Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Association Between Plasma Levels of Manganese and Periodontal Status: A Study Based on the Fourth Korean National Health and Nutrition Examination Survey
Hyang-Sun Kim, Ph.D.,* Ji-A Park, BS,† Jun-Sung Na,‡ Kyoung-Hoon Lee,§ Kwang-Hak Bae, Ph.D.†∥
* †
Department of Physiology, College of Medicine, Seoul National University, Seoul, Korea.
Department of Preventive and Public Health Dentistry, School of Dentistry, Seoul National University, Seoul, Korea. ‡
Korean Minjok Leadership Academy, Hoengseong-gun, Gangwon-do, Korea. §
Daejeonjungang High School, Daejeon, Korea.
Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
∥
Background: This study aims to evaluate the association between plasma levels of manganese (Mn) and periodontal status in a representative sample of Korean adults. Methods: This study analyzed plasma levels of Mn and periodontal status in 1,679 participants, all of whom were older than 19 years. Plasma levels of Mn were divided into four categories: 1st quartile (1.544 µg/dL). Periodontal status was assessed using the Community Periodontal Index (CPI). Multivariate logistic regression analyses were performed after adjusting for sociodemographic variables, oral and general health behavior, oral health status and systemic conditions. All analyses took into consideration the complex sampling design and multivariate analyses were performed in the subgroups. Results: Multivariate logistic regression analyses revealed a significant association between plasma levels of Mn and higher CPI in a total sample. There was a moderate association between the 1st quartile in plasma levels of Mn and higher CPI in males (odds ratio [OR]: 2.13; 95% confidential interval [CI]: 1.25-3.63) and current smokers (OR: 2.07; 95% CI: 1.04-4.11), compared to 4th quartile. Conclusion: Periodontal status is significantly associated with plasma levels of Mn in Korean adults, especially in men and smokers.
KEY WORDS Periodontal disease, manganese, National Health and Nutrition Examination Survey
Periodontitis is a chronic and long-lasting low-grade inflammatory disease1 that leads to a break-down of the connective tissue and bone that anchors the teeth to the jaws.2 It is highly prevalent worldwide, contributes to the global burden of chronic diseases and represents a major public health problem in many countries.3, 4 In Korea, the prevalence of periodontitis is 29.4% among adults.5 Periodontitis is also related to systemic alterations such as atherosclerotic vascular disease and metabolic syndrome.6, 7 Several studies have reported increased levels of oxidative stress parameters in patients with periodontitis and suggested a positive association between periodontitis and oxidative stress.8-13 1
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Additionally, it was suggested that periodontitis generates excessive reactive oxygen species (ROS) which can inhibit the regulatory mechanisms in the body, which can worsen systemic diseases such as diabetes, and vice versa.14-15 Manganese (Mn) is a micronutrient involved in macronutrient metabolism, including carbohydrate and protein metabolism. Mn is also found in some bridge-forming enzymes and antioxidant enzymes.16 Especially, it is a cofactor of superoxide dismutase (SOD), which is an antioxidant enzyme that scavenges free radicals in almost all cells17-21 and regulates oxidative resistance as a nuclear transcription factor.22 Mn-containing SOD (Mn-SOD) which is one of subgroups of SOD mainly protects mitochondria of eukaryotes from oxidative damages.23,24 Mn was also reported as more active antioxidant than other transition metals like copper in kinetic analysis.25 Dietary Mn is rich in foods such as nuts, legumes, tea and whole grains.16 Therefore, one potential explanation for the association between Mn and periodontitis could be suggested that higher Mn concentration in the blood enhances SOD activity and lowers oxidative stress levels, thereby reducing inflammation associated with periodontitis. This hypothesis can be supported by an animal study that found synthetic, Mn-containing SOD mimetics may be useful in the treatment of periodontitis26 and another study that reported an association between periodontal disease and Mn in saliva.27 However, there have been no study on the association between plasma levels of Mn and periodontitis. Therefore, this study aims to evaluate the association between plasma levels of Mn and periodontal status in a representative sample of Korean adults.
MATERIALS AND METHODS Study Design and Subject Selection The data used in this study are a subset of the fourth Korean National Health and Nutrition Examination Survey (KNHANES)5 conducted in 2009 by the Korea Center for Disease Control and Prevention (KCDC). The sampling protocol for the KNHANES was designed to involve a complex, stratified and multistage probability-cluster survey of a representative sample of the non-institutionalized civilian population of Korea. The survey was performed by the Korean Ministry of Health and Welfare. The target population of the survey included all non-institutionalized civilian Korean individuals aged 1 year or older. The survey employed multistage stratified probability sampling units based on geographic area, gender and age, which were determined based on the household registries of the 2005 National Census Registry,28 the most recent 5-year national census in Korea. Using the 2005 census data, 200 primary sampling units (PSU) were selected across Korea. The final sample set for KNHANES included 4,600 households and 10,533 participants. Of these participants, 7,095 individuals who were 19 years of age or older had a periodontal examination. Among them, 1,679 individuals who had data for plasma levels of Mn comprised the final sample group for this study. A detailed description of the sampling method is described in the KNHANES report.5 Clinical Variables Periodontal status. The WHO community periodontal index (CPI)29 was used to assess periodontal status. Higher CPI was defined as a CPI greater than or equal to ‘code 3’, which indicates that at least one site had a probing pocket depth > 3.5 mm (code 4 > 5.5 mm). Index tooth numbers were 2, 3, 8, 14, 15, 18 19, 24, 30 and 31. A CPI probe that met the WHO guidelines29 was used.¶ The mouth was divided into sextants, and approximately 20 g force was used when probing. In the 2009 KNHANES, 27 trained dentists examined 2
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
