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Published in: Diabetologia 7/2009

01-07-2009 | Article

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

Authors: F. Piarulli, G. Sartore, A. Ceriello, E. Ragazzi, R. Reitano, L. Nollino, C. Cosma, D. Fedele, A. Lapolla

Published in: Diabetologia | Issue 7/2009

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Abstract

Aims/hypothesis

This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes.

Methods

The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA1c, malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile.

Results

Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 μg/min) and 62 with microalbuminuria (AER ≥20 μg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean ± SD): fasting plasma glucose 9.41 ± 2.88 vs 8.19 ± 1.93 mmol/l, p < 0.05; HbA1c 7.97 ± 1.51 vs 7.39 ± 1.03%, p < 0.05; MDA 1.18 ± 0.35 vs 1.02 ± 0.29 µmol/l, p < 0.05; pentosidine 98.5 ± 24.6 vs 82.9 ± 20.9 pmol/ml, p < 0.005; and AGE 13.2 ± 4.8 vs 10.6 ± 3.8 µg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA1c r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = −0.55, p < 0.001; TRAP r = −0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA1c and MDA, but not pentosidine or AGE.

Conclusions/interpretation

Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.
Literature
1.
go back to reference Deckert T, Yokoyama H, Mathiesen E et al (1996) Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin-dependent diabetes. BMJ 1312:871–874 Deckert T, Yokoyama H, Mathiesen E et al (1996) Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin-dependent diabetes. BMJ 1312:871–874
2.
go back to reference Gall MA, Borch-Johnsen K, Hougaard P, Nielsen FS, Parving HH (1995) Albuminuria and poor glycemic control predict mortality in non-insulin-dependent diabetes mellitus. Diabetes 44:1301–1309CrossRef Gall MA, Borch-Johnsen K, Hougaard P, Nielsen FS, Parving HH (1995) Albuminuria and poor glycemic control predict mortality in non-insulin-dependent diabetes mellitus. Diabetes 44:1301–1309CrossRef
3.
go back to reference Stehouwer CDA (1997) von Willebrand factor, dysfunction of the vascular endothelium, and the development of renal and vascular complications in diabetes. In: Mogensen CE (ed) The kidney and hypertension in diabetes mellitus. Kluwer, Boston, pp 155–163 Stehouwer CDA (1997) von Willebrand factor, dysfunction of the vascular endothelium, and the development of renal and vascular complications in diabetes. In: Mogensen CE (ed) The kidney and hypertension in diabetes mellitus. Kluwer, Boston, pp 155–163
4.
go back to reference Schmidt AM, Crandall J, Hori O, Cao R, Lakatta E (1996) Elevated plasma levels of vascular cell adhesion molecule-1 (VCAM-1) in diabetic patients with microalbuminuria: a marker of vascular dysfunction and progressive vascular disease. Br J Haematol 92:747–750PubMedCrossRef Schmidt AM, Crandall J, Hori O, Cao R, Lakatta E (1996) Elevated plasma levels of vascular cell adhesion molecule-1 (VCAM-1) in diabetic patients with microalbuminuria: a marker of vascular dysfunction and progressive vascular disease. Br J Haematol 92:747–750PubMedCrossRef
5.
go back to reference Naidoo DP (2002) The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. Cardiovasc J S Afr 13:194–199PubMed Naidoo DP (2002) The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. Cardiovasc J S Afr 13:194–199PubMed
6.
go back to reference Satchell SC, Tooke JE (2008) What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia 51:714–725PubMedCrossRef Satchell SC, Tooke JE (2008) What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia 51:714–725PubMedCrossRef
7.
go back to reference Brownlee M (2005) The pathophysiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMedCrossRef Brownlee M (2005) The pathophysiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMedCrossRef
8.
go back to reference Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790PubMedCrossRef Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790PubMedCrossRef
9.
