Skip to main content

Linkage Between Periodontal Disease and Diabetes Mellitus

  • Chapter
  • First Online:
Oral Infections and General Health

Abstract

The past decades have significantly widened the perspectives of the chronic oral infectious disease known as periodontitis. The disease is regarded as a bacterial infection resulting in low-grade inflammation of the periodontal tissues, and both the associated release of pro-inflammatory mediators and the presence of bacteria in the periodontal pockets, which, as the result of daily procedures, may spread after penetration of the vasculature, are possible mediators of systemic consequences. This chapter deals with the possible association between periodontitis and diabetes mellitus which is believed to possess in a two-way interrelationship.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aggarwal A, Panat SR. Oral health behavior and HbA1c in Indian adults with type 2 diabetes. J Oral Sci. 2012;54:293–301.

    Article  PubMed  Google Scholar 

  • Albandar JM, Tinoco EM. Global epidemiology of periodontal disease in children and young persons. Periodontol 2000. 2002;29:153–76.

    Article  PubMed  Google Scholar 

  • Al-Khabbaz AK. Type 2 diabetes mellitus and periodontal disease severity. Oral Health Prev Dent. 2014;12:77–82.

    PubMed  Google Scholar 

  • Allen EM, Matthews JB, O’ Halloran DJ, Griffiths HR, Chapple IL, et al. Oxidative and inflammatory status in Type 2 diabetes patients with periodontitis. J Clin Periodontol. 2011;38:894–901.

    Article  PubMed  Google Scholar 

  • Amar S, Gokce N, Morgan S, Loukideli M, Van Dyke TE, Vita JA. Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation. Arterioscler Thromb Vasc Biol. 2003;23:1245–9.

    Article  PubMed  Google Scholar 

  • American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;32 suppl 1:S62–7.

    Article  PubMed Central  Google Scholar 

  • Andersen CCP, Buschard K, Flyvbjerg A, Stoltze K, Holmstrup P. Periodontitis deteriorates metabolic control in type 2 diabetic goto-kakizaki rats. J Periodontol. 2006;77:350–6.

    Article  Google Scholar 

  • Andersen CCP, Flyvbjerg A, Buschard K, Holmstrup P. Periodontitis is associated with aggravation of prediabetes in zucker fatty rats. J Periodontol. 2007a;78:559–65.

    Article  Google Scholar 

  • Andersen CCP, Flyvbjerg A, Buschard K, Holmstrup P. Relationship between periodontitis and diabetes: Lessons from rodent studies. J Periodontol. 2007b;78:1264–75.

    Article  Google Scholar 

  • Andersen CCP, Holmstrup P, Buschard K, Flyvbjerg A. Renal alterations in prediabetic rats with periodontitis. J Periodontol. 2008;79:684–90.

    Article  Google Scholar 

  • Anonymous. From the centers for disease control and prevention: blindness caused by diabetes – Massachusetts, 1987–1994. JAMA. 1996;276:1865–1866.

    Google Scholar 

  • Artese HP, Foz AM, Rabelo Mde S, Gomes GH, Orlandi M, Suvan J, D’Aiuto F, Romito GA. Periodontal therapy and systemic inflammation in type 2 diabetes mellitus: a meta-analysis. PLoS One. 2015;10, e0128344. doi:10.1371/journal.pone.0128344. eCollection 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  • Atieh MA, Faggion CM, Seymour GJ. Cytokines in patients with type 2 diabetes and chronic periodontitis: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2014;104:e38–e45.

    Article  PubMed  Google Scholar 

  • Bell GI, Polonsky KS. Diabetes mellitus and genetically programmed defects in beta-cell function. Nature. 2001;414(6865):788–91.

    Article  PubMed  Google Scholar 

  • Benjamin SM, Valdez R, Geiss LS, Rolka DB, Narayan KM. Estimated number of adults with prediabetes in the U.S in 2000: opportunities for prevention. Diabetes Care. 2003;26:645–9.

    Article  PubMed  Google Scholar 

  • Borgnakke WS, Ylöstalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. J Periodontol 2013. 2013;84:S135–52.

