SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects

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 tubules. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. DPP4 inhibitor...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of the Endocrine Society 2020-05, Vol.4 (Supplement_1)
Hauptverfasser: Awal, Hassan, Domingues, Cleyton, Dore, Fiona, Kundu, Nabanita, Ahmadi, Neeki, Magan, Fosso, Witkin, Linda, Batistich, Bethany, Safai, Shauna, Amdur, Richard, Sen, Sabyasachi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue Supplement_1
container_start_page
container_title Journal of the Endocrine Society
container_volume 4
creator Awal, Hassan
Domingues, Cleyton
Dore, Fiona
Kundu, Nabanita
Ahmadi, Neeki
Magan, Fosso
Witkin, Linda
Batistich, Bethany
Safai, Shauna
Amdur, Richard
Sen, Sabyasachi
description 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 tubules. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. DPP4 inhibitor increase endogenous SDF1a which has been shown to increase CD34+ cells migration and thereby improve CVD risk. However, cellular mechanisms of DPP4i mediated improvement of CVD in patients with Type 2 Diabetes with established CKD is not established. Hypothesis: Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may recover endothelial function in a diabetic kidney disease (DKD) population. Methods: 31 subjects taking 1–2 grams of metformin and/or Insulin were enrolled in this 12 weeks, double blind, two-arm, randomized placebo matched trial, with 5 mg Linagliptin compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 6.5–10%, and all stages of CKD 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. During trial HbA1C was maintained between 7–8% for all subjects. Every subject was used as their own control. A mixed model regression analysis was done with p value
doi_str_mv 10.1210/jendso/bvaa046.430
format Article
fullrecord <record><control><sourceid>pubmedcentral_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7209126</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_7209126</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1420-57bfbbf41c0c714fd988dc49ba8fd3083a490b99be1dfa7416f19246352297433</originalsourceid><addsrcrecordid>eNpVkd1KAzEQRhdRsGhfwKvcSzV_djc3QmmtFoqKrdch2UzalG2yJGmh7-BDu6UiejXDfHyHgVMUNwTfEUrw_Qa8SeFe75XCfHjHGT4repSXdEBESc__7JdFP6UNxpgIxgXnveJr8fk6eCgr9BEaQMGiufNq1bg2O4-CR-MJ47foyZuQ19A41aD3GFbgXQ4RjaFpElLeoFHMEI_pIjtrPaSEuv4H-O403fk6u44127bKRTBoeWgBUTRxSkOGhBY7vYE6p-viwqomQf9nXhWf06fl-GUwf3uejUfzQU04xd272mptOalxXRJujagqU3OhVWUNwxVTXGAthAZirCo5GVoiKB-yB0pFyRm7Kh5P3Hant2Bq8DmqRrbRbVU8yKCc_J94t5arsJclxYLQYQegJ0AdQ0oR7G-XYHl0Ik9O5I8T2Tlh3-hrg74</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects</title><source>DOAJ Directory of Open Access Journals</source><source>Oxford Journals Open Access Collection</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Awal, Hassan ; Domingues, Cleyton ; Dore, Fiona ; Kundu, Nabanita ; Ahmadi, Neeki ; Magan, Fosso ; Witkin, Linda ; Batistich, Bethany ; Safai, Shauna ; Amdur, Richard ; Sen, Sabyasachi</creator><creatorcontrib>Awal, Hassan ; Domingues, Cleyton ; Dore, Fiona ; Kundu, Nabanita ; Ahmadi, Neeki ; Magan, Fosso ; Witkin, Linda ; Batistich, Bethany ; Safai, Shauna ; Amdur, Richard ; Sen, Sabyasachi</creatorcontrib><description><![CDATA[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 tubules. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. DPP4 inhibitor increase endogenous SDF1a which has been shown to increase CD34+ cells migration and thereby improve CVD risk. However, cellular mechanisms of DPP4i mediated improvement of CVD in patients with Type 2 Diabetes with established CKD is not established. Hypothesis: Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may recover endothelial function in a diabetic kidney disease (DKD) population. Methods: 31 subjects taking 1–2 grams of metformin and/or Insulin were enrolled in this 12 weeks, double blind, two-arm, randomized placebo matched trial, with 5 mg Linagliptin compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 6.5–10%, and all stages of CKD 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. During trial HbA1C was maintained between 7–8% for all subjects. Every subject was used as their own control. 