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The evaluation of serum asymmetric dimethyl arginine, fetuin-A and ankle-brachial index values in type 2 diabetic patients with and without microalbuminuria

Year 2019, Volume: 58 Issue: 4, 397 - 405, 30.12.2019

Aslı Kılavuz Bakiye Göker Sumru Savaş Çığır Biray Avcı Fulden Saraç Cumhur Gündüz

https://doi.org/10.19161/etd.623697

Abstract

Aim: We aimed to compare atherosclerosis markers in patients with type 2 diabetes mellitus with and without microalbuminuria.

Material and Methods: Eighty type 2 diabetes mellitus patients with and without microalbuminuria aged between 40-60 years were enrolled in this study. Serum levels of asymmetric dimethylarginine, fetuin-A and laboratory parameters such as lipid profile and A1c were evaluated. Ankle-brachial indexes were measured.

Results: No statistically significant correlation was found between microalbuminuria and total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, A1c, plasma fasting glucose, body mass index, ankle-brachial index. Patients with microalbuminuria had significantly lower serum fetuin-A levels in comparison with subjects of non-microalbuminuria (p=0.008).

However, a significant negative correlation was achieved between fetuin-A levels and microalbuminuria. We found that lower fetuin-A levels were associated with peripheric arterial disease, defined as ankle-brachial index ≤ 0.9 (p=0.001). There was a statistically significant correlation between microalbuminuria and serum asymmetric dimethylarginine levels. Patients with microalbuminuria had significantly higher serum asymmetric dimethylarginine levels in comparison with subjects with non-microalbuminuria (p=0.013).

Conclusion: Based on our results, it can be suggested that serum asymmetric dimethyl arginine is superior to fetuin-A in patients with type 2 diabetes mellitus and microalbuminuria for atherosclerotic process.







Keywords

Diabetes mellitus type 2 serum asymmetric dimethylarginine fetuin A ankle brachial index microalbuminuria.

