Periodontal Disease and Systemic Interactions (Periodontal Medicine): Current Epidemiological Evidence

  • James D. BeckEmail author
  • Kamaira H. Philips
  • Sanjana S. Rao
Host Parasite Interactions in Periodontal Disease (C Genco and D Kinane, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Host Parasite Interactions in Periodontal Disease
  2. Topical Collection on Host Parasite Interactions in Periodontal Disease


Purpose of Review

To review recent literature on the effects of periodontal diseases on type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) with emphasis on the contributions of Dr. Robert Genco.

Recent Findings

Numbers of missing teeth are positively related to levels of infection and inflammation. Most studies find a positive relationship between periodontitis and incident CVD and T2DM and the ability of periodontal treatment to reduce CVD risk factors and HbA1C levels, but controversy due to negative findings remains.


Recent finding that tooth loss is related to levels of inflammation is important as it provides clues to how tooth loss is related to systemic diseases. New studies involving microorganisms and host response are important, as they underlie clinical signs. Basic problems, such as periodontal case definitions, type of treatments, timing of treatment, and follow-up times need to be addressed in order to reduce inconsistent findings in epidemiologic studies and clinical trials.


Periodontal disease Type 2 diabetes mellitus Atherosclerosis Cardiovascular disease Epidemiology 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Taubman MA, Robert J. Genco: pioneer in oral science advancement. J Dent Res. 2018;97(7):737–41. Scholar
  2. 2.
    Miller WD. The human mouth as a focus of infection. Lancet. 1891;138(3546):340–2.CrossRefGoogle Scholar
  3. 3.
    Cecil RL, Angevine DM. Clinical and experimental observations on focal infection, with an analysis of 200 cases of rheumatoid arthritis. Ann Intern Med. 1938;12(5):577–84.CrossRefGoogle Scholar
  4. 4.
    DeStefano F, Anda RF, Kahn HS, Williamson DF, Russell CM. Dental disease and risk of coronary heart disease and mortality. Bmj. 1993;306(6879):688–91.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Mattila KJ, Nieminen MS, Valtonen VV, Rasi VP, Kesäniemi YA, Syrjälä SL, et al. Association between dental health and acute myocardial infarction. Bmj. 1989;298(6676):779–81.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Mattila KJ, Valle MS, Nieminen MS, Valtonen VV, Hietaniemi KL. Dental infections and coronary atherosclerosis. Atherosclerosis. 1993;103(2):205–11.PubMedCrossRefGoogle Scholar
  7. 7.
    Scannapieco F, Genco R. Association of periodontal infections with atherosclerotic and pulmonary diseases. J Periodontal Res. 1999;34(7):340–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Haraszthy V, Zambon J, Trevisan M, Zeid M, Genco R. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000;71(10):1554–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Wu T, Trevisan M, Genco RJ, Dorn JP, Falkner KL, Sempos CT. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch Intern Med. 2000;160(18):2749–55.PubMedCrossRefGoogle Scholar
  10. 10.
    Genco R, Offenbacher S, Beck J. Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms. J Am Dent Assoc. 2002;133:14S–22S.PubMedCrossRefGoogle Scholar
  11. 11.
    Couper DJ, Beck JD, Falkner KL, Graham SP, Grossi SG, Gunsolley JC, et al. The periodontitis and vascular events (PAVE) pilot study: recruitment, retention, and community care controls. J Periodontol. 2008;79(1):80–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Beck JD, Couper DJ, Falkner KL, Graham SP, Grossi SG, Gunsolley JC, et al. The periodontitis and vascular events (PAVE) pilot study: adverse events. J Periodontol. 2008;79(1):90–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Offenbacher S, Beck JD, Moss K, Mendoza L, Paquette DW, Barrow DA, et al. Results from the periodontitis and vascular events (PAVE) study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease. J Periodontol. 2009;80(2):190–201.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Andriankaja OM, Genco RJ, Dorn J, Dmochowski J, Hovey K, Falkner KL, et al. The use of different measurements and definitions of periodontal disease in the study of the association between periodontal disease and risk of myocardial infarction. J Periodontol. 2006;77(6):1067–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Andriankaja OM, Genco RJ, Dorn J, Dmochowski J, Hovey K, Falkner KL, et al. Periodontal disease and risk of myocardial infarction: the role of gender and smoking. Eur J Epidemiol. 2007;22(10):699–705.PubMedCrossRefGoogle Scholar
