Endogenous plasma glucagon-like peptide-1 following acute dietary fibre consumption

SCFA resulting from the microbial fermentation of carbohydrates have been linked to increased glucagon-like peptide-1 (GLP-1) secretion from the gastrointestinal tract in cell and animal models; however, there is little direct evidence in human subjects to confirm this. The present study was designed to investigate whether endogenous plasma GLP-1 concentrations increase following acute consumption of 48 g dietary fibre (as resistant starch (RS) from high-amylose maize type 2 RS (HAM-RS2)) compared with a matched placebo. A total of thirty healthy males participated in the present randomised cross-over study where HAM-RS2 or placebo was consumed as part of standardised breakfast and lunch meals. Changes to GLP-1, glucose, insulin and C-peptide were assessed half hourly for 7 h. Following the breakfast meal, plasma GLP-1 concentrations were lower with HAM-RS2 compared with the placebo (P =0·025). However, there was no significant difference between the supplements following the lunch meal. Plasma insulin concentrations were significantly lower following the lunch meal (P =0·034) with HAM-RS2 than with the placebo, but were not different after breakfast. Plasma glucose and C-peptide concentrations did not differ at any point. These results suggest that increased dietary fibre intake, in the form of HAM-RS2, does not acutely increase endogenous GLP-1 concentrations in human subjects. Further fibre feeding studies are required to determine whether GLP-1 concentrations may increase following longer-term consumption.

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The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes

Scientific Reports ◽

10.1038/s41598-021-90191-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Suvanjaa Sivalingam ◽

Emil List Larsen ◽

Daniel H. van Raalte ◽

Marcel H. A. Muskiet ◽

Mark M. Smits ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Nucleic Acid ◽

Urinary Excretion ◽

Post Hoc Analysis ◽

Significant Difference ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Post Hoc

AbstractGlucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.

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Lixisenatide: A New Daily GLP-1 Agonist for Type 2 Diabetes Management

Annals of Pharmacotherapy ◽

10.1177/1060028017689878 ◽

2017 ◽

Vol 51 (5) ◽

pp. 401-409 ◽

Cited By ~ 8

Author(s):

Delilah McCarty ◽

Megan Coleman ◽

Cassie L. Boland

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Gastric Emptying ◽

Diabetes Management ◽

Human Subjects ◽

Data Extraction ◽

Postprandial Blood Glucose ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the glucagon-like peptide-1 receptor agonist (GLP-1RA), lixisenatide, in the treatment of type 2 diabetes mellitus. Data Sources: A PubMed (1966-2016) search was conducted using the following keywords: lixisenatide, AVE0010, glucagon-like peptide-1 agonist, and type 2 diabetes. References were reviewed to identify additional sources. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacology, pharmacokinetics, efficacy, or safety of lixisenatide in human subjects. Data Synthesis: Lixisenatide lowers blood glucose through a glucose-dependent increase in insulin release from pancreatic β-cells and a decreased release of glucagon from pancreatic α-cells. Additionally, lixisenatide delays gastric emptying and increases satiety. Lixisenatide has been studied head to head against exenatide and insulin glulisine. It has also been studied as monotherapy and in combination with metformin, sulfonylureas, pioglitazone, and insulin glargine. In the GetGoal clinical trial series, lixisenatide resulted in a hemoglobin A1C reduction of 0.6% to 1% and a reduction in body weight of 0.2 to 2.96 kg. The adverse effect profile of lixisenatide was consistent with that of other GLP-1RAs, with nausea, vomiting, and diarrhea most commonly reported. Conclusion: Lixisenatide provides an additional GLP-1RA option, which may have more postprandial blood glucose-lowering effects than the other agents in the class because of its shorter half-life and effects on delaying gastric emptying.