the periodontal status of the participants. The inter-examiner mean of Kappa value was 0.77 (0.53 to 0.94).29 Manganese. Mn was measured at the level of whole blood (µg/dL). This was analyzed using 1 ml of blood from the participant, and was based on the standard addition method using the flameless atomic absorption spectrometer-graphite furnace.5 Plasma levels of Mn were divided into four categories: 1st quartile (1.544 µg/dL). Covariates. Socio-demographic variables included gender, age, household income and education level. Household income was calculated as the family income adjusted for the number of family members. Education level was defined as the highest diploma the participant had received. Oral health behaviors included daily frequency of tooth-brushing and use of dental floss or an interdental brush. Smoking status was included as a general health behavior, and participants were divided into three groups depending on the status: non-smokers (those who had never smoked or had smoked fewer than 100 cigarettes in their lifetime); current smokers (those who currently smoked and had smoked 100 cigarettes or more in their lifetime); past smokers (those who had smoked in the past but were not current smokers). Oral health status was based on the number of decayed permanent teeth (DT), while systemic conditions included diabetes and obesity. Statistical Analysis The complex sampling design of the survey was considered, and individual weighted factors were used when obtaining variances. Multivariate logistic regression analyses were applied to examine the relationships between plasma levels of Mn and periodontal status. The odds ratios (ORs) of Mn for higher CPI were adjusted for the aforementioned covariates in a logistic model. Because of significant interactions between periodontal status, gender and smoking status, subgroup analyses were performed to gain stratified estimates according to gender and smoking status. Statistical analyses were performed using SPSS statistical software version 19.0.#
RESULTS The prevalence of higher CPI, defined as a CPI code ≥ 3, was 30.9% (that of code 4 was 5.9%). Tables 1, 2 and 3 list characteristics of participants categorized by periodontal status. Table 4 showed a significant association between plasma levels of Mn and higher CPI in the multivariate logistic regression model for a total sample (OR of 1st quartile: 1.52; 95% confidential interval [CI]: 1.07-2.15). Meanwhile, the results of the sub-group analyses presented in table 4 showed the association was different according to the strata of gender and smoking. Compared to the 4th quartile, there was a moderate association between 1st quartile plasma levels of Mn and higher CPI in males (OR: 2.13; 95% CI: 1.25-3.63) and current smokers (OR: 2.07; 95% CI: 1.04-4.11). However, there was no significant association between plasma levels of Mn and higher CPI in females and non-smokers.
DISCUSSION In this study, it was found that the plasma levels of Mn were associated with periodontal status in total after adjusting for socio-demographic variables, oral and general health behaviors, and oral and general health status, and that gender and smoking could modify the effect of Mn on periodontal status as the association was significant only for men and current smokers. 3
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Mn-SOD reduced inflammatory destruction of periodontal tissue in a rat model study.26 This may support the assertion in the present study that suggests Mn is associated with periodontitis, even though it did not demonstrate the effect of Mn itself. Another study also found that the participants with periodontal disease had the lower levels of Mn and SOD in saliva compared to the participants without periodontal disease.27 Although these two studies support our findings that Mn levels are associated with periodontitis, the present study is the first epidemiologic research on the association between Mn in blood and periodontal status. In addition, the present study used a representative sample of Korean adults and considered various confounders and effect modifiers. Overall, the group with lower plasma Mn had less favorable periodontal status in this study, and their link may be explained by oxidative stress. ROS play an important role in tissue destruction via microbial and host-mediated pathways.26, 31 Destructive inflammation by ROS also occurs in periodontal tissue.8,32 Superoxide anion, the target substrate of SOD mediates several pro-inflammatory responses.26, 33 Mn is an essential cofactor in the activation of mitochondrial SOD, and elevated levels of Mn-SOD in the blood were observed when Mn was injected.34 Thus, Mn deficiency would decrease the total level of antioxidant enzymes and inhibit the role of Mn-SOD as a nuclear transcription factor regulating oxidative resistance.22 The reduction in antioxidant mediators would result in an inability to inhibit an oxidative attack, thereby increasing inflammatory destruction of connective tissue and alveolar bone in periodontal tissue. This study was the first to confirm the association between blood levels of Mn and periodontal status. There are few reports on the role and its mechanism of Mn as an antioxidant in human,17 and no previous studies have demonstrated a causal relationship between Mn, antioxidant systems including SOD and periodontal disease. Therefore, further studies should attempt to elucidate the relationship between Mn and periodontal disease as mediated by oxidative stress. Meanwhile, the subgroup analysis in this study found that gender and smoking status modify the association between plasma Mn and periodontal status. Gender and smoking were also reported to be modifying factors related to the association of cadmium and lead with periodontitis in a national survey.35 Many studies have indirectly or directly demonstrated that cigarette smoking increases oxidative stress and smoking cessation improves oxidative stress levels.36-39 As low concentrations of Mn in the blood could reflect low levels of the antioxidant enzyme, SOD,34 the antioxidant capacity of individuals with low levels of plasma Mn may not be able to handle the increased amount of ROS found in smokers. In terms of gender, the significant association between plasma Mn and periodontal status was only observed in males. This gender difference may be explained by estrogen, a major sex hormone in women. Several studies have reported that estrogen levels are positively related to antioxidant capacity and antioxidant gene expression.40-43 Estrogen could regulate circulating redox status by activating several antioxidant enzymatic systems including SOD, catalase and glutathione antioxidant groups.40-42 In addition, it has been observed that oxidative stress is higher in postmenopausal women.42, 44, 45 Thus, it can be supposed estrogen may make women less susceptible to oxidative stress than men. However, this study did not consider menopausal status and other factors affecting internal estrogen levels. In addition, even if estrogen was a factor, there may be other explanations for the gender differences observed in this study. Additional research is needed to determine the mechanism behind gender as a modifying factor in the relationship between Mn and periodontal status. This study has several limitations. Although CPI is an easy way to assess the prevalence of periodontitis in population surveys and epidemiological studies,35 it may overestimate or underestimate periodontal status due to the use of representative teeth and pseudo-pockets. 35, 47 In addition, this was a 4
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
cross-sectional study, and therefore it is not possible to determine the direction of causality between Mn levels and periodontal status. Nonetheless, this is the first epidemiologic study to report an association between Mn levels in blood and periodontal status in a nationally representative sample of adults.
