ARTERIAL STIFFNESS AND ENDOTHELIAL FUNCTION FOR THE RISK ASSESSMENT OF NEW DIABETIC RETINOPATHY DEVELOPMENT IN TYPE 2 DIABETES

Abstract Aims/hypothesis Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. Methods We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro. Results Rivaroxaban treatment for 20 weeks (n = 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml, p = 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1, p = 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1, p = 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events. Conclusions/interpretation Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding. Trial registration: ClinicalTrials.gov NCT02164578. Funding The study was supported by a research grant from Bayer Vital AG, Germany. Graphical abstract

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Neutrophil–Lymphocyte ratio is associated with arterial stiffness in diabetic retinopathy in type 2 diabetes

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2014.11.006 ◽

2015 ◽

Vol 29 (2) ◽

pp. 245-249 ◽

Cited By ~ 24

Author(s):

Rui-tao Wang ◽

Ji-rong Zhang ◽

Ying Li ◽

Tiemin Liu ◽

Kai-jiang Yu

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Arterial Stiffness ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

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The effects of empagliflozin on arterial stiffness, endothelial function and ventriculoarterial coupling in type 2 diabetes mellitus: 1 year follow up

European Heart Journal ◽

10.1093/ehjci/ehaa946.3354 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I Ikonomidis ◽

J Thymis ◽

G Pavlidis ◽

D Birba ◽

A Kalogeris ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Arterial Stiffness ◽

Endothelial Function ◽

Boundary Region ◽

Endothelial Glycocalyx ◽

Insulin Group ◽

Central Systolic Blood Pressure

Abstract Introduction Sodium glucose cotransporters inhibitors (SGLT2i) are currently used in the treatment of patients with type 2 diabetes mellitus (T2DM) who pose high cardiovascular risk. However their effects on arterial stiffness, endothelial function and ventriculoarterial coupling have not been described. Methods We recruited 120 patients with T2DM. They received either the SGLT2i empagliflozin (n=60) or insulin (n=60). We measured at baseline and after 1 year of treatment: 1) Perfused Boundary Region (PBR 5–25μm) to evaluate endothelial glycocalyx integrity via Glycocheck, 2) Pulse wave Velocity (PWVc-f), 3)central systolic blood pressure (cSBP), 4) central Pulse Pressure (cPP) via Complior,5) the ratio PWV/GLS by echocardiography to assess ventriculoarterial coupling (VA coupling). Results The patients were matched for age, gender, smoking, hypertension and hyperlipidemia (p=NS). Hemoglobin A1c was deteriorated in both groups (8.1% vs 8.2%, p=NS). The baseline measurements of aforementioned markers did not differ between the 2 groups (p=NS). PWV was correlated with cSBP (r=0.4.p<0.05) and cPP (r=0.35, p<0.05) for all participants at baseline. After 1 year of treatment both groups achieved significant reduction of HbA1c. Patients treated with insulin showed an increase of PWV in contrary with empagliflogin group (11.4±0.5 to 12.6±0.4 vs 11.7±0.5 to 10.9±0.4, correspondingly, p<0.05). cSBP declined considerably in empagliflozin group (135±10 to 129±10 vs 134±9 to 136±9 respectively, p<0.05) and cPP remained approximately steady (47±8 to 48±8 vs 49±6 to 55±6 respectively, p<0.05) compared with insulin group. PBR dropped in SGLT2i group (2.20±0.2 to 1.98±0.2, p<0.05) whereas PBR fluctuated at the same level in insulin group (2.18±0.2 to 2.15±0.3, p=NS).PWV/GLS fell in both groups but the reduction was more prominent in empagliflozin group (−0.72±0.1 to −0.67±0.1 vs −0.72±0.1 to −0.60±0.1 respectively, p<0.05). Conclusion 1 year treatment with empagliflozin resulted in improved markers of arterial stiffness, ventriculoarterial coupling and endothelial function, independently of glycemic control. Funding Acknowledgement Type of funding source: None

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Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: A randomized trial.

10.21203/rs.3.rs-51124/v2 ◽

2020 ◽

Author(s):

Antonino Tuttolomondo ◽

Anna Cirrincione ◽

Alessandra Casuccio ◽

Alessandro Del Cuore ◽

Mario Daidone ◽

...

Keyword(s):

Type 2 Diabetes ◽

Arterial Stiffness ◽

Endothelial Function ◽

Randomized Trial ◽

Conventional Therapy ◽

Total Serum ◽

Total Serum Cholesterol ◽

Vascular Health ◽

Antidiabetic Treatment

Abstract Background: Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage. Aims: We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditiona antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes. Methods: Men and women (aged ≥50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucoselowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels. Results: At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy . Conclusions: Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.

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Increased Arterial Stiffness as a Predictor for Onset and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2021/9124656 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yaxin An ◽

Yuxian Yang ◽

Bin Cao ◽

Huan Dong ◽

Aihua Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Logistic Regression ◽

Diabetic Retinopathy ◽

Regression Analysis ◽

Arterial Stiffness ◽

New Onset

Introduction. Brachial–ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications. This study was aimed at investigating the correlations of baPWV with both the presence and severity of diabetic retinopathy (DR) at baseline and at exploring the predictive role of baPWV in the new onset/progression of DR in the follow-up analysis. Methods. The prospective cohort study recruited 2,473 Chinese patients with T2DM, of whom 663 participants were finally included in the follow-up analysis. The presence and grading of DR were performed by the modified Early Treatment Diabetic Retinopathy Study. Uni- or multivariate linear and logistic regression models and Cox proportional-hazards regression analysis were conducted. Results. Of 2,473 patients with T2DM at baseline, 734 individuals were assessed to have DR and further categorized into 630 with non-sight-threatening DR (NSTDR) and 104 with STDR. In addition to the positive relationship between increased baPWV and the presence of DR, multinominal logistic regression analysis revealed that higher tertiles of baPWV were significantly related to the NSTDR (T2: OR = 1.62 (1.22, 2.15), p < 0.001 , and T3: OR = 2.58 (1.86, 3.58), p < 0.001 ) and STDR group (T3: OR = 3.87 (1.87, 8.02), p < 0.001 ). During a follow-up (mean period of 16.4 months), 111 participants had new onset/progression of DR. The cox regressions showed that high baseline baPWV was correlated with increased risk of development/progression of DR ( HR = 2.24 , 95% CI (1.24, 4.03), p = 0.007 , for T2 baPWV and HR = 2.90 , 95% CI (1.49, 5.64), p = 0.002 , for T3 baPWV) after adjustments for multiple factors. Conclusions. Our results demonstrated that baseline baPWV might be an independent predictor in new onset/worsening of DR, suggesting that increased arterial stiffness might be involved in the development of DR. Follow-up studies with a longer duration are needed.

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