Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes?

Background. The incretin effect is impaired in patients with type 2 diabetes. Aim. To assess the relation between the incretin hormone GLP-1 and the prediabetic subtypes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and the combined IFG/IGT to investigate whether a low GLP-1 response may be a predictor of prediabetes in adults. Method. 298 articles were found using a broad search phrase on the PubMed database and after the assessment of titles and abstracts 19 articles were included. Results and Discussion. Studies assessing i-IFG/IFG and i-IGT/IGT found both increased, unaltered, and reduced GLP-1 levels. Studies assessing IFG/IGT found unaltered or reduced GLP-1 levels. When assessing the five studies with the largest sample size, it clearly suggests a decreased GLP-1 response in IFG/IGT subjects. Several other factors (BMI, glucagon, age, and nonesterified fatty acids (NEFA)), including medications (metformin), may also influence the secretion of GLP-1. Conclusion. This review suggests that the GLP-1 response is a variable in prediabetes possibly due to a varying GLP-1-secreting profile during the development and progression of type 2 diabetes or difference in the measurement technique. Longitudinal prospective studies are needed to assess whether a reduced GLP-1 response is a predictor of diabetes.

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Effects of glucagon-like peptide 1 receptor agonist on short-chain fatty acids, carbohydrate and lipid metabolism in patients with type 2 diabetes

Endocrine Abstracts ◽

10.1530/endoabs.63.gp208 ◽

2019 ◽

Author(s):

Lilit Egshatyan ◽

Nane Khachaturian ◽

Svetlana Silvestrova ◽

Ashot Mkrtumyan

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Lipid Metabolism ◽

Receptor Agonist ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Carbohydrate And Lipid Metabolism ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Glucose-dependent insulinotropic polypeptide - a new link in the development of obesity

Obesity and metabolism ◽

10.14341/omet2015116-19 ◽

2015 ◽

Vol 12 (1) ◽

pp. 16-19 ◽

Cited By ~ 2

Author(s):

Ekaterina Alekseevna Shestakova ◽

Aleksandr Victorovich Il'in ◽

Marina Vladimirovna Shestakova ◽

Ivan Ivanovich Dedov

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Body Mass Index ◽

Insulin Secretion ◽

Lipid Metabolism ◽

Body Mass ◽

Incretin Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Objective. Glucose-dependent insulinotropic polypeptide (GIP) as well as glucagon-like peptide-1 (GLP-1) is intestinal incretin hormone that stimulates insulin secretion in response to feeding. Much evidence of GIP contribution to obesity development has been found recently.Aim. The aim of the study was to evaluate glucose-stimulated GIP and GLP-1 secretion in people with type 2 diabetes (T2D) risk factors and different body mass index (BMI).Materials and methods. Total GIP and GLP-1 secretion was estimated in 127 patients with T2D risk factors during OGTT (75 g glucose) on 0, 30 and 120 minutes.Results. Patients with BMI≥ 35 kg/m2 had significantly higher fasting and stimulated GIP levels than participants with less BMI. GIP secretion was also higher in patients was insulinresistance, estimated by HOMA-IR, comparing to non-insulinresistant patients. Difference in GLP-1 secretion in patients within several BMI groups was nonsignificant.Conclusion. Our results suggest GIP is related to obesity degree, that means it can play a role in lipid metabolism and obesity development.

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Novel therapeutics for type 2 diabetes: Incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors

Pharmacology & Therapeutics ◽

10.1016/j.pharmthera.2009.06.002 ◽

2009 ◽

Vol 124 (1) ◽

pp. 113-138 ◽

Cited By ~ 113

Author(s):

E.J. Verspohl

Keyword(s):

Type 2 Diabetes ◽

Dipeptidyl Peptidase ◽

Incretin Hormone ◽

Dipeptidyl Peptidase 4 ◽

Novel Therapeutics ◽

Receptor Agonists ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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A sandwich ELISA for measurement of the primary glucagon-like peptide-1 metabolite

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00005.2017 ◽

2017 ◽

Vol 313 (3) ◽

pp. E284-E291 ◽

Cited By ~ 4

Author(s):

Nicolai J. Wewer Albrechtsen ◽

Ali Asmar ◽

Frederik Jensen ◽

Signe Törang ◽

Lene Simonsen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Sandwich Elisa ◽

