Albuminuria, C-reactive protein, and socioeconomic factors are associated with periodontal status in subjects with type 2 diabetes

  • Hiroki Yokoyama
  • Tatsuo Yamamoto
  • Michio Tanaka
  • Chieko Kudo
  • Koichi Hidaka
  • Nobuichi Kuribayashi
  • Masato Minabe
Original Article


Diabetes and periodontitis may increase risk of cardiovascular disease. Whether albuminuria, C-reactive protein (CRP), and socioeconomic factors, known as cardiovascular risks in subjects with poorly controlled diabetes, are independently associated with periodontal status in well-controlled diabetes remains to be elucidated. In 503 subjects with type 2 diabetes, the cross-sectional associations of clinical and socioeconomic factors with periodontal parameters were investigated. Periodontal parameters on all teeth included the probing pocket depth at 6 sites per tooth, bleeding on probing, the plaque score, tooth mobility, and the number of teeth. The subjects had a mean HbA1c value of 6.85% and a median CRP value of 0.06 mg/dL, and 27.9% of the subjects had albuminuria. Albuminuria and CRP values had significant associations with several periodontal parameters, whereas other variables including HbA1c did not. Subjects with albuminuria had significantly higher HbA1c, CRP, and % sites of pocket depth ≥ 4 mm than subjects with normoalbuminuria; additionally, those with high CRP (≥ median) had significantly higher body mass index, HbA1c, % sites of pocket depth ≥ 4 mm, and plaque score than those with low CRP. In multiple linear regression analysis, albuminuria, CRP, education, smoking, and dental attendance exhibited significant associations with periodontal parameters, independent of the effect of age, sex, body mass index, and diabetes therapy. Albuminuria, CRP, education, smoking, and dental attendance were independently associated with periodontal parameters even in subjects with a mean of HbA1c of 6.85%, implying the importance of these factors for the prevention of cardiovascular disease.


Periodontitis Type 2 diabetes Albuminuria C-reactive protein Education Dental attendance 



Cardiovascular disease


C-reactive protein


Blood pressure


National Health and Nutrition Examination Survey


Glycated hemoglobin A1c


Low density lipoprotein


High density lipoprotein


Probing pocket depth


Japan Diabetes Society


Bleeding on probing


Body mass index




Urinary albumin-to-creatinine ratio


Glomerular filtration rate


Coronary heart disease



Ms. Miki Satoh and Mr. Suguho Takahashi (Jiyugaoka Medical Clinic, Obihiro, Japan) are thanked for their skillful data collection and managing research office.


No particular fund.

Compliance with ethical standards

Ethical approval

The study protocol was approved on Oct. 27th in 2014 by the Jiyugaoka Medical Clinic Ethical Board number #250716. All participants provided written informed consent and the study was carried out in accordance with the Helsinki Declaration II.

Conflict of interest

All authors have no conflicts of interest to disclose.