    Google Scholar 

  • Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.

    Article  PubMed  Google Scholar 

  • Bullon P, Morillo JM, Ramirez-Tortosa MC, Quiles JL, Newman HN, Battino M, et al. Metabolic syndrome and periodontitis: is oxidative stress a common link? J Dent Res 2009. 2009;88:503–18.

    Google Scholar 

  • Cao JJ, Sun L, Gao H. Diet-induce obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice. Ann N Y Acad Sci. 2010;1192:292–7.

    Article  PubMed  Google Scholar 

  • Casanova L, Hughes FJ, Preshaw PM. Diabetes and periodontal disease: a two-way relationship. Br Dent J. 2014;217:433–7.

    Article  PubMed  Google Scholar 

  • Corbella S, Francetti L, Taschieri S, De Siena F, Fabbro MD. Effect of periodontal treatment on glycemic control of patients with diabetes: a systematic review and meta-analysis. J Diabetes Investig. 2013;4:502–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cruz NG, Sousa LP, Sousa MO, Pietrani NT, Fernandes AP, Gomes KB. The linkage between inflammation and Type 2 diabetes mellitus. Diabetes Res Clin Pract. 2013;99:85–92.

    Article  PubMed  Google Scholar 

  • Degenhardt TP, Thorpe SR, Baynes JW. Chemical modification of proteins by methylglyoxal. Cell Mol Biol (Noisy-le-Grand). 1998;44:1139–45.

    Google Scholar 

  • Demmer RT, Desvarieux M, Holtfreter B, Jacobs Jr DR, Wallaschofski H, Nauck M, Völzke H, Kocher T. Periodontal status and A1C change: longitudinal results from the study of health in Pomerania (SHIP). Diabetes Care. 2010;33:1037–43.

    Article  PubMed  PubMed Central  Google Scholar 

  • Demmer RT, Jacobs Jr DR, Singh R, Zuk A, Rosenbaum M, Papapanou PN, Desvarieux M. Periodontal bacteria and prediabetes prevalence in ORIGINS: the oral infections, glucose intolerance, and insulin resistance study. J Dent Res. 2015;94:201s–11.

    Article  PubMed  PubMed Central  Google Scholar 

  • Devanoorkar A, Kathariya R, Guttiganur N, Gopalakrishnan D, Bagchi P. Resistin: a potential biomarker for periodontitis influence diabetes mellitus and diabetes induced periodontitis. Dis Markers 2014;1–7.

    Google Scholar 

  • Dolan TA, Gilbert GH, Ringelberg ML, Legler DW, Antonson DE, Foerster U, Heft MW. Behavioral risk indicators of attachment loss in adult Floridians. J Clin Periodontol. 1997;24:223–32.

    Article  PubMed  Google Scholar 

  • Elter JR, Hinderliter AL, Offenbacher S, Beck JD, Caughey M, Brodala N, Madianos PN. The effects of periodontal therapy on vascular endothelial function: a pilot trial. Am Heart J. 2006;151:147.

    Article  Google Scholar 

  • Engebretson SP, Vossughi F, Hey-Hadavi J, Emingil G, Grbic JT. The influence of diabetes in gingival crevicular fluid beta-glucuronidase and interleukin-8. J Clin Periodontol. 2006;33:784–90.

    Article  PubMed  Google Scholar 

  • Garcia D, Tarima S, Okunseri C. Periodontitis and glycemic control in diabetes: NHANES 2009 to 2012. J Periodontol. 2015;86:499–506.

    Article  PubMed  Google Scholar 

  • Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010;89:1349–63.

    Article  PubMed  Google Scholar 

  • Genco RJ, Grossi SG, Ho A, Nishimura F, Murayama Y. A proposed model linking inflammation to obesity, diabetes, and periodontal infections. J Periodontol. 2005;76(11 suppl):2075–84.

    Article  PubMed  Google Scholar 

  • Glavind L, Lund B, Löe H. The relationship between periodontal state and diabetes duration, insulin dosage and retinal changes. J Periodontol. 1968;39:341–7.