go back to reference Lee TS, MacGregor LC, Fluharty SJ, King GL (1989) Differential regulation of protein kinase C and (Na, K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells. J Clin Invest 83:90–94PubMedCrossRef Lee TS, MacGregor LC, Fluharty SJ, King GL (1989) Differential regulation of protein kinase C and (Na, K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells. J Clin Invest 83:90–94PubMedCrossRef
10.
go back to reference Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 23:599–622PubMedCrossRef Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 23:599–622PubMedCrossRef
11.
go back to reference Maxwell SR, Thomason H, Sandler D et al (1997) Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus. Eur J Clin Invest 271:484–490CrossRef Maxwell SR, Thomason H, Sandler D et al (1997) Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus. Eur J Clin Invest 271:484–490CrossRef
12.
go back to reference Beisswenger PJ, Moore LL, Brinck-Johnsen T, Curphey TJ (1993) Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy. J Clin Invest 92:212–217PubMedCrossRef Beisswenger PJ, Moore LL, Brinck-Johnsen T, Curphey TJ (1993) Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy. J Clin Invest 92:212–217PubMedCrossRef
13.
go back to reference Berg TJ, Bangstad HJ, Torjesen PA, Osterby R, Bucala R, Hanssen KF (1997) Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin-dependent diabetes mellitus. Metabolism 46:661–665PubMedCrossRef Berg TJ, Bangstad HJ, Torjesen PA, Osterby R, Bucala R, Hanssen KF (1997) Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin-dependent diabetes mellitus. Metabolism 46:661–665PubMedCrossRef
14.
go back to reference Miura J, Yamagishi S, Uchigata Y et al (2003) Serum levels of N-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with type 1 diabetes. J Diabetes Complications 17:16–21PubMedCrossRef Miura J, Yamagishi S, Uchigata Y et al (2003) Serum levels of N-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with type 1 diabetes. J Diabetes Complications 17:16–21PubMedCrossRef
15.
go back to reference Aso Y, Takanashi K, Sekine K et al (2004) Dissociation between urinary pyrraline and pentosidine concentrations in diabetic patients with advanced nephropathy. J Lab Clin Med 144:92–99PubMedCrossRef Aso Y, Takanashi K, Sekine K et al (2004) Dissociation between urinary pyrraline and pentosidine concentrations in diabetic patients with advanced nephropathy. J Lab Clin Med 144:92–99PubMedCrossRef
16.
go back to reference Turk N, Mornar A, Mrzljak V, Turk Z (2003) Urinary excretion of advanced glycation end products in patients with type 2 diabetes and various stages of proteinuria. Diabetes Metab 30:187–192CrossRef Turk N, Mornar A, Mrzljak V, Turk Z (2003) Urinary excretion of advanced glycation end products in patients with type 2 diabetes and various stages of proteinuria. Diabetes Metab 30:187–192CrossRef
17.
go back to reference Wautier MP, Massin P, Guillausseau PJ et al (2003) N(carboxymethyl) lysine as a biomarker for microvascular complications in type 2 diabetic patients. Diabetes Metab 29:44–52PubMedCrossRef Wautier MP, Massin P, Guillausseau PJ et al (2003) N(carboxymethyl) lysine as a biomarker for microvascular complications in type 2 diabetic patients. Diabetes Metab 29:44–52PubMedCrossRef
18.
go back to reference Hirata K, Kubo K (2004) Relationship between blood levels of N-carboxymethyl-lysine and pentosidine and the severity of microangiopathy in type 2 diabetes. Endocr J 51:537–544PubMedCrossRef Hirata K, Kubo K (2004) Relationship between blood levels of N-carboxymethyl-lysine and pentosidine and the severity of microangiopathy in type 2 diabetes. Endocr J 51:537–544PubMedCrossRef
19.
go back to reference Gallou G, Ruelland A, Legras B, Maugendre D, Allannic H, Cloarec L (1993) Plasma malondialdehyde in type 1 and type 2 diabetic patients. Clin Chim Acta 214:227–234PubMedCrossRef Gallou G, Ruelland A, Legras B, Maugendre D, Allannic H, Cloarec L (1993) Plasma malondialdehyde in type 1 and type 2 diabetic patients. Clin Chim Acta 214:227–234PubMedCrossRef