CONCLUSION Periodontal status is significantly associated with plasma levels of Mn in Korean adults, especially in men and smokers. The underlying mechanisms and causality of the relationship between Mn and periodontitis remain to be determined through prospective cohort studies. CONFLICT OF INTEREST AND SOURCE OF FUNDING STATEMENT The study was self-supported, but the Korea Center for Disease Control and Prevention (Cheongwongun, Korea) provided data from the Fourth Korea National Health and Nutrition Examination Survey to be used in the study. The authors declare no conflicts of interest related to this study.
ACKNOWLEDGEMENTS The authors declare no conflicts of interest related to this study.
REFERENCES 1.
Li P, He L, Sha YQ, Luan QX. Relationship of metabolic syndrome to chronic periodontitis. J Periodontol 2009;80:541549.
2.
Williams RC. Periodontal disease. N Engl J Med 1990;323:373-382.
3.
Albander JM, Bunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol 1999;70:13-29.
4.
Petersen PE, Ogawa H. The global burden of periodontal disease: towards integration with chronic disease prevention and control. Periodontol 2000 2012;60:15-39.
5.
Korea Center for Disease Control and Prevention & Ministry of Health and Welfare. Korean National Health and Examination Surveys: the 4th surveys (in Korean). Available at: https://knhanes.cdc.go.kr/knhanes/index.do. Accessed March 22, 2014.
6.
Lockhart PB, Bolger AF, Papapanou PN, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation 2012;125:2520-2544.
7.
Nibali L, Tatarakis N, Needleman I, et al. Clinical review: Association between metabolic syndrome and periodontitis: a systematic review and meta-analysis. J Clin Endocrinol Metab 2013;98:913-920.
8.
D'Aiuto F, Nibali L, Parkar M, Patel K, Suvan J, Donos N. Oxidative stress, systemic inflammation, and severe periodontitis. J Dent Res 2010;89:1241-1246.
9.
Aziz AS, Kalekar MG, Suryakar AN, et al. Assessment of some biochemical oxidative stress markers in male smokers with chronic periodontitis. Indian J Clin Biochem 2013;28:374-380.
10. Bullon P, Morillo JM, Ramirez-Tortosa MC, Quiles JL, Newman HN, Battino M. Metabolic syndrome and periodontitis: is oxidative stress a common link? J Dent Res 2009;88:503-518. 11. Baltacıoğlu E, Yuva P, Aydın G, et al. Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: a new biomarker for periodontal disease? [published online ahead of print March 17, 2014]. J Periodontol; doi:10.1902/jop.2014.130654.
5
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
12. Tomofuji T, Irie K, Sanbe T, et al. Periodontitis and increase in circulating oxidative stress. Jpn Dent Sci Rev 2009;45:46-51. 13. Ekuni D, Endo Y, Irie K, et al. Imbalance of oxidative/anti-oxidative status induced by periodontitis is involved in apoptosis of rat submandibular glands. Arch Oral Biol 2010;55:170-176. 14. Trivedi S, Lal N, Mahdi AA, Mittal M, Singh B, Pandey S. Evaluation of antioxidant enzymes activity and malondialdehyde levels in chronic periodontitis patients with diabetes. J Periodontol 2014;85:713-720. 15. Allen EM, Matthews JB, O'Connor R, O'Halloran D, Chapple IL. Periodontitis and type 2 diabetes: is oxidative stress the mechanistic link? Scott Med J 2009;54:41-47. 16. Wardlaw GM, Hampl JS. Perspectives in Nutrition, 7th ed. Boston: McGraw-Hill Higher Education; 2007:439-440. 17. Berg JM, Tymoczko JL, Stryer L. Biochemistry, 6th ed. New York: W. H. Freeman; 2007:518-519. 18. Culotta VC. Superoxide dismutase, oxidative stress, and cell metabolism. Curr Top Cell Regul 2000;36:117-132. 19. Smith MW, Doolittle RF. A comparison of evolutionary rates of the two major kinds of superoxide dismutase. J Mol Evol 1992;34:75-84. 20. Zhang Y, Zhang HM, Shi Y, et al. Loss of manganese superoxide dismutase leads to abnormal growth and signal transduction in mouse embryonic fibroblasts. Free Radic Biol Med 2010;49:1255-1262. 21. Alscher RG, Erturk N, Heath LS. Role of superoxide dismutase (SODs) in controlling oxidative stress in plants. J Exp Bot 2002;53:1331-1341. 22. Tsang CK, Liu Y, Thomas J, Zhang Y, Zheng XF. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat Commun 2014;5:3446. 23. Borgstahl GE, Parge HE, Hickey MJ, Beyer WF Jr, Hallewell RA, Tainer JA. The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. Cell 1992;71:107-118. 24. Matés JM, Pérez-Gómez C, Núñez de Castro I. Antioxidant enzymes and human diseases. Clin Biochem 1999;32:595603. 25. Coassin M, Ursini F, Bindoli A. Antioxidant effect of manganese. Arch Biochem Biophys 1992;299:330-333. 26. Di Paola R, Mazzon E, Rotondo F, et al. Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic. Eur J Pharmacol 2005;516:151-157. 27. Zhang MF, Huang YJ, Zhang HF, Tang W, Zhou J. Oxidative stress and susceptibility of periodontal disease (in Chinese). Shanghai Kou Qiang Yi Xue 2013;22:571-576. 28. Statistics Korea. 2005 National Census Registry (in Korean). Available at: https://census.go.kr/hcensus/index.jsp. Accessed June 3, 2014. 29. World Health Organization. Oral Health Surveys: Basic Methods, 4th ed. Geneva: World Health Organization; 1997:639. 30. Korea Center for Disease Control and Prevention. Standardization for Oral Health Survey in KNHANES (2009). Cheongwongun: Korea Center for Disease Control and Prevention; 2010:53-56. 31. Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 1991;91:14S–22S. 32. Chapple IL, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 2007;43:160-232. 33. Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev 2001;53:135-159. 34. Genther ON, Hansen SL. A multielement trace mineral injection improves liver copper and selenium concentrations and manganese superoxide dismutase activity in beef steers. J Anim Sci 2014;92:695-704. 35. Won YS, Kim JH, Kim YS, Bae KH. Association of internal exposure of cadmium and lead with periodontal disease: a study of the Fourth Korean National Health and Nutrition Examination Survey. J Clin Periodontol 2013;40:118-124
