Abstract
Background
Nonenzymatic modification of proteins by reducing sugars leads to the formation of advanced glycation end products (AGEs), whose process has been reported to progress under diabetes. Recently, diet has been found to be a major environmental source of proinflammatory AGEs in humans. Further, fats or meat‐derived products processed by high heat such as broiling have been shown to contain more AGEs than carbohydrates boiled for longer periods. Since circulating levels of low‐density lipoprotein cholesterol (LDL‐C) are also regulated by dietary cholesterol, it is conceivable that intake of cholesterol‐rich foods could regulate serum levels of AGEs in humans. In this study, we investigated whether LDL‐C levels are one of the independent determinants of circulating AGEs levels in a nondiabetic general population.
Methods
A total of 170 nondiabetic Japanese subjects underwent a complete history, physical examination, determination of blood chemistries, and serum AGEs.
Results
Univariate analysis showed that AGEs levels were associated with LDL‐C (P < 0.05) and fasting plasma glucose levels (P < 0.05). By the use of multiple stepwise regression analyses, LDL‐C (P < 0.01) and fasting plasma glucose levels (P < 0.05) remained significant and were independently related to AGEs levels (R 2 = 0.069).
Conclusions
The present study is the first demonstration that LDL‐C levels are one of the independent determinants of serum levels of AGEs in a nondiabetic general population. Intake of cholesterol‐rich foods may regulate serum levels of AGEs in nondiabetic subjects. Copyright © 2009 Wiley Periodicals, Inc.
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References
- 1. Vlassara H, Bucala R, Striker L. Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest 1994; 70: 138–151. [PubMed] [Google Scholar]
- 2. Brownlee M. Advanced protein glycosylation in diabetes and aging. Ann Rev Med 1995; 46: 223–234. [DOI] [PubMed] [Google Scholar]
- 3. Yamagishi S, Imaizumi T. Diabetic vascular complications: pathophysiology, biochemical basis and potential therapeutic strategy. Curr Pharm Des 2005; 11: 2279–2299. [DOI] [PubMed] [Google Scholar]
- 4. Yamagishi S, Ueda S, Okuda S. Food‐derived advanced glycation end products (AGEs): a novel therapeutic target for various disorders. Curr Pharm Des 2007; 13: 2832–2836. [DOI] [PubMed] [Google Scholar]
- 5. Koschinsky T, He CJ, Mitsuhashi T, et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997; 94: 6474–6479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. He C, Sabol J, Mitsuhashi T, Vlassara H. Dietary glycotoxins: inhibition of reactive products by aminoguanidine facilitates renal clearance and reduces tissue sequestration. Diabetes 1999; 48: 1308–1315. [DOI] [PubMed] [Google Scholar]
- 7. Lin RY, Reis ED, Dore AT, et al. Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice. Atherosclerosis 2002; 163: 303–311. [DOI] [PubMed] [Google Scholar]
- 8. Uribarri J, Cai W, Sandu O, et al. Diet‐derived advanced glycation end products are major contributors to the body's AGE pool and induce inflammation in healthy subjects. Ann NY Acad Sci 2005; 1043: 461–466. [DOI] [PubMed] [Google Scholar]
- 9. Yamagishi S, Nakamura K, Matsui T, Sato T, Takeuchi M. Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver. Med Hypothese 2006; 67: 1463–1464. [DOI] [PubMed] [Google Scholar]
- 10. Grundy SM, Denke MA. Dietary influences on serum lipids and lipoproteins. J Lipid Res 1990; 31: 1149–1172. [PubMed] [Google Scholar]
- 11. Takeuchi M, Makita Z, Bucala R, et al. Immunological evidence that non‐carboxymethyllysine advanced glycation end‐products produced from short chain sugars and dicarbonyl compounds in vivo. Molecular Med 2000; 6: 114–125. [PMC free article] [PubMed] [Google Scholar]
- 12. Yamagishi S, Adachi H, Nakamura K, et al. Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects. Metabolism 2006; 55: 1227–1231. [DOI] [PubMed] [Google Scholar]
- 13. Nakamura K, Yamagishi S, Matsui T, et al. Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are correlated with AGEs in both diabetic and nondiabetic subjects. Clin Exp Med 2007; 7: 188–190. [DOI] [PubMed] [Google Scholar]
- 14. Meerwaldt R, Links T, Graaff R, et al. Simple noninvasive measurement of skin autofluorescence. Ann NY Acad Sci 2005; 1043: 290–298. [DOI] [PubMed] [Google Scholar]
- 15. Yamagishi S, Adachi H, Takeuchi M, et al. Serum level of advanced glycation end‐products (AGEs) is an independent determinant of plasminogen activator inhibitor‐1 (PAI‐1) in nondiabetic general population. Horm Metab Res 2007; 39: 845–848. [DOI] [PubMed] [Google Scholar]
- 16. Kilhovd BK, Juutilainen A, Lehto S, et al. High serum levels of advanced glycation end products predict increased coronary heart disease mortality in nondiabetic women but not in nondiabetic men: a population‐based 18‐year follow‐up study. Arterioscler Thromb Vasc Biol 2005; 25: 815–820. [DOI] [PubMed] [Google Scholar]
- 17. Saisho Y, Komiya N, Hirose H. Effect of valsartan, an angiotensin II receptor blocker, on markers of oxidation and glycation in Japanese type 2 diabetic subjects: blood pressure‐independent effect of valsartan. Diabetes Res Clin Pract 2006; 74: 201–203. [DOI] [PubMed] [Google Scholar]
- 18. Yamagishi S, Nakamura K, Matsui T. Potential utility of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator‐activated receptor‐gamma (PPAR‐gamma)‐modulating activity for the treatment of cardiometabolic disorders. Curr Mol Med 2007; 7: 463–469. [DOI] [PubMed] [Google Scholar]
- 19. Miura J, Yamagishi S, Uchigata Y, et al. Serum levels of non‐carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with type 1 diabetes. J Diabetes Complications 2003; 17: 16–21. [DOI] [PubMed] [Google Scholar]