Eating Behaviours and Prevalence of Gastroesophageal Reflux Disease in Japanese Adult Patients With Type 2 Diabetes Mellitus: The Dogo Study.

OBJECTIVES: In the general population, late-night dinner is positively associated with gastroesophageal reflux disease (GERD). No evidence exists regarding the relationship between eating behaviours and GERD in patients with type 2 diabetes mellitus, though the prevalence of GERD in patients with type 2 diabetes is higher than in those without diabetes. We conducted this study to investigate the association between eating behaviours and GERD in Japanese patients with type 2 diabetes. METHODS: The study's subjects were 817 Japanese patients with type 2 diabetes. GERD was defined as being present when a subject had a Quality of Life and Utility Evaluation Survey Technology (QUEST) score of 4 or higher. The assessment of eating behaviour was performed by self-administered questionnaire. Subjects were considered positive for late-night dinner if they answered yes to the question "Do you eat dinner within 2 hours before bedtime at least 3 times per week? RESULTS: The prevalence values of GERD, skipping breakfast, bedtime snacking, late-night dinner and fast eating were 32.0%, 13.7%, 27.1%, 28.8%, and 44.4%, respectively. Late-night dinner was independently positively associated with GERD in patients with type 2 diabetes; the adjusted odds ratio was 1.46 (95% CI 1.03 to 2.05). No relationships were found between skipping breakfast, bedtime snacking or fast eating and GERD. CONCLUSIONS: Late-night dinner may be positively associated with GERD in Japanese patients with type 2 diabetes.

Differences in the risk of fatty liver for onset of impaired fasting glucose according to baseline plasma glucose levels.

BACKGROUND: It remains unclear whether fatty liver is a risk factor for the onset of abnormal glucose tolerance in any patient. The objective of this study was to clarify the relationship between fatty liver and the onset of impaired fasting glucose according to baseline fasting plasma glucose (FPG) levels. METHODS: This community-based longitudinal cohort study included 7,905 adults (3,863 men, 4,042 women; age range, 18-80 years) who had at least two annual checkups between 2003 and 2013. Those with FPG levels ≥110 mg/dl, taking anti-diabetic agents, and/or testing positive for hepatitis B surface antigen or anti-hepatitis C virus antibody were excluded, leaving 7,203 participants eligible for inclusion. All participants were divided into quartiles derived from their FPG levels at baseline. FPG ≥110 mg/dl during the observation period was defined as onset of IFG. RESULTS: Onset of IFG was found in 7.7 % of men and 2.1 % of women (p < 0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerol, high-density lipoprotein cholesterol, uric acid, creatinine, family history of diabetes, alcohol consumption, and current smoking, a positive association was found between fatty liver and the onset of IFG in both sexes with the highest quartile of FPG levels [men: adjusted hazard ratio (aHR) 1.823, 95 % confidence interval (CI) 1.316-2.534, p < 0.001; women: aHR 2.016, 95 % CI 1.117-3.6, p = 0.02]. CONCLUSIONS: Our results suggest that fatty liver is independently associated with an increased risk of developing IFG in individuals with high FPG.

Age and Prevalence of Esophageal Reflux Disease in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

BACKGROUND: Only limited epidemiological evidence exists regarding the relationship between age and gastroesophageal reflux disease (GERD) among Japanese patients with type 2 diabetes mellitus. AIM: The purpose of the present study is to investigate this issue among Japanese patients with type 2 diabetes mellitus. METHODS: A multicenter cross-sectional study was conducted in 847 Japanese patients with type 2 diabetes mellitus. Subjects were divided into quartiles according to age: (1) 19 ≤ age < 56, (2) 56 ≤ age < 64, (3) 64 ≤ age < 71, and (4) 71 ≤ age < 89. GERD was defined as present when a subject had a Carlsson-Dent self-administered questionnaire (QUEST) score ≥4. RESULTS: The prevalence of GERD was 31.5 %. Younger age was independently associated with a higher prevalence of GERD: the adjusted odds ratios (95 % confidence intervals) for GERD in relation to age < 56, 56 ≤ age < 64, 64 ≤ age < 71, and ≥71 were 3.73 (2.16-6.53), 1.98 (1.21-3.27), 1.66 (1.05-2.68), and 1.00 (reference), respectively (P for trend = 0.001). Among 201 patients with PPI or histamine H2-receptor antagonist (H2RA), less than 56 years of age was independently positively associated with GERD: the adjusted OR was 5.68 (95 % CI 1.55-22.18) (P for trend = 0.02). CONCLUSIONS: Younger age may be independently positively associated with GERD among Japanese type 2 diabetes mellitus patients, regardless of the use of PPI or H2RA.