6
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
36. Kato T, Umeda A, Miyagawa K, et al. Varenicline-assisted smoking cessation decreases oxidative stress and restores endothelial function [published online ahead of print March 20, 2014]. Hypertens Res 2014; doi: 10.1038/hr.2014.52. 37. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol 2004;43:1731–1737. 38. Kato T, Inoue T, Morooka T, Yoshimoto N, Node K. Short-term passive smoking causes endothelial dysfunction via oxidative stress in nonsmokers. Can J Physiol Pharmacol 2006;84:523–529. 39. Zhou JF, Yan XF, Guo FZ, Sun NY, Qian ZJ, Ding DY. Effects of cigarette smoking and smoking cessation on plasma constituents and enzyme activities related to oxidative stress. Biomed Environ Sci 2000;13:44–55. 40. Bellanti F, Matteo M, Rollo T, et al. Sex hormones modulate circulating antioxidant enzymes: Impact of estrogen therapy. Redox Biol 2013;1:340-346. 41. Massafra C, Gioia D, De Felice C, et al. Effects of estrogens and androgens on erythrocyte antioxidant superoxide dismutase, catalase and glutathione peroxidase activities during the menstrual cycle. J Endocrinol 2000;167:447–452. 42. Bednarek-Tupikowska G, Bohdanowicz-Pawlak A, Bidzinska B, Milewicz A, Antonowicz-Juchniewicz J, Andrzejak R. Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women. Gynecol Endocrinol 2001;15:298–303. 43. Serviddio G, Loverro G, Vicino M. Modulation of endometrial redox balance during the menstrual cycle: relation with sex hormones. J Clin Endocrinol Metab 2002;87:2843–2848. 44. Signorelli SS, Neri S, Sciacchitano S. Behaviour of some indicators of oxidative stress in postmenopausal and fertile women. Maturitas 2006;53:77–82. 45. Sanchez-Rodriguez MA, Zacarias-Flores M, Arronte-Rosales A, Correa-Munoz E, Mendoza-Nunez VM. Menopause as risk factor for oxidative stress. Menopause 2012;19:361-367. 46. Kwon YE, Ha JE, Paik DI, Jin BH, Bae KH. The relationship between periodontitis and metabolic syndrome among a Korean nationally representative sample of adults. J Clin Periodontol 2011;38:781-786. 47. Kingman A, Albandar JM. Methodological aspects of epidemiological studies of periodontal diseases. Periodontol 2000 2002;29:11-30.
Corresponding author: Kwang-Hak Bae, Department of Preventive and Public Health Dentistry, School of Dentistry, Seoul National University, 28, Yeongeuon-dong, Jongno-gu, Seoul, 110-749, Korea (South), Tel: +82-2-740-8747, Fax: +82-2-765-1722, E-mail: [email protected] Submitted April 23, 2014; accepted for publication July 07, 2014.
7
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Table 1. Univariate comparisons of socio-demographic characteristics in participants with lower and higher CPI Lower CPI Higher CPI n %* (95% CI) n %* (95% CI) † Age (n=1679) 38.60 (37.81 – 39.39) 48.99 (47.72 – 50.26)† Gender (n=1679) 65.2 (61.234.8 (31.0Male 497 311 69.0) 38.8) 76.9 (73.223.1 (19.8Female 652 219 80.2) 26.8) Highest diploma (n=1672) 52.6 (46.047.4 (40.8Primary school 195 157 59.2) 54.0) 63.3 (55.436.7 (29.5Middle school 127 75 70.5) 44.6) 73.8 (69.226.2 (22.1High school 461 177 77.9) 30.8) 76.0 (71.124.0 (19.7≥ University or college 363 117 80.3) 28.9) ‡ Household income (n=1668) 64.2 (58.335.8 (30.2< 25 % 173 116 69.8) 41.7) 64.8 (59.435.2 (30.225 - 50 % 261 148 69.8) 40.6) 71.2 (65.328.8 (23.650 - 75 % 346 142 76.4) 34.7) 75.8 (70.824.2 (19.8> 75 % 361 121 80.2) 29.2) *
Weighted percent and 95% confidence interval
†
Weighted mean and 95% confidence interval
‡
Household income: monthly average family equivalent income (=monthly average household income/√[the number of household members])
8
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Table 2. Univariate comparisons of oral and systemic health status and manganese levels in participants with lower and higher CPI Lower CPI Higher CPI n %* (95% CI) n %* (95% CI) † Active caries (n=1679) 0.74 (0.63–0.85) 0.94 (0.75–1.13)† Diabetes (n=1679) No 1097 71.2 (67.9-74.2) 476 28.8 (25.8-32.1) Yes 52 51.0 (39.1-62.8) 54 49.0 (37.2-60.9) BMI‡ (n=1670) Underweight 57 79.4 (67.7-87.6) 14 20.6 (12.4-32.3) Normal 745 71.6 (68.0-74.9) 340 28.4 (25.1-32.0) Obese 340 65.7 (60.6-70.5) 174 34.3 (29.5-39.4) Manganese§ (n=1679) 1st quartile 259 63.4 (58.3-68.2) 161 36.6 (31.8-41.7) 2nd quartile 287 70.5 (64.5-75.8) 132 29.5 (24.2-35.5) 3rd quartile 293 71.3 (65.9-76.2) 126 28.7 (23.8-34.1) 4th quartile 310 76.2 (71.3-80.6) 111 23.8 (19.4-28.7) *
Weighted percent and 95% confidence interval
†
Weighted mean and 95% confidence interval
‡
Underweight:
DOI: 10.1902/jop.2014.140250
Association Between Plasma Levels of Manganese and Periodontal Status: A Study Based on the Fourth Korean National Health and Nutrition Examination Survey
Hyang-Sun Kim, Ph.D.,* Ji-A Park, BS,† Jun-Sung Na,‡ Kyoung-Hoon Lee,§ Kwang-Hak Bae, Ph.D.†∥
* †
Department of Physiology, College of Medicine, Seoul National University, Seoul, Korea.
