Effect of Exercise on ADMA Level in Type 2 Diabetes Mellitus

Year 2012, , 62 - 67, 01.01.2012

Bengur Taşkıran Betül Uğur Altun Selma Arzu Vardar Ahmet Muzaffer Demir Çetin Hakan Karadağ Armağan Altun

https://doi.org/10.5152/balkanmedj.2011.001

Abstract

Objective: The increase in symmetric (SDMA) and asymmetric dimethyl arginine (ADMA) is associated with endothelial dysfunction. The aim of this study was to evaluate the effect of exercise on ADMA and SDMA levels and related ratios in type 2 DM. Material and Methods: Thirty-six women with type 2 DM and 44 healthy women were recruited to the study. Fourteen and 19 subjects, respectively, attended four-weeks of moderate intensity exercise. Plasma SDMA, ADMA, and L-arginine levels were measured by the HPLC method initially, after the first exercise session, and after one month. Results: All measurements were within the normal range in both groups and did not change significantly immediately after exercise and after the first month. In the healthy group, L-arginine/ADMA and L-arginine/SDMA ratios after one month were significantly higher than the initial values (p<0.022 and p=0.017, respectively). After one month of exercise, L-arginine/ADMA and L-arginine/SDMA ratios increased in diabetics and decreased in healthy subjects when compared to those after the first exercise session (p=0.026 and p=0.037, respectively). Conclusion: We suggest that L-arginine/ADMA and L-arginine/SDMA ratios should be used in spite of absolute values. These molecules have a substantial role in the beneficial effects of exercise in healthy subjects while their role is small in diabetics. Turkish Başlık: Tip 2 Diabetes Mellitusta Egzersizin Adma Düzeyine Etkisi Anahtar Kelimeler: ADMA, arginin, egzersiz, diabetes mellitus tip 2 Amaç: Simetri (SDMA) ve asimetri dimetil argininde (ADMA)artış endotelyal disfonksiyona işaret eder. Bu projenini amacı tip 2 diabetes mellitusta egzersizden sonraki düzeylerini incelemektir. Hastalar ve Yöntemler: Tip 2 DM bulunan 36 kadın ve 44 sağlıklı kadın dahil edildi. Sırasıyla 14 ve 19'u 4 haftalık orta yoğunlukta egzersize alındı. Başlangıçta, ilk egzersiz seansından sonra ve bir ay sonra plazmada SDMA, ADMA ve L-arginin düzeyleri HPLC yöntemiyle ölçüldü. Bulgular: Her iki grupta da tüm ölçümler normal aralıktaydı ve ne egzersizden sonra ne de bir ayın sonunda belirgin olarak değişmedi. Egzersiz yapan sağlıklı grupta bir ayın sonunda L-arginin/ADMA ve L-arginin/SDMA oranları başlangıç değerlerine göre belirgin olarak yüksek bulundu (sırasıyla, p<0.022 ve 0.017). Bir aylık egzersizin sonunda, ilk egzersiz seansı sonundaki değerlere göre oranlar diyabetiklerde arttı ve sağlıklı kişilerde azaldı. Sonuç: Mutlak değerlerden ziyade L-arginin/ADMA ve L-arginin/SDMA oranlarının kullanılması gerektiğini düşünüyoruz. Sağlıklı kişilerde egzersizin yararlı etkileri açısından bu moleküllerin önemli rolü bulunurken diyabetiklerde bu rol çok azdır.

