Gingival advanced glycation end-products in diabetes mellitus-associated chronic periodontitis: an immunohistochemical study
A. Zizzi
Department of Biomedical Sciences and Public Health - Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Antonio Zizzi and Giacomo Tirabassi contributed equally and are both to be considered as first authors.Search for more papers by this authorG. Tirabassi
Department of Clinical and Molecular Sciences - Endocrinology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Antonio Zizzi and Giacomo Tirabassi contributed equally and are both to be considered as first authors.Search for more papers by this authorS. D. Aspriello
Department of Odontostomatological and Specialized Clinical Sciences - Periodontology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Search for more papers by this authorM. Piemontese
Department of Odontostomatological and Specialized Clinical Sciences - Periodontology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Search for more papers by this authorCorresponding Author
C. Rubini
Department of Biomedical Sciences and Public Health - Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Corrado Rubini, MD, Department of Biomedical Sciences and Public Health, Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of Marche, Via Conca, 71, 60020 Ancona, Italy
Tel: +390715964804
Fax: +390715964809
e-mail: [email protected]
Search for more papers by this authorG. Lucarini
Department of Clinical and Molecular Sciences - Histology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Search for more papers by this authorA. Zizzi
Department of Biomedical Sciences and Public Health - Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Antonio Zizzi and Giacomo Tirabassi contributed equally and are both to be considered as first authors.Search for more papers by this authorG. Tirabassi
Department of Clinical and Molecular Sciences - Endocrinology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Antonio Zizzi and Giacomo Tirabassi contributed equally and are both to be considered as first authors.Search for more papers by this authorS. D. Aspriello
Department of Odontostomatological and Specialized Clinical Sciences - Periodontology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Search for more papers by this authorM. Piemontese
Department of Odontostomatological and Specialized Clinical Sciences - Periodontology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Search for more papers by this authorCorresponding Author
C. Rubini
Department of Biomedical Sciences and Public Health - Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Corrado Rubini, MD, Department of Biomedical Sciences and Public Health, Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of Marche, Via Conca, 71, 60020 Ancona, Italy
Tel: +390715964804
Fax: +390715964809
e-mail: [email protected]
Search for more papers by this authorG. Lucarini
Department of Clinical and Molecular Sciences - Histology, School of Medicine, Polytechnic University of Marche, Ancona, Italy
Search for more papers by this authorAbstract
Background and Objective
The accumulation of advanced glycation end-products (AGEs) seems to play an important role in the development of diabetes mellitus (DM)-associated periodontitis; however, some aspects of this issue are still scarcely known, such as the expression of AGEs in type 1 DM-associated periodontitis and the clinical factors able to affect their accumulation. This study aimed to clarify these points by evaluating the expression of AGEs in DM-associated periodontitis.
Material and Methods
Sixteen systemically and periodontally healthy subjects and 48 subjects suffering from generalized, severe, chronic periodontitis (16 with type 1 DM, 16 with type 2 DM and 16 systemically healthy subjects) were studied clinically, periodontally and metabolically. The immunohistochemical expression of AGEs in gingival tissues was also evaluated.
Results
Subjects affected with type 1 DM presented a significantly higher percentage of AGE-positive cells than did subjects affected with type 2 DM, not only in the epithelium, but also in vessels and fibroblasts. A positive and significant correlation was found between gingival expression of AGEs and length of time affected with DM both in type 1 and type 2 DM; glycated hemoglobin, lipid profile, body mass index and age did not correlate significantly with gingival AGEs in any of the classes of subjects studied.
Conclusions
Gingival AGEs are increased in both type 1 and type 2 DM-associated periodontitis; however, the clinical parameter that determines their accumulation, and therefore their degree of influence on the development of DM-associated periodontitis, may be the duration of DM.
References
- 1Mealey BL, Rose LF. Diabetes mellitus and inflammatory periodontal diseases. Curr Opin Endocrinol Diabetes Obes 2008; 15: 135–141.
- 2Sakallioğlu EE, Aliyev E, Lütfioğlu M, Yavuz U, Açikgöz G. Vascular endothelial growth factor (VEGF) levels of gingiva and gingival crevicular fluid in diabetic and systemically healthy periodontitis patients. Clin Oral Investig 2007; 11: 115–120.
- 3Salvi GE, Collins JG, Yalda B, Arnold RR, Lang NP, Offenbacher S. Monocytic TNF alpha secretion patterns in IDDM patients with periodontal diseases. J Clin Periodontol 1997; 24: 8–16.
