92-LB: Linagliptin Improves CD34+ Progenitor Cells and Urine Exosomes
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. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP-4 inh...
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| container_title | Diabetes (New York, N.Y.) |
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| creator | AWAL, HASSAN NANDULA, SESHAGIRI RAO KUNDU, NABANITA 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. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP-4 inhibitors such as Linagliptin (LG) on CVD risk in patients with type 2 diabetes with established CKD has not been established.
Hypothesis: Linagliptin, a DPP-4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD)
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 DM subjects (30-70 years old), A1c 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 were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value |
| doi_str_mv | 10.2337/db20-92-LB |
| format | Article |
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Hypothesis: Linagliptin, a DPP-4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD)
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 DM subjects (30-70 years old), A1c 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 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.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db20-92-LB</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Antioxidants ; Cardiovascular diseases ; Catalase ; CD18 antigen ; CD34 antigen ; Cell migration ; Cell number ; Cell surface ; CXCR4 protein ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Endothelium ; Energy expenditure ; Exosomes ; Flow cytometry ; Gene expression ; High density lipoprotein ; Insulin ; Kidney diseases ; Low density lipoprotein ; Metformin ; Statistical analysis ; Stem cells ; Superoxide dismutase ; Vascular endothelial growth factor</subject><ispartof>Diabetes (New York, N.Y.), 2020-06, Vol.69 (Supplement_1)</ispartof><rights>Copyright American Diabetes Association Jun 1, 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids></links><search><creatorcontrib>AWAL, HASSAN</creatorcontrib><creatorcontrib>NANDULA, SESHAGIRI RAO</creatorcontrib><creatorcontrib>KUNDU, NABANITA</creatorcontrib><creatorcontrib>SEN, SABYASACHI</creatorcontrib><title>92-LB: Linagliptin Improves CD34+ Progenitor Cells and Urine Exosomes</title><title>Diabetes (New York, N.Y.)</title><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. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP-4 inhibitors such as Linagliptin (LG) on CVD risk in patients with type 2 diabetes with established CKD has not been established.
Hypothesis: Linagliptin, a DPP-4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD)
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 DM subjects (30-70 years old), A1c 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 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.</description><subject>Antioxidants</subject><subject>Cardiovascular diseases</subject><subject>Catalase</subject><subject>CD18 antigen</subject><subject>CD34 antigen</subject><subject>Cell migration</subject><subject>Cell number</subject><subject>Cell surface</subject><subject>CXCR4 protein</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Endothelium</subject><subject>Energy expenditure</subject><subject>Exosomes</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>High density lipoprotein</subject><subject>Insulin</subject><subject>Kidney diseases</subject><subject>Low density lipoprotein</subject><subject>Metformin</subject><subject>Statistical analysis</subject><subject>Stem cells</subject><subject>Superoxide dismutase</subject><subject>Vascular endothelial growth factor</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNotkEFLAzEUhIMoWKsXf0HAmxLNy9tsGm92rVpY0EMFbyG7m5Qt201NWtF_79bKHObyMTMMIZfAbwWiumsqwZkWrJwekRFo1AyF-jgmI85BMFBanZKzlFac83zQiMz-4Htatr1ddu1m2_Z0vt7E8OUSLR4xu6FvMSxd325DpIXrukRt39D32PaOzr5DCmuXzsmJt11yF_8-Joun2aJ4YeXr87x4KFmdIzBpEQEy9FrrfCJAWuGs15n3Va2VU1IC1FA5bKSXzua6crVsLE58g1LVAsfk6hA77PvcubQ1q7CL_dBoRAY6kyIXMFDXB6qOIaXovNnEdm3jjwFu9i-Z_UtGC1NO8RdZglg1</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>AWAL, HASSAN</creator><creator>NANDULA, SESHAGIRI RAO</creator><creator>KUNDU, NABANITA</creator><creator>SEN, SABYASACHI</creator><general>American Diabetes Association</general><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20200601</creationdate><title>92-LB: Linagliptin Improves CD34+ Progenitor Cells and Urine Exosomes</title><author>AWAL, HASSAN ; NANDULA, SESHAGIRI RAO ; KUNDU, NABANITA ; SEN, SABYASACHI</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c631-5a331143f99968215a2eaf94ffbc97e75511c1be3d5f5ea69bec5da38fd357c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antioxidants</topic><topic>Cardiovascular diseases</topic><topic>Catalase</topic><topic>CD18 antigen</topic><topic>CD34 antigen</topic><topic>Cell migration</topic><topic>Cell number</topic><topic>Cell surface</topic><topic>CXCR4 protein</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Endothelium</topic><topic>Energy expenditure</topic><topic>Exosomes</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>High density lipoprotein</topic><topic>Insulin</topic><topic>Kidney diseases</topic><topic>Low density lipoprotein</topic><topic>Metformin</topic><topic>Statistical analysis</topic><topic>Stem cells</topic><topic>Superoxide dismutase</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>AWAL, HASSAN</creatorcontrib><creatorcontrib>NANDULA, SESHAGIRI RAO</creatorcontrib><creatorcontrib>KUNDU, NABANITA</creatorcontrib><creatorcontrib>SEN, SABYASACHI</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>AWAL, HASSAN</au><au>NANDULA, SESHAGIRI RAO</au><au>KUNDU, NABANITA</au><au>SEN, SABYASACHI</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>92-LB: Linagliptin Improves CD34+ Progenitor Cells and Urine Exosomes</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2020-06-01</date><risdate>2020</risdate><volume>69</volume><issue>Supplement_1</issue><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>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. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP-4 inhibitors such as Linagliptin (LG) on CVD risk in patients with type 2 diabetes with established CKD has not been established.
Hypothesis: Linagliptin, a DPP-4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD)
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 DM subjects (30-70 years old), A1c 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 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.</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db20-92-LB</doi></addata></record> |
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| subjects | Antioxidants Cardiovascular diseases Catalase CD18 antigen CD34 antigen Cell migration Cell number Cell surface CXCR4 protein Diabetes Diabetes mellitus (non-insulin dependent) Endothelium Energy expenditure Exosomes Flow cytometry Gene expression High density lipoprotein Insulin Kidney diseases Low density lipoprotein Metformin Statistical analysis Stem cells Superoxide dismutase Vascular endothelial growth factor |
| title | 92-LB: Linagliptin Improves CD34+ Progenitor Cells and Urine Exosomes |
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