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      Evaluating All Potential Oral Complications of Diabetes Mellitus

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          Abstract

          Diabetes mellitus (DM) is associated with several microvascular and macrovascular complications, such as retinopathy, nephropathy, neuropathy, and cardiovascular diseases. The pathogenesis of these complications is complex, and involves metabolic and hemodynamic disturbances, including hyperglycemia, insulin resistance, dyslipidemia, hypertension, and immune dysfunction. These disturbances initiate several damaging processes, such as increased reactive oxygen species (ROS) production, inflammation, and ischemia. These processes mainly exert their damaging effect on endothelial and nerve cells, hence the susceptibility of densely vascularized and innervated sites, such as the eyes, kidneys, and nerves. Since the oral cavity is also highly vascularized and innervated, oral complications can be expected as well. The relationship between DM and oral diseases has received considerable attention in the past few decades. However, most studies only focus on periodontitis, and still approach DM from the limited perspective of elevated blood glucose levels only. In this review, we will assess other potential oral complications as well, including: dental caries, dry mouth, oral mucosal lesions, oral cancer, taste disturbances, temporomandibular disorders, burning mouth syndrome, apical periodontitis, and peri-implant diseases. Each oral complication will be briefly introduced, followed by an assessment of the literature studying epidemiological associations with DM. We will also elaborate on pathogenic mechanisms that might explain associations between DM and oral complications. To do so, we aim to expand our perspective of DM by not only considering elevated blood glucose levels, but also including literature about the other important pathogenic mechanisms, such as insulin resistance, dyslipidemia, hypertension, and immune dysfunction.

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          Most cited references304

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          Periodontal diseases

          The Lancet, 366(9499), 1809-1820
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            Smoking and drinking in relation to oral and pharyngeal cancer.

            A case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on the tobacco and alcohol use of 1114 patients and 1268 population-based controls. Because of the large study size, it could be shown that the risks of these cancers among nondrinkers increased with amount smoked, and conversely that the risks among nonsmokers increased with the level of alcohol intake. Among consumers of both products, risks of oropharyngeal cancer tended to combine more in a multiplicative than additive fashion and were increased more than 35-fold among those who consumed two or more packs of cigarettes and more than four alcoholic drinks/day. Cigarette, cigar, and pipe smoking were separately implicated, although it was shown for the first time that risk was not as high among male lifelong filter cigarette smokers. Cessation of smoking was associated with a sharply reduced risk of this cancer, with no excess detected among those having quit for 10 or more years, suggesting that smoking affects primarily a late stage in the process of oropharyngeal carcinogenesis. The risks varied by type of alcoholic beverage, being higher among those consuming hard liquor or beer than wine. The relative risk patterns were generally similar among whites and blacks, and among males and females, and showed little difference when oral and pharyngeal cancers were analyzed separately. From calculations of attributable risk, we estimate that tobacco smoking and alcohol drinking combine to account for approximately three-fourths of all oral and pharyngeal cancers in the United States.
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              Case definitions for use in population-based surveillance of periodontitis.

              Many definitions of periodontitis have been used in the literature for population-based studies, but there is no accepted standard. In early epidemiologic studies, the two major periodontal diseases, gingivitis and periodontitis, were combined and considered to be a continuum. National United States surveys were conducted in 1960 to 1962, 1971 to 1974, 1981, 1985 to 1986, 1988 to 1994, and 1999 to 2000. The case definitions and protocols used in the six national surveys reflect a continuing evolution and improvement over time. Generally, the clinical diagnosis of periodontitis is based on measures of probing depth (PD), clinical attachment level (CAL), the radiographic pattern and extent of alveolar bone loss, gingival inflammation measured as bleeding on probing, or a combination of these measures. Several other patient characteristics are considered, and several factors, such as age, can affect measurements of PD and CAL. Accuracy and reproducibility of measurements of PD and CAL are important because case definitions for periodontitis are based largely on either or both measurements, and relatively small changes in these values can result in large changes in disease prevalence. The classification currently accepted by the American Academy of Periodontology (AAP) was devised by the 1999 International Workshop for a Classification of Periodontal Diseases and Conditions. However, in 2003 the Centers for Disease Control and Prevention and the AAP appointed a working group to develop further standardized clinical case definitions for population-based studies of periodontitis. This classification defines severe periodontitis and moderate periodontitis in terms of PD and CAL to enhance case definitions and further demonstrates the importance of thresholds of PD and CAL and the number of affected sites when determining prevalence.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                18 February 2019
                2019
                : 10
                : 56
                Affiliations
                [1] 1Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit , Amsterdam, Netherlands
                [2] 2Department of Vascular Medicine, Amsterdam UMC , Amsterdam, Netherlands
                [3] 3Department of Internal Medicine, Spaarne Gasthuis , Hoofddorp, Netherlands
                Author notes

                Edited by: Ioan Andrei Veresiu, Iuliu Haţieganu University of Medicine and Pharmacy, Romania

                Reviewed by: Federico Biscetti, Catholic University of Sacred Heart, Italy; Mohd Ashraf Ganie, Sher-I-Kashmir Institute of Medical Sciences, India

                *Correspondence: Martijn J. L. Verhulst m.verhulst@ 123456acta.nl

                This article was submitted to Diabetes, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2019.00056
                6439528
                30962800
                59388640-14b4-47f4-a654-e37fa9efdcf4
                Copyright © 2019 Verhulst, Loos, Gerdes and Teeuw.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 August 2018
                : 22 January 2019
                Page count
                Figures: 2, Tables: 8, Equations: 0, References: 392, Pages: 49, Words: 41395
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                diabetes mellitus,oral complications,hyperglycemia,insulin resistance,dyslipidemia,hypertension,immune dysfunction

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