Dataset Information

Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial.

ABSTRACT:

Aim

To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms.

Materials and methods

Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled. Measurements were made at baseline, after 2 weeks prior to significant weight loss and after 14 weeks. The primary outcomes were measures of endothelial function: flow-mediated vasodilation (FMD), plasminogen activator inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR).

Results

Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and PAI-1, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup analyses in individuals with baseline FMD below the median, indicative of greater endothelial dysfunction, showed an improvement in FMD by all three treatments. GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1. There was no effect of treatment on UACR. Finally, liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte chemoattractant protein-1 (MCP-1).

Conclusion

Liraglutide and diet reduce weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not change FMD in obese individuals with prediabetes with normal endothelial function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic chemokine MCP-1, indicating that this beneficial effect is independent of weight loss.

SUBMITTER: Mashayekhi M

PROVIDER: S-EPMC10306232 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial.

Mashayekhi Mona M Beckman Joshua A JA Nian Hui H Garner Erica M EM Mayfield Dustin D Devin Jessica K JK Koethe John R JR Brown Jonathan D JD Cahill Katherine N KN Yu Chang C Silver Heidi H Niswender Kevin K Luther James M JM Brown Nancy J NJ

Diabetes, obesity & metabolism 20221110 2

<h4>Aim</h4>To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms.<h4>Materials and methods</h4>Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controll ...[more]

PMID: 36306151

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Project description:BackgroundTo evaluate the association of vitamin D and thyroid-stimulating hormone (TSH) with weight loss (WL) percentage (%) in patients with diabetes/prediabetes and Class II/III obesity.MethodsA retrospective cohort study was designed. Data were collected from a database of a referral endocrinology clinic that is prospectively and systematically generated. After exclusion of unavailable cases, the study enrolled 285 patients (51 ± 11 years old, female/male = 208/77; diabetes/prediabetes = 159/126; no/on levothyroxine replacement = 176/109; Class II/III obesity = 184/101, respectively) who maintained euthyroidism and were followed up for ≥6 months. The data were analyzed to determine the predictors of WL%.ResultsCompared with baseline, in the median 22 months of follow-up, the whole study group lost 5.1% of their baseline body weight. As most obesity management trials define success as 'at least 10% of WL compared to baseline', we stratified the patients based on WL% extents. The distribution was as follow: Group 1 (n = 61) lost ≥10% body weight, Group 2 (n = 162) lost < 10% body weight, while Group 3 (n = 62) gained weight by the final visit. In groups 1 and 2 (weight losers), the serum thyroid stimulatig hormone (TSH) and parathyroid hormone (PTH) levels decreased and the free thyroxine (fT4), calcium, phosphorus, and 25-hydroxyvitamin D (25(OH)D) levels increased. In Group 3 (weight gainers), these changes were not observed (except for an increase in calcium levels). Regression analysis revealed that the final visit TSH (β = - 0.14, p < 0.05), 25(OH) D (β = 0.15, p < 0.05), and phosphorus (β = 0.20, p < 0.05) levels predicted WL%. However, if patients with autoimmune thyroiditis were excluded from the analysis, the decrease in TSH levels was not statistically significant.ConclusionsSerum TSH, phosphorus, and 25(OH) D levels predict WL% in euthyroid patients with diabetes/prediabetes and morbid obesity. TSH predictivity seems to be a function of thyroid autoimmunity present with increased frequency in this cohort. Greater levels of phosphorus within the reference range and a sufficient vitamin D status are associated with a greater WL%.

Dataset Information

Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial.

Aim

Materials and methods

Results

Conclusion

Publications

Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial.

Similar Datasets

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