- 4Manouchehr-Pour M, Spagnuolo PJ, Rodman HM, Bissada NF. Comparison of neutrophil chemotactic response in diabetic patients with mild and severe periodontal disease. J Periodontol 1981; 52: 410–415.
- 5McMullen JA, Van Dyke TE, Horoszewicz HU, Genco RJ. Neutrophil chemotaxis in individuals with advanced periodontal disease and a genetic predisposition to diabetes mellitus. J Periodontol 1981; 52: 167–173.
- 6Ramamurthy NS, Golub LM. Diabetes increases collagenase activity in extracts of rat gingiva and skin. J Periodontal Res 1983; 18: 23–30.
- 7Sasaki T, Ramamurthy NS, Yu Z, Golub LM. Tetracycline administration increases protein (presumably procollagen) synthesis and secretion in periodontal ligament fibroblasts of streptozotocin-induced diabetic rats. J Periodontal Res 1992; 27: 631–639.
- 8Mølvig J, Baek L, Christensen P et al. Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. Scand J Immunol 1988; 27: 705–716.
- 9Goh SY, Cooper ME. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93: 1143–1152.
- 10Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988; 318: 1315–1321.
- 11Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia 2001; 44: 129–146.
- 12Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med 1995; 46: 223–234.
- 13Katz J, Yoon TY, Mao S, Lamont RJ, Caudle RM. Expression of the receptor of advanced glycation end products in the gingival tissue of smokers with generalized periodontal disease and after nornicotine induction in primary gingival epithelial cells. J Periodontol 2007; 78: 736–741.
- 14Schmidt AM, Weidman E, Lalla E et al. Advanced glycation endproducts (AGEs) induce oxidant stress in the gingiva: a potential mechanism underlying accelerated periodontal disease associated with diabetes. J Periodontal Res 1996; 31: 508–515.
- 15Katz J, Bhattacharyya I, Farkhondeh-Kish F, Perez FM, Caudle RM, Heft MW. Expression of the receptor of advanced glycation end products in gingival tissues of type 2 diabetes patients with chronic periodontal disease: a study utilizing immunohistochemistry and RT-PCR. J Clin Periodontol 2005; 32: 40–44.
- 16Takeda M, Ojima M, Yoshioka H et al. Relationship of serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients. J Periodontol 2006; 77: 15–20.
- 17 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2006; 29(suppl 1): S43–S48.
- 18Aspriello SD, Zizzi A, Tirabassi G et al. Diabetes mellitus-associated periodontitis: differences between type 1 and type 2 diabetes mellitus. J Periodontal Res 2011; 46: 164–169.
- 19Aspriello SD, Zizzi A, Lucarini G et al. Vascular endothelial growth factor and microvessel density in periodontitis patients with and without diabetes. J Periodontol 2009; 80: 1783–1789.
- 20Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999; 4: 1–6.
- 21Lindhe J, Ranney R, Lamster I et al. Consensus report: chronic periodontitis. Ann Periodontol 1999; 4: 38.
10.1902/annals.1999.4.1.38 Google Scholar
- 22Löe H. The gingival index, the plaque index and the retention index systems. J Periodontol 1967; 38: 610–616.
- 23Mühlemann HR, Son S. Gingival sulcus bleeding – a leading symptom in initial gingivitis. Helv Odontol Acta 1971; 15: 107–113.
- 24Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat 1979; 6: 65–70.
- 25Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes 2008; 26: 77–82.
10.2337/diaclin.26.2.77 Google Scholar
- 26Unnikrishnan RI, Rema M, Pradeepa R et al. Prevalence and risk factors of diabetic nephropathy in an urban South Indian population: the Chennai Urban Rural Epidemiology Study (CURES 45). Diabetes Care 2007; 30: 2019–2024.
- 27Bacon CG, Hu FB, Giovannucci E, Glasser DB, Mittleman MA, Rimm EB. Association of type and duration of diabetes with erectile dysfunction in a large cohort of men. Diabetes Care 2002; 25: 1458–1463.
- 28Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Mott DM, Bennett PH. Sequential changes in serum insulin concentration during development of non-insulin-dependent diabetes. Lancet 1989; 1: 1356–1359.
- 29El-Kebbi IM, Ziemer DC, Cook CB, Miller CD, Gallina DL, Phillips LS. Comorbidity and glycemic control in patients with type 2 diabetes. Arch Intern Med 2001; 161: 1295–1300.
- 30Ahmed N, Thornalley PJ. Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes Metab 2007; 9: 233–245.
- 31Cloos PA, Christgau S. Non-enzymatic covalent modifications of proteins: mechanisms, physiological consequences and clinical applications. Matrix Biol 2002; 21: 39–52.
- 32Saremi A, Nelson RG, Tulloch-Reid M et al. Periodontal disease and mortality in type 2 diabetes. Diabetes Care 2005; 28: 27–32.
- 33Al-Shammari KF, Al-Ansari JM, Moussa NM, Ben-Nakhi A, Al-Arouj M, Wang HL. Association of periodontal disease severity with diabetes duration and diabetic complications in patients with type 1 diabetes mellitus. J Int Acad Periodontol 2006; 8: 109–114.
- 34Jakus V, Rietbrock N. Advanced glycation end-products and the progress of diabetic vascular complications. Physiol Res 2004; 53: 131–142.
- 35Beisswenger PJ, Moore LL, Curphey TJ. Relationship between glycemic control and collagen-linked advanced glycosylation end products in type I diabetes. Diabetes Care 1993; 16: 689–694.
- 36Kratochvilová M, Zakiyanov O, Kalousová M, Kříha V, Zima T, Tesař V. Associations of serum levels of advanced glycation end products with nutrition markers and anemia in patients with chronic kidney disease. Ren Fail 2011; 33: 131–137.
- 37Amin MN, Mosa AA, El-Shishtawy MM. Clinical study of advanced glycation end products in Egyptian diabetic obese and non-obese patients. Int J Biomed Sci 2011; 7: 191–200.
- 38Chang JB, Chu NF, Syu JT, Hsieh AT, Hung YR. Advanced glycation end products (AGEs) in relation to atherosclerotic lipid profiles in middle-aged and elderly diabetic patients. Lipids Health Dis 2011; 10: 228.
- 39Cutler CW, Shinedling EA, Nunn M et al. Association between periodontitis and hyperlipidemia: cause or effect? J Periodontol 1999; 70: 1429–1434.
- 40Genco RJ. Current view of risk factors for periodontal diseases. J Periodontol 1996; 67: 1041–1049.
- 41Pataro AL, Costa FO, Cortelli SC, Cortelli JR, Abreu MH, Costa JE. Association between severity of body mass index and periodontal condition in women. Clin Oral Investig 2011; 16: 727–734.
- 42Saito T, Shimazaki Y. Metabolic disorders related to obesity and periodontal disease. Periodontol 2000 2007; 43: 254–266.
- 43Goodson JM, Groppo D, Halem S, Carpino E. Is obesity an oral bacterial disease? J Dent Res 2009; 88: 519–523.
- 44Sato Y, Kondo T, Ohshima T. Estimation of age of human cadavers by immunohistochemical assessment of advanced glycation end products in the hippocampus. Histopathology 2001; 38: 217–220.
- 45Wells-Knecht KJ, Brinkmann E, Wells-Knecht MC et al. New biomarkers of Maillard reaction damage to proteins. Nephrol Dial Transplant 1996; 11: 41–47.
- 46Beattie JR, Pawlak AM, McGarvey JJ, Stitt AW. Sclera as a surrogate marker for determining AGE-modifications in Bruch's membrane using a Raman spectroscopy-based index of aging. Invest Ophthalmol Vis Sci 2011; 52: 1593–1598.
- 47Verzijl N, DeGroot J, Thorpe SR et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 2000; 275: 39027–39031.
- 48Dyer DG, Dunn JA, Thorpe SR et al. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest 1993; 91: 2463–2469.
- 49Amir J, Waite M, Tobler J et al. The role of hyperglycemia in mechanisms of exacerbated inflammatory responses within the oral cavity. Cell Immunol 2011; 272: 45–52.
- 50Rajeev K, Karthika R, Mythili R, Krishnan V, Nirmal M. Role of receptors of advanced glycation end-products (RAGE) in type 2 diabetic and non-diabetic individuals with chronic periodontal disease: an immunohistochemical study. J Investig Clin Dent 2011; 2: 287–292.
- 51Yu S, Li H, Ma Y, Fu Y. Matrix metalloproteinase-1 of gingival fibroblasts influenced by advanced glycation end products (AGEs) and their association with receptor for AGEs and nuclear factor-κB in gingival connective tissue. J Periodontol 2012; 83: 119–126.