20.
go back to reference Ozdemir G, Ozden M, Maral H, Kuskay S, Cetinalp P, Tarkun I (2005) Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria. Ann Clin Biochem 42:99–104PubMedCrossRef Ozdemir G, Ozden M, Maral H, Kuskay S, Cetinalp P, Tarkun I (2005) Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria. Ann Clin Biochem 42:99–104PubMedCrossRef
21.
go back to reference Huggett AST, Nixon DA (1957) Use of glucose oxidase peroxidase and O-dianisine in the determination of blood and urine glucose. Lancet 2:368–370CrossRef Huggett AST, Nixon DA (1957) Use of glucose oxidase peroxidase and O-dianisine in the determination of blood and urine glucose. Lancet 2:368–370CrossRef
22.
go back to reference Jaynes PK, Willis MC, Chon PP (1993) Evaluation of minicolumn chromatographic procedure for the measurement of HbA1c. Clin Biochem 39:2162–2165 Jaynes PK, Willis MC, Chon PP (1993) Evaluation of minicolumn chromatographic procedure for the measurement of HbA1c. Clin Biochem 39:2162–2165
23.
go back to reference Allain CC, Poon LS, Chan CS, Richmond W, Fu PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20:470–475PubMed Allain CC, Poon LS, Chan CS, Richmond W, Fu PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20:470–475PubMed
24.
go back to reference Lipid Research Clinics Program (1982) Lipid and lipoprotein analysis. In: Hainline A, Karon J, Lippel K (eds) Manual of laboratory operations. Washington DC, pp 63–77 Lipid Research Clinics Program (1982) Lipid and lipoprotein analysis. In: Hainline A, Karon J, Lippel K (eds) Manual of laboratory operations. Washington DC, pp 63–77
25.
go back to reference Fossati P, Prencipe L (1982) Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28:2077–2080PubMed Fossati P, Prencipe L (1982) Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28:2077–2080PubMed
26.
go back to reference Rowe DJ, Dawnay A, Watts GF (1990) Microalbuminuria in diabetes mellitus: review and recommendations for the measurement of albumin in urine. Ann Clin Biochem 27:297–312PubMed Rowe DJ, Dawnay A, Watts GF (1990) Microalbuminuria in diabetes mellitus: review and recommendations for the measurement of albumin in urine. Ann Clin Biochem 27:297–312PubMed
27.
go back to reference Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine Nephron 16:31–41 Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine Nephron 16:31–41
28.
go back to reference Odetti P, Fogarthy J, Sell D, Monnier VM (1992) Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects. Diabetes 41:153–159PubMedCrossRef Odetti P, Fogarthy J, Sell D, Monnier VM (1992) Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects. Diabetes 41:153–159PubMedCrossRef
29.
go back to reference Makita Z, Vlassara H, Cerami A, Bucala R (1992) Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem 267:5133–5138PubMed Makita Z, Vlassara H, Cerami A, Bucala R (1992) Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem 267:5133–5138PubMed
30.
go back to reference Hendricks T, Assmann RF (1998) On the fluorimetric assay of circulating lipoperoxides. Clin Chim Acta 174:263–270CrossRef Hendricks T, Assmann RF (1998) On the fluorimetric assay of circulating lipoperoxides. Clin Chim Acta 174:263–270CrossRef
31.
go back to reference Ghiselli A, Serafini M, Maiani G, Azzini E, Ferro-Luzzi A (1995) A fluorescence-based method for measuring total plasma antioxidant capacity. Free Radic Biol Med 18:29–36PubMedCrossRef Ghiselli A, Serafini M, Maiani G, Azzini E, Ferro-Luzzi A (1995) A fluorescence-based method for measuring total plasma antioxidant capacity. Free Radic Biol Med 18:29–36PubMedCrossRef
32.
go back to reference Laidman DL, Hall GS (1971) Adsorption column chromatography of tocopherols. In: McCormick DB, Wright LD (eds) Methods in enzymology, part C: vitamins and coenzymes, vol 18. Academic Press, New York, pp 349–356CrossRef Laidman DL, Hall GS (1971) Adsorption column chromatography of tocopherols. In: McCormick DB, Wright LD (eds) Methods in enzymology, part C: vitamins and coenzymes, vol 18. Academic Press, New York, pp 349–356CrossRef
