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DOI: 10.1055/s-2006-949525
© Georg Thieme Verlag KG Stuttgart · New York
Periodontal Infection and Dyslipidemia in Type 2 Diabetics: Association with Increased HMG-CoA Reductase Expression
Publication History
Received 8 September 2005
Accepted after revision 3 January 2006
Publication Date:
29 August 2006 (online)
Abstract
Recent studies have suggested that the periodontal disease, chronic sub-clinical inflammation, is associated with atherosclerosis, although “cause or effect” relationship is still unclear. The aim of this study was to assess the association between the degree of periodontal infection and lipid profiles in diabetic subjects. Additionally, the association of such sub-clinical inflammation with HMG-CoA reductase gene expression was evaluated. One hundred and thirty-one non-obese relatively well-controlled Japanese type 2 diabetic patients were enrolled for the study. Although no significant association was observed between serum triglycerides, HLD-cholesterol and antibody titer to Porphyromonas gingivalis (Pg), the most predominant periodontal pathogen in adults, LDL-cholesterol was significantly associated with antibody titer to Pg. Concomitantly, the same works out to be true for total cholesterol. To understand the possible mechanisms underlying this association, we evaluated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase gene expression in cultured HepG2 cells stimulated by either bacterial lipopolysaccharide (LPS) or inflammatory cytokines. Although Pg and E. coli LPS had no effect on HMG-CoA reductase gene expression, both tumor necrosis factor-α and interleukin-6 (IL-6), especially IL-6 at low concentration, markedly up-regulated HMG-CoA reductase gene expression. It can be concluded that Pg infection is associated with increased LDL-cholesterol in diabetic subjects, which may be accompanied by increased cholesterol synthesis by inflammatory cytokines.
Key words
Infection - diabetes - atherosclerosis - dyslipidemia - HMG-CoA reductase
References
- 1 Bierman EL. George Lyman Duff Memorial Lecture. Atherogenesis in diabetes. Arterioscler Thromb Vasc Biol. 1992; 12 647-656
- 2 UK Prospective Diabetes Study (UKPDS) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352 837-853
- 3 Ridker PM, Cushman M, Stampfer MJ. >et al . Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997; 336 973-979
- 4 Nelson RG, Shlossman M, Budding LM. >et al . Periodontal disease and NIDDM in Pima Indians. Diabetes Care. 1990; 13 836-840
- 5 Taniguchi A, Nishimura F, Murayama Y. >et al . Porphyromonas gingivalis infection is associated with carotid atherosclerosis in non-obese Japanese type 2 diabetic patients. Metabolism. 2003; 52 142-145
- 6 DeStefano F, Anda RF, Kahn HS. >et al . Dental disease and risk of coronary heart disease and mortality. BMJ. 1993; 306 688-691
- 7 Saremi A, Nelson RG, Tulloch-Reid M. >et al . Periodontal disease and mortality in type 2 diabetes. Diabetes Care. 2005; 28 27-32
- 8 Murayama Y, Nagai A, Okamura K. >et al . Serum immunoglobulin G antibody to periodontal bacteria. Adv Dent Res. 1988; 2 339-345
- 9 Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999; 340 448-454
- 10 Nishimura F, Taniguchi A, Iwamoto Y. >et al . Porphyromonas gingivalis infection is associated with elevated C-reactive protein in nonobese Japanese type 2 diabetic subjects. Diabetes Care. 2002; 25 1888
- 11 Slade GD, Ghezzi EM, Heiss. >et al . Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study. Arch Intern Med. 2003; 163 1172-1179
- 12 Iwamoto Y, Nishimura F, Soga. >et al . Antimicrobial periodontal treatment decreases serum C-reactive protein, tumor necrosis factor-alpha, but not adiponectin levels in patients with chronic periodontitis. J Periodontol. 2003; 74 1231-1236
- 13 D'Aiuto F, Parkar M, Andreou G. >et al . Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res. 2004; 83 156-160
- 14 Iwamoto Y, Nishimura F, Nakagawa M. >et al . The effect of antimicrobial periodontal treatment on circulating tumor necrosis factor-alpha and glycated hemoglobin level in patients with type 2 diabetes. J Periodontol. 2001; 72 774-778
- 15 Uysal KT, Wiesbrock SM, Marino MW. >et al . Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997; 389 610-614
- 16 World Health Organization . Diabetes Mellitus. Report of a WHO Study Group. Geneva, World Health Org (Tech. Rep. Ser., no.727) 1985;
- 17 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18 499-502
- 18 Onoue S, Imai T, Kumada H. >et al . Serum antibodies of periodontitis patients compared to the lipopolysaccharides of Porphyromonas gingivalis and Fusobacterium nucleatum. Microbiol Immunol. 2003; 47 51-55
- 19 Kato A, Ogasawara T, Homma T. >et al . Lipopolysaccharide-binding protein critically regulates lipopolysaccharide-induced IFN-beta signaling pathway in human monocytes. J Immunol. 2004; 172 6185-6194
- 20 Molvig 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
- 21 Liu S, Gallo DJ, Green AM. >et al . Role of toll-like receptors in changes in gene expression and NF-kappa B activation in mouse hepatocytes stimulated with lipopolysaccharide. Infect Immun. 2002; 70 3433-3442
- 22 Rattazzi M, Puato M, Faggin E. >et al . C-reactive protein and interleukin-6 in vascular disease: culprits or passive bystanders?. J Hypertens. 2003; 21 1787-1803
- 23 Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation. 2001; 103 1194-1197
- 24 Taskinen S, Kovanen PT, Jarva H. >et al . Binding of C-reactive protein to modified low-density-lipoprotein particles: identification of cholesterol as a novel ligand for C-reactive protein. Biochem J. 2002; 367 403-412
- 25 Feingold KR, Grunfeld C. Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. J Clin Invest. 1987; 80 184-190
- 26 Memon RA, Grunfeld C, Moser AH. >et al . Tumor necrosis factor mediates the effects of endotoxin on cholesterol and triglyceride metabolism in mice. Endocrinology. 1993; 132 2246-2253
- 27 Jain A, Batista Jr EL, Serhan C. >et al . Role for periodontitis in the progression of lipid deposition in an animal model. Infect Immun. 2003; 71 6012-6018
- 28 D'Aiuto F, Nibali L, Parker M. et al . Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res. 2005; 84 269-273
Correspondence
F. NishimuraDDS
Department of Patho-physiology/Periodontal Science·Okayama University·Graduate School of Medicine·Dentistry and Pharmaceutical Sciences
2-5-1 Shikata-cho·Okayama700-8525·Japan
Phone: +81/86/235 66 76
Fax: +81/86/235 66 79
Email: fusanori@md.okayama-u.ac.jp