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      Phytate Decreases Formation of Advanced Glycation End-Products in Patients with Type II Diabetes: Randomized Crossover Trial

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          Abstract

          Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant in cereals, legumes, and nuts and it has the ability to chelate metal cations. The binding of IP6 to transition metals suggests that it could be used for the treatment of metal-catalyzed protein glycation, which appears to trigger diabetes-related diseases. Our in vitro studies showed that IP6 reduced the formation of Fe 3+-catalyzed advanced glycation end-products (AGEs). This led us to perform a randomized cross-over trial to investigate the impact of the daily consumption IP6 on protein glycation in patients with type 2 diabetes mellitus (T2DM; n = 33). Thus, we measured AGEs, glycated hemoglobin (HbA1c), several vascular risk factors, and urinary IP6 at baseline and at the end of the intervention period. Patients who consumed IP6 supplements for 3 months had lower levels of circulating AGEs and HbA1c than those who did not consume IP6. This is the first report to show that consumption of IP6 inhibits protein glycation in patients with T2DM. Considering that AGEs contribute to microvascular and macrovascular complications in T2DM, our data indicates that dietary supplementation with IP6 should be considered as a therapy to prevent the formation of AGEs and therefore, the development of diabetes-related diseases in patients with T2DM.

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          Dyslipidemia in type 2 diabetes mellitus.

          Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus. The characteristic features of diabetic dyslipidemia are a high plasma triglyceride concentration, low HDL cholesterol concentration and increased concentration of small dense LDL-cholesterol particles. The lipid changes associated with diabetes mellitus are attributed to increased free fatty acid flux secondary to insulin resistance. The availability of multiple lipid-lowering drugs and supplements provides new opportunities for patients to achieve target lipid levels. However, the variety of therapeutic options poses a challenge in the prioritization of drug therapy. The prevalence of hypercholesterolemia is not increased in patients with diabetes mellitus, but mortality from coronary heart disease increases exponentially as a function of serum cholesterol levels, and lowering of cholesterol with statins reduces diabetic patients' relative cardiovascular risk. Although drug therapy for dyslipidemia must be individualized, most people with diabetes mellitus are candidates for statin therapy, and often need treatment with multiple agents to achieve therapeutic goals.
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            Type 2 diabetes and the risk of Parkinson's disease.

            To evaluate whether type 2 diabetes at baseline is a risk factor for Parkinson's disease. We prospectively followed 51,552 Finnish men and women 25-74 years of age without a history of Parkinson's disease at baseline. History of diabetes and other study parameters were determined at baseline using standardized measurements. Ascertainment of the Parkinson's disease status was based on the nationwide Social Insurance Institution's drug register data. Hazard ratios of incident Parkinson's disease associated with the history of type 2 diabetes were estimated. During a mean follow-up period of 18.0 years, 324 men and 309 women developed incident Parkinson's disease. Age- and study year-adjusted hazard ratios of incident Parkinson's disease among subjects with type 2 diabetes, compared with those without it, were 1.80 (95% CI 1.03-3.15) in men, 1.93 (1.05-3.53) in women, and 1.85 (1.23-2.80) in men and women combined (adjusted also for sex). Further adjustment for BMI, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, alcohol drinking, and coffee and tea consumption affected the results only slightly. The multivariate adjusted association between type 2 diabetes and the risk of Parkinson's disease was also confirmed in stratified subgroup analysis. These data suggest that type 2 diabetes is associated with an increased risk of Parkinson's disease. Surveillance bias might account for higher rates in diabetes. The mechanism behind this association between diabetes and Parkinson's disease is not known.
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              Current views on type 2 diabetes.

              Type 2 diabetes mellitus (T2DM) affects a large population worldwide. T2DM is a complex heterogeneous group of metabolic disorders including hyperglycemia and impaired insulin action and/or insulin secretion. T2DM causes dysfunctions in multiple organs or tissues. Current theories of T2DM include a defect in insulin-mediated glucose uptake in muscle, a dysfunction of the pancreatic beta-cells, a disruption of secretory function of adipocytes, and an impaired insulin action in liver. The etiology of human T2DM is multifactorial, with genetic background and physical inactivity as two critical components. The pathogenesis of T2DM is not fully understood. Animal models of T2DM have been proved to be useful to study the pathogenesis of, and to find a new therapy for, the disease. Although different animal models share similar characteristics, each mimics a specific aspect of genetic, endocrine, metabolic, and morphologic changes that occur in human T2DM. The purpose of this review is to provide the recent progress and current theories in T2DM and to summarize animal models for studying the pathogenesis of the disease.
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                Author and article information

                Contributors
                psanchis@ssib.es
                lmasmiquel@hsll.es
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                25 June 2018
                25 June 2018
                2018
                : 8
                : 9619
                Affiliations
                [1 ]GRID grid.413457.0, Endocrinology Department, , Research Unit, Hospital Son Llàtzer, Institute of Health Sciences Research [IUNICS- IdISBa], ; 07198 Palma of Mallorca, Spain
                [2 ]ISNI 0000000118418788, GRID grid.9563.9, Laboratory of Renal Lithiasis Research, , University of Balearic Islands, Institute of Health Sciences Research [IUNICS- IdISBa], ; 07122 Palma of Mallorca, Spain
                [3 ]GRID grid.413457.0, Laboratory Department, , Hospital Son Llàtzer, ; 07198 Palma of Mallorca, Spain
                [4 ]ISNI 0000000118418788, GRID grid.9563.9, Department of Chemistry, , University of Balearic Islands, Ctra. Valldemossa km 7.5, ; 07122 Palma of Mallorca, Spain
                Article
                27853
                10.1038/s41598-018-27853-9
                6018557
                29941991
                83728809-08f3-4c35-9ca3-73eca4de716f
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 March 2018
                : 12 June 2018
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