Microvascular Density and Circulating Endothelial Progenitor Cells Before and After Treatment with Incretin Mimetics in Diabetic Patients

Ciuceis, Carolina De; Agabiti-Rosei, Claudia; Rossini, Claudia; Caletti, Stefano; Coschignano, Maria Antonietta; Ferrari-Toninelli, Giulia; Ragni, G; Cappelli, Carlo; Cerudelli, B.; Airò, Paolo; Scarsi, Mirko; Tincani, Anǵela; Porteri, Enzo; Rizzoni, Damiano

doi:10.1007/s40292-018-0279-7

Cited by 11 publications

(10 citation statements)

References 51 publications

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“…We observed no difference between groups in CPCs, which include EPCs, and no significant change from baseline with liraglutide. A previous small study in 11 individuals with T2D, exploring the impact of GLP‐1RAs on the number of EPCs, reported an increase in EPCs with exenatide but not with liraglutide, consistent with our findings 14 . Although the authors of this previous study did not give specific reasons for this differential effect of the two GLP‐1RAs on the number of EPCs, they postulated that exenatide could exert a greater beneficial effect on the EPC pool through its anti‐inflammatory and antioxidant capabilities.…”

Section: Discussionsupporting

confidence: 92%

“…A previous small study in 11 individuals with T2D, exploring the impact of GLP-1RAs on the number of EPCs, reported an increase in EPCs with exenatide but not with liraglutide, consistent with our findings. 14 Although the authors of this previous study did not give specific reasons for this differential effect of the two GLP-1RAs on the number of EPCs, they postulated that exenatide could exert a greater beneficial effect on the EPC pool through its anti-inflammatory and antioxidant capabilities. Other placebo-controlled studies have shown conflicting effects of sitagliptin on the number of CPCs (including EPCs), with one study showing no effect, while another showed an increase in the CD34+/KDR phenotype only.…”

Section: Discussionmentioning

confidence: 92%

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Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial

Ahmad

Waller

Sargeant

et al. 2021

Diabetes Obesity Metabolism

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The mechanisms behind the beneficial cardiovascular effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) compared with dipeptidyl peptidase‐4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP‐1RA liraglutide (1.8 mg once‐daily) and the DPP4i sitagliptin (100 mg once‐daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs). LYDIA was a 26‐week, randomized, active‐comparator trial in 61 adults with type 2 diabetes and obesity (mean ± SD: age 43.8 ± 6.5 years, body mass index 35.3 ± 6.4 kg/m2, HbA1c 7.5% ± 0.83% [58.5 ± 9.1 mmol/mol]). Vascular endothelial growth factor (VEGF) and stromal cell‐derived factor‐1‐alpha (SDF‐1ɑ), both of which are implicated in endothelial function, were higher at 26 weeks with liraglutide therapy compared with sitagliptin (mean between‐group difference [95% CI]: 77.03 [18.29, 135.77] pg/mL, p = .010; and 996.25 [818.85, 1173.64] pg/mL, p < .001, respectively). There were no between‐group differences in CPCs, nitric oxide, C‐reactive protein, interleukin‐6, tumour necrosis factor alpha and advanced glycation end‐products. These analyses suggest a favourable impact of liraglutide on VEGF and SDF‐1ɑ levels compared with sitagliptin. These factors may therefore be implicated in the differential cardiovascular effects observed between these agents in large cardiovascular outcome trials. However, these are secondary analyses from a previous trial and thus hypothesis‐generating. Purposive trials are required to examine these findings further.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial

Ahmad

Waller

Sargeant

et al. 2021

Diabetes Obesity Metabolism

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“…10,11 Exenatide is a commonly used clinical GLP-1 receptor (GLP-1R) agonist. A number of clinical trials that have been completed thus far have found that [12][13][14][15] exenatide can not only effectively reduce the blood glucose level of patients with T2DM but also has obvious effects other than hypoglycaemic effects, such as weight loss, lower blood pressure, blood lipid regulation, and improved endothelial dysfunction caused by hyperglycaemia and hyperlipidaemia.…”

