Seshagiri Rao Nandula1,2, Nabanita Kundu1, Hassan B Awal3, Beda Brichacek1, Mona Fakhri1, Nikhila Aimalla1, Adrian Elzarki3,1, Richard L Amdur3, Sabyasachi Sen4,5,6. 1. Department of Medicine, The George Washington University, 2300 Eye Street, SMHS, Room 462,, Washington, DC, 20037, USA. 2. Department of Medicine and Endocrinology, Veterans Affairs Medical Center, Washington, DC, USA. 3. The GW Medical Faculty Associates, Washington, DC, USA. 4. The GW Medical Faculty Associates, Washington, DC, USA. ssen1@gwu.edu. 5. Department of Medicine, The George Washington University, 2300 Eye Street, SMHS, Room 462,, Washington, DC, 20037, USA. ssen1@gwu.edu. 6. Department of Medicine and Endocrinology, Veterans Affairs Medical Center, Washington, DC, USA. ssen1@gwu.edu.
Abstract
BACKGROUND:Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) 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. Effect of sodium glucose channel inhibitors (SGLT2i) such as Canagliflozin (CG) on a cellular biomarker such as CD34+ve progenitor cells, which may help predict CVD risk, in patients with T2DM with established CKD has not been explored. METHODS: This is a pilot study where 29 subjects takingmetformin and/or Insulin were enrolled in a 16 week, double blind, randomized placebo matched trial, with a low dose 100 mg CG as the intervention group compared to matched placebo. Type 2 diabetes subjects (30-70 years old), with hemoglobin A1c (HbA1c) of 7-10%, were enrolled. CD34+vecell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, serum biochemistry pertaining to cardio-metabolic health, resting energy expenditure and body composition were measured. Data were collected at week 0, 8 and 16. A mixed model regression analysis was done and p value less than 0.05 was considered statistically significant. RESULTS: A significant expression of CXCR4 receptor with a concomittant increase in migratory function of CD34+ve cells was observed in CG treated group as compared to placebo group. Gene expression analysis of CD34+ve cells showed an increase in expression of antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and notable endothelial markers (PECAM1, VEGF-A, and NOS3). A significant reduction in glucose and HbA1c levels were observed along with improved systolic and diastolic blood pressure in the CG group. A significant increase in adiponectin (p = 0.006) was also noted in treatment group. Urinary exosomal protein leak in urine, examining podocyte health (podocalyxin, Wilm's tumor and nephrin) showed reduction with CG CONCLUSION: Low dose Canagliflozin has a beneficial effect on CD34+ cell function, serum biochemistry and urinary podocyte specific exosomes in type 2 diabetes.
RCT Entities:
BACKGROUND: Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) 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. Effect of sodiumglucose channel inhibitors (SGLT2i) such asCanagliflozin (CG) on a cellular biomarker such asCD34+ve progenitor cells, which may help predict CVD risk, in patients with T2DM with established CKD has not been explored. METHODS: This is a pilot study where 29 subjects taking metformin and/or Insulin were enrolled in a 16 week, double blind, randomized placebo matched trial, with a low dose 100 mg CGas the intervention group compared to matched placebo. Type 2 diabetes subjects (30-70 years old), with hemoglobin A1c (HbA1c) of 7-10%, were enrolled. CD34+ve cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, serum biochemistry pertaining to cardio-metabolic health, resting energy expenditure and body composition were measured. Data were collected at week 0, 8 and 16. A mixed model regression analysis was done and p value less than 0.05 was considered statistically significant. RESULTS: A significant expression of CXCR4 receptor with a concomittant increase in migratory function of CD34+ve cells was observed in CG treated group as compared to placebo group. Gene expression analysis of CD34+ve cells showed an increase in expression of antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and notable endothelial markers (PECAM1, VEGF-A, and NOS3). A significant reduction in glucose and HbA1c levels were observed along with improved systolic and diastolic blood pressure in the CG group. A significant increase in adiponectin (p = 0.006) was also noted in treatment group. Urinary exosomal protein leak in urine, examining podocyte health (podocalyxin, Wilm's tumor and nephrin) showed reduction with CG CONCLUSION: Low dose Canagliflozin has a beneficial effect on CD34+ cell function, serum biochemistry and urinary podocyte specific exosomes in type 2 diabetes.
Authors: Norm Rosenthal; Gary Meininger; Kirk Ways; David Polidori; Mehul Desai; Rong Qiu; Maria Alba; Frank Vercruysse; Dainius Balis; Wayne Shaw; Robert Edwards; Scott Bull; Nicholas Di Prospero; Sue Sha; Paul Rothenberg; William Canovatchel; Keith Demarest Journal: Ann N Y Acad Sci Date: 2015-08-25 Impact factor: 5.691
Authors: Kenneth W Mahaffey; Bruce Neal; Vlado Perkovic; Dick de Zeeuw; Greg Fulcher; Ngozi Erondu; Wayne Shaw; Elisa Fabbrini; Tao Sun; Qiang Li; Mehul Desai; David R Matthews Journal: Circulation Date: 2017-11-13 Impact factor: 29.690
Authors: Karin Rådholm; Gemma Figtree; Vlado Perkovic; Scott D Solomon; Kenneth W Mahaffey; Dick de Zeeuw; Greg Fulcher; Terrance D Barrett; Wayne Shaw; Mehul Desai; David R Matthews; Bruce Neal Journal: Circulation Date: 2018-07-31 Impact factor: 29.690
Authors: Brendon L Neuen; Toshiaki Ohkuma; Bruce Neal; David R Matthews; Dick de Zeeuw; Kenneth W Mahaffey; Greg Fulcher; Mehul Desai; Qiang Li; Hsiaowei Deng; Norm Rosenthal; Meg J Jardine; George Bakris; Vlado Perkovic Journal: Circulation Date: 2018-10-09 Impact factor: 29.690
Authors: Sarah J Mancini; Daria Boyd; Omar J Katwan; Anastasiya Strembitska; Tarek A Almabrouk; Simon Kennedy; Timothy M Palmer; Ian P Salt Journal: Sci Rep Date: 2018-03-27 Impact factor: 4.379
Authors: Adrian Farid Elzarki; Seshagiri Rao Nandula; Hassan Awal; Gary L Simon; Sabyasachi Sen Journal: Stem Cell Res Ther Date: 2022-03-07 Impact factor: 6.832
Authors: Carmen Llorens-Cebrià; Mireia Molina-Van den Bosch; Ander Vergara; Conxita Jacobs-Cachá; Maria José Soler Journal: Biomolecules Date: 2022-01-16