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      Effect of Diabetes Mellitus Type 2 on Salivary Glucose – A Systematic Review and Meta-Analysis of Observational Studies

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      PLoS ONE
      Public Library of Science

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          Abstract

          Background

          Early screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM.

          Methods and Findings

          We conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge's g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37).

          Conclusions

          Our systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients.

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          Most cited references10

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          Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement.

          (2008)
          Updated U.S. Preventive Services Task Force (USPSTF) recommendation about screening for type 2 diabetes mellitus in adults. To estimate the balance of benefits and harms of screening, the USPSTF updated its 2003 evidence review, adding evidence from new trials as well as updates on earlier studies. The review for this current recommendation focused on evidence that early treatment prevented long-term adverse outcomes of diabetes, including cardiovascular events, visual impairment, renal failure, and amputation. Screen for type 2 diabetes in asymptomatic adults with sustained blood pressure (either treated or untreated) greater than 135/80 mm Hg. (B recommendation) Current evidence is insufficient to assess the balance of benefits and harms of routine screening in asymptomatic adults with blood pressure of 135/80 mm Hg or lower. (I statement).
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            Mixed salivary glucose levels and candidal carriage in patients with diabetes mellitus.

            The glucose concentration in unstimulated mixed saliva and serum was assayed and correlated with oral candidal colonization in 41 diabetics and 34 healthy control subjects. In diabetic patients, salivary glucose concentration was significantly higher than in the controls and was directly related to blood glucose concentration. Although the difference in the frequency and quantity of oral candidal isolation failed to reach significance between the two groups, diabetic patients who carried Candida intraorally had significantly higher salivary glucose concentrations than those in whom Candida could not be isolated.
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              Diabetes-related molecular signatures in infrared spectra of human saliva

              Background There is an ongoing need for improvements in non-invasive, point-of-care tools for the diagnosis and prognosis of diabetes mellitus. Ideally, such technologies would allow for community screening. Methods In this study, we employed infrared spectroscopy as a novel diagnostic tool in the prediction of diabetic status by analyzing the molecular and sub-molecular spectral signatures of saliva collected from subjects with diabetes (n = 39) and healthy controls (n = 22). Results Spectral analysis revealed differences in several major metabolic components - lipid, proteins, glucose, thiocyanate and carboxylate - that clearly demarcate healthy and diseased saliva. The overall accuracy for the diagnosis of diabetes based on infrared spectroscopy was 100% on the training set and 88.2% on the validation set. Therefore, we have established that infrared spectroscopy can be used to generate complex biochemical profiles in saliva and identify several potential diabetes-associated spectral features. Conclusions Infrared spectroscopy may represent an appropriate tool with which to identify novel diseases mechanisms, risk factors for diabetic complications and markers of therapeutic efficacy. Further study into the potential utility of infrared spectroscopy as diagnostic and prognostic tool for diabetes is warranted.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                15 July 2014
                : 9
                : 7
                : e101706
                Affiliations
                [1 ]Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal
                [2 ]Serviço de Análises Clinicas - Centro Hospitalar de Setúbal (CHS), Setúbal, Portugal
                University of Florida, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: IB PM. Performed the experiments: PM BF. Analyzed the data: PM IB. Contributed reagents/materials/analysis tools: IB BF PM. Wrote the paper: PM IB.

                Article
                PONE-D-14-02122
                10.1371/journal.pone.0101706
                4098915
                25025218
                dec6363b-d4f5-4244-a618-3a0f84bd9652
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 February 2014
                : 10 June 2014
                Page count
                Pages: 15
                Funding
                This work was supported by Egas Moniz grant # EMIB 2003-01 ( http://www.egasmoniz.com.pt/pt-pt.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Endocrinology
                Diabetic Endocrinology
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Oral Medicine

                Uncategorized
                Uncategorized

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