    Article  PubMed  Google Scholar 

  • Glumer C, Jørgensen T, Borch-Johnsen K, Inter99 study. Prevalences of diabetes and impaired glucose regulation in a Danish population: the inter99 study. Diabetes Care. 2003;26:2335–40.

    Article  PubMed  Google Scholar 

  • Golub LM, Nicoll GA, Iacono VJ, Ramamurthy NS. In vivo crevicular leukocyte response to a chemotactic challenge: inhibition by experimental diabetes. Infect Immun. 1982;37:1013–20.

    PubMed  PubMed Central  Google Scholar 

  • Graves DT, Kayal RA. Diabetic complications and dysregulated innate immunity. Front Biosci. 2008;13:1227–39.

    Article  PubMed  PubMed Central  Google Scholar 

  • Greenberg BL, Glick M. Screening for unidentified increased systemic disease risk in a dental setting. Am J Public Health. 2012;102(7):e10; author reply e10-1. doi:10.2105/AJPH.2012.300729. Epub 2012 May 17.

    Google Scholar 

  • Greenberg BL, Kantor ML, Jiang SS, Glick M. Patients’ attitudes toward screening for medical conditions in a dental setting. J Public Health Dent. 2012;72:28–35.

    Article  PubMed  Google Scholar 

  • Grossi SG, Genco RJ, Machtei EE, Ho AW, Koch G, Dunford R, Zambon JJ, Hausmann E. Assessment of risk for periodontal disease II. Risk indicators for alveolar bone loss. J Periodontol. 1995;66:23–9.

    Article  PubMed  Google Scholar 

  • Grossi SG, Zambon JJ, Ho AW, Koch G, Dunford RG, Machtei EE, Norderyd OM, Genco RJ. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol. 1994;65:260–7.

    Article  PubMed  Google Scholar 

  • Guariguata L, Whiting D, Weil C, Unwin N. The International Diabetes Federation diabetes atlas methodology for estimation global and national prevalence of diabetes in adults. Diabetes Res Clin Pract. 2011;94:322–32.

    Article  PubMed  Google Scholar 

  • Heianza Y, Hara S, Arase Y, Saito K, Fujiwara K, Tsuji H. HbA1c 5.7–6.4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study. Lancet. 2011;378:147–55.

    Article  PubMed  Google Scholar 

  • Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-lined insulin resistance. Science. 1993;259(5091):87–91.

    Article  PubMed  Google Scholar 

  • Hugoson A, Thorstensson H, Falk H, Kuylenstierna J. Periodontal conditions in insulin-dependent diabetics. J Clin Periodontol. 1989;16:215–23.

    Article  PubMed  Google Scholar 

  • Iughetti L, Marino R, Bertolani MF, Bernasconi S. Oral health in children and adolescents with IDDM – a review. J Pediatr Endocrinol Metab. 1999;12:603–10.

    Article  Google Scholar 

  • Janket SJ. Scaling and root-planing (SRP) may improve glycemic control and lipid profile in patients with chronic periodontitis (CP) and type 2 diabetes (DM2) in a specific subgroup: a meta-analysis of randomized clinical trials. J Evid Based Dent Pract. 2014;14:31–3.

    Article  PubMed  Google Scholar 

  • Johnson DR, O’Connor JC, Satpathy A, Freund GG. Cytokines in type 2 diabetes. Vitam Horm. 2006;74:405–41.

    Article  PubMed  Google Scholar 

  • Kahn SE. Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001;86:4047–58.

    PubMed  Google Scholar 

  • Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham Study. JAMA. 1979;241:2035–8.

    Article  PubMed  Google Scholar 

  • Kaul K, Tarr JM, Ahmad SI, Kohner EM, Chibber R. Introduction to diabetes mellitus. Adv Exp Med Biol. 2012;771:1–11.

    PubMed  Google Scholar 

  • King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontol. 2008;79 suppl 8:1527–44.

    Article  PubMed  Google Scholar 

  • Kolb H, Mandrup-Poulsen T. The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia. 2010;53:10–20.

