Received Date : 18-May-2016
Accepted Article
Revised Date
: 25-Nov-2016
Accepted Date : 18-Jan-2017 Article type
: Original Article
The number of microvascular complications is associated with an increased risk for severity of periodontitis in type 2 diabetic patients: Results of a multicenter hospital-based cross-sectional study
Running title: Microangiopathy and periodontitis
Hiroshi Nittaa,1, Sayaka Katagiria,1, Toshiyuki Nagasawaa,2, Yuichi Izumib,3, Isao Ishikawaa, Hajime Izumiyamaa, Isao Uchimuraa, Masao Kanazawac, Hiroshige Chibac, Akira Matsuoc,4, Kazunori Utsunomiyad, Haruyasu Tanabed, Izumi Takeie, Soichiro Asanamie, Hiroshi Kajiof, Toaki Onof, Yoichi Hayashig, Kiichi Uekig, Masatomi Tsujih, Yoichi Kurachih, Toshikazu Yamanouchii, Yoshimi Ichinokawai, Toshiki Inokuchij, Akiko Fukuij, Shigeru Miyazakik, Takashi Miyauchik, Reiko Kawaharal, Hideki Ogiuchil, Narihito Yoshiokam, Jun Negishim, Masatomo Morin, Kenji Mogin, Yasushi Saitoo, Hideki Tanzawao, Tetsuo Nishikawap, Norihiko Takadap, Kishio Nanjoq,5, Nobuo Moritaq, Naoto Nakamurar, Narisato Kanamurar, Hirofumi Makinos, Fusanori Nishimuras,6, Kunihisa Kobayashit, Yoshinori Higuchit,7, Toshiie Sakatau, Shigetaka Yanagisawau, Chuwa Teib, Yuichi Andov,8, Nobuhiro Hanadav,9, Shuji Inouew,*
a
Medical and Dental Hospitals, Tokyo Medical and Dental University, Tokyo 113-8510, Japan b
Kagoshima University Medical and Dental Hospital, Kagoshima 890-8520, Japan
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jdi.12633 This article is protected by copyright. All rights reserved.
c
Tokyo Medical University Hospital, Tokyo 160-0023, Japan
d
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Jikei University Hospital, Tokyo 105-8471, Japan
e
Keio University Hospital, Tokyo 160-0016, Japan
f
Center Hospital of the National Center for Global Health and Medicine, Tokyo 162-8655, Japan g
Nihon University Itabashi Hospital, Tokyo 173-0032, Japan
h
Showa University Hospital, Tokyo 142-8666, Japan
i
Teikyo University Hospital, Tokyo 173-0003, Japan
j
Toho University Omori Hospital, Tokyo 143-8541, Japan
k
Tokyo Teishin Hospital, Tokyo 102-0071, Japan
l
Tokyo Women’s Medical University Hospital, Tokyo 162-0054, Japan
m
Hokkaido University Hospital, Sapporo 060-8648, Japan
n
Gunma University Hospital, Maebashi 371-0034, Japan
o
Chiba University Hospital, Chiba 260-0856, Japan
p
Yokohama Rosai Hospital, Yokohama 222-0036, Japan
q
Wakayama Medical University Hospital, Wakayama 641-0012, Japan
r
University Hospital, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
s
Okayama University Hospital, Okayama 700-0914, Japan
t
National Hospital Organization Kyusyu Medical Center, Fukuoka 815-0065, Japan
u
Oita University Hospital, Yufu 879-5503, Japan
v
Department of Oral Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan w
Department of Nutrition and Physiology, Faculty of Home Economics, Kyoritsu Women's University, Tokyo 101-8437, Japan
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Corresponding author:
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Shuji Inoue, MD, PhD. Department of Nutrition and Physiology, Faculty of Home Economics, Kyoritsu Women's University, 2-1-1 Hitotsubashi, Chiyoda-ku, Tokyo 101-8437 Japan. Tel: +81-48-3670; Fax: +81-48-3670 Email:
[email protected] 1
HN and SK contributed equally to this work.
2
Present Address: Health Sciences University of Hokkaido, Ishikari, 061-0293, Japan
3
Present Address: Medical and Dental Hospitals, Tokyo Medical and Dental University, Tokyo 113-8510, Japan 4
Present Address: Tokyo Medical University, Department of Oral and Maxillofacial Surgery, Ibaraki Medical Center, Ibaraki, 300-3095, Japan 5
Present Address: Wakayama Rosai Hospital, Wakayama, 640-8505, Japan
6
Present Address: Department of Periodontology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan 7 8
Present Address: Fukuoka Dental College, Fukuoka, 814-0193, Japan
Present Address: National Institute of Public Health, Wako, 351-0197 Japan
9
Present Address: Department of Translational Research, Tsurumi University School of Dental Medicine, Yokohama, 230-8501, Japan ABSTRACT Aims/Introduction: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetic patients. Materials and Methods: This multi-center hospital-based cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control. This article is protected by copyright. All rights reserved.