33.
go back to reference Armitage P (1971) Statistical methods in medical research. Blackwell, Oxford Armitage P (1971) Statistical methods in medical research. Blackwell, Oxford
34.
go back to reference Lipkovich I, Smith EP (2002) Biplot and singular value decomposition macros for Excel. J Statistical Software 7:1–15 Lipkovich I, Smith EP (2002) Biplot and singular value decomposition macros for Excel. J Statistical Software 7:1–15
35.
go back to reference Aitchinson J, Greenacre M (2002) Biplots of compositional data. Appl Stat 51:375–392 Aitchinson J, Greenacre M (2002) Biplots of compositional data. Appl Stat 51:375–392
36.
go back to reference Dinneen SF, Gerstein HC (1997) The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. Arch Int Med 157:1413–1418CrossRef Dinneen SF, Gerstein HC (1997) The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. Arch Int Med 157:1413–1418CrossRef
37.
go back to reference Lapolla A, Piarulli F, Sartore G et al (2007) Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease. Diabetes Care 30:670–676PubMedCrossRef Lapolla A, Piarulli F, Sartore G et al (2007) Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease. Diabetes Care 30:670–676PubMedCrossRef
38.
go back to reference Aslan M, Sabuncu T, Kocyigit A, Celik H, Selek S (2007) Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients. Nutr Metab Cardiovasc Dis 17:734–740PubMedCrossRef Aslan M, Sabuncu T, Kocyigit A, Celik H, Selek S (2007) Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients. Nutr Metab Cardiovasc Dis 17:734–740PubMedCrossRef
39.
go back to reference Karamouzis I, Sarafidis PA, Karamouzis M et al (2008) Increase in oxidative stress but not in antioxidant capacity with advancing stages of chronic kidney disease. Am J Nephrol 28:397–404PubMedCrossRef Karamouzis I, Sarafidis PA, Karamouzis M et al (2008) Increase in oxidative stress but not in antioxidant capacity with advancing stages of chronic kidney disease. Am J Nephrol 28:397–404PubMedCrossRef
40.
go back to reference DeRubertis FR, Craven PA, Melhem MF, Salah EM (2004) Attenuation of renal injury in db/db mice overexpressing superoxide dismutase: evidence for reduced superoxide-nitric oxide interaction. Diabetes 53:762–768PubMedCrossRef DeRubertis FR, Craven PA, Melhem MF, Salah EM (2004) Attenuation of renal injury in db/db mice overexpressing superoxide dismutase: evidence for reduced superoxide-nitric oxide interaction. Diabetes 53:762–768PubMedCrossRef
41.
go back to reference Giannini C, Lombardo F, Currò F et al (2007) Effects of high-dose vitamin E supplementation on oxidative stress and microalbuminuria in young adult patients with childhood onset type 1 diabetes mellitus. Diabetes Metab Res Rev 23:539–546PubMedCrossRef Giannini C, Lombardo F, Currò F et al (2007) Effects of high-dose vitamin E supplementation on oxidative stress and microalbuminuria in young adult patients with childhood onset type 1 diabetes mellitus. Diabetes Metab Res Rev 23:539–546PubMedCrossRef
42.
go back to reference Lonn E, Yusuf S, Hoogwerf B, HOPE Study; MICRO-HOPE Study et al (2002) Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Diabetes Care 25:1919–1927PubMedCrossRef Lonn E, Yusuf S, Hoogwerf B, HOPE Study; MICRO-HOPE Study et al (2002) Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Diabetes Care 25:1919–1927PubMedCrossRef
43.
go back to reference Yokoyama M, Torita M, Yoshizawa M, Usuda R (2001) Indication of vitamin E on microalbuminuria in patients with incipient diabetic nephropathy. Diabetes Metab 27:611–612PubMed Yokoyama M, Torita M, Yoshizawa M, Usuda R (2001) Indication of vitamin E on microalbuminuria in patients with incipient diabetic nephropathy. Diabetes Metab 27:611–612PubMed
Metadata
Title
Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients
Authors
F. Piarulli
G. Sartore
A. Ceriello
E. Ragazzi
R. Reitano
L. Nollino
C. Cosma
D. Fedele
A. Lapolla
Publication date
01-07-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1367-y

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