Department of Preventive and Public Health Dentistry, School of Dentistry, Seoul National University, Seoul, Korea. ‡
Korean Minjok Leadership Academy, Hoengseong-gun, Gangwon-do, Korea. §
Daejeonjungang High School, Daejeon, Korea.
Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
∥
Background: This study aims to evaluate the association between plasma levels of manganese (Mn) and periodontal status in a representative sample of Korean adults. Methods: This study analyzed plasma levels of Mn and periodontal status in 1,679 participants, all of whom were older than 19 years. Plasma levels of Mn were divided into four categories: 1st quartile (1.544 µg/dL). Periodontal status was assessed using the Community Periodontal Index (CPI). Multivariate logistic regression analyses were performed after adjusting for sociodemographic variables, oral and general health behavior, oral health status and systemic conditions. All analyses took into consideration the complex sampling design and multivariate analyses were performed in the subgroups. Results: Multivariate logistic regression analyses revealed a significant association between plasma levels of Mn and higher CPI in a total sample. There was a moderate association between the 1st quartile in plasma levels of Mn and higher CPI in males (odds ratio [OR]: 2.13; 95% confidential interval [CI]: 1.25-3.63) and current smokers (OR: 2.07; 95% CI: 1.04-4.11), compared to 4th quartile. Conclusion: Periodontal status is significantly associated with plasma levels of Mn in Korean adults, especially in men and smokers.
KEY WORDS Periodontal disease, manganese, National Health and Nutrition Examination Survey
Periodontitis is a chronic and long-lasting low-grade inflammatory disease1 that leads to a break-down of the connective tissue and bone that anchors the teeth to the jaws.2 It is highly prevalent worldwide, contributes to the global burden of chronic diseases and represents a major public health problem in many countries.3, 4 In Korea, the prevalence of periodontitis is 29.4% among adults.5 Periodontitis is also related to systemic alterations such as atherosclerotic vascular disease and metabolic syndrome.6, 7 Several studies have reported increased levels of oxidative stress parameters in patients with periodontitis and suggested a positive association between periodontitis and oxidative stress.8-13 1
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Additionally, it was suggested that periodontitis generates excessive reactive oxygen species (ROS) which can inhibit the regulatory mechanisms in the body, which can worsen systemic diseases such as diabetes, and vice versa.14-15 Manganese (Mn) is a micronutrient involved in macronutrient metabolism, including carbohydrate and protein metabolism. Mn is also found in some bridge-forming enzymes and antioxidant enzymes.16 Especially, it is a cofactor of superoxide dismutase (SOD), which is an antioxidant enzyme that scavenges free radicals in almost all cells17-21 and regulates oxidative resistance as a nuclear transcription factor.22 Mn-containing SOD (Mn-SOD) which is one of subgroups of SOD mainly protects mitochondria of eukaryotes from oxidative damages.23,24 Mn was also reported as more active antioxidant than other transition metals like copper in kinetic analysis.25 Dietary Mn is rich in foods such as nuts, legumes, tea and whole grains.16 Therefore, one potential explanation for the association between Mn and periodontitis could be suggested that higher Mn concentration in the blood enhances SOD activity and lowers oxidative stress levels, thereby reducing inflammation associated with periodontitis. This hypothesis can be supported by an animal study that found synthetic, Mn-containing SOD mimetics may be useful in the treatment of periodontitis26 and another study that reported an association between periodontal disease and Mn in saliva.27 However, there have been no study on the association between plasma levels of Mn and periodontitis. Therefore, this study aims to evaluate the association between plasma levels of Mn and periodontal status in a representative sample of Korean adults.
MATERIALS AND METHODS Study Design and Subject Selection The data used in this study are a subset of the fourth Korean National Health and Nutrition Examination Survey (KNHANES)5 conducted in 2009 by the Korea Center for Disease Control and Prevention (KCDC). The sampling protocol for the KNHANES was designed to involve a complex, stratified and multistage probability-cluster survey of a representative sample of the non-institutionalized civilian population of Korea. The survey was performed by the Korean Ministry of Health and Welfare. The target population of the survey included all non-institutionalized civilian Korean individuals aged 1 year or older. The survey employed multistage stratified probability sampling units based on geographic area, gender and age, which were determined based on the household registries of the 2005 National Census Registry,28 the most recent 5-year national census in Korea. Using the 2005 census data, 200 primary sampling units (PSU) were selected across Korea. The final sample set for KNHANES included 4,600 households and 10,533 participants. Of these participants, 7,095 individuals who were 19 years of age or older had a periodontal examination. Among them, 1,679 individuals who had data for plasma levels of Mn comprised the final sample group for this study. A detailed description of the sampling method is described in the KNHANES report.5 Clinical Variables Periodontal status. The WHO community periodontal index (CPI)29 was used to assess periodontal status. Higher CPI was defined as a CPI greater than or equal to ‘code 3’, which indicates that at least one site had a probing pocket depth > 3.5 mm (code 4 > 5.5 mm). Index tooth numbers were 2, 3, 8, 14, 15, 18 19, 24, 30 and 31. A CPI probe that met the WHO guidelines29 was used.¶ The mouth was divided into sextants, and approximately 20 g force was used when probing. In the 2009 KNHANES, 27 trained dentists examined 2
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