  16. 16.
    Dorn JM, Genco RJ, Grossi SG, Falkner KL, Hovey KM, Iacoviello L, et al. Periodontal disease and recurrent cardiovascular events in survivors of myocardial infarction (MI): the Western New York acute MI study. J Periodontol. 2010;81(4):502–11. Scholar
  17. 17.
    Friedewald VE, Kornman KS, Beck JD, Genco R, Goldfine A, Libby P, et al. The American Journal of Cardiology and Journal of Periodontology editors’ consensus: periodontitis and atherosclerotic cardiovascular disease. J Periodontol. 2009;80(7):1021–32.PubMedCrossRefGoogle Scholar
  18. 18.
    El Kholy K, Genco RJ, Van Dyke TE. Oral infections and cardiovascular disease. Trends Endocrinol Metab. 2015;26(6):315–21. Scholar
  19. 19.
    • Cheng F, Zhang M, Wang Q, Xu H, Dong X, Gao Z, et al. Tooth loss and risk of cardiovascular disease and stroke: a dose-response meta analysis of prospective cohort studies. PLoS One. 2018;13(3):e0194563 This study was important for a number of reasons. It involved a meta-analysis of 17 longitudinal studies that included 879,084 participants. The quality of all studies was judged to be high and the studies showed consistent results. The meta-analysis showed statistically significant increment association between tooth loss and cardiovascular disease and stroke risk. Subgroups analysis indicated that tooth loss was associated with a significant risk of cardiovascular disease and stroke in Asians and Caucasians, meaning that not all groups are at risk. In addition, there was a significant dose-response relationship was observed between tooth loss and cardiovascular disease and stroke risk, which is one of the criteria that indicates the relationship might be causal. Google Scholar
  20. 20.
    Vedin O, Hagström E, Östlund O, Avezum A, Budaj A, Flather MD, et al. Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease. Int J Cardiol. 2017;245:271–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Dwiyanti S, Soeroso Y, Sunarto H, Radi B, editors. Relationship between quantitative measurement of Porphyromonas gingivalis on dental plaque with periodontal status of patients with coronary heart disease. AIP Conference Proceedings; 2017: AIP Publishing.Google Scholar
  22. 22.
    Aoyama N, Kobayashi N, Hanatani T, Ashigaki N, Yoshida A, Shiheido Y, et al. Periodontal condition in Japanese coronary heart disease patients: a comparison between coronary and non-coronary heart diseases. J Periodontal Res. 2019;54(3):259–65.PubMedCrossRefGoogle Scholar
  23. 23.
    • Aoyama N, Suzuki JI, Kobayashi N, Hanatani T, Ashigaki N, Yoshida A, et al. Associations among tooth loss, systemic inflammation and antibody titers to periodontal pathogens in Japanese patients with cardiovascular disease. J Periodontal Res. 2018;53(1):117–22. study is important because it provides some clues as to why tooth loss is often found to be related to cardiovascular disease. They found that the levels of C- reactive protein were higher in patients with 1–9 teeth than in those with 10–19 teeth and with ≥ 20 teeth. In addition, the level of IgG antibody to Porphyromonas gingivalisin the group with 10–19 teeth was statistically higher than that in the group with ≥ 20 teeth. Thus, it appears that people who have lost a lot of teeth have higher levels of systemic inflammation and appear to have an antibody response toPorphyromonas gingivalis,a known periodontal pathogen. PubMedCrossRefGoogle Scholar
  24. 24.
    Goodwin RD, Stein MB. Association between childhood trauma and physical disorders among adults in the United States. Psychol Med. 2004;34(3):509–20.PubMedCrossRefGoogle Scholar
  25. 25.
    De Bellis MD, Zisk A. The biological effects of childhood trauma. Child Adolesc Psychiatr Clin. 2014;23(2):185–222.CrossRefGoogle Scholar
  26. 26.
    Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC. Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Arch Gen Psychiatry. 2009;66(1):72–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Sansone RA, Pole M, Dakroub H, Butler M. Childhood trauma, borderline personality symptomatology, and psychophysiological and pain disorders in adulthood. Psychosomatics. 2006;47(2):158–62.PubMedCrossRefGoogle Scholar
  28. 28.
