Using adult stem cells to monitor endothelial dysfunction in diabetes mellitus

https://doi.org/10.1016/j.jdiacomp.2020.107588Get rights and content

Highlights

  • The review article highlights the major trials using diabetes medications that focus on cardiovascular (CV) outcomes.

  • The article tries to highlight the need for cellular CV outcomes while ascertaining CVOT outcome trials using novel diabetes medications.

  • Peripheral blood derived CD34+ve endothelial progenitor cells may be the right cell based outcome measure while studying the novel diabetes medications.

Abstract

Diabetes affects approximately 10.5% of adults in the United States and this is projected to nearly double by 2025. Both type 2 diabetes (T2DM) and obesity are associated with endothelial dysfunction, oxidative stress, endothelial cell inflammation, cardiovascular pro-thrombotic states and are the most common causes of endothelial dysfunction, chronic kidney disease (CKD) and cardiovascular disease (CVD). Lately several new diabetes medications have come to clinical use that claim CVD risk improvement, however modalities used to test and monitor CVD risk are not cell based, which bring into question the reproducibility of these studies. Our review is designed to highlight cardiovascular risk reduction with novel diabetes medications while emphasizing cellular outcomes as a biomarker of cardiovascular risk.

We are going to highlight studies that comment on peripheral blood derived CD34+ hematopoietic progenitor cells, as biomarkers of endothelial function. CD34+ cells have been extensively investigated by us and several other laboratories for the last two decades, as a viable cardiovascular function biomarker. In this context we will also discuss relevant CVD risk reduction trials that used novel diabetes medications.

Section snippets

Introduction and background

Diabetes affects approximately 10.5% of adults in the United States and this is projected to nearly double by 2025.1 It is the seventh leading cause of death in the US.1 Both type 2 diabetes (T2DM) and obesity are associated with endothelial dysfunction, oxidative stress, endothelial cell inflammation, cardiovascular pro-thrombotic states and are the most common causes of endothelial dysfunction, chronic kidney disease (CKD) and cardiovascular disease (CVD).2., 3., 4.

Oral diabetes medication

Diabetes medications that reduce CVD risk

The United Kingdom Prospective Diabetes Study, and Diabetes Control and Complications Trial have shown that aggressive glucose control, especially early in the natural history of the disease, might result in a significant reduction of microvascular as well as macro vascular complications.28,29 The pathogenesis of vascular disease in diabetes is complex and multifactorial30; however, endothelial dysfunction is a hallmark of type 2 diabetes mellitus (T2DM).28 The endothelium forms the inner layer

Why stem cells

Stem cells are nonspecialized cells which can differentiate into specialized organ or tissue specific cells. Predominantly, stem cells are divided into embryonic and somatic or adult stem cells (ASCs). The role of stem cells on embryonic development has remained as the main focus in regenerative medicine for long time compared to ASCs. ASCs can be found in different tissue including bone marrow, peripheral blood, blood vessels, skeletal muscle, adipose tissue, brain and many other tissues by

Effect of novel diabetes medications on endothelial progenitor cells

As mentioned above, EPCs can act as a cellular biomarker that is more reliable than serum based markers for estimating and following endothelial dysfunction in early T2DM patients. Thus, investigating EPCs could help develop a cardio-vascular disease (CVD) risk estimation.50,51,24

Dipeptidyl peptidase-4 (DPP-4) inhibitors, as mentioned before, are a popular class of antidiabetic medications, have been shown to achieve improved glycemic control by lowering glycosylated hemoglobin (HbA1c), without

Abbreviations

    T2DM

    type 2 diabetes mellitus

    SGLT2i

    sodium-glucose co-transporter 2 (SGLT2) inhibitors

    GLP-1

    glucagon-like peptide 1

    DPP4i

    dipeptidyl peptidase-4 (DPP-4) inhibitors

    ECs

    endothelial cells

    EPC

    endothelial progenitor cells

    MSC

    mesenchymal stromal cells

    MNC

    mononuclear cells

    CVD

    cardio-vascular disease

    CFU

    Colony Forming Unit

    SDF-1

    stromal cell-derived factor

    VEGF

    vascular endothelial growth factor

    CXCR4

    C-X-C chemokine receptor type 4

    SOD1

    superoxide dismutase 1

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    Conflict of interest: Authors do not have any conflict of interest to disclose.

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