the periodontal status of the participants. The inter-examiner mean of Kappa value was 0.77 (0.53 to 0.94).29 Manganese. Mn was measured at the level of whole blood (µg/dL). This was analyzed using 1 ml of blood from the participant, and was based on the standard addition method using the flameless atomic absorption spectrometer-graphite furnace.5 Plasma levels of Mn were divided into four categories: 1st quartile (1.544 µg/dL). Covariates. Socio-demographic variables included gender, age, household income and education level. Household income was calculated as the family income adjusted for the number of family members. Education level was defined as the highest diploma the participant had received. Oral health behaviors included daily frequency of tooth-brushing and use of dental floss or an interdental brush. Smoking status was included as a general health behavior, and participants were divided into three groups depending on the status: non-smokers (those who had never smoked or had smoked fewer than 100 cigarettes in their lifetime); current smokers (those who currently smoked and had smoked 100 cigarettes or more in their lifetime); past smokers (those who had smoked in the past but were not current smokers). Oral health status was based on the number of decayed permanent teeth (DT), while systemic conditions included diabetes and obesity. Statistical Analysis The complex sampling design of the survey was considered, and individual weighted factors were used when obtaining variances. Multivariate logistic regression analyses were applied to examine the relationships between plasma levels of Mn and periodontal status. The odds ratios (ORs) of Mn for higher CPI were adjusted for the aforementioned covariates in a logistic model. Because of significant interactions between periodontal status, gender and smoking status, subgroup analyses were performed to gain stratified estimates according to gender and smoking status. Statistical analyses were performed using SPSS statistical software version 19.0.#
RESULTS The prevalence of higher CPI, defined as a CPI code ≥ 3, was 30.9% (that of code 4 was 5.9%). Tables 1, 2 and 3 list characteristics of participants categorized by periodontal status. Table 4 showed a significant association between plasma levels of Mn and higher CPI in the multivariate logistic regression model for a total sample (OR of 1st quartile: 1.52; 95% confidential interval [CI]: 1.07-2.15). Meanwhile, the results of the sub-group analyses presented in table 4 showed the association was different according to the strata of gender and smoking. Compared to the 4th quartile, there was a moderate association between 1st quartile plasma levels of Mn and higher CPI in males (OR: 2.13; 95% CI: 1.25-3.63) and current smokers (OR: 2.07; 95% CI: 1.04-4.11). However, there was no significant association between plasma levels of Mn and higher CPI in females and non-smokers.
DISCUSSION In this study, it was found that the plasma levels of Mn were associated with periodontal status in total after adjusting for socio-demographic variables, oral and general health behaviors, and oral and general health status, and that gender and smoking could modify the effect of Mn on periodontal status as the association was significant only for men and current smokers. 3
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Mn-SOD reduced inflammatory destruction of periodontal tissue in a rat model study.26 This may support the assertion in the present study that suggests Mn is associated with periodontitis, even though it did not demonstrate the effect of Mn itself. Another study also found that the participants with periodontal disease had the lower levels of Mn and SOD in saliva compared to the participants without periodontal disease.27 Although these two studies support our findings that Mn levels are associated with periodontitis, the present study is the first epidemiologic research on the association between Mn in blood and periodontal status. In addition, the present study used a representative sample of Korean adults and considered various confounders and effect modifiers. Overall, the group with lower plasma Mn had less favorable periodontal status in this study, and their link may be explained by oxidative stress. ROS play an important role in tissue destruction via microbial and host-mediated pathways.26, 31 Destructive inflammation by ROS also occurs in periodontal tissue.8,32 Superoxide anion, the target substrate of SOD mediates several pro-inflammatory responses.26, 33 Mn is an essential cofactor in the activation of mitochondrial SOD, and elevated levels of Mn-SOD in the blood were observed when Mn was injected.34 Thus, Mn deficiency would decrease the total level of antioxidant enzymes and inhibit the role of Mn-SOD as a nuclear transcription factor regulating oxidative resistance.22 The reduction in antioxidant mediators would result in an inability to inhibit an oxidative attack, thereby increasing inflammatory destruction of connective tissue and alveolar bone in periodontal tissue. This study was the first to confirm the association between blood levels of Mn and periodontal status. There are few reports on the role and its mechanism of Mn as an antioxidant in human,17 and no previous studies have demonstrated a causal relationship between Mn, antioxidant systems including SOD and periodontal disease. Therefore, further studies should attempt to elucidate the relationship between Mn and periodontal disease as mediated by oxidative stress. Meanwhile, the subgroup analysis in this study found that gender and smoking status modify the association between plasma Mn and periodontal status. Gender and smoking were also reported to be modifying factors related to the association of cadmium and lead with periodontitis in a national survey.35 Many studies have indirectly or directly demonstrated that cigarette smoking increases oxidative stress and smoking cessation improves oxidative stress levels.36-39 As low concentrations of Mn in the blood could reflect low levels of the antioxidant enzyme, SOD,34 the antioxidant capacity of individuals with low levels of plasma Mn may not be able to handle the increased amount of ROS found in smokers. In terms of gender, the significant association between plasma Mn and periodontal status was only observed in males. This gender difference may be explained by estrogen, a major sex hormone in women. Several studies have reported that estrogen levels are positively related to antioxidant capacity and antioxidant gene expression.40-43 Estrogen could regulate circulating redox status by activating several antioxidant enzymatic systems including SOD, catalase and glutathione antioxidant groups.40-42 In addition, it has been observed that oxidative stress is higher in postmenopausal women.42, 44, 45 Thus, it can be supposed estrogen may make women less susceptible to oxidative stress than men. However, this study did not consider menopausal status and other factors affecting internal estrogen levels. In addition, even if estrogen was a factor, there may be other explanations for the gender differences observed in this study. Additional research is needed to determine the mechanism behind gender as a modifying factor in the relationship between Mn and periodontal status. This study has several limitations. Although CPI is an easy way to assess the prevalence of periodontitis in population surveys and epidemiological studies,35 it may overestimate or underestimate periodontal status due to the use of representative teeth and pseudo-pockets. 35, 47 In addition, this was a 4
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
cross-sectional study, and therefore it is not possible to determine the direction of causality between Mn levels and periodontal status. Nonetheless, this is the first epidemiologic study to report an association between Mn levels in blood and periodontal status in a nationally representative sample of adults.