References

  • David KM. Definition of diabetes mellitus. In: Rose BD (ed). Uptodate. Wellesley: 2009: 17 (1). [Cited 26 May 2018]. Available from: http://www.uptodate.com.
  • St Clair L, Ballantyne CM. Biological surrogates for enhancing cardiovascular risk prediction in type 2 diabetes mellitus. Am J Cardiol 2007; 99: 80B-8B.
  • Lorant DP, Grujicic M, Hoebaus C, et al. Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease. Diabetes care 2011; 34: 156–61.
  • Roos M, Oikonomou D, von Eynatten M, et al. Associations of fetuin-A levels with vascular disease in type 2 diabetes patients with early diabetic nephropathy. Cardiovascular diabetology 2010; 9: 48.
  • Mogensen CE. Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia 1999; 42: 263–85. 404 Ege Tıp Dergisi
  • Garg JP, Bakris GL. Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease. Vascular medicine 2002; 7 (1): 35-43.
  • Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med 1997; 157: 1413-8.
  • Spittell JA Jr. Diagnosis and management of occlusive peripheral arterial disease. Curr Probl Cardiol 1990; 15: 1.
  • Resnick HE, Lindsay RS, McDermott MM, et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study. Circulation 2004; 109: 733–9.
  • Barclay L, Vega C. Fetuin-A linked with incident diabetes. JAMA 2008; 300: 182-8.
  • Schafer C, Heiss A, Schwarz A, et al. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003; 112: 357–66.
  • Stefan N, Hennige AM, Staiger H, et al. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes care 2006; 29: 853–7.
  • Hennige AM, Staiger H, Wicke C, et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One 2008; 3 (3): 1765.
  • Eraso LH, Ginwala N, Qasim AN, et al. Association of lower plasma fetuin-A levels with peripheral arterial disease in type 2 diabetes. Diabetes care 2010; 33: 408–10.
  • Krzyzanowska K, Mittermayer F, Shnawa N, 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.
  • Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31 (7): 1281-357.
  • Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129 (2): 1–45.
  • American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes care 2003; 26: 3333–41.
  • Naidoo DP. The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. Cardiovascular journal of South Africa 2002; 13: 194-9.
  • Li M, Xu M, Bi Y, et al. Association between higher serum fetuin-a concentrations and abnormal albuminuria in middle-aged and elderly chinese with normal glucose tolerance. Diabetes care 2010; 33 (11): 2462-4.
  • Krisztián V, Károly C, László K. The role of fetuin-A in cardiovascular diseases. Orv Hetil 2013; 155 (1): 16–23.
  • Ix JH, Wassel CL, Kanaya AM, et al. Fetuin A and incident diabetes mellitus in older persons. JAMA 2008; 300: 182-8.
  • Stefan N, Haring HU, Schulze MB. Association of serum fetuin A level and diabetes risk. JAMA 2008; 300: 2247-8.
  • 24. Mori K, Emoto M, Inaba M. Fetuin A: A multifunctional protein. Recent patents on endocrine, metabolic & immune drug discovery 2011; 5: 124-46.
  • Eleftheriadou I, Grigoropoulou P, Kokkinos A, et al. Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus. J Diabetes Complications 2017; 31: 599–604.
  • Stefan N, Fritsche A, Weikert C, et al. Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes 2008; 57: 2762-7. Cilt 58 Sayı 4, Aralık 2019 / Volume 58 Issue 4, December 2019 405
  • Weikert C, Stefan N, Schulze MB, et al. Plasma fetuin-a levels and the risk of myocardial infarction and ischemic stroke. Circulation 2008; 118: 2555-62.
  • Jirak P, Mirna M, Wernly B, et al. Analysis of novel cardiovascular biomarkers in patients with peripheral artery disease (PAD). Minerva Med doi: 10.23736/S0026-4806.18.05628-8.
  • Guo L, Cheng Y, Wang X, et al. Association between microalbuminuria and cardiovascular disease in type 2 diabetes mellitus of the Beijing Han nationality. Acta Diabetol 2012; 49 (1): 65-71.
  • 30. Makhdoomi K, Mohammadi A, Yekta Z, Aghasi MR, Zamani N, Vossughian S. Correlation between ankle-brachial index and microalbuminuria in type 2 diabetes mellitus. Iranian journal of kidney diseases 2013; 7: 204-9.
  • Tseng CH, Chong CK, Tseng CP, Tai TY. The association between urinary albumin excretion and ankle-brachial index in elderly Taiwanese patients with type 2 diabetes mellitus. Age Ageing 2008; 37: 77-82.
  • Choi SW, Yun WJ, Kim HY, et al. Association between albuminuria, carotid atherosclerosis, arterial stiffness, and peripheral arterial disease in Korean type 2 diabetic patients. Kidney Blood Press Res 2010; 33: 111-8.
  • Cao JJ, Barzilay JI, Peterson D, et al. The association of microalbuminuria with clinical cardiovascular diseasemand subclinical atherosclerosis in the elderly: the Cardiovascular Health Study. Atherosclerosis 2006; 187: 372-7.
  • Hanai K, Babazono T, Nyumura I, et al. Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes. Nephrol Dial Transplant 2009; 24: 1884–8.
  • Cavusoglu E, Ruwende C, Chopra V, 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 2010; 210 (1): 226–31.
  • Celik M, Cerrah S, Arabul M, Akalin A. Relation of asymmetric dimethylarginine levels to macrovascular disease and inflammation markers in type 2 diabetic patients. Journal of diabetes research 2014;2014:139215. doi: 10.1155/2014/139215.
  • Ozdogan O, Cekic B. Is there a correlation between plasma levels of asymmetric dimethylarginine (ADMA) levels and atherosclerosis in type 2 diabetes patients in Turkey? The Medical Bulletin of Sisli Etfal Hospital 2017; 51 (1): 63-70.
  • Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007; 115: 459-67.
  • Bernard S, Serusclat A, Targe F, et al. Incremental predictive value of carotid ultrasonography in the assessment of coronary risk in a cohort of asymptomatic type 2 diabetic subjects. Diabetes care 2005; 28: 1158-62.
  • Karakoç A, Sahin A, Polat ES, et al. Serum apelin and ADMA levels in type 2 diabetics with and without vascular complications. Diabetes & metabolic syndrome 2016;10(2 Suppl 1):106-9.
  • Hsu CP, Hsu PF, Chung MY, Lin SJ, Lu TM. Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control. Cardiovascular diabetology 2014; 13: 156.
  • Paiva H, Lehtimaki T, Laakso J, et al. Plasma concentrations of asymmetric-dimethylarginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabolism 2003; 52 (3): 303-7.
  • Witte EC, Lambers Heerspink HJ, de Zeeuw D, Bakker SJ, de Jong PE, Gan-sevoort R. First morning voids are more reliable than spot urine samples to assess microalbuminuria. J Am Soc Nephrol 2009; 20: 436–43.