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Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

European Journal of Preventive Cardiology ◽

10.1177/2047487320903638 ◽

2020 ◽

Vol 27 (18) ◽

pp. 1922-1930 ◽

Cited By ~ 3

Author(s):

Vishnu Priya Pulipati ◽

Venkatesh Ravi ◽

Priyanjali Pulipati

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Meta Analysis ◽

Composite Endpoint ◽

Primary Composite Endpoint ◽

Significant Difference ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Background Glucagon-like peptide-1 receptor agonists (GLP1RAs) are relatively newer anti-hyperglycemic agents, which have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus. Design We performed a meta-analysis of randomized controlled trials to evaluate the cardiovascular outcomes of GLP1RAs compared to placebo in type 2 diabetes mellitus patients. We performed an additional subgroup analysis to evaluate the role of GLP1RAs in patients with chronic kidney disease. Methods MEDLINE, Cochrane and ClinicalTrials.gov databases were searched from inception to 15 July 2019. The authors extracted relevant information from articles and independently assessed the study quality. Results Compared to placebo, GLP1RAs demonstrated a significant reduction in all-cause mortality (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.82–0.95; P < 0.001), cardiovascular mortality (OR 0.88, 95% CI 0.81–0.96; P = 0.004), primary composite endpoint (OR 0.86, 95% CI 0.80–0.91; P < 0.001) and non-fatal stroke (OR 0.86, 95% 0.77–0.95; P = 0.004). There was no statistical difference in non-fatal myocardial infarction (OR 0.92, 95% CI 0.83–1.01; P = 0.09). In subgroup analyses of patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m2 and less than 30 ml/min/1.73 m2, there was no significant difference in the primary composite endpoint. Conclusions GLP1RAs demonstrated a significant reduction in all-cause mortality, cardiovascular mortality, primary composite endpoint and non-fatal stroke in patients with type 2 diabetes mellitus. There was no significant difference in the primary composite endpoint in patients with type 2 diabetes mellitus and chronic kidney disease.

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No correlation between insulin and islet amyloid polypeptide after stimulation with glucagon-like peptide-1 in type 2 diabetes

Acta Endocrinologica ◽

10.1530/eje.0.1370643 ◽

1997 ◽

pp. 643-649 ◽

Cited By ~ 6

Author(s):

B Ahren ◽

M Gutniak

Keyword(s):

Type 2 Diabetes ◽

Healthy Subjects ◽

Human Subjects ◽

Serum Insulin ◽

Islet Amyloid Polypeptide ◽

Islet Amyloid ◽

Healthy Human ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

OBJECTIVES: To examine whether glucagon-like peptide-1 (GLP-1), which has been suggested as a new therapeutic agent in type 2 diabetes, affects circulating islet amyloid polypeptide (IAPP), a B-cell peptide of potential importance for diabetes pathophysiology. DESIGN: GLP-1 was administered in a buccal tablet (400 micrograms) to seven healthy subjects and nine subjects with type 2 diabetes. Serum IAPP and insulin levels were measured before and after GLP-1 administration. RESULTS: In the fasting state, serum IAPP was 4.1 +/- 0.3 pmol/l in the controls vs 9.8 +/- 0.9 pmol/l in the subjects with type 2 diabetes (P < 0.001). IAPP correlated with insulin only in controls (r = 0.74, P = 0.002) but not in type 2 diabetes (r = 0.26, NS). At 15 min after GLP-1, circulating IAPP increased to (6.0 +/- 0.5 pmol/l in controls P = 0.009) and to 13.8 +/- 1.2 pmol/l in type 2 diabetes (P = 0.021). In both groups, serum insulin increased and blood glucose decreased compared with placebo. In controls serum IAPP increased in parallel with insulin (r = 0.79, P = 0.032), whereas in type 2 diabetes the increase in IAPP did not correlate with the increase in insulin. CONCLUSION: Type 2 diabetes is associated with elevated circulating IAPP; GLP-1stimulates IAPP secretion both in healthy human subjects and in type 2 diabetes; IAPP secretion correlates with insulin secretion only in healthy subjects and not in type 2 diabetes.

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