Active Form ◽

Primary Metabolite ◽

Incretin Hormone ◽

Dipeptidyl Peptidase 4 ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract. It is best known for its glucose-dependent insulinotropic effects. GLP-1 is secreted in its intact (active) form (7–36NH2) but is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the primary metabolite (9–36NH2) before reaching the targets via the circulation. Although originally thought to be inactive or antagonistic, GLP-1 9–36NH2 may have independent actions, and it is therefore relevant to be able to measure it. Because reliable assays were not available, we developed a sandwich ELISA recognizing both GLP-1 9–36NH2 and nonamidated GLP-1 9–37. The ELISA was validated using analytical assay validation guidelines and by comparing it to a subtraction-based method, hitherto employed for estimation of GLP-1 9–36NH2. Its accuracy was evaluated from measurements of plasma obtained during intravenous infusions (1.5 pmol × kg−1 × min−1) of GLP-1 7–36NH2 in healthy subjects and patients with type 2 diabetes. Plasma levels of the endogenous GLP-1 metabolite increased during a meal challenge in patients with type 2 diabetes, and treatment with a DPP-4 inhibitor fully blocked its formation. Accurate measurements of the GLP-1 metabolite may contribute to understanding its physiology and role of GLP-1 in diabetes.

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Diabetes and obesity. The role of agonists glucagon-like peptide-1 of in the treatment of type 2 diabetes

Diabetes Mellitus ◽

10.14341/dm9623 ◽

2018 ◽

Vol 21 (4) ◽

pp. 293-300 ◽

Cited By ~ 1

Author(s):

Nina A. Petunina ◽

Milena Е. Telnova

Keyword(s):

Type 2 Diabetes ◽

Insulin Response ◽

Diabetic Patients ◽

Incretin Effect ◽

Receptor Agonists ◽

Number Of Patients ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Diabetes And Obesity

Significant number of patients with type 2 diabetes mellitus are obese. It is known that even glucose intolerance, as well as diabetes, can lead to vascular complications. At the same time, weight loss can reduce the risk of type 2 diabetes in obese and pre-diabetic patients. According to available data, a significant decrease in the incretin effect is observed in patients with type 2 diabetes and obese individuals. Thus, a decrease in the incretin effect leads to a violation of the insulin response to the intake of carbohydrates, and, consequently, an increase in the level of glucose in the blood. It was also found that the decrease in the incretin effect in patients with type 2 diabetes can be associated with a lower secretion of glucagon-like peptide-1. The interest is represented by groups of antidiabetic drugs capable of regulating glycemia by affecting the secretion of insulin and glucagon, depending on its level. Such drugs include glucagon-like peptide-1 receptor agonists. The article shows the advantage of prolonged action in patients with type 2 diabetes and obesity of the glucagon-like peptide 1 receptor agonists (albiglutide, dulaglutide, exenatide with slow release) dosing 1 time a week.

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Evolution of glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes

Diabetes Mellitus ◽

10.14341/dm8804 ◽

2017 ◽

Vol 20 (4) ◽

pp. 286-298 ◽

Cited By ~ 2

Author(s):

Gagik R. Galstyan ◽

Evgeniya A. Karataeva ◽

Ekaterina A. Yudovich

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Antidiabetic Drugs ◽

Incretin Effect ◽

Once Daily ◽

Short Acting ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Long Acting

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are a class of antidiabetic drugs developed over the past 15 years. GLP-1, a gastrointestinal peptide hormone that contributes to the postprandial incretin effect, stimulates glucose-dependent insulin secretion. The incretin effect is greatly diminished in type 2 diabetes, but can be restored by GLP-1RAs. These drugs also exert other GLP-1 effects, including reducing glucagon secretion, delaying gastric emptying, reducing food intake, improving cardiac ventricular function, and lowering blood pressure. Short-acting GLP-1RAs are administered once daily (lixisenatide) or twice daily (exenatide); long-acting GLP 1RAs are administered once daily (liraglutide) or once weekly (slow-release exenatide, dulaglutide, albiglutide). All GLP-1RAs significantly reduce glycated hemoglobin (HbA1c) in patients with type 2 diabetes whose glycemic control is inadequate with oral antidiabetic drugs. Compared with other antidiabetic medications, GLP-1RAs provide better glycemic control with the additional benefit of weight loss. Within this class, long-acting GLP-1RAs are more efficacious than short-acting GLP-1RAs, with similar or lower risk of hypoglycemia and lower incidence of gastrointestinal adverse effects. Head-to-head trials and a network meta-analysis suggest that once daily liraglutide is the most effective GLP-1RA in reducing HbA1c. Dulaglutide is the only once-weekly GLP 1RA demonstrated to be noninferior to liraglutide. The once-weekly GLP-1RAs offer additional advantages to patients, including fewer injections and easy-to-use, single-dose pen devices. Despite the relatively recent development of GLP-1RAs, international diabetes guidelines recognize the benefits of this class of drugs and recommend them as a treatment option for patients with type 2 diabetes.

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