Mikroalbüminürisi olan ve olmayan tip 2 diyabetik hastalarda serum asimetrik dimetil arjinin, fetuin-A ve ankle-brakial indeks değerlerinin değerlendirilmesi

Year 2019, Volume: 58 Issue: 4, 397 - 405, 30.12.2019

Aslı Kılavuz Bakiye Göker Sumru Savaş Çığır Biray Avcı Fulden Saraç Cumhur Gündüz

https://doi.org/10.19161/etd.623697

Abstract

Amaç: Çalışmamızda mikroalbüminürisi olan ve olmayan tip 2 diabetes mellituslu hastalarda ateroskleroz belirteçlerini karşılaştırmayı amaçladık.

Gereç ve Yöntem: Bu çalışmaya 40-60 yaşları arasında, tip 2 diyabetli mikroalbüminürik ve mikroalbuminürisi olmayan 80 hasta dahil edildi. Hastaların serum asimetrik dimetil arjinin, fetuin-A düzeyleri, lipit profili ile açlık ve tokluk glukoz, A1c gibi laboratuvar parametreleri değerlendirildi. Ankle-brakiyal indeks (ABİ) ölçümleri yapıldı.

Bulgular: Mikroalbüminüri ile total kolesterol, trigliserid, LDL kolesterol, HDL kolesterol, A1c, plazma açlık glukozu, vücut kitle indeksi, ankle-brakiyal indeksi arasında istatistiksel olarak anlamlı bir ilişki bulunmadı. mikroalbüminürisi olan hastalar mikroalbüminürisi olmayan hastalara göre anlamlı olarak daha düşük serum fetuin-A düzeylerine sahipti (p = 0,008). Ancak, fetuin-A düzeyleri ve mikroalbüminüri arasında anlamlı negatif korelasyon elde edildi. Düşük fetuin-A düzeylerinin, ABİ ≤ 0,9 olarak tanımlanan periferik arter hastalığı ile ilişkili olduğu belirlendi (p = 0,001). Mikroalbüminüri ve serum asimetrik dimetil arjinin düzeyleri arasında istatistiksel olarak anlamlı ilişki saptandı. Mikroalbüminürisi olan hastaların, olmayanlara göre anlamlı olarak daha yüksek serum asimetrik dimetil arjinin düzeylerine sahip olduğu belirlendi (p = 0,013).

Sonuç: Çalışmamızın sonuçlarına göre, aterosklerotik süreçte tip 2 diabetes mellituslu mikroalbüminürisi olan hastalarda serum asimetrik dimetil arjininin fetuin-A'ya üstün olduğu ileri sürülebilir.

Keywords

diabetes mellitus tip 2 serum asimetrik dimetil arjinin fetuin A ankle brakiyal indeks mikroalbüminüri.

