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      Little enhancement of meal‐induced glucagon‐like peptide 1 secretion in Japanese: Comparison of type 2 diabetes patients and healthy controls

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          Abstract

          Although glucose‐dependent insulinotropic polypeptide (GIP) levels have been characterized previously, GLP‐1 levels in Asians remain unclear. Here, we investigate total and intact levels of GLP‐1, as well as GIP during oral glucose and meal tolerance tests (OGTT and MTT) in Japanese patients with or without type 2 diabetes (T2DM). Seventeen Japanese healthy controls and 18 age‐matched and untreated patients with T2DM of short duration participated in the present study. Fasting levels of total GPL‐1 were similar between the two groups (approximately 15 pM), and intact GLP‐1 levels were considerably low in both groups (less than 1 pM). In both groups, total GLP‐1 reached a peak 30 min after glucose ingestion (30–40 pM), whereas intact GLP‐1 levels remained low with no significant peak. In MTT, total and intact GLP‐1 showed no obvious peak. The current data indicate that intact GLP‐1 levels are considerably low in the Japanese and that meal‐induced enhancement of GLP‐1 secretion is negligible in the Japanese. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00010.x, 2010)

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          Most cited references 22

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          The biology of incretin hormones.

          Gut peptides, exemplified by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted in a nutrient-dependent manner and stimulate glucose-dependent insulin secretion. Both GIP and GLP-1 also promote beta cell proliferation and inhibit apoptosis, leading to expansion of beta cell mass. GLP-1, but not GIP, controls glycemia via additional actions on glucose sensors, inhibition of gastric emptying, food intake and glucagon secretion. Furthermore, GLP-1, unlike GIP, potently stimulates insulin secretion and reduces blood glucose in human subjects with type 2 diabetes. This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes.
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            Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.

            In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.
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              Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis.

              Pharmacotherapies that augment the incretin pathway have recently become available, but their role in the management of type 2 diabetes is not well defined. To assess the efficacy and safety of incretin-based therapy in adults with type 2 diabetes based on randomized controlled trials published in peer-reviewed journals or as abstracts. We searched MEDLINE (1966-May 20, 2007) and the Cochrane Central Register of Controlled Trials (second quarter, 2007) for English-language randomized controlled trials involving an incretin mimetic (glucagonlike peptide 1 [GLP-1] analogue) or enhancer (dipeptidyl peptidase 4 [DPP4] inhibitor). We also searched prescribing information, relevant Web sites, reference lists and citation sections of recovered articles, and abstracts presented at recent conferences. Randomized controlled trials were selected if they were at least 12 weeks in duration, compared incretin therapy with placebo or other diabetes medication, and reported hemoglobin A(1c) data in nonpregnant adults with type 2 diabetes. Two reviewers independently assessed trials for inclusion and extracted data. Differences were resolved by consensus. Meta-analyses were conducted for several efficacy and safety outcomes. Of 355 potentially relevant articles identified, 51 were retrieved for detailed evaluation and 29 met the inclusion criteria. Incretins lowered hemoglobin A(1c) compared with placebo (weighted mean difference, -0.97% [95% confidence interval {CI}, -1.13% to -0.81%] for GLP-1 analogues and -0.74% [95% CI, -0.85% to -0.62%] for DPP4 inhibitors) and were noninferior to other hypoglycemic agents. Glucagonlike peptide 1 analogues resulted in weight loss (1.4 kg and 4.8 kg vs placebo and insulin, respectively) while DPP4 inhibitors were weight neutral. Glucagonlike peptide 1 analogues had more gastrointestinal side effects (risk ratio, 2.9 [95% CI, 2.0-4.2] for nausea and 3.2 [95% CI, 2.5-4.4] for vomiting). Dipeptidyl peptidase 4 inhibitors had an increased risk of infection (risk ratio, 1.2 [95% CI, 1.0-1.4] for nasopharyngitis and 1.5 [95% CI, 1.0-2.2] for urinary tract infection) and headache (risk ratio, 1.4 [95% CI, 1.1-1.7]). All but 3 trials had a 30-week or shorter duration; thus, long-term efficacy and safety could not be evaluated. Incretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes, with modest efficacy and a favorable weight-change profile. Careful postmarketing surveillance for adverse effects, especially among the DPP4 inhibitors, and continued evaluation in longer-term studies and in clinical practice are required to determine the role of this new class among current pharmacotherapies for type 2 diabetes.
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                Author and article information

                Journal
                J Diabetes Investig
                J Diabetes Investig
                10.1111/(ISSN)2040-1124
                JDI
                ST
                Journal of Diabetes Investigation
                Blackwell Publishing Ltd (Oxford, UK )
                2040-1116
                2040-1124
                03 March 2010
                22 April 2010
                : 1
                : 1-2 ( doiID: 10.1111/jdi.2010.1.issue-1-2 )
                : 56-59
                Affiliations
                [ 1 ]Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, Osaka
                [ 2 ]Department of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, Tokyo, Japan
                [ 3 ]Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
                [ 4 ]Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan
                Author notes
                [* ] Corresponding author. Dr Daisuke Yabe Tel.: +81‐6‐6458‐5821 Fax: +81‐6‐6458‐6994 E‐mail address: ydaisuke-kyoto@ 123456umin.ac.jp
                Article
                JDI10
                10.1111/j.2040-1124.2010.00010.x
                4020678
                a1c7e2da-5e02-4031-ba54-732f1b1049b7
                © 2010 Asian Association for the Study of Diabetes and Blackwell Publishing Asia Pty Ltd
                Page count
                Figures: 1, Tables: 1, Pages: 4
                Product
                Categories
                Articles
                Clinical Science and Care
                Short Report
                Custom metadata
                2.0
                February/April 2010
                Converter:WILEY_ML3GV2_TO_NLM version:3.9.3 mode:remove_FC converted:04.02.2014

                dpp‐4, gip, glp‐1

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