Keywords

ADMA, arginin, egzersiz, diabetes mellitus tip 2

Effect of Exercise on ADMA Level in Type 2 Diabetes Mellitus

Abstract

References

• American Diabetes Association. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care 2007;30 Suppl 1:S48-65. [CrossRef]
• Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabe- tes mellitus: a meta-analysis of controlled clinical trials. JAMA 2001;286:1218-27. [CrossRef]
• Bode-Böger SM, Scalera F, Ignarro LJ. The L-arginine paradox: Importance of the L-arginine/asymmetrical dimethylarginine ra- tio. Pharmacol Ther 2007;114:295-306. [CrossRef]
• Kawata T, Daimon M, Hasegawa R, Teramoto K, Toyoda T, Sekine T, et al. Effect of angiotensin-converting enzyme inhibitor on se- rum asymmetric dimethylarginine and coronary circulation in pa- tients with type 2 diabetes mellitus. Int J Cardiol 2009;132:286-8. [CrossRef]
• Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumula- tion of an endogenous inhibitor of nitric oxide synthesis in chron- ic renal failure. Lancet 1992;339:572-5. [CrossRef]
• Bode-Böger SM, Scalera F, Kielstein JT, Martens-Lobenhoffer J, Breithardt G, Fobker M, et al. Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary ar- tery disease. J Am Soc Nephrol 2006;17:1128-34. [CrossRef]
• Blardi P, de Lalla A, Pieragalli D, de Franco V, Meini S, Ceccatelli L, et al. Effect of iloprost on plasma asymmetric dimethylargi- nine and plasma and platelet serotonin in patients with periph- eral arterial occlusive disease. Prostaglandins Other Lipid Mediat 2006;80:175-82. [CrossRef]
• Böger RH. Asymmetric dimethylarginine (ADMA) and cardiovas- cular disease: insights from prospective clinical trials. Vasc Med 2005;10 Suppl 1:S19-25. [CrossRef]
• Oguz A, Uzunlulu M, Yorulmaz E, Yalçin Y, Hekim N, Fici F. Effect of nebivolol and metoprolol treatments on serum asymmetric di- methylarginine levels in hypertensive patients with type 2 diabe- tes mellitus. Anadolu Kardiyol Derg 2007;7:383-7.
• Abbasi F, Asagmi T, Cooke JP, Lamendola C, McLaughlin T, Reav- en GM, et al. Plasma concentrations of asymmetric dimethylargi- nine are increased in patients with type 2 diabetes mellitus. Am J Cardiol 2001;88:1201-3. [CrossRef]
• Sugai M, Ohta A, Ogata Y, Nakanishi M, Ueno S, Kawata T, et al. Asymmetric dimethylarginine (ADMA) in the aqeous humor of diabetic patients. Endocr J 2007;54:303-9. [CrossRef]
• Malecki MT, Undas A, Cyganek K, Mirkiewicz-Sieradzka B, Wolkow P, Osmenda G, et al. Plasma asymmetric dimethylargi- nine (ADMA) is associated with retinopathy in type 2 diabetes mellitus. Diabetes Care 2007;30:2899-901. [CrossRef]
• Fleck C, Schweitzer F, Karge E, Busch M, Stein G. Serum concen- trations of asymmetric (ADMA) and symmetric (SDMA) dimethyl- arginine in patients with chronic kidney diseases. Clin Chim Acta 2003;336:1-12. [CrossRef]
• Mittermayer F, Pleiner J, Krzyzanowska K, Wiesinger GF, Fran- cesconi M, Wolzt M. Regular physical exercise normalizes ele- vated asymmetrical dimethylarginine concentrations in patients with type 1 diabetes mellitus. Wien Klin Wochenschr 2005;117: 816-20. [CrossRef]
• American Diabetes Association. Diagnosis and classification of dia- betes mellitus. Diabetes Care 2008;31 Suppl 1:S55-60. [CrossRef]
• World Health Organization. Physical status: the use and interpre- tation of anthropometry: report of a WHO expert committee. World Health Organ Tech Rep Ser 1995;854:1-452.
• Matthews DR, Hosker JR, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin con- centrations in man. Diabetologia 1985;28:412-9. [CrossRef]
• Teräslinna P, Ismail AH, MacLeod DF. Nomogram by Astrand and Ryhming as a predictor of maximum oxygen intake. J Appl Physi- ol 1966;21:513-5.
• Teerlink T, Nijveldt RJ, de Jong S, van Leeuwen PA. Determina- tion of arginine, asymmetric dimethylarginine, and symmetric di- methyllarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem 2002;303:131-7. [CrossRef]
• Päivä H, Lehtimäki T, Laakso J, Ruokonen I, Rantalaiho V, Wirta O, et al. Plasma concentrations of asymmetric-dimethyl-arginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabo- lism 2003;52:303-7. [CrossRef]
• Yamagishi S, Ueda S, Nakamura K, Matsui T, Okuda S. Role of asymmetric dimethylarginine (ADMA) in diabetic vascular com- plications. Curr Pharm Des 2008;14:2613-8. [CrossRef]
• Surdacki A, Stochmal E, Szurkowska M, Bode-Böger SM, Mar- tens-Lobenhoffer J, Stochmal A, et al. Nontraditional athero- sclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance. Metabolism 2007;56:77-86. [CrossRef]
• Yamagishi S, Ueda S, Okuda S. A possible involvement of cross- talk between advanced glycation end products (AGEs) and asym- metric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor in accelerated atherosclerosis in diabetes. Med Hypotheses 2007;69:922-4. [CrossRef]
• Krzyzanowska K, Mittermayer F, Shnawa N, Hofer M, Schnabler J, Etmüller Y, et al. Asymmetrical dimethylarginine is related to renal function, chronic inflammation and macroangiopathy in patients with Type 2 diabetes and albuminuria. Diabet Med 2007;24:81-6. [CrossRef]
• Makino H, Doi K, Hiuge A, Nagumo A, Okada S, Miyamoto Y, et al. Impaired flow-mediated vasodilatation and insulin resistance in type 2 diabetic patients with albuminuria. Diabetes Res Clin Pract 2008;79:177-82. [CrossRef]
• Yasuda S, Miyazaki S, Kanda M, Goto Y, Suzuki M, Harano Y, et al. Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asym- metric dimethylarginine and endogenous inhibitor of nitric oxide synthase. Eur Heart J 2006;27:1159-65. [CrossRef]
• Gomes VA, Casella-Filho A, Chagas ACP, Tanus-Santos JE. En- hanced concentrations of relevant markers of nitric oxide forma- tion after exercise training in patients with metabolic syndrome. Nitric Oxide 2008;19:345-50. [CrossRef]
• Niebauer J, Clark AL, Webb-Peploe KM, Böger R, Coats AJS. Home-based exercise training modulates pro-oxidant sub- strates in patients with chronic heart failure. Eur J Heart Fail 2005;7:183-8. [CrossRef]
• Boulé NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta- analysis of the effect of structured exercise training on cardio- respiratory fitness in type 2 diabetes mellitus. Diabetologia 2003;46:1071-81. [CrossRef]