References

  • David KM. Definition of diabetes mellitus. In: Rose BD (ed). Uptodate. Wellesley: 2009: 17 (1). [Cited 26 May 2018]. Available from: http://www.uptodate.com.
  • St Clair L, Ballantyne CM. Biological surrogates for enhancing cardiovascular risk prediction in type 2 diabetes mellitus. Am J Cardiol 2007; 99: 80B-8B.
  • Lorant DP, Grujicic M, Hoebaus C, et al. Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease. Diabetes care 2011; 34: 156–61.
  • Roos M, Oikonomou D, von Eynatten M, et al. Associations of fetuin-A levels with vascular disease in type 2 diabetes patients with early diabetic nephropathy. Cardiovascular diabetology 2010; 9: 48.
  • Mogensen CE. Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia 1999; 42: 263–85. 404 Ege Tıp Dergisi
  • Garg JP, Bakris GL. Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease. Vascular medicine 2002; 7 (1): 35-43.
  • Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med 1997; 157: 1413-8.
  • Spittell JA Jr. Diagnosis and management of occlusive peripheral arterial disease. Curr Probl Cardiol 1990; 15: 1.
  • Resnick HE, Lindsay RS, McDermott MM, et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study. Circulation 2004; 109: 733–9.
  • Barclay L, Vega C. Fetuin-A linked with incident diabetes. JAMA 2008; 300: 182-8.
  • Schafer C, Heiss A, Schwarz A, et al. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003; 112: 357–66.
  • Stefan N, Hennige AM, Staiger H, et al. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes care 2006; 29: 853–7.
  • Hennige AM, Staiger H, Wicke C, et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One 2008; 3 (3): 1765.
  • Eraso LH, Ginwala N, Qasim AN, et al. Association of lower plasma fetuin-A levels with peripheral arterial disease in type 2 diabetes. Diabetes care 2010; 33: 408–10.
  • Krzyzanowska K, Mittermayer F, Shnawa N, 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.
  • Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31 (7): 1281-357.
  • Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129 (2): 1–45.
  • American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes care 2003; 26: 3333–41.
  • Naidoo DP. The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. Cardiovascular journal of South Africa 2002; 13: 194-9.
  • Li M, Xu M, Bi Y, et al. Association between higher serum fetuin-a concentrations and abnormal albuminuria in middle-aged and elderly chinese with normal glucose tolerance. Diabetes care 2010; 33 (11): 2462-4.
  • Krisztián V, Károly C, László K. The role of fetuin-A in cardiovascular diseases. Orv Hetil 2013; 155 (1): 16–23.
  • Ix JH, Wassel CL, Kanaya AM, et al. Fetuin A and incident diabetes mellitus in older persons. JAMA 2008; 300: 182-8.
  • Stefan N, Haring HU, Schulze MB. Association of serum fetuin A level and diabetes risk. JAMA 2008; 300: 2247-8.
  • 24. Mori K, Emoto M, Inaba M. Fetuin A: A multifunctional protein. Recent patents on endocrine, metabolic & immune drug discovery 2011; 5: 124-46.
  • Eleftheriadou I, Grigoropoulou P, Kokkinos A, et al. Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus. J Diabetes Complications 2017; 31: 599–604.
  • Stefan N, Fritsche A, Weikert C, et al. Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes 2008; 57: 2762-7. Cilt 58 Sayı 4, Aralık 2019 / Volume 58 Issue 4, December 2019 405
  • Weikert C, Stefan N, Schulze MB, et al. Plasma fetuin-a levels and the risk of myocardial infarction and ischemic stroke. Circulation 2008; 118: 2555-62.
  • Jirak P, Mirna M, Wernly B, et al. Analysis of novel cardiovascular biomarkers in patients with peripheral artery disease (PAD). Minerva Med doi: 10.23736/S0026-4806.18.05628-8.
  • Guo L, Cheng Y, Wang X, et al. Association between microalbuminuria and cardiovascular disease in type 2 diabetes mellitus of the Beijing Han nationality. Acta Diabetol 2012; 49 (1): 65-71.
  • 30. Makhdoomi K, Mohammadi A, Yekta Z, Aghasi MR, Zamani N, Vossughian S. Correlation between ankle-brachial index and microalbuminuria in type 2 diabetes mellitus. Iranian journal of kidney diseases 2013; 7: 204-9.
  • Tseng CH, Chong CK, Tseng CP, Tai TY. The association between urinary albumin excretion and ankle-brachial index in elderly Taiwanese patients with type 2 diabetes mellitus. Age Ageing 2008; 37: 77-82.
  • Choi SW, Yun WJ, Kim HY, et al. Association between albuminuria, carotid atherosclerosis, arterial stiffness, and peripheral arterial disease in Korean type 2 diabetic patients. Kidney Blood Press Res 2010; 33: 111-8.
  • Cao JJ, Barzilay JI, Peterson D, et al. The association of microalbuminuria with clinical cardiovascular diseasemand subclinical atherosclerosis in the elderly: the Cardiovascular Health Study. Atherosclerosis 2006; 187: 372-7.
  • Hanai K, Babazono T, Nyumura I, et al. Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes. Nephrol Dial Transplant 2009; 24: 1884–8.
  • Cavusoglu E, Ruwende C, Chopra V, 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 2010; 210 (1): 226–31.
  • Celik M, Cerrah S, Arabul M, Akalin A. Relation of asymmetric dimethylarginine levels to macrovascular disease and inflammation markers in type 2 diabetic patients. Journal of diabetes research 2014;2014:139215. doi: 10.1155/2014/139215.
  • Ozdogan O, Cekic B. Is there a correlation between plasma levels of asymmetric dimethylarginine (ADMA) levels and atherosclerosis in type 2 diabetes patients in Turkey? The Medical Bulletin of Sisli Etfal Hospital 2017; 51 (1): 63-70.
  • Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007; 115: 459-67.
  • Bernard S, Serusclat A, Targe F, et al. Incremental predictive value of carotid ultrasonography in the assessment of coronary risk in a cohort of asymptomatic type 2 diabetic subjects. Diabetes care 2005; 28: 1158-62.
  • Karakoç A, Sahin A, Polat ES, et al. Serum apelin and ADMA levels in type 2 diabetics with and without vascular complications. Diabetes & metabolic syndrome 2016;10(2 Suppl 1):106-9.
  • Hsu CP, Hsu PF, Chung MY, Lin SJ, Lu TM. Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control. Cardiovascular diabetology 2014; 13: 156.
  • Paiva H, Lehtimaki T, Laakso J, et al. Plasma concentrations of asymmetric-dimethylarginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabolism 2003; 52 (3): 303-7.
  • Witte EC, Lambers Heerspink HJ, de Zeeuw D, Bakker SJ, de Jong PE, Gan-sevoort R. First morning voids are more reliable than spot urine samples to assess microalbuminuria. J Am Soc Nephrol 2009; 20: 436–43.
There are 43 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Articles
Authors

Aslı Kılavuz 0000-0002-0474-9911

Bakiye Göker 0000-0002-5714-7455

Sumru Savaş 0000-0003-4836-3786

Çığır Biray Avcı 0000-0002-2748-3124

Fulden Saraç 0000-0001-9281-2492

Cumhur Gündüz 0000-0002-6593-3237

Publication Date December 30, 2019
Submission Date November 9, 2018
Published in Issue Year 2019Volume: 58 Issue: 4

Cite

Vancouver Kılavuz A, Göker B, Savaş S, Biray Avcı Ç, Saraç F, Gündüz C. Mikroalbüminürisi olan ve olmayan tip 2 diyabetik hastalarda serum asimetrik dimetil arjinin, fetuin-A ve ankle-brakial indeks değerlerinin değerlendirilmesi. EJM. 2019;58(4):397-405.
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