33
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Gastric Inhibitory Polypeptide Receptor Methylation in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes: A Case-Control Study

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          GIP action in type 2 diabetic (T2D) patients is altered. We hypothesized that methylation changes could be present in GIP receptor of T2D patients. This study aimed to assess the differences in DNA methylation profile of GIPR promoter between T2D patients and age- and Body Mass Index (BMI)-matched controls. We included 93 T2D patients (cases) that were uniquely on diet (without any anti-diabetic pharmacological treatment). We matched one control (with oral glucose tolerance test negative, non diabetic), by age and BMI, for every case. Cytokines and hormones were determined by ELISA. DNA was extracted from whole blood and DNA methylation was assessed using the Sequenom EpiTYPER system. Our results showed that T2D patients were more insulin resistant and had a poorer β cell function than their controls. Fasting adiponectin was lower in T2D patients as compared to controls (7.0±3.8 µgr/mL vs. 10.0±4.2 µgr/mL). Levels of IL 12 in serum were almost double in T2D patients (52.8±58.3 pg/mL vs. 29.7±37.4 pg/mL). We found that GIPR promoter was hypomethylated in T2D patients as compared to controls. In addition, HOMA-IR and fasting glucose correlated negatively with mean methylation of GIPR promoter, especially in T2D patients. This case-control study confirms that newly diagnosed, drug-naïve T2D patients are more insulin resistant and have worse β cell function than age- and BMI-matched controls, which is partly related to changes in the insulin-sensitizing metabolites (adiponectin), in the proinflammatory profile (IL12) and we suggest in the methylation pattern of GIPR. Our study provides novel findings on GIPR promoter methylation profile which may improve our ability to understand type 2 diabetes pathogenesis.

          Related collections

          Most cited references15

          • Record: found
          • Abstract: found
          • Article: not found

          Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry.

          Methylation is one of the major epigenetic processes pivotal to our understanding of carcinogenesis. It is now widely accepted that there is a relationship between DNA methylation, chromatin structure, and human malignancies. DNA methylation is potentially an important clinical marker in cancer molecular diagnostics. Understanding epigenetic modifications in their biological context involves several aspects of DNA methylation analysis. These aspects include the de novo discovery of differentially methylated genes, the analysis of methylation patterns, and the determination of differences in the degree of methylation. Here we present a previously uncharacterized method for high-throughput DNA methylation analysis that utilizes MALDI-TOF mass spectrometry (MS) analysis of base-specifically cleaved amplification products. We use the IGF2/H19 region to show that a single base-specific cleavage reaction is sufficient to discover methylation sites and to determine methylation ratios within a selected target region. A combination of cleavage reactions enables the complete evaluation of all relevant aspects of DNA methylation, with most CpGs represented in multiple reactions. We successfully applied this technology under high-throughput conditions to quantitatively assess methylation differences between normal and neoplastic lung cancer tissue samples from 48 patients in 47 genes and demonstrate that the quantitative methylation results allow accurate classification of samples according to their histopathology.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The homeostasis model in the San Antonio Heart Study.

            Both insulin resistance and decreased insulin secretion have been shown to predict the development of NIDDM. However, methods to assess insulin sensitivity and secretion are complicated and expensive to apply in epidemiological studies. The homeostasis model assessment (HOMA) has been suggested as a method to assess insulin resistance and secretion from the fasting glucose and insulin concentrations. However, this method has not been extensively evaluated, particularly in different ethnic groups. We applied the HOMA model to cross-sectional analyses of the San Antonio Heart Study (n = 2,465). HOMA insulin resistance (IR) was very strongly correlated with fasting insulin (r = 0.98) and HOMA beta-cell function (beta-cell) was moderately correlated with the 30-min increment in insulin concentration over the 30-min increment in glucose concentration (delta I30/delta G30) in an oral glucose tolerance test (OGTT) (r = 0.44). NIDDM was characterized by both high HOMA IR and low HOMA beta-cell function. In Mexican-Americans, HOMA IR in NIDDM subjects was 9.5 compared with 2.7 in normal glucose tolerance (NGT) subjects. In contrast, HOMA beta-cell function showed only small differences in Mexican-Americans (176 NIDDM; 257 NGT). However, the delta I30/delta G30 (pmol/mmol) showed much larger differences (75 NIDDM; 268 NGT). When modeled separately, impaired glucose tolerance (IGT) was characterized by high HOMA IR and high HOMA beta-cell function. However, when analyzed in the same regression model, high HOMA IR and low HOMA beta-cell function characterized subjects with IGT. These results were similar in both ethnic groups. Mexican-Americans had increased insulin resistance (as judged by both HOMA IR and fasting insulin) and insulin secretion (by HOMA beta-cell and delta I30/delta G30) relative to non-Hispanic whites. We conclude that HOMA provides a useful model to assess insulin resistance and beta-cell function in epidemiological studies in which only fasting samples are available and that, further, it is critical to take into account the degree of insulin resistance in assessing insulin secretion by the HOMA model.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications.