    Article  PubMed  Google Scholar 

  • Kongstad J, Hvidtfeldt UA, Grønbaek M, Stoltze K, Holmstrup P. The relationship between body mass index and periodontitis in the Copenhagen city heart study. J Periodontol. 2009;80:1246–53.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Lakschevitz F, Aboodi G, Tenenbaum H, Glogauer M. Diabetes and periodontal diseases: interplay and links. Curr Diabetes Rev. 2011;7:433–9.

    Article  PubMed  Google Scholar 

  • Lalla E, Lamster IB, Feit M, Huang L, Spessot A, Qu W, Kislinger T, Lu Y, Stern DM, Schmidt AM. Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. J Clin Invest. 2000;105:1117–24.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lalla E, Lamster IB, Stern DM, Schmidt AM. Receptor for advance glycation and products, inflammation, and accelerated periodontal disease in diabetes: mechanisms and insights into therapeutic modalities. Ann Periodontol. 2001;6:113–8.

    Article  PubMed  Google Scholar 

  • Löe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16:329–34.

    Article  PubMed  Google Scholar 

  • Lontchi-Yimagou E, Sobngwi E, Matsha TE, Kengne AP. Diabetes mellitus and inflammation. Curr Diab Rep. 2013;13:435–44.

    Article  PubMed  Google Scholar 

  • Manson JE, Colditz GA, Stampfer MJ, Willett WC, Krolewski AS, Rosner B, Arky RA, Speizer FE, Hennekens CH. A prospective study of maturity-onset diabetes mellitus an risk of coronary heart disease and stroke in women. Arch Intern Med. 1991;151:1141–7.

    Article  PubMed  Google Scholar 

  • Morain WD, Colen LB. Wound healing in diabetes mellitus. Clin Plast Surg. 1990;17:493–501.

    PubMed  Google Scholar 

  • Nikolajczyk BS, Jagannathan-Bogdan M, Denis GV. The outliers become a stampede ad immunometabolism reaches a tipping point. Immunol Rev. 2012;249:253–75.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nikolajczyk BS, Jagannathan-Bogdan M, Shin H, Gyurko R. State of the union between metabolism and the immune system in type 2 diabetes. Genes Immun. 2011;12:239–50.

    Article  PubMed  Google Scholar 

  • Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. 2011;378(9785):169–81.

    Article  PubMed  Google Scholar 

  • Ochoa SP, Ospina CA, Colorado KJ, Montoya YP, Saldarriaga AF, Miranda GM, Muñoz PN, Gómez ME, Yepes FL, Botero JE. Periodontal condition and tooth loss in diabetic patients. Biomedica. 2012;32:52–9.

    PubMed  Google Scholar 

  • Onal M, Xiong J, Chen X, Thostenson JD, Almeida M, Manolagas SC, O’Brien CA. Receptor activator of nuclear factor kappaB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem. 2012;287:29851–60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Orbak R, Simsek S, Orbak Z, Kavrut F, Colak M. The influence of type-1 diabetes mellitus on dentition and oral health in children and adolescents. Yonsei Med J. 2008;49:357–65.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pinhas-Hamiel O, Zeitler P. The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr. 2005;146:693–700.

    Article  PubMed  Google Scholar 

  • Pischon N, Heng N, Bernimoulin JP, Kleber BM, Willich SN, Pischon T. Obesity, inflammation, and periodontal disease. J Dent Res. 2007;86:400–9.

    Article  PubMed  Google Scholar 

  • Poplawska-Kita A, Siewko K, Szpak P, Król B, Telejko B, Klimiuk PA, Stokowska W, Górska M, Szelachowska M. Association between type 1 diabetes and periodontal health. Adv Med Sci. 2014;59:126–31.

    Article  PubMed  Google Scholar 

  • Preshaw PM, Bissett SM. Periodontitis: oral complication of diabetes. Endocrinol Metab Clin North Am. 2013;42:849–67.

    Article  PubMed  Google Scholar 

  • Rojo-Botello NR, Garcia-Hernándes AL, Moreno-Fierros L. Expression of toll-like receptors 2, 4 and 9 is increased in gingival tissue from patients with type 2 diabetes and chronic periodontitis. J Periodontal Res. 2012;47:62–73.

