-190.
42. Monnier L., Colette C., Mas E., Michel F., Cristol J.P., Boegner C., et al. Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy. Diabetologia 2010, 53:562-571.
43. Cengiz E., Tamborlane W.V. A tale of two compartments: interstitial versus blood glucose monitoring. Diabetes Technol Ther 2009, 11(Suppl. 1):S11-S16.
44. Arabadjief D., Nichols J.H. Assessing glucose meter accuracy. Curr Med Res Opin 2006, 22:2167-2174.
45. Hanefeld M., Koehler C., Schaper F., Fuecker K., Henkel E., Temelkova-Kurktschiev T. Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals. Atherosclerosis 1999, 144:229-235.
46. Hanefeld M. Post-prandial hyperglycaemia and vascular disease. Int J Clin Pract Suppl 2000, 13-18.
47. Kawano H., Motoyama T., Hirashima O., Hirai N., Miyao Y., Sakamoto T., et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 1999, 34:146-154.
48. Marfella R., Esposito K., Giugliano D. Effect of high glucose on vasculature. Circulation 2003, 108. e74; author reply e74.
49. Galley H.F., Webster N.R. Physiology of the endothelium. Br J Anaesth 2004, 93:105-113.
50. Vallance P. Vascular endothelium: its physiology and pathophysiology. Oxford Textbook of Medicine 2003, vol. 2:789-790. OUP, Oxford, UK. D.C.T. Warrell, J.D. Firth (Eds.).
51. Kearney M.T., Duncan E.R., Kahn M., Wheatcroft S.B. Insulin resistance and endothelial cell dysfunction: studies in mammalian models. Exp Physiol 2008, 93:158-163.
52. Hahn C., Schwartz M.A. Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 2009, 10:53-62.
53. G H D., W J., G I., C W., W M., S C. Endothelial mechanotransduction, nitric oxide and vascular inflammation. J Intern Med 2006, 259:351-363.
54. Mann G.E., Yudilevich D.L., Sobrevia L. Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells. Physiol Rev 2003, 83:183-252.
55. Jansson P.A. Endothelial dysfunction in insulin resistance and type 2 diabetes. J Intern Med 2007, 262:173-183.
56. Rask-Madsen C., King G.L. Mechanisms of Disease: endothelial dysfunction in insulin resistance and diabetes. Nat Clin Pract End Met 2007, 3:46-56.
57. Eugenio C., Ralph A.D. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes/Metabolism Res Rev 2006, 22:423-436.
58. Bruckdorfer R. The basics about nitric oxide. Mol Aspects Med 2005, 26:3-31.
59. Palmer R.M.J., Ferrige A.G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987, 327:524-526.
60. Garg U.C., Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989, 83:1774-1777.
61. Radomski M., Palmer R.M., Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 1987, 92:639-646.
62. Chan N.N., Chan J.C. Asymmetric dimethylarginine (ADMA): a potential link between endothelial dysfunction and cardiovascular diseases in insulin resistance syndrome?. Diabetologia 2002, 45:1609-1616.
63. Ceolotto G., Gallo A., Papparella I., Franco L., Murphy E., Iori E., et al. Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-Dependent mechanism 10.1161/ATVBAHA.107.155762. Arterioscler Thromb Vasc Biol 2007, 27:2627-2633.
64. Esposito K., Nappo F., Marfella R., Giugliano G., Giugliano F., Ciotola M., et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002, 106:2067-2072.
65. Ceriello A., Falleti E., Bortolotti N., Motz E., Cavarape A., Russo A., et al. Increased circulating intercellular adhesion molecule-1 levels in type II diabetic patients: the possible role of metabolic control and oxidative stress. Metabolism 1996, 45:498-501.
66. Yamamoto K., Takeshita K., Kojima T., Takamatsu J., Saito H. Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res 2005, 66:276-285.
67. Bridges J.P., Gilbert J.S., Colson D., Gilbert S.A., Dukes M.P., Ryan M.J., et al. Oxidative stress contributes to Soluble Fms-like Tyrosine Kinase-1 induced vascular dysfunction in Pregnant Rats. Am J Hypertens 2009, 22:564-568.
68. Boger R.H., Lentz S.R., Bode-Boger S.M., Knapp H.R., Haynes W.G. Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans. Clin Sci 2001, 100:161-167.
69. Hirono Y., Yoshimoto T., Suzuki N., Sugiyama T., Sakurada M., Takai S., et al. Angiotensin II Receptor Type 1-Mediated Vascular Oxidative Stress and Proinflammatory Gene Expression in Aldosterone-Induced Hypertension: the Possible Role of Local Renin-Angiotensin System 10.1210/en.2006-1157. Endocrinology 2007, 148:1688-1696.
70. Cooke J.P. ADMA: its role in vascular disease. Vasc Med 2005, 10(Suppl. 1):S11-S17.
71. Sydow K., Mondon C.E., Cooke J.P. Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA. Vasc Med 2005, 10(Suppl. 1):S35-S43.
72. Stuhlinger M.C., Abbasi F., Chu J.W., Lamendola C., McLaughlin T.L., Cooke J.P., et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 2002, 287:1420-1426.
