The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial

Dore, Fiona J.; Domingues, Cleyton C.; Ahmadi, Neeki; Kundu, Nabanita; Kropotova, Yana; Houston, Sara; Rouphael, Carol; Mammadova, Aytan; Witkin, Linda; Khiyami, Anamil; Amdur, Richard L.; Sen, Sabyasachi

doi:10.1186/s12933-018-0709-9

Cited by 37 publications

(37 citation statements)

References 58 publications

(69 reference statements)

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“…In support of this we also found significant increase in the endothelial markers and functional genes (PECAM1, VEGF-A and vWF and NOS3) in linagliptin group as compared to placebo group (Figure 2A ). These observations are in agreement with our previous published results suggesting patho-physiological role of ROS activation and therapeutic reduction in CD34+ve cells in diabetes (33).…”

Section: Primary Outcome: Cellularsupporting

confidence: 94%

Linagliptin, when compared to placebo, improves CD34+ve Endothelial Progenitor Cells in Type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin, a randomized controlled trial.

Awal

Nandula

Domingues

et al. 2020

Preprint

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Introduction: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both Type 2 Diabetes and Chronic Kidney Disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP4 inhibitors such as Linagliptin (LG) on CVD risk, in patients with Type 2 Diabetes with established CKD has notbeen established. Hypothesis : Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD) population. Methods : 31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. Type 2 diabetes subjects (30-70 years old), HbA1c of 6.5-10%, CKD Stage 1-3 were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as Arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value <0.05 considered significant. Results : A double positive CD34/CD184 cell count had a statistically significant increase (p<0.02) as determined by flow cytometry in LG group where CD184 is SDF1a cell surface receptor. Though mRNA differences in CD34+ve was more pronounced CD34- cell mRNA analysis showed increase in antioxidants (SOD2, Catalase and CPX) and prominent endothelial markers (PECAM1, VEGF-A, vWF and NOS3). Arterial stiffness measures such as augmentation Index (AI) (p<0.04) and pulse wave analysis (PWV) were improved (reduced in stiffness) in LG group. A reduction in LDL: HDL ratio was noted in treatment group (p <0.04). Urinary exosome protein examining podocyte health (Podocalxyin, Wilms tumor and Nephrin) showed reduction or improvement. Conclusions : In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks

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Section: Primary Outcome: Cellularsupporting

confidence: 94%

Linagliptin, when compared to placebo, improves CD34+ve Endothelial Progenitor Cells in Type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin, a randomized controlled trial.

Awal

Nandula

Domingues

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Metformin activates AMPK phosphorylation, which reduces oxidative stress, reduces the production of inflammatory cytokines, and increases eNOS (endothelial nitric oxide synthase) activity, which may be an important mechanism for metformin cardiovascular protection. Recent studies have also shown that metformin has protective effects on vascular endothelial function and angiogenesis [72], which may be the pathway of metformin's cardiovascular protective effects. However, this protective effect also has some limitations.…”

Section: Discussionmentioning

confidence: 98%

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

Han

Xie

Liu

et al. 2019

Cardiovasc Diabetol

234

150

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Background Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Methods Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). Results In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don’t use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = − 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = − 0.02) and LDL (MD = − 0.08). Conclusion Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.

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“…With the highest expression specificity in vascular endothelial cells, CD34 has been termed a pan-endothelial cell marker and is superior to other markers of endothelial cells. 22 Therefore, CD34 + endothelial cells were used for detection in miR145 mimic/ inhibitor-transfected RAECs to verify the proliferation of specific endothelial cell populations. Detection turned out to verified successfully, because miR145 mimics boosted the expression of CD34 + endothelial cells in RAECs.…”

Section: Discussionmentioning

confidence: 99%

<p>miR145 Regulates the Proliferation and Apoptosis of Rat Vascular Endothelial Cells under Hyperglycemia by Targeting the <em>ANGPT2</em> Gene and Involving the NFκB Signaling Pathway</p>

Zhang¹,

Tang²,

Zhang³

et al. 2020

DMSO

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The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial

Cited by 37 publications

References 58 publications

Linagliptin, when compared to placebo, improves CD34+ve Endothelial Progenitor Cells in Type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin, a randomized controlled trial.

Linagliptin, when compared to placebo, improves CD34+ve Endothelial Progenitor Cells in Type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin, a randomized controlled trial.

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

<p>miR145 Regulates the Proliferation and Apoptosis of Rat Vascular Endothelial Cells under Hyperglycemia by Targeting the <em>ANGPT2</em> Gene and Involving the NFκB Signaling Pathway</p>

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