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      Dietary Vitamin C Intake Reduces the Risk of Type 2 Diabetes in Chinese Adults: HOMA-IR and T-AOC as Potential Mediators

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          Abstract

          Despite growing interest in the protective role that dietary antioxidant vitamins may have in the development of type 2 diabetes (T2D), little epidemiological evidence is available in non-Western populations especially about the possible mediators underlying in this role. The present study aimed to investigate the association of vitamin C and vitamin E intakes with T2D risk in Chinese adults and examine the potential mediators. 178 incident T2D cases among 3483 participants in the Harbin People Health Study (HPHS), and 522 newly diagnosed T2D among 7595 participants in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases (HDNNCDS) were studied. In the multivariable-adjusted logistics regression model, the relative risks (RRs) were 1.00, 0.75, and 0.76 ( P trend = 0.003) across tertiles of vitamin C intake in the HDNNCDS, and this association was validated in the HPHS with RRs of 1.00, 0.47, and 0.46 ( P trend = 0.002). The RRs were 1.00, 0.72, and 0.76 ( P trend = 0.039) when T2D diagnosed by haemoglobin A 1c in the HDNNCDS. The mediation analysis discovered that insulin resistance (indicated by homeostasis model assessment) and oxidative stress (indicated by plasma total antioxidative capacity) partly mediated this association. But no association was evident between vitamin E intake and T2D. In conclusion, our research adds further support to the role of vitamin C intake in reducing the development of T2D in the broader population studied. The results also suggested that this association was partly mediated by inhibiting or ameliorating oxidative stress and insulin resistance.

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          Most cited references19

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          The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes.

          S E Kahn (2003)
          The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the hyperbolic relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this hyperbolic relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes.
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            Reactive oxygen species enhance insulin sensitivity.

            Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high-fat-diet-induced insulin resistance. The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo.
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              Diabetes mellitus. Report of a WHO Study Group.

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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, CA USA )
                1932-6203
                29 September 2016
                2016
                : 11
                : 9
                : e0163571
                Affiliations
                [1 ]Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R. China
                [2 ]The Second afflicted Hospital of Harbin Medical University, Harbin, P. R. China
                Johns Hopkins University Bloomberg School of Public Health, UNITED STATES
                Author notes

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

                • Conceptualization: CHS.

                • Formal analysis: CLZ RQS.

                • Funding acquisition: CHS XYW.

                • Investigation: YC.

                • Methodology: XYW.

                • Project administration: CHS.

                • Software: CLZ.

                • Supervision: CHS.

                • Validation: RQS.

                • Visualization: YL.

                • Writing – original draft: CLZ LXN.

                • Writing – review & editing: XYW YL.

                Article
                PONE-D-16-04810
                10.1371/journal.pone.0163571
                5042374
                27685994
                ca66e836-da0f-4b9f-9a27-8675088c32a3
                © 2016 Zhou et al

                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
                : 2 February 2016
                : 11 September 2016
                Page count
                Figures: 0, Tables: 5, Pages: 13
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: 81130049
                Award Recipient :
                Funded by: the National Natural Science Foundation of China
                Award ID: 81573134
                Award Recipient :
                Funded by: the National Natural Science Foundation of China
                Award ID: 81202282
                Award Recipient :
                Funded by: Public Health School of Harbin Medical University
                Award ID: 2012
                Award Recipient :
                This work was supported by funds from the National Natural Science Foundation of China (81130049) received by CHS, the National Natural Science Foundation of China (81573134, 81202282) received by XYW, and the Public Health School of Harbin Medical University(2012) received by XYW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical sciences
                Chemistry
                Chemical compounds
                Organic compounds
                Vitamins
                Vitamin C
                Physical sciences
                Chemistry
                Organic chemistry
                Organic compounds
                Vitamins
                Vitamin C
                Physical sciences
                Chemistry
                Chemical compounds
                Organic compounds
                Vitamins
                Vitamin E
                Physical sciences
                Chemistry
                Organic chemistry
                Organic compounds
                Vitamins
                Vitamin E
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and health sciences
                Diagnostic medicine
                Diabetes diagnosis and management
                HbA1c
                Biology and life sciences
                Biochemistry
                Proteins
                Hemoglobin
                HbA1c
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Insulin Resistance
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Insulin Resistance
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Insulin Resistance
                Medicine and Health Sciences
                Vascular Medicine
                Coronary Heart Disease
                Medicine and Health Sciences
                Cardiology
                Coronary Heart Disease
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                All relevant data are within the paper and its Supporting Information files.

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