    •• Pussinen PJ, Paju S, Koponen J, Viikari JSA, Taittonen L, Laitinen T, et al. Association of childhood oral infections with cardiovascular risk factors and subclinical atherosclerosis in adulthood. JAMA Netw Open. 2019;2(4). very important study investigates whether childhood oral infections or inflammatory conditions are associated with the risk of adulthood subclinical atherosclerosis. The study followed 755 participants for up for 27 years into adulthood and found that a number of clinical signs of oral infections in childhood were associated with both cumulative exposure to cardiovascular risk factors during the follow-up and subclinical atherosclerosis in adulthood. These types of questions are being asked in other fields, and the findings in this study initially appear to support those findings, which have many implications for child health. PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Dietrich T, Sharma P, Walter C, Weston P, Beck J. The epidemiological evidence behind the association between periodontitis and incident atherosclerotic cardiovascular disease. J Clin Periodontol. 2013;40:S70–84.PubMedCrossRefGoogle Scholar
  30. 30.
    Dietrich T, Webb I, Stenhouse L, Pattni A, Ready D, Wanyonyi KL, et al. Evidence summary: the relationship between oral and cardiovascular disease. Br Dent J. 2017;222(5):381–5. Scholar
  31. 31.
    Shimada Y, Komatsu Y, Ikezawa-Suzuki I, Tai H, Sugita N, Yoshie H. The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. J Periodontol. 2010;81(8):1118–23.PubMedCrossRefGoogle Scholar
  32. 32.
    Toker H, Poyraz O, Eren K. Effect of periodontal treatment on IL-1β, IL-1ra, and IL-10 levels in gingival crevicular fluid in patients with aggressive periodontitis. J Clin Periodontol. 2008;35(6):507–13.PubMedCrossRefGoogle Scholar
  33. 33.
    Piconi S, Trabattoni D, Luraghi C, Perilli E, Borelli M, Pacei M, et al. Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness. FASEB J. 2009;23(4):1196–204.PubMedCrossRefGoogle Scholar
  34. 34.
    Tonetti MS, D'Aiuto F, Nibali L, Donald A, Storry C, Parkar M, et al. Treatment of periodontitis and endothelial function. N Engl J Med. 2007;356(9):911–20.PubMedCrossRefGoogle Scholar
  35. 35.
    D’Aiuto F, Parkar M, Andreou G, Suvan J, Brett PM, Ready D, 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(2):156–60.PubMedCrossRefGoogle Scholar
  36. 36.
    Williams RC Jr, Mahan CJ. Periodontal disease and diabetes in young adults. J Am Med Assoc. 1960;172:776–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Sanz M, Ceriello A, Buysschaert M, Chapple I, Demmer RT, Graziani F, et al. Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J Clin Periodontol. 2018;45(2):138–49.PubMedCrossRefGoogle Scholar
  38. 38.
    Nelson RG, Shlossman M, Budding LM, Pettitt DJ, Saad MF, Genco RJ, et al. Periodontal disease and NIDDM in Pima Indians. Diabetes Care. 1990;13(8):836–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Saremi A, Nelson RG, Tulloch-Reid M, Hanson RL, Sievers ML, Taylor GW, et al. Periodontal disease and mortality in type 2 diabetes. Diabetes Care. 2005;28(1):27–32.PubMedCrossRefGoogle Scholar
  40. 40.
    Shultis WA, Weil EJ, Looker HC, Curtis JM, Shlossman M, Genco RJ, et al. Effect of periodontitis on overt nephropathy and end-stage renal disease in type 2 diabetes. Diabetes Care. 2007;30(2):306–11.PubMedCrossRefGoogle Scholar
  41. 41.
    Grossi SG, Skrepcinski FB, DeCaro T, Zambon JJ, Cummins D, Genco RJ. Response to periodontal therapy in diabetics and smokers. J Periodontol. 1996;67:1094–102.PubMedCrossRefGoogle Scholar
  42. 42.
    • D’Aiuto F, Gkranias N, Bhowruth D, Khan T, Orlandi M, Suvan J, et al. Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial. Lancet Diabetes Endocrinol. 2018;6(12):954–65. results from clinical trials designed to improve glycemic control in patients with type 2 diabetes have had mixed results. This study is important because it continued care throughout the time of the study. In this important clinical trial 264 patients were randomly assigned to IPT (n = 133) or CPT (n= 131), in order to determine whether periodontal treatment reduced the level of glycemic control in people with type 2 diabetes. IPT involved whole mouth subgingival scaling, surgical periodontal therapy [if the participants showed good oral hygiene practice; otherwise dental cleaning again], and supportive periodontal therapy every 3 months until completion of the study) or control periodontal treatment. CPT was supra-gingival scaling and polishing at the same timepoints as in the IPT group. Compared with CPT, IPT reduced HbA1, in patients with type 2 diabetes and moderate-to-severe periodontitis after 12 months. These results suggest that routine oral health assessment and treatment of periodontitis could be important for effective management of type 2 diabetes. CrossRefGoogle Scholar
  43. 43.