Carbonic Anhydrate I Epitope Peptide Improves Inflammation in a Murine Model of Inflammatory Bowel Disease.

BACKGROUND: Carbonic anhydrase I (CA I), a major cecal bacterial antigen, improves inflammatory bowel disease (IBD) symptoms in a murine model. The aim of this study was to identify the responsible epitope region within the CA I protein and evaluate its effect on inflammation using a murine IBD model. METHODS: Candidate peptides within the CA I protein sequence that interact with major histocompatibility complex class II were chosen and their immune responses were evaluated using mesentery lymph nodes (MLNs) from a CD4CD25 T-cell transfer murine colitis model. Mice were treated with regulatory dendritic cells (Reg-DCs)-pulsed CA I peptide. We assessed their clinical signs, histopathology, induction of cytokines and transcription factors, and generation of CD103CD11c dendritic cells and regulatory T cells (Tregs). RESULTS: We identified 4 candidate epitope peptides of CA I. Among these, Reg-DCs pulsed with CA I 58-73 peptide (Reg-DCsCA I 58-73) alone ameliorated colitis. Reg-DCsCA I 58-73-treated mice showed higher mRNA expression levels of forkhead box protein 3, aldehyde dehydrogenase family 1a2, transforming growth factor-ß, and interleukin (Il)10, when compared with lower mRNA expression of retinoic acid-related orphan receptor gamma and Il17a in MLNs. Compared with control mice, these mice also showed higher numbers of Foxp3CD4CD25 Tregs and CD103CD11c dendritic cells in MLNs and colon. Administration of Reg-DCsCA I 58-73 induced antigen-specific Tregs in MLNs of colitic mice. CONCLUSIONS: CA I 58-73 peptide induces antigen-specific therapeutic effect in a murine IBD model using Reg-DCs, indicating that CA I 58-73 is a candidate epitope for IBD immunotherapy.

The ligand binding ability of dopamine D1 receptors synthesized using a wheat germ cell-free protein synthesis system with liposomes.

G-protein coupled receptors (GPCRs) share a common seven-transmembrane topology and mediate cellular responses to a variety of extracellular signals. However, structural and functional approaches to GPCRs have often been limited by the difficulty of producing a sufficient amount of receptor protein using conventional expression systems. We synthesized human dopamine D1 receptors using a wheat cell-free protein synthesis system with liposomes and then analyzed their receptor binding ability. We determined the specific binding of [(3)H]SCH23390 to the synthesized receptors generated from a cell-free protein synthesis system or rat striatal membranes. From Scatchard plot analysis, the dissociation constant (Kd) and the maximum density (Bmax) of the synthesized receptors were 6.61±0.06 nM and 1.85±0.05 pmol/mg protein, respectively. The same analysis for rat striatal membrane gave a Kd of 2.67±0.05 nM and Bmax of 0.70±0.10 pmol/mg protein. Using a competition binding assay, Ki values of antagonists, SCH23390, LE300 and SKF83566, for the synthetic receptors were the same as those for rat striatal membranes, but Ki values of agonists, A68930, SKF38393 and dopamine, were 5-17 fold higher than those for rat striatal membranes. These results suggest that the dopamine D1 receptors synthesized in liposomes have a functional binding capacity. The different patterns of binding of antagonists and agonists to the synthetic receptors and rat striatal membranes indicate that G proteins are involved in agonist binding to dopamine D1 receptors. The cell-free protein synthesis method with liposomes will be invaluable for the functional analysis of GPCRs.