73. Toutouzas K., Riga M., Stefanadi E., Stefanadis C. Asymmetric dimethylarginine (ADMA) and other endogenous nitric oxide synthase (NOS) inhibitors as an important cause of vascular insulin resistance. Horm Metab Res 2008, 40:655-659.
74. Leone A., Moncada S., Vallance P., Calver A., Collier J. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. The Lancet 1992, 339:572-575.
75. Palm F., Onozato M.L., Luo Z., Wilcox C.S. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol 2007, 293:H3227-H3245.
76. Polotskaia A., Wang M., Patschan S., Addabbo F., Chen J., Goligorsky M.S. Regulation of arginine methylation in endothelial cells: role in premature senescence and apoptosis. Cell Cycle 2007, 15:2524-2530.
77. Vallance P., Leiper J. Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol 2004, 24:1023-1030.
78. Boger R.H. Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond. Ann Med 2006, 38:126-136.
79. Böger R.H., Zoccali C. ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Atheroscler Suppl 2003, 4:23-28.
80. MacAllister R., Parry H., Kimoto M., Ogawa T., Russell R.J., Hodson H., et al. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996, 119:1533-1540.
81. Wilcken D.E., Sim A.S., Wang J., Wang X.L. Asymmetric dimethylarginine (ADMA) in vascular, renal and hepatic disease and the regulatory role of L-arginine on its metabolism. Mol Genet Metab 2007, 91:309-317. discussion 308.
82. Cetinalp-Demircan P., Can A., Bekpinar S., Unlucerci Y., Orhan Y. Unchanged asymmetric dimethylarginine levels in non-diabetic, premenopausal obese women who have common risk factors for cardiovascular disease. Endocrine 2007, 31:100-104.
83. Schulze F., Lenzen H., Hanefeld C., Bartling A., Osterziel K.J., Goudeva L., et al. Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study. Am Heart J 2006, 152(493):e491-e498.
84. Cavusoglu E, Ruwende C, Chopra V, Poludasu S, Yanamadala S, Frishman WH, et al,: Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography. Atherosclerosis;210:226-231.
85. Krzyzanowska K., Mittermayer F., Wolzt M., Schernthaner G. Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care 2007, 30:1834-1839.
86. Lajer M., Tarnow L., Jorsal A., Teerlink T., Parving H.H., Rossing P. Plasma concentration of asymmetric dimethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy. Diabetes Care 2008, 31:747-752.
87. Maas R. Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA). Vasc Med 2005, 10(Suppl. 1):S49-S57.
88. Lin K.Y., Ito A., Asagami T., Tsao P.S., Adimoolam S., Kimoto M., et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002, 106:987-992.
89. Eid H.M., Lyberg T., Arnesen H., Seljeflot I. Insulin and adiponectin inhibit the TNFalpha-induced ADMA accumulation in human endothelial cells: the role of DDAH. Atherosclerosis 2007, 194:e1-e8.
90. Abbasi F., Asagmi T., Cooke J.P., Lamendola C., McLaughlin T., Reaven G.M., et al. Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus. Am J Cardiol 2001, 88:1201-1203.
91. Böger R., Sydow K., Borlak J., Thum T., Lenzen H., Schubert B., et al. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res 2000, 87:99-105.
92. Ito A., Egashira K., Narishige T., Muramatsu K., Takeshita A. Angiotensin-converting enzyme activity is involved in the mechanism of increased endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes mellitus. Circ J 2002, 66:811-815.
93. Blackwell S. The biochemistry, measurement and current clinical significance of asymmetric dimethylarginine. Ann Clin Biochem 2010, 47:17-28.
94. Konukoglu D., Firtina S., Serin O. The relationship between plasma asymmetrical dimethyl-L-arginine and inflammation and adhesion molecule levels in subjects with normal, impaired, and diabetic glucose tolerance. Metabolism 2008, 57:110-115.
95. Marliss E.B., Chevalier S., Gougeon R., Morais J.A., Lamarche M., Adegoke O.A., et al. Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover. Diabetologia 2006, 49:351-359.
96. Fard A., Tuck C.H., Donis J.A., Sciacca R., Di Tullio M.R., Wu H.D., 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, 20:2039-2044.
97. Eid H.M., Reims H., Arnesen H., Kjeldsen S.E., Lyberg T., Seljeflot I. Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia. Metabolism 2007, 56:464-469.
98. Beltowski J., Kedra A. Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy. Pharmacol Rep 2006, 58:159-178.
99. Lajoix A.D., Pugniere M., Roquet F., Mani J.C., Dietz S., Linck N., et al. Changes in the dimeric state of neuronal nitric oxide synthase affect the kinetics of secretagogue-induced insulin response. Diabetes 2004, 53:1467-1474.
100. Namiranian K., Mittermayer F., Artwohl M., Pleiner J., Schaller G., Mayer B.X., et al. Free fatty acids do not acutely increase asymmetrical dimethylarginine concentrations. Horm Metab Res 2005, 37:768-772.