    Genco RJ, Schifferle RE, Dunford RG, Falkner KL, Hsu WC, Balukjian J. Screening for diabetes mellitus in dental practices: a field trial. J Am Dent Assoc. 2014;145(1):57–64. Scholar
  44. 44.
    Borgnakke WS, Ylöstalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. J Clin Periodontol. 2013;40:S135–S52.PubMedCrossRefGoogle Scholar
  45. 45.
    Demmer RT, Jacobs DR, Desvarieux M. Periodontal disease and incident type 2 diabetes: results from the First National Health and Nutrition Examination Survey and its epidemiologic follow-up study. Diabetes Care. 2008;31(7):1373–9.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Winning L, Patterson CC, Neville CE, Kee F, Linden GJ. Periodontitis and incident type 2 diabetes: a prospective cohort study. J Clin Periodontol. 2017;44(3):266–74.PubMedCrossRefGoogle Scholar
  47. 47.
    Ide R, Hoshuyama T, Wilson D, Takahashi K, Higashi T. Periodontal disease and incident diabetes: a seven-year study. J Dent Res. 2011;90(1):41–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Myllymäki V, Saxlin T, Knuuttila M, Rajala U, Keinänen-Kiukaanniemi S, Anttila S, et al. Association between periodontal condition and the development of type 2 diabetes mellitus—results from a 15-year follow-up study. J Clin Periodontol. 2018;45(11):1276–86.PubMedCrossRefGoogle Scholar
  49. 49.
    Abariga SA, Whitcomb BW. Periodontitis and gestational diabetes mellitus: a systematic review and meta-analysis of observational studies. BMC Pregnancy and Childbirth. 2016;16(1):344.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Engebretson SP, Hyman LG, Michalowicz BS, Schoenfeld ER, Gelato MC, Hou W, et al. The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial. Jama. 2013;310(23):2523–32.Google Scholar
  51. 51.
    Koromantzos PA, Makrilakis K, Dereka X, Katsilambros N, Vrotsos IA, Madianos PN. A randomized, controlled trial on the effect of non-surgical periodontal therapy in patients with type 2 diabetes. Part I: effect on periodontal status and glycaemic control. J Clin Periodontol. 2011;38(2):142–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Madianos PN, Koromantzos PA. An update of the evidence on the potential impact of periodontal therapy on diabetes outcomes. J Clin Periodontol. 2018;45(2):188–95.PubMedCrossRefGoogle Scholar
  53. 53.
    Al Mubarak S, Rass MA, Alsuwyed A, Al-Zoman K, Al Sohail A, Sobki S, et al. A new paradigm between mechanical scaling and root planing combined with adjunctive chemotherapy for glycated hemoglobin improvement in diabetics. Int J Diabetes Mellit. 2010;2(3):158–64.CrossRefGoogle Scholar
  54. 54.
    Botero J, Yepes F, Ochoa S, Hincapie J, Roldan N, Ospina C, et al. Effects of periodontal non-surgical therapy plus azithromycin on glycemic control in patients with diabetes: a randomized clinical trial. J Periodontal Res. 2013;48(6):706–12.Google Scholar
  55. 55.
    Koçak E, Sağlam M, Kayış SA, Dündar N, Kebapçılar L, Loos BG, et al. Nonsurgical periodontal therapy with/without diode laser modulates metabolic control of type 2 diabetics with periodontitis: a randomized clinical trial. Lasers Med Sci. 2016;31(2):343–53.PubMedCrossRefGoogle Scholar
  56. 56.
    Sun W-L, Chen L-L, Zhang S-Z, Wu Y-M, Ren Y-Z, Qin G-M. Inflammatory cytokines, adiponectin, insulin resistance and metabolic control after periodontal intervention in patients with type 2 diabetes and chronic periodontitis. Intern Med. 2011;50(15):1569–74.PubMedCrossRefGoogle Scholar
  57. 57.
    Beck JD, Moss KL, Morelli T, Offenbacher S. Periodontal profile class is associated with prevalent diabetes, coronary heart disease, stroke, and systemic markers of C-reactive protein and interleukin-6. J Periodontol. 2018;89(2):157–65.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Morelli T, Moss KL, Preisser JS, Beck JD, Divaris K, Wu D, et al. Periodontal profile classes predict periodontal disease progression and tooth loss. J Periodontol. 2018;89(2):148–56.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Sen S, Giamberardino LD, Moss K, Morelli T, Rosamond WD, Gottesman RF, et al. Periodontal disease, regular dental care use, and incident ischemic stroke. Stroke. 2018;49(2):355–62.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • James D. Beck
    • 1
    Email author
  • Kamaira H. Philips
    • 2
  • Sanjana S. Rao
    • 2
  1. 1.Division of Comprehensive Oral Health/Periodontology, Adams School of DentistryUniversity of North CarolinaChapel HillUSA
  2. 2.Division of Oral and Craniofacial Health Sciences, Adams School of DentistryUniversity of North CarolinaChapel HillUSA

Personalised recommendations