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 treatment group though there was no statistically significant increase in CD34+ cell number, or colony formation units. Gene expression analysis on CD34+ cells showed reduced expression of TP53 (p<0.04). Arterial stiffness measures such as augmentation Index (p<0.04) along with augmentation pressure (p<0.02) were significantly reduced in the treatment group. A reduction in LDL: HDL ratio was noted in treatment group (p <0.04). No change in renal function was noted during the 12 week period.. We are currently analyzing urinary exosome based data to enquire further into renal function Conclusions: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in arterial stiffness and LDL parameters within 12 weeks of intervention.]]></description><identifier>ISSN: 2472-1972</identifier><identifier>EISSN: 2472-1972</identifier><identifier>DOI: 10.1210/jendso/bvaa046.430</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Cardiovascular Endocrinology</subject><ispartof>Journal of the Endocrine Society, 2020-05, Vol.4 (Supplement_1)</ispartof><rights>Endocrine Society 2020. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209126/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209126/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Awal, Hassan</creatorcontrib><creatorcontrib>Domingues, Cleyton</creatorcontrib><creatorcontrib>Dore, Fiona</creatorcontrib><creatorcontrib>Kundu, Nabanita</creatorcontrib><creatorcontrib>Ahmadi, Neeki</creatorcontrib><creatorcontrib>Magan, Fosso</creatorcontrib><creatorcontrib>Witkin, Linda</creatorcontrib><creatorcontrib>Batistich, Bethany</creatorcontrib><creatorcontrib>Safai, Shauna</creatorcontrib><creatorcontrib>Amdur, Richard</creatorcontrib><creatorcontrib>Sen, Sabyasachi</creatorcontrib><title>SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects</title><title>Journal of the Endocrine Society</title><description><![CDATA[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 tubules. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. DPP4 inhibitor increase endogenous SDF1a which has been shown to increase CD34+ cells migration and thereby improve CVD risk. However, cellular mechanisms of DPP4i mediated improvement of CVD in patients with Type 2 Diabetes with established CKD is not established. Hypothesis: Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may recover endothelial function in a diabetic kidney disease (DKD) population. Methods: 31 subjects taking 1–2 grams of metformin and/or Insulin were enrolled in this 12 weeks, double blind, two-arm, randomized placebo matched trial, with 5 mg Linagliptin compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 6.5–10%, and all stages of CKD 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. During trial HbA1C was maintained between 7–8% for all subjects. Every subject was used as their own control. 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 treatment group though there was no statistically significant increase in CD34+ cell number, or colony formation units. Gene expression analysis on CD34+ cells showed reduced expression of TP53 (p<0.04). Arterial stiffness measures such as augmentation Index (p<0.04) along with augmentation pressure (p<0.02) were significantly reduced in the treatment group. A reduction in LDL: HDL ratio was noted in treatment group (p <0.04). No change in renal function was noted during the 12 week period.. We are currently analyzing urinary exosome based data to enquire further into renal function Conclusions: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in arterial stiffness and LDL parameters within 12 weeks of intervention.]]></description><subject>Cardiovascular Endocrinology</subject><issn>2472-1972</issn><issn>2472-1972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpVkd1KAzEQRhdRsGhfwKvcSzV_djc3QmmtFoqKrdch2UzalG2yJGmh7-BDu6UiejXDfHyHgVMUNwTfEUrw_Qa8SeFe75XCfHjHGT4repSXdEBESc__7JdFP6UNxpgIxgXnveJr8fk6eCgr9BEaQMGiufNq1bg2O4-CR-MJ47foyZuQ19A41aD3GFbgXQ4RjaFpElLeoFHMEI_pIjtrPaSEuv4H-O403fk6u44127bKRTBoeWgBUTRxSkOGhBY7vYE6p-viwqomQf9nXhWf06fl-GUwf3uejUfzQU04xd272mptOalxXRJujagqU3OhVWUNwxVTXGAthAZirCo5GVoiKB-yB0pFyRm7Kh5P3Hant2Bq8DmqRrbRbVU8yKCc_J94t5arsJclxYLQYQegJ0AdQ0oR7G-XYHl0Ik9O5I8T2Tlh3-hrg74</recordid><startdate>20200508</startdate><enddate>20200508</enddate><creator>Awal, Hassan</creator><creator>Domingues, Cleyton</creator><creator>Dore, Fiona</creator><creator>Kundu, Nabanita</creator><creator>Ahmadi, Neeki</creator><creator>Magan, Fosso</creator><creator>Witkin, Linda</creator><creator>Batistich, Bethany</creator><creator>Safai, Shauna</creator><creator>Amdur, Richard</creator><creator>Sen, Sabyasachi</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20200508</creationdate><title>SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects</title><author>Awal, Hassan ; Domingues, Cleyton ; Dore, Fiona ; Kundu, Nabanita ; Ahmadi, Neeki ; Magan, Fosso ; Witkin, Linda ; Batistich, Bethany ; Safai, Shauna ; Amdur, Richard ; Sen, Sabyasachi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1420-57bfbbf41c0c714fd988dc49ba8fd3083a490b99be1dfa7416f19246352297433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cardiovascular Endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Awal, Hassan</creatorcontrib><creatorcontrib>Domingues, Cleyton</creatorcontrib><creatorcontrib>Dore, Fiona</creatorcontrib><creatorcontrib>Kundu, Nabanita</creatorcontrib><creatorcontrib>Ahmadi, Neeki</creatorcontrib><creatorcontrib>Magan, Fosso</creatorcontrib><creatorcontrib>Witkin, Linda</creatorcontrib><creatorcontrib>Batistich, Bethany</creatorcontrib><creatorcontrib>Safai, Shauna</creatorcontrib><creatorcontrib>Amdur, Richard</creatorcontrib><creatorcontrib>Sen, Sabyasachi</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the Endocrine Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Awal, Hassan</au><au>Domingues, Cleyton</au><au>Dore, Fiona</au><au>Kundu, Nabanita</au><au>Ahmadi, Neeki</au><au>Magan, Fosso</au><au>Witkin, Linda</au><au>Batistich, Bethany</au><au>Safai, Shauna</au><au>Amdur, Richard</au><au>Sen, Sabyasachi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects</atitle><jtitle>Journal of the Endocrine Society</jtitle><date>2020-05-08</date><risdate>2020</risdate><volume>4</volume><issue>Supplement_1</issue><issn>2472-1972</issn><eissn>2472-1972</eissn><abstract><![CDATA[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 tubules. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. DPP4 inhibitor increase endogenous SDF1a which has been shown to increase CD34+ cells migration and thereby improve CVD risk. However, cellular mechanisms of DPP4i mediated improvement of CVD in patients with Type 2 Diabetes with established CKD is not established. Hypothesis: Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may recover endothelial function in a diabetic kidney disease (DKD) population. Methods: 31 subjects taking 1–2 grams of metformin and/or Insulin were enrolled in this 12 weeks, double blind, two-arm, randomized placebo matched trial, with 5 mg Linagliptin compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 6.5–10%, and all stages of CKD 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. During trial HbA1C was maintained between 7–8% for all subjects. Every subject was used as their own control. 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 treatment group though there was no statistically significant increase in CD34+ cell number, or colony formation units. Gene expression analysis on CD34+ cells showed reduced expression of TP53 (p<0.04). Arterial stiffness measures such as augmentation Index (p<0.04) along with augmentation pressure (p<0.02) were significantly reduced in the treatment group. A reduction in LDL: HDL ratio was noted in treatment group (p <0.04). No change in renal function was noted during the 12 week period.. We are currently analyzing urinary exosome based data to enquire further into renal function Conclusions: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in arterial stiffness and LDL parameters within 12 weeks of intervention.]]></abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1210/jendso/bvaa046.430</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2472-1972
ispartof Journal of the Endocrine Society, 2020-05, Vol.4 (Supplement_1)
issn 2472-1972
2472-1972
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7209126
source DOAJ Directory of Open Access Journals; Oxford Journals Open Access Collection; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Cardiovascular Endocrinology
title SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T00%3A33%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmedcentral_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=SUN-578%20Role%20of%20Linagliptin%20on%20CD34+%20Endothelial%20Progenitor%20Cells%20and%20Arterial%20Stiffness%20in%20Renal%20Function%20Impaired%20Type%202%20Diabetes%20Subjects&rft.jtitle=Journal%20of%20the%20Endocrine%20Society&rft.au=Awal,%20Hassan&rft.date=2020-05-08&rft.volume=4&rft.issue=Supplement_1&rft.issn=2472-1972&rft.eissn=2472-1972&rft_id=info:doi/10.1210/jendso/bvaa046.430&rft_dat=%3Cpubmedcentral_cross%3Epubmedcentral_primary_oai_pubmedcentral_nih_gov_7209126%3C/pubmedcentral_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true