Results: After adjusting for confounding factors, multiple logistic regression analysis showed
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that the severity of periodontitis was significantly associated with the number of microvascular complications (OR 1.3; 95%Cl, 1.1–1.6), HbA1c ≥8.0% (64 mmol/mol) (OR 1.6; 95%Cl, 1.1–2.3), and older age (≥50 years) (OR 1.7; 95%Cl, 1.1–2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high HbA1c (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years), and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration, and HbA1c showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05). Conclusions: The number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, while poor glycemic control is a risk factor for increased prevalence and severity of periodontitis.
Key words: Type 2 Diabetes, Periodontitis, Microangiopathy INTRODUCTION Periodontitis is a chronic infectious disease triggered by a bacterial biofilm of dental
plaque. This biofilm leads to pocket formation, which progresses to inflammation-mediated loss of connective tissue attachment and alveolar bone destruction, eventually resulting in tooth loss1, 2. Many studies have demonstrated that both type 1 and type 2 diabetes mellitus increase the prevalence and severity of periodontitis, and that the effects are more evident in type 2 diabetic patients3-6.
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Poor glycemic control has been considered an important risk factor for periodontitis.
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The prevalence and severity of periodontitis in type 2 diabetic patients have been reported to be increased7-14, because chronic hyperglycemia (long-term poor glycemic control) increases host susceptibly to infectious bacteria in the periodontium. Diabetic microangiopathic change has been also considered as a risk factor for periodontitis15. However, evidence for microangiopathy as a risk factor for periodontitis has so far been insufficient. Long-term poor glycemic control causes microangiopathic changes, such as retinopathy,
nephropathy, and neuropathy, as morphological alterations, in type 2 diabetic patients16, 17. Similarly, such changes to the periodontal tissue18 may increase host susceptibility to infectious bacteria in the periodontium. Therefore, we hypothesized that microangiopathy may increase the risk of periodontitis in type 2 diabetic patients because microangiopathic capillary changes in the periodontal tissue may be similar to those observed in retinopathy, nephropathy, or neuropathy. Few studies have shown that microvascular complications, including retinopathy19-23,
nephropathy22, 24, 25, and neuropathy22, 26, are associated with periodontitis in type 2 diabetic patients. However, these studies investigated the associations individually, rather than comprehensively evaluating whether all microvascular complications are related to periodontitis. The aim of this multi-center hospital-based cross-sectional study was to systematically
and comprehensively explore the relationships between microvascular complications and periodontitis in type 2 diabetic patients by comparing the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without any complications. This study also explored the relationship between glycemic control status and
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periodontitis by comparing the prevalence and severity of periodontitis among type 2 diabetic
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patients with different degrees of glycemic control.
MATERIALS AND METHODS Subjects A total of 635 type 2 diabetic patients aged 25–81 years were recruited from among
those who presented to diabetes clinics at 21 institutions; the list of institutions is presented in Appendix S1. All medical histories of the subjects were documented, and physical and biochemical examinations, followed by dental examinations, were performed at each facility. Ultimately, 620 patients were included in the analysis after excluding those with missing data. The study protocol was approved by the ethics committee at each institution. Written
informed consent was obtained from each subject at the respective diabetes and dental clinics.
Diagnosis of Diabetic Microvascular Complications and Stratification of Glycemic Control Status Retinopathy was diagnosed based on the presence of characteristic microvascular
changes in the retina, such as hemorrhage, exudate, edema, and fibrous proliferation, as detected by ophthalmoscopy through dilated pupils27. The diagnosis of diabetic nephropathy was based on the presence of proteinuria or microalbuminuria in 24-hour urine samples (≥30 mg/24 hours)27. Neuropathy was diagnosed based on the presence of at least two positive
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findings among abnormal sensation, vibration abnormality on both sides of the ankle, and
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ankle tendon reflex abnormality on both sides27. Glycemic control was stratified into the following four grades: “poor,” HbA1c ≥8.0%
(64 mmol/mol); “fair,” HbA1c ≥7.0% (53 mmol/mol) and