  1. 1.
    Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–22.CrossRefGoogle Scholar
  2. 2.
    UKPDS Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes. (UKPDS 34). Lancet. 1988;352:854–65.Google Scholar
  3. 3.
    McMillan DE. Increased levels of acute-phase serum proteins in diabetes. Metabolism. 1989;38:1042–6.CrossRefGoogle Scholar
  4. 4.
    Rodríguez-Morán M, Guerrero-Romero F. Increased levels of C-reactive protein in noncontrolled type II diabetic subjects. J Diabetes Complications. 1999;13:211–5.CrossRefGoogle Scholar
  5. 5.
    Fröhlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, Muche R, Brenner H, Koenig W. Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care. 2000;23:1835–9.CrossRefGoogle Scholar
  6. 6.
    James GD, Baker P, Badrick E, et al. Ethnic and social disparity in glycaemic control in type 2 diabetes; cohort study in general practice 2004–9. J R Soc Med. 2012;105:300–8.CrossRefGoogle Scholar
  7. 7.
    Houle J, Lauzier-Jobin F, Beaulieu MD, Meunier S, Coulombe S, Côté J, Lespérance F, Chiasson JL, Bherer L, Lambert J. Socioeconomic status and glycemic control in adult patients with type 2 diabetes: a mediation analysis. BMJ Open Diabetes Res Care. 2016;4:e000184.CrossRefGoogle Scholar
  8. 8.
    Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W. Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res. 2014;93:1045–53.CrossRefGoogle Scholar
  9. 9.
    Nesse W, Abbas F, van der Ploeg I, Spijkervet FK, Dijkstra PU, Vissink A. Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol. 2008;35:668–73.CrossRefGoogle Scholar
  10. 10.
    Blaizot A, Vergnes JN, Nuwwareh S, Amar J, Sixou M. Periodontal diseases and cardiovascular events: meta-analysis of observational studies. Int Dent J. 2009;59:197–209.PubMedGoogle Scholar
  11. 11.
    Kebschull M, Demmer RT, Papapanou PN. “Gum bug, leave my heart alone!”—epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis. J Dent Res. 2010;89:879–902.CrossRefGoogle Scholar
  12. 12.
    Rydén L, Buhlin K, Ekstrand E, de Faire U, Gustafsson A, Holmer J, Kjellström B, Lindahl B, Norhammar A, Nygren Å, Näsman P, Rathnayake N, Svenungsson E, Klinge B. Periodontitis increases the risk of a first myocardial infarction: a report from the PAROKRANK study. Circulation. 2016;133:576–83.PubMedGoogle Scholar
  13. 13.
    Saremi A, Nelson RG, Tulloch-Reid M, Hanson RL, Sievers ML, Taylor GW, Shlossman M, Bennett PH, Genco R, Knowler WC. Periodontal disease and mortality in type 2 diabetes. Diabetes Care. 2005;28:27–32.CrossRefGoogle Scholar
  14. 14.
    Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M, Knowler WC, Pettitt DJ. Severe periodontitis and risk for poor glycemic control in patients with non-insulin-dependent diabetes mellitus. J Periodontol. 1996;67(10 Suppl):1085–93.CrossRefGoogle Scholar
  15. 15.
    Garcia D, Tarima S, Okunseri C. Periodontitis and glycemic control in diabetes: NHANES 2009 to 2012. J Periodontol. 2015;86:499–506.CrossRefGoogle Scholar
  16. 16.
    Mohamed HG, Idris SB, Ahmed MF, Bøe OE, Mustafa K, Ibrahim SO, Astrøm AN. Association between oral health status and type 2 diabetes mellitus among Sudanese adults: a matched case-control study. PLoS One. 2013;8:e82158.CrossRefGoogle Scholar
  17. 17.
    Preshaw PM, Alba AL, Herrera D, Jepsen S, Konstantinidis A, Makrilakis K, Taylor R. Periodontitis and diabetes: a two-way relationship. Diabetologia. 2012;55:21–31.CrossRefGoogle Scholar
  18. 18.
    Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in U.S. diabetes care, 1999–2010. N Engl J Med. 2013;368:1613–24.CrossRefGoogle Scholar
  19. 19.
    Yokoyama H, Oishi M, Takamura H, Yamasaki K, Shirabe SI, Uchida D, Sugimoto H, Kurihara Y, Araki SI, Maegawa H. Large-scale survey of rates of achieving targets for blood glucose, blood pressure, and lipids and prevalence of complications in type 2 diabetes (JDDM 40). BMJ Open Diabetes Res Care. 2016;4:e000294.CrossRefGoogle Scholar
  20. 20.
    Kowall B, Holtfreter B, Völzke H, Schipf S, Mundt T, Rathmann W, Kocher T. Pre-diabetes and well-controlled diabetes are not associated with periodontal disease: the SHIP Trend Study. J Clin Periodontol. 2015;42:422–30.CrossRefGoogle Scholar
  21. 21.
    Holm-Pedersen P, Schultz-Larsen K, Christiansen N, Avlund K. Tooth loss and subsequent disability and mortality in old age. J Am Geriatr Soc. 2008;56:429–35.CrossRefGoogle Scholar
  22. 22.
    Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ. CDC periodontal disease surveillance workgroup prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res. 2012;91:914–20.CrossRefGoogle Scholar
  23. 23.
    Katagiri S, Nitta H, Nagasawa T, Izumi Y, Kanazawa M, Matsuo A, Chiba H, Fukui M, Nakamura N, Oseko F, Kanamura N, Inagaki K, Noguchi T, Naruse K, Matsubara T, Miyazaki S, Miyauchi T, Ando Y, Hanada N, Inoue S. Effect of glycemic control on periodontitis in type 2 diabetic patients with periodontal disease. J Diabetes Investig. 2013;4:320–5.CrossRefGoogle Scholar
  24. 24.
    Tsakos G, Demakakos P, Breeze E, Watt RG. Social gradients in oral health in older adults: findings from the English longitudinal survey of aging. Am J Public Health. 2011;101:1892–9.CrossRefGoogle Scholar