Section: Introductionmentioning

confidence: 99%

Effects of Exenatide on Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes

Zhang¹,

Chen²,

Jia³

et al. 2021

DDDT

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To explore the effect of the glucagon-like peptide-1 receptor agonist exenatide on coagulation function and platelet aggregation in patients with type 2 diabetes mellitus (T2DM). Methods: Thirty patients with newly diagnosed T2DM were enrolled as the case group, and 30 healthy people with matching age and sex were selected as the control group. Patients in the case group received exenatide treatment for 8 weeks. The general clinical data and biochemical indicators of all subjects were collected; and their peripheral blood platelet count, coagulation index, nitric oxide (NO), platelet membrane glycoprotein (CD62p), platelet activation complex-1 (PAC-1) and platelet aggregation induced by collagen, epinephrine (EPI), arachidonic acid (AA), and adenosine diphosphate (ADP) were detected. Results: The fibrinogen, CD62p, PAC-1, and platelet aggregation rates of the case group (pretreatment) are higher than those in the control group (EPI 77.90±6.31 vs 60.15±5.37, ADP 52.89±9.36 vs 47.90±6.16, and AA 76.09±3.14 vs.55.18±3.55); and the NO level is lower in the case group than in the control group (p<0.05, respectively). After 8 weeks of exenatide treatment in the case group, the CD62p, PAC-1, and platelet aggregation rates were lower than before the treatment (EPI: 61.96±8.94 vs 77.90±6.31 and AA: 50.98±6.73 vs 76.09±3.14); and the NO level was higher than before the treatment (p<0.05, respectively). Pearson correlation analysis showed that the changes in platelet aggregation rates (Δ EPI and ΔAA) of the patients in the case group after 8 weeks of exenatide treatment were positively correlated with the changes in body mass index, waist circumference, weight, blood lipids, fasting plasma glucose, haemoglobin A1c, fibrinogen, CD62p, and PAC-1 and negatively correlated with the changes in high-density lipoprotein and NO (p<0.05). Multiple linear regression analysis showed that the changes in NO, CD62p and PAC-1 were independent risk factors affecting the changes in platelet aggregation rates. Conclusion:The GLP-1R agonist exenatide can inhibit the activation state of platelets in patients with T2DM and inhibit thrombosis, which is beneficial to reduce the risk of cardiovascular events.

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“…Exenatide is a commonly used clinical GLP-1 receptors (GLP-1R) agonist. A number of clinical trials that have been completed so far have found that [12][13][14][15] exenatide can not only effectively reduce the blood glucose level of patients with T2DM, but also has obvious effects other than hypoglycemic effects, such as losing weight, lowering blood pressure, regulating blood lipids, and improving endothelial dysfunction caused by hyperglycemia and hyperlipidemia. Studies have con rmed that GLP-1R are high expressed in mouse and human platelets [16].…”

Section: Introductionmentioning

confidence: 99%

Effects of Exenatide on Blood Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes

Zhang

Chen

Jia

et al. 2021

Preprint

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Background: To explore the effect of glucagon-like peptide-1 receptor (GLP-1R) agonist exenatide on blood coagulation function and platelet aggregation function in patients with type 2 diabetes mellitus (T2DM).Method: Thirty patients with newly diagnosed T2DM were enrolled as the case group, and 30 healthy people with matching age and sex were selected as the control group. Patients in the case group received exenatide treatment for 8 weeks. Collect the general clinical data and biochemical indicators of the patients in the case group before and after 8 weeks of exenatide treatment and the control subjects, and detect their peripheral blood platelet count (×1012 g/L), plasma prothrombin time (PT, s), prothrombin time activity (PTA, %), activated partial thromboplastin time (APTT, s), international normalized ratio (INR), fibrinogen (FIB, g/L), plasma thrombin time (TT, s) , Fibrin degradation products (FDP, μg/mL), D-dimer (DD, μg/mL), nitric oxide (NO, μmol/L), CD62p (%), platelet activation complex-1 (PAC-1, %) and platelet aggregation induced by collagen, epinephrine, arachidonic acid (AA, %), and adenosine diphosphate (ADP, %).Results: There was no significant difference in platelet count, PLT, PT, PTA, APTT, TT, INR, FDP, DD between the case group and the control group; the FIB, CD62p, PAC-1, platelet aggregation rates of the case group (EPI 87.23±6.84 , ADP 87.51±9.21, AA 90.17±3.19) is higher than normal control group (EPI 82.15±5.37, ADP 82.38±6.42, AA 83.41±6.17, P＜0.05), NO level is lower than normal control group (68.1±14.7 vs. 79.4±11.2, P<0.05); After 8 weeks of exenatide treatment in the case group, CD62p, PAC-1, and platelet aggregation rates were lower than before (EPI: 81.62±9.02 vs. 87.23±6.84, AA: 84.62±7.12 vs. 90.17±3.19, P＜0.05), the level of NO was higher than before (89.6±15.8 vs. 68.1±14.7); Pearson correlation analysis showed that the changes in platelet aggregation rates (Δ EPI, ΔAA) of patients in the case group after 8 weeks of exenatide treatment were positively correlated with the changes in body mass index (BMI, kg/m2), waist circumference (cm), weight (kg), total cholesterol (TCH, mmol/L), triglycerides (TG, mmol/L), low-density lipoprotein (LDL-C, mmol/L), fasting plasma glucose (FPG, mmol/L), Hemoglobin A1c (HbA1c, %), CD62p, PAC-1 (P<0.05), and negatively correlated with the change of high density lipoprotein (HDL-C, mmol/L) and NO (P<0.05). Multiple linear regression analysis showed that the changes of NO, CD62p and PAC-1 were independent risk factors affecting the changes of platelet aggregation rates.Conclusions: The GLP-1R agonist exenatide can inhibit the activation state of platelets in patients with T2DM, reduce the platelet aggregation rate, and inhibit thrombosis, which is beneficial to reduce the risk of cardiovascular events.

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Microvascular Density and Circulating Endothelial Progenitor Cells Before and After Treatment with Incretin Mimetics in Diabetic Patients

Abstract: Treatment with exenatide, but not with liraglutide, was able to increase the number of circulating EPCs, possibly through an antioxidative/antiinflammatory effect.

Cited by 11 publications

References 51 publications

Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial

Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial

Effects of Exenatide on Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes

Effects of Exenatide on Blood Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes

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