CONCLUSION Periodontal status is significantly associated with plasma levels of Mn in Korean adults, especially in men and smokers. The underlying mechanisms and causality of the relationship between Mn and periodontitis remain to be determined through prospective cohort studies. CONFLICT OF INTEREST AND SOURCE OF FUNDING STATEMENT The study was self-supported, but the Korea Center for Disease Control and Prevention (Cheongwongun, Korea) provided data from the Fourth Korea National Health and Nutrition Examination Survey to be used in the study. The authors declare no conflicts of interest related to this study.
ACKNOWLEDGEMENTS The authors declare no conflicts of interest related to this study.
REFERENCES 1.
Li P, He L, Sha YQ, Luan QX. Relationship of metabolic syndrome to chronic periodontitis. J Periodontol 2009;80:541549.
2.
Williams RC. Periodontal disease. N Engl J Med 1990;323:373-382.
3.
Albander JM, Bunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol 1999;70:13-29.
4.
Petersen PE, Ogawa H. The global burden of periodontal disease: towards integration with chronic disease prevention and control. Periodontol 2000 2012;60:15-39.
5.
Korea Center for Disease Control and Prevention & Ministry of Health and Welfare. Korean National Health and Examination Surveys: the 4th surveys (in Korean). Available at: https://knhanes.cdc.go.kr/knhanes/index.do. Accessed March 22, 2014.
6.
Lockhart PB, Bolger AF, Papapanou PN, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation 2012;125:2520-2544.
7.
Nibali L, Tatarakis N, Needleman I, et al. Clinical review: Association between metabolic syndrome and periodontitis: a systematic review and meta-analysis. J Clin Endocrinol Metab 2013;98:913-920.
8.
D'Aiuto F, Nibali L, Parkar M, Patel K, Suvan J, Donos N. Oxidative stress, systemic inflammation, and severe periodontitis. J Dent Res 2010;89:1241-1246.
9.
Aziz AS, Kalekar MG, Suryakar AN, et al. Assessment of some biochemical oxidative stress markers in male smokers with chronic periodontitis. Indian J Clin Biochem 2013;28:374-380.
10. Bullon P, Morillo JM, Ramirez-Tortosa MC, Quiles JL, Newman HN, Battino M. Metabolic syndrome and periodontitis: is oxidative stress a common link? J Dent Res 2009;88:503-518. 11. Baltacıoğlu E, Yuva P, Aydın G, et al. Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: a new biomarker for periodontal disease? [published online ahead of print March 17, 2014]. J Periodontol; doi:10.1902/jop.2014.130654.
5
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
12. Tomofuji T, Irie K, Sanbe T, et al. Periodontitis and increase in circulating oxidative stress. Jpn Dent Sci Rev 2009;45:46-51. 13. Ekuni D, Endo Y, Irie K, et al. Imbalance of oxidative/anti-oxidative status induced by periodontitis is involved in apoptosis of rat submandibular glands. Arch Oral Biol 2010;55:170-176. 14. Trivedi S, Lal N, Mahdi AA, Mittal M, Singh B, Pandey S. Evaluation of antioxidant enzymes activity and malondialdehyde levels in chronic periodontitis patients with diabetes. J Periodontol 2014;85:713-720. 15. Allen EM, Matthews JB, O'Connor R, O'Halloran D, Chapple IL. Periodontitis and type 2 diabetes: is oxidative stress the mechanistic link? Scott Med J 2009;54:41-47. 16. Wardlaw GM, Hampl JS. Perspectives in Nutrition, 7th ed. Boston: McGraw-Hill Higher Education; 2007:439-440. 17. Berg JM, Tymoczko JL, Stryer L. Biochemistry, 6th ed. New York: W. H. Freeman; 2007:518-519. 18. Culotta VC. Superoxide dismutase, oxidative stress, and cell metabolism. Curr Top Cell Regul 2000;36:117-132. 19. Smith MW, Doolittle RF. A comparison of evolutionary rates of the two major kinds of superoxide dismutase. J Mol Evol 1992;34:75-84. 20. Zhang Y, Zhang HM, Shi Y, et al. Loss of manganese superoxide dismutase leads to abnormal growth and signal transduction in mouse embryonic fibroblasts. Free Radic Biol Med 2010;49:1255-1262. 21. Alscher RG, Erturk N, Heath LS. Role of superoxide dismutase (SODs) in controlling oxidative stress in plants. J Exp Bot 2002;53:1331-1341. 22. Tsang CK, Liu Y, Thomas J, Zhang Y, Zheng XF. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat Commun 2014;5:3446. 23. Borgstahl GE, Parge HE, Hickey MJ, Beyer WF Jr, Hallewell RA, Tainer JA. The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. Cell 1992;71:107-118. 24. Matés JM, Pérez-Gómez C, Núñez de Castro I. Antioxidant enzymes and human diseases. Clin Biochem 1999;32:595603. 25. Coassin M, Ursini F, Bindoli A. Antioxidant effect of manganese. Arch Biochem Biophys 1992;299:330-333. 26. Di Paola R, Mazzon E, Rotondo F, et al. Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic. Eur J Pharmacol 2005;516:151-157. 27. Zhang MF, Huang YJ, Zhang HF, Tang W, Zhou J. Oxidative stress and susceptibility of periodontal disease (in Chinese). Shanghai Kou Qiang Yi Xue 2013;22:571-576. 28. Statistics Korea. 2005 National Census Registry (in Korean). Available at: https://census.go.kr/hcensus/index.jsp. Accessed June 3, 2014. 29. World Health Organization. Oral Health Surveys: Basic Methods, 4th ed. Geneva: World Health Organization; 1997:639. 30. Korea Center for Disease Control and Prevention. Standardization for Oral Health Survey in KNHANES (2009). Cheongwongun: Korea Center for Disease Control and Prevention; 2010:53-56. 31. Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 1991;91:14S–22S. 32. Chapple IL, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 2007;43:160-232. 33. Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev 2001;53:135-159. 34. Genther ON, Hansen SL. A multielement trace mineral injection improves liver copper and selenium concentrations and manganese superoxide dismutase activity in beef steers. J Anim Sci 2014;92:695-704. 35. Won YS, Kim JH, Kim YS, Bae KH. Association of internal exposure of cadmium and lead with periodontal disease: a study of the Fourth Korean National Health and Nutrition Examination Survey. J Clin Periodontol 2013;40:118-124
6
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
36. Kato T, Umeda A, Miyagawa K, et al. Varenicline-assisted smoking cessation decreases oxidative stress and restores endothelial function [published online ahead of print March 20, 2014]. Hypertens Res 2014; doi: 10.1038/hr.2014.52. 37. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol 2004;43:1731–1737. 38. Kato T, Inoue T, Morooka T, Yoshimoto N, Node K. Short-term passive smoking causes endothelial dysfunction via oxidative stress in nonsmokers. Can J Physiol Pharmacol 2006;84:523–529. 39. Zhou JF, Yan XF, Guo FZ, Sun NY, Qian ZJ, Ding DY. Effects of cigarette smoking and smoking cessation on plasma constituents and enzyme activities related to oxidative stress. Biomed Environ Sci 2000;13:44–55. 40. Bellanti F, Matteo M, Rollo T, et al. Sex hormones modulate circulating antioxidant enzymes: Impact of estrogen therapy. Redox Biol 2013;1:340-346. 41. Massafra C, Gioia D, De Felice C, et al. Effects of estrogens and androgens on erythrocyte antioxidant superoxide dismutase, catalase and glutathione peroxidase activities during the menstrual cycle. J Endocrinol 2000;167:447–452. 42. Bednarek-Tupikowska G, Bohdanowicz-Pawlak A, Bidzinska B, Milewicz A, Antonowicz-Juchniewicz J, Andrzejak R. Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women. Gynecol Endocrinol 2001;15:298–303. 43. Serviddio G, Loverro G, Vicino M. Modulation of endometrial redox balance during the menstrual cycle: relation with sex hormones. J Clin Endocrinol Metab 2002;87:2843–2848. 44. Signorelli SS, Neri S, Sciacchitano S. Behaviour of some indicators of oxidative stress in postmenopausal and fertile women. Maturitas 2006;53:77–82. 45. Sanchez-Rodriguez MA, Zacarias-Flores M, Arronte-Rosales A, Correa-Munoz E, Mendoza-Nunez VM. Menopause as risk factor for oxidative stress. Menopause 2012;19:361-367. 46. Kwon YE, Ha JE, Paik DI, Jin BH, Bae KH. The relationship between periodontitis and metabolic syndrome among a Korean nationally representative sample of adults. J Clin Periodontol 2011;38:781-786. 47. Kingman A, Albandar JM. Methodological aspects of epidemiological studies of periodontal diseases. Periodontol 2000 2002;29:11-30.
Corresponding author: Kwang-Hak Bae, Department of Preventive and Public Health Dentistry, School of Dentistry, Seoul National University, 28, Yeongeuon-dong, Jongno-gu, Seoul, 110-749, Korea (South), Tel: +82-2-740-8747, Fax: +82-2-765-1722, E-mail: [email protected] Submitted April 23, 2014; accepted for publication July 07, 2014.
7
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Table 1. Univariate comparisons of socio-demographic characteristics in participants with lower and higher CPI Lower CPI Higher CPI n %* (95% CI) n %* (95% CI) † Age (n=1679) 38.60 (37.81 – 39.39) 48.99 (47.72 – 50.26)† Gender (n=1679) 65.2 (61.234.8 (31.0Male 497 311 69.0) 38.8) 76.9 (73.223.1 (19.8Female 652 219 80.2) 26.8) Highest diploma (n=1672) 52.6 (46.047.4 (40.8Primary school 195 157 59.2) 54.0) 63.3 (55.436.7 (29.5Middle school 127 75 70.5) 44.6) 73.8 (69.226.2 (22.1High school 461 177 77.9) 30.8) 76.0 (71.124.0 (19.7≥ University or college 363 117 80.3) 28.9) ‡ Household income (n=1668) 64.2 (58.335.8 (30.2< 25 % 173 116 69.8) 41.7) 64.8 (59.435.2 (30.225 - 50 % 261 148 69.8) 40.6) 71.2 (65.328.8 (23.650 - 75 % 346 142 76.4) 34.7) 75.8 (70.824.2 (19.8> 75 % 361 121 80.2) 29.2) *
Weighted percent and 95% confidence interval
†
Weighted mean and 95% confidence interval
‡
Household income: monthly average family equivalent income (=monthly average household income/√[the number of household members])
8
Journal of Periodontology; Copyright 2014
DOI: 10.1902/jop.2014.140250
Table 2. Univariate comparisons of oral and systemic health status and manganese levels in participants with lower and higher CPI Lower CPI Higher CPI n %* (95% CI) n %* (95% CI) † Active caries (n=1679) 0.74 (0.63–0.85) 0.94 (0.75–1.13)† Diabetes (n=1679) No 1097 71.2 (67.9-74.2) 476 28.8 (25.8-32.1) Yes 52 51.0 (39.1-62.8) 54 49.0 (37.2-60.9) BMI‡ (n=1670) Underweight 57 79.4 (67.7-87.6) 14 20.6 (12.4-32.3) Normal 745 71.6 (68.0-74.9) 340 28.4 (25.1-32.0) Obese 340 65.7 (60.6-70.5) 174 34.3 (29.5-39.4) Manganese§ (n=1679) 1st quartile 259 63.4 (58.3-68.2) 161 36.6 (31.8-41.7) 2nd quartile 287 70.5 (64.5-75.8) 132 29.5 (24.2-35.5) 3rd quartile 293 71.3 (65.9-76.2) 126 28.7 (23.8-34.1) 4th quartile 310 76.2 (71.3-80.6) 111 23.8 (19.4-28.7) *
Weighted percent and 95% confidence interval
†
Weighted mean and 95% confidence interval
‡
Underweight:
