Homocysteine levels in patients of type 2 diabetes mellitus with diabetic nephropathy and its clinical implications
Keywords:
Homocysteine, Diabetic Nephropathy, Microalbuminuria, Type 2 Diabetes Mellitus
Abstract
Introduction: Diabetic nephropathy is one of the most common and serious complications of long standing type 2 diabetes mellitus. Microalbuminuria is a strong predictor of diabetic nephropathy. Homocysteine level plays an important role in pathogenesis of diabetic microvascular complications, particularly diabetic nephropathy. Vitamin B12, Folic acid and Vitamin B6 facilitate homocysteine metabolism.
Methods: This case- control study was carried out at a tertiary care centre. Total 150 subjects were enrolled, which included 60 cases of type 2 diabetes with microalbuminuria, 60 cases of type 2 diabetes without microalbuminuria and 30 healthy controls. Besides routine investigations, fasting blood glucose, glycated haemoglobin, and homocysteine levels in serum were measured. All subjects were screened for microalbuminuria. Statistical analysis was done.
Results: Homocysteine levels, fasting blood glucose and glycated haemoglobin were significantly higher in patients of type 2 diabetes with microalbuminuria as compared to those without microalbuminuria (p = 0.00, p = 0.01, p = 0.01). Strong positive correlation was observed between the homocysteine levels and degree of microalbuminuria(r = +0.758, p = 0.00), and also between the fasting blood glucose levels and degree of microalbuminuria (r = +0.259, p = 0.02).
Conclusions: It would be useful to perform an early screening for raised homocysteine levels and for low vitamin levels in the patients of uncontrolled diabetics. This would help to evaluate the need of folic acid, Vitamin B12 and Vitamin B6 supplements since these supplements can be beneficial for delaying the progress of diabetic nephropathy in these patients.
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References
1. King H, Rewers M. Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group. Diabetes Care. 1993 Jan;16(1):157-77.
2. Zargar AH, Wani AI, Masoodi SR, Laway BA, Bashir MI. Mortality in diabetes mellitus--data from a developing region of the world. Diabetes Res Clin Pract. 1999 Jan;43(1):67-74.
3. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983 May;32 Suppl 2:64-78.
4. Lehmann R, Spinas GA. [Diabetic nephropathy: significance of microalbuminuria and proteinuria in Type I and Type II diabetes mellitus]. Praxis (Bern 1994). 1995 Oct 31;84(44):1265-71.
5. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989 Apr;32(4):219-26.
6. 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 Jul 14;157(13):1413-8.
7. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S; HOPE Study Investigators. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001 Jul 25;286(4):421-6.
8. Mudd SH, Uhlendorf BW, Freeman JM, Finkelstein JD, Shih VE. Homocysteinuria associated with decreased methylene tetrahydrofolate reductase activity. Biochem Biophys Res Commun 1972 Jan; 46(2): 905-912, PMID: 5057914
9. Mudd SH, Poole JR. Labile methyl balances for normal humans on various dietary regimens. Metabolism. 1975 Jun;24(6):721-35.
10. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969 Jul;56(1):111-28.
11. Cattaneo M. Hyperhomocysteinemia and thrombosis. Lipids 2001 Jan;36(1): pp. S13- S26.
12. Heijer M, Keijzer MB. Hyperhomocysteinemia as a risk factor for venous thrombosis. Clin Chem Lab Med. 2001 Aug;39(8):710-3.
13. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-8.
14. Hoogeveen EK, Kostense PJ, Becks PJ, Mackay AJ, Jakobs C, Bouter LM, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin dependent diabetes mellitus: A population-based study. Arteriosclerosis Thrombosis and Vascular Biology 1998; 18: 133-38, doi: 10.1161/01.ATV.18.1.133
15. Davies L, Wilmshurst EG, McElduff A, Gunton J, Clifton-Bligh P, Fulcher GR. The relationship among homocysteine, creatinine clearance, and albuminuria in patients with type 2 diabetes. Diabetes Care. 2001 Oct;24(10):1805-9.
16. Hultberg B, Agardh E, Andersson A, Brattström L, Isaksson A, Israelsson B, Agardh CD. Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus. Scand J Clin Lab Invest. 1991 May;51(3):277-82.
17. Wollesen F, Brattström L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int. 1999 Mar;55(3):1028-35.
18. Fonseca VA, Reynolds T, Fink LM. Hyperhomocysteinemia and microalbuminuria in diabetes. Diabetes Care. 1998 Jun;21(6):1028.
19. Chico A, Pérez A, Córdoba A, Arcelús R, Carreras G, de Leiva A, González-Sastre F, Blanco-Vaca F. Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link betweendiabetic nephropathy and cardiovascular disease? Diabetologia. 1998 Jun;41(6):684-93.
20. Lanfredini M, Fiorina P, Peca MG, Veronelli A, Mello A, Astorri E, Dall'Aglio P, Craveri A. Fasting and post-methionine load homocyst(e)ine values are correlated with microalbuminuria and could contribute to worsening vascular damage in non-insulin-dependent diabetes mellitus patients. Metabolism. 1998 Aug;47(8):915-21.
21. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem. 1993 Sep;39(9):1764-79.
22. Nehler MR, Taylor LM Jr, Porter JM Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovasc Pathol. 1997 Jan;6(1):1-9. doi: 10.1016/S1054-8807(96)00064-6.
23. Gomes MB, Lucchetti MR, Gonclaves MFR, Gazzolla H, Dimetz T, Matos H. Influence of first morning urine volume, fasting blood glucose and glycosylated haemoglobin on first morning urinary albumin concentration. Braz J Med Biol Res.1997 Feb; 30(2): 191-96, PMID: 9239304.
24. Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, Miedema K, Mosca A, Mauri P, Paroni R, Thienpont L, Umemoto M, Weykamp C; International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med. 2002 Jan;40(1):78-89.
25. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
26. Sheikh SA, Baig JA, Iqbal T, Kazmi T, Baig M, Husain SS. Prevalence of microalbuminuria with relation to glycemic control in type-2 diabetic patients in Karachi. J Ayub Med Coll Abbottabad. 2009 Jul-Sep;21(3):83-6.
27. Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006 Apr 12;295(14):1707-8.
28. Jager A, Kostense PJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Donker AJ, Stehouwer CD. Serum homocysteine levels are associated with the development of (micro)albuminuria: the Hoorn study. Arterioscler Thromb Vasc Biol. 2001 Jan;21(1):74-81.
29. Friedman AN, Hunsicker LG, Selhub J, Bostom AG; Collaborative Study Group. Proteinuria as a predictor of total plasma homocysteine levels in type 2 diabetic nephropathy. Diabetes Care. 2002 Nov;25(11):2037-41.
30. Hofmann MA, Kohl B, Zumbach MS, Borcea V, Bierhaus A, Henkels M, Amiral J, Fiehn W, Ziegler R, Wahl P, Nawroth PP. Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM. Diabetes Care. 1997 Dec;20(12):1880-6.
31. Fanapour PC, Yug B, Kochar MS. Hyperhomocysteinemia: an additional cardiovascular risk factor. WMJ. 1999 Dec;98(8):51-4.
32. Lippi G, Arosio E, Prior M, Guidi G. Biochemical risk factors for cardiovascular disease in an aged male population: emerging vascular pathogens. Angiology. 2001 Oct;52(10):681-7.
33. Lussier-Cacan S, Xhignesse M, Piolot A, Selhub J, Davignon J, Genest J Jr. Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits. Am J Clin Nutr. 1996 Oct;64(4):587-93.
34. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993 Dec 8;270(22):2693-8.
35. Mudd SH. Diseases of sulphur metabolism: implications for the methionine-homocysteine cycle, and vitamin responsiveness. Ciba Found Symp. 1979;(72):239-58.
36. Mudd SH. Diseases of sulphur metabolism: implications for the methionine-homocysteine cycle, and vitamin responsiveness. Ciba Found Symp. 1979;(72):239-58
2. Zargar AH, Wani AI, Masoodi SR, Laway BA, Bashir MI. Mortality in diabetes mellitus--data from a developing region of the world. Diabetes Res Clin Pract. 1999 Jan;43(1):67-74.
3. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983 May;32 Suppl 2:64-78.
4. Lehmann R, Spinas GA. [Diabetic nephropathy: significance of microalbuminuria and proteinuria in Type I and Type II diabetes mellitus]. Praxis (Bern 1994). 1995 Oct 31;84(44):1265-71.
5. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989 Apr;32(4):219-26.
6. 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 Jul 14;157(13):1413-8.
7. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S; HOPE Study Investigators. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001 Jul 25;286(4):421-6.
8. Mudd SH, Uhlendorf BW, Freeman JM, Finkelstein JD, Shih VE. Homocysteinuria associated with decreased methylene tetrahydrofolate reductase activity. Biochem Biophys Res Commun 1972 Jan; 46(2): 905-912, PMID: 5057914
9. Mudd SH, Poole JR. Labile methyl balances for normal humans on various dietary regimens. Metabolism. 1975 Jun;24(6):721-35.
10. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969 Jul;56(1):111-28.
11. Cattaneo M. Hyperhomocysteinemia and thrombosis. Lipids 2001 Jan;36(1): pp. S13- S26.
12. Heijer M, Keijzer MB. Hyperhomocysteinemia as a risk factor for venous thrombosis. Clin Chem Lab Med. 2001 Aug;39(8):710-3.
13. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-8.
14. Hoogeveen EK, Kostense PJ, Becks PJ, Mackay AJ, Jakobs C, Bouter LM, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin dependent diabetes mellitus: A population-based study. Arteriosclerosis Thrombosis and Vascular Biology 1998; 18: 133-38, doi: 10.1161/01.ATV.18.1.133
15. Davies L, Wilmshurst EG, McElduff A, Gunton J, Clifton-Bligh P, Fulcher GR. The relationship among homocysteine, creatinine clearance, and albuminuria in patients with type 2 diabetes. Diabetes Care. 2001 Oct;24(10):1805-9.
16. Hultberg B, Agardh E, Andersson A, Brattström L, Isaksson A, Israelsson B, Agardh CD. Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus. Scand J Clin Lab Invest. 1991 May;51(3):277-82.
17. Wollesen F, Brattström L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int. 1999 Mar;55(3):1028-35.
18. Fonseca VA, Reynolds T, Fink LM. Hyperhomocysteinemia and microalbuminuria in diabetes. Diabetes Care. 1998 Jun;21(6):1028.
19. Chico A, Pérez A, Córdoba A, Arcelús R, Carreras G, de Leiva A, González-Sastre F, Blanco-Vaca F. Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link betweendiabetic nephropathy and cardiovascular disease? Diabetologia. 1998 Jun;41(6):684-93.
20. Lanfredini M, Fiorina P, Peca MG, Veronelli A, Mello A, Astorri E, Dall'Aglio P, Craveri A. Fasting and post-methionine load homocyst(e)ine values are correlated with microalbuminuria and could contribute to worsening vascular damage in non-insulin-dependent diabetes mellitus patients. Metabolism. 1998 Aug;47(8):915-21.
21. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem. 1993 Sep;39(9):1764-79.
22. Nehler MR, Taylor LM Jr, Porter JM Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovasc Pathol. 1997 Jan;6(1):1-9. doi: 10.1016/S1054-8807(96)00064-6.
23. Gomes MB, Lucchetti MR, Gonclaves MFR, Gazzolla H, Dimetz T, Matos H. Influence of first morning urine volume, fasting blood glucose and glycosylated haemoglobin on first morning urinary albumin concentration. Braz J Med Biol Res.1997 Feb; 30(2): 191-96, PMID: 9239304.
24. Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, Miedema K, Mosca A, Mauri P, Paroni R, Thienpont L, Umemoto M, Weykamp C; International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med. 2002 Jan;40(1):78-89.
25. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
26. Sheikh SA, Baig JA, Iqbal T, Kazmi T, Baig M, Husain SS. Prevalence of microalbuminuria with relation to glycemic control in type-2 diabetic patients in Karachi. J Ayub Med Coll Abbottabad. 2009 Jul-Sep;21(3):83-6.
27. Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006 Apr 12;295(14):1707-8.
28. Jager A, Kostense PJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Donker AJ, Stehouwer CD. Serum homocysteine levels are associated with the development of (micro)albuminuria: the Hoorn study. Arterioscler Thromb Vasc Biol. 2001 Jan;21(1):74-81.
29. Friedman AN, Hunsicker LG, Selhub J, Bostom AG; Collaborative Study Group. Proteinuria as a predictor of total plasma homocysteine levels in type 2 diabetic nephropathy. Diabetes Care. 2002 Nov;25(11):2037-41.
30. Hofmann MA, Kohl B, Zumbach MS, Borcea V, Bierhaus A, Henkels M, Amiral J, Fiehn W, Ziegler R, Wahl P, Nawroth PP. Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM. Diabetes Care. 1997 Dec;20(12):1880-6.
31. Fanapour PC, Yug B, Kochar MS. Hyperhomocysteinemia: an additional cardiovascular risk factor. WMJ. 1999 Dec;98(8):51-4.
32. Lippi G, Arosio E, Prior M, Guidi G. Biochemical risk factors for cardiovascular disease in an aged male population: emerging vascular pathogens. Angiology. 2001 Oct;52(10):681-7.
33. Lussier-Cacan S, Xhignesse M, Piolot A, Selhub J, Davignon J, Genest J Jr. Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits. Am J Clin Nutr. 1996 Oct;64(4):587-93.
34. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993 Dec 8;270(22):2693-8.
35. Mudd SH. Diseases of sulphur metabolism: implications for the methionine-homocysteine cycle, and vitamin responsiveness. Ciba Found Symp. 1979;(72):239-58.
36. Mudd SH. Diseases of sulphur metabolism: implications for the methionine-homocysteine cycle, and vitamin responsiveness. Ciba Found Symp. 1979;(72):239-58
CITATION
DOI: 10.17511/ijmrr.2015.i9.195
Published: 2015-10-31
How to Cite
1.
Singla H, Panag K, Batta A, Goyal G. Homocysteine levels in patients of type 2 diabetes mellitus with diabetic nephropathy and its clinical implications. Int J Med Res Rev [Internet]. 2015Oct.31 [cited 2024Apr.23];3(9):1070-6. Available from: https://ijmrr.medresearch.in/index.php/ijmrr/article/view/366
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Original Article
OAI - Open Archives Initiative