              Faced with a global epidemic of type 2 diabetes (T2D), it is critical that researchers improve our understanding of the pathogenesis of T2D and related vascular complications. These findings may ultimately lead to novel treatment options for disease prevention or delaying progression. Two major paradigms jointly underlie the development of T2D and related coronary artery disease, diabetic nephropathy, and diabetic retinopathy. These paradigms include the genetic risk variants and behavioral/environmental factors. This article systematically reviews the literature supporting genetic determinants in the pathogenesis of T2D and diabetic vasculopathy, and the functional implications of these gene variants on the regulation of beta-cell function and glucose homeostasis. We update the discovery of diabetes and diabetic vasculopathy risk variants, and describe the genetic technologies that have uncovered them. Also, genomic linkage between obesity and T2D is discussed. There is a complementary role for behavioral and environmental factors modulating the genetic susceptibility and diabetes risk. Epidemiological and clinical data demonstrating the effects of behavioral and novel environmental exposures on disease expression are reviewed. Finally, a succinct overview of recent landmark clinical trials addressing glycemic control and its impact on rates of vascular complications is presented. It is expected that novel strategies to exploit the gene- and exposure-related underpinnings of T2D will soon result.
                Bookmark

                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
                2013
                23 September 2013
                : 8
                : 9
                : e75474
                Affiliations
                [1 ]Department of Endocrinology and Nutrition, Hospital Clinic-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
                [2 ]Les Corts Primary Health Care Centre, Transverse group for research in primary care-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
                [3 ]Diabetes and Obesity Laboratory-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
                [4 ]Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, Barcelona, Spain
                [5 ]University of Barcelona, Barcelona, Spain
                University of Lancaster, United Kingdom
                Author notes

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

                Conceived and designed the experiments: SC RG. Performed the experiments: ER EF-R MP. Analyzed the data: SC BK. Contributed reagents/materials/analysis tools: ER EF-R MP. Wrote the paper: SC. Recruited patients: SC AS LG. Critical review and contribution to writing: FH AN.

                Article
                PONE-D-13-31408
                10.1371/journal.pone.0075474
                3781044
                24086540
                0fa50a33-5898-4faf-8da7-17eda688f390
                Copyright @ 2013

                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
                : 1 August 2013
                : 15 August 2013
                Page count
                Pages: 6
                Funding
                This work was supported by the FIS Grant PI 1000219, the MEDIGENE project, grant agreement number 279171, funded by the EC Seventh Framework Programme theme FP7-HEALTH-2011 and by the Spanish Ministry of Science and Innovation (under de the grant agreement number SAF 2010-19527). CIBER de Diabetes y Enfermedades Metabólicas is an initiative of the Spanish Ministry of Science and Innovation. The Rio Hortega Grant from the Spanish Ministry of Science and Innovation was awarded to Silvia Canivell. Eduardo Fernandez-Rebollo (EF-R) has been the recipient of a BIOTRACK Postdoctoral Fellowship in Institut d’Investigacions Biomèdiques August Pi i Sunyer, supported by the European Community's Seventh Framework Programme (EC FP7/2009-2013) under the agreement no. 229673. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article