  25. 25.
    Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation. 2001;103:1813–8.CrossRefGoogle Scholar
  26. 26.
    Slade GD, Ghezzi EM, Heiss G, Beck JD, Riche E, Offenbacher S. Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study. Arch Intern Med. 2003;163:1172–9.CrossRefGoogle Scholar
  27. 27.
    Feldt-Rasmussen B. Microalbuminuria, endothelial dysfunction and cardiovascular risk. Diabetes Metab. 2000;26(Suppl 4):64–6.PubMedGoogle Scholar
  28. 28.
    Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S, HOPE Study Investigators. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286:421–6.CrossRefGoogle Scholar
  29. 29.
    Shultis WA, Weil EJ, Looker HC, Curtis JM, Shlossman M, Genco RJ, Knowler WC, Nelson RG. Effect of periodontitis on overt nephropathy and end-stage renal disease in type 2 diabetes. Diabetes Care. 2007;30:306–11.CrossRefGoogle Scholar
  30. 30.
    Han K, Nam GE, Kim DH, Park JB, Ko Y, Roh YK, Cho KH, Park YG. Association of periodontitis with urinary albumin excretion in korean adults with diabetes: the 2012 Korea National Health and Nutrition Examination Survey. Medicine (Baltimore). 2015;94:e1839.CrossRefGoogle Scholar
  31. 31.
    Lang NP, Adler R, Joss A, Nyman S. Absence of bleeding on probing. An indicator of periodontal stability. J Clin Periodontol. 1990;17:714–21.CrossRefGoogle Scholar
  32. 32.
    O’Leary TJ, Drake RB, Naylor JE. The plaque control record. J Periodontol. 1972;43:38.CrossRefGoogle Scholar
  33. 33.
    Miller SC. Textbook of periodontia. Philadelphia: Blakiston Co; 1950. p. 91.Google Scholar
  34. 34.
    Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol. 2014;220:T47–59.CrossRefGoogle Scholar
  35. 35.
    Stehouwer CD, Fischer HR, van Kuijk AW, Polak BC, Donker AJ. Endothelial dysfunction precedes development of microalbuminuria in IDDM. Diabetes. 1995;44:561–4.CrossRefGoogle Scholar
  36. 36.
    Yokoyama H, Sone H, Saito K, Yamada D, Honjo J, Haneda M. Flow-mediated dilation is associated with microalbuminuria independent of cardiovascular risk factors in type 2 diabetes—interrelations with arterial thickness and stiffness. J Atheroscler Thromb. 2011;18:744–52.CrossRefGoogle Scholar
  37. 37.
    Yokoyama H, Jensen JS, Myrup B, Mathiesen ER, Rønn B, Deckert T. Raised serum sialic acid concentration precedes onset of microalbuminuria in IDDM. A 10-year follow-up study. Diabetes Care. 1996;19:435–40.CrossRefGoogle Scholar
  38. 38.
    Yokoyama H, Araki S, Haneda M, Matsushima M, Kawai K, Hirao K, Oishi M, Sugimoto K, Sone H, Maegawa H, Kashiwagi A, Japan Diabetes Clinical Data Management Study Group. Chronic kidney disease categories and renal-cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25). Diabetologia. 2012;55:1911–8.CrossRefGoogle Scholar
  39. 39.
    de Oliveira C, Watt R, Hamer M. Toothbrushing, inflammation, and risk of cardiovascular disease: results from Scottish Health Survey. BMJ. 2010;340:c2451.CrossRefGoogle Scholar
  40. 40.
    Kajikawa M, Nakashima A, Maruhashi T, Iwamoto Y, Iwamoto A, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Goto C, Taguchi A, Noma K, Higashi Y. Poor oral health, that is, decreased frequency of tooth brushing, is associated with endothelial dysfunction. Circ J. 2014;78:950–4.CrossRefGoogle Scholar
  41. 41.
    Tonetti MS, D’Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J. Treatment of periodontitis and endothelial function. N Engl J Med. 2007;356:911–20.CrossRefGoogle Scholar
  42. 42.
    Morita I, Nakagaki H, Yoshii S, Tsuboi S, Hayashizaki J, Igo J, Mizuno K, Sheiham A. Gradients in periodontal status in Japanese employed males. J Clin Periodontol. 2007;34:952–6.CrossRefGoogle Scholar
  43. 43.
    Yamamoto T, Kondo K, Aida J, Fuchida S, Hirata Y, JAGES group. Association between the longest job and oral health: Japan Gerontological Evaluation Study project cross-sectional study. BMC Oral Health. 2014;14:130.CrossRefGoogle Scholar
  44. 44.
    Engebretson SP, Hyman LG, Michalowicz BS, Schoenfeld ER, Gelato MC, Hou W, Seaquist ER, Reddy MS, Lewis CE, Oates TW, Tripathy D, Katancik JA, Orlander PR, Paquette DW, Hanson NQ, Tsai MY. 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;310:2523–32.CrossRefGoogle Scholar
  45. 45.
    Kaur PK, Narula SC, Rajput R, Sharma KR, Tewari S. Periodontal and glycemic effects of nonsurgical periodontal therapy in patients with type 2 diabetes stratified by baseline HbA1c. J Oral Sci. 2015;57:201–11.CrossRefGoogle Scholar

Copyright information

© The Japan Diabetes Society 2018

Authors and Affiliations

  • Hiroki Yokoyama
    • 1
  • Tatsuo Yamamoto
    • 2
  • Michio Tanaka
    • 2
  • Chieko Kudo
    • 3
  • Koichi Hidaka
    • 3
  • Nobuichi Kuribayashi
    • 4
  • Masato Minabe
    • 3
  1. 1.Jiyugaoka Medical ClinicInternal MedicineObihiroJapan
  2. 2.Division of Dental Sociology, Department of Oral Science, Graduate School of DentistryKanagawa Dental UniversityYokosukaJapan
  3. 3.Division of Periodontology, Department of Interdisciplinary Medicine, Graduate School of DentistryKanagawa Dental UniversityYokosukaJapan
  4. 4.Misaki Naika ClinicFunabashiJapan

Personalised recommendations