    Article  PubMed  Google Scholar 

  • Ryan ME, Carnu O, Kamer A. The influence of diabetes on the periodontal tissues. J Am Dent Assoc. 2003;134(Spec No):34S–40.

    Article  PubMed  Google Scholar 

  • Saito T, Shimazaki Y. Metabolic disorders related to obesity and periodontal disease. Periodontol 2000. 2007;43:254–66.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • SEARCH for Diabetes in Youth Study Group, Liese AD. The burden of diabetes mellitus among US youth: prevalence estimates form the SEARC for Diabetes in Youth Study. Pediatrics. 2006;118:1510–8.

    Article  Google Scholar 

  • Sgolastra F, Severino M, Pietropaoli D, Gatto R, Monaco A. Effectiveness of periodontal treatment to improve metabolic control in patients with chronic periodontitis and type 2 diabetes: a meta-analysis of randomized clinical trials. J Periodontol. 2013;84:958–73.

    Article  PubMed  Google Scholar 

  • Sima C, Rhourida K, van Dyke TE, Gyurko R. Type 1 diabetes predisposes to enhanced gingival leukocyte margination and macromolecule extravasation in vivo. J Periodontal Res. 2010;45:748–56.

    Article  PubMed  PubMed Central  Google Scholar 

  • Skrepcinski FB, Niendorff WJ. Periodontal disease in American Indians and Alaska Natives. J Public Health Dent. 2000;60:261–6.

    Article  PubMed  Google Scholar 

  • Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Periodontol. 2013a;84(4 Suppl):S113–34. doi:10.1902/jop.2013.134005.

    Google Scholar 

  • Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Clin Periodontol. 2013b;40 suppl 14:S113–34. doi:10.1111/jcpe.12059.

    Google Scholar 

  • Tervonen T, Karjalainen K. Periodontal disease related to diabetic status. A pilot study of the response to periodontal therapy in type 1 diabetes. J Clin Periodontol. 1997;24:505–10.

    Article  PubMed  Google Scholar 

  • The Expert Committee on the Diagnosis, Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20:1183–97.

    Article  Google Scholar 

  • Thorstensson H, Hugoson A. Periodontal disease in long-duration insulin-dependent diabetics. J Clin Periondontol. 1993;20:352–8.

    Article  Google Scholar 

  • 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;352:837–53.

    Article  Google Scholar 

  • Valensi P, Giroux C, Seeboth-Ghalayini B, Attali JR. Diabetic peripheral neuropathy: effect of age, duration of diabetes, glycemic control and vascular factors. J Diabetes Complications. 1997;11:27–34.

    Article  PubMed  Google Scholar 

  • Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–53.

    Article  PubMed  Google Scholar 

  • Wu Y-Y, Xiao E, Graves DT. Diabetes mellitus related bone metabolism and periodontal disease. Int J Oral Sci. 2015;7:63–72.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xavier AC, Silva IN, Costa Fde O, Corrêa DS. Periodontal status in children and adolescents with type 1 diabetes mellitus. Arq Bras Endocrinol Matabol. 2009;53:348–54.

    Article  Google Scholar 

  • Zhou X, Zhang W, Liu X, Zhang W, Li Y. Interrelationship between diabetes and periodontitis: role of hyperlipidemia. Arch Oral Biol. 2015;60:667–74.

    Article  PubMed  Google Scholar 

  • Zhu M, Nikolajczyk BS. Immune cells link obesity-associated type 2 diabetes and periodontitis. J Dent Res. 2014;93:346–52.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414(6865):785–7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Palle Holmstrup PhD, Dr.Odont., Odont.Dr. (h.c.) .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Holmstrup, P., Flyvbjerg, A. (2016). Linkage Between Periodontal Disease and Diabetes Mellitus. In: Lynge Pedersen, A. (eds) Oral Infections and General Health. Springer, Cham. https://doi.org/10.1007/978-3-319-25091-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-25091-5_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-25089-2

  • Online ISBN: 978-3-319-25091-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics