scholarly journals 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.

2020 ◽  
Author(s):  
Hassan B Awal ◽  
Seshagiri Rao Nandula ◽  
Cleyton C Domingues ◽  
Fiona J Dore ◽  
Nabanita Kundu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Risk Indicator ◽  
Cvd Risk ◽  
Endothelial Progenitor

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 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

scholarly journals Role of Canagliflozin on function of CD34+ endothelial progenitor cells (EPC) in patients with type 2 diabetes

2020 ◽  
Author(s):  
Seshagiri Rao Nandula ◽  
Nabanita Kundu ◽  
Hassan Awal ◽  
Beda Brichacek ◽  
Mona Fakhri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Functional Improvement ◽  
P Value ◽  
Risk Indicator ◽  
Cvd Risk ◽  
Endothelial Progenitor

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 (SGLT2 inhibitors) such as Canagliflozin (CG) on a cellular CVD risk indicator such as CD34+ve cells, in patients with T2DM with established CKD has not been explored,Methods: 29 subjects taking metformin and/or Insulin were enrolled in a 16 weeks, double blind, randomized placebo matched trial, with a low dose 100 mg CG compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 7–10%,. 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, 8 and 16. A mixed model regression analysis was done with p value less than 0.05 were considered significant.Results: Gene expression analysis of CD34+ve cells showed increase in antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX). A significant increase in gene expression of endothelial markers PECAM1 (p=0.002), VEGF-A(p= 0.04) and CXCR4 receptor (p= 0.06) followed by an increase in migratory function of CD34+ve cells is observed in Canagliflozin treated group as compared to placebo group. A significant reduction in glucose (p=0.01) levels was observed along with improved systolic and diastolic blood pressure in the CG group. Significant increase in adiponectin (p=0.02) was also noted in treatment group. Urinary exosomal protein examining podocyte health (podocalyxin, Wilm’s tumor and nephrin) showed improvement.Conclusion: We conclude that Canagliflozin on addition to metformin and/or Insulin, in subjects with type 2 diabetes demonstrates a functional improvement of CD34+ Endothelial Progenitor Cell function and gene expression and improves endothelial function

scholarly journals Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Seshagiri Rao Nandula ◽  
Nabanita Kundu ◽  
Hassan B. Awal ◽  
Beda Brichacek ◽  
Mona Fakhri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Low Dose ◽  
Serum Biochemistry ◽  
Risk Indicator ◽  
Cvd Risk ◽  
Endothelial Progenitor

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 taking metformin 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+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.

Effect of Aerobic and Resistance Training on Endothelial Progenitor Cells in Mice with Type 2 Diabetes

2020 ◽  
Vol 22 (4) ◽  
pp. 189-197
Author(s):  
Xia Dai ◽  
Lu Zhai ◽  
Qiang Su ◽  
BeiBei Luo ◽  
Chun Wei ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Resistance Training ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor

scholarly journals P0159PROTEINURIC PHENOTYPE OF CHRONIC KIDNEY DISEASE IS ASSOCIATED WITH WORSE PROFILE OF 24-H CENTRAL BP AND HIGHER ARTERIAL STIFFNESS IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Viktoria Chernomorets ◽  
Elena Troitskaya ◽  
Zhanna Kobalava
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Kidney Function ◽  
Night Time ◽  
Hypertensive Patients

Abstract Background and Aims 24-h blood pressure (BP) may be superior to office BP in the prediction of cardiovascular mortality and also central aortic BP may better predict outcomes than brachial one. Hypertensive patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) have higher risk and poorer BP control than patients with normal glycemic state and renal function. 24-h profile of central BP and arterial stiffness according to CKD phenotypes are not well described in this population. The aim of the study was to evaluate the associations of kidney function and proteinuria with 24-h central BP and parameters of arterial stiffness in hypertensive patients with T2DM and CKD. Method 90 patients with hypertension (HTN), T2DM and CKD (eGFR 30-60 ml/min/1.73 m2 and morning spot urine albumin–creatinine ratio (UACR) &lt;300 mg/g) were included. 66% of them were females, median age was 60 years, 69% were smokers, 53% obese, 77% with dyslipidemia. Median duration of T2DM and HTN was 7.5 years and 18 years, respectively. All received antihypertensive drugs (77% – combinations of 2 or 3 drugs) and glucose lowering therapy (insulin in 58%). The analysis was performed according to CKD phenotype: proteinuric (UACR 30-300 mg/g) and non-proteinuric (UACR &lt;30 mg/g) and according to CKD stage assessed by GFR (G3a and G3b, KDIGO (2012)). Office brachial BP was measured with a validated oscillometric device. Office aortic BP and arterial stiffness were assessed with applanation tonometry (SphygmoCor AtCor). 24-hour ABPM of brachial and aortic BP was performed with BPLab Vasotens. All results are presented as median values. P&lt;0.05 was considered significant. Results Median brachial BP was 156/83 mmHg, aortic BP 139/90 mmHg. Median eGFR was 53 ml/min/1.73 m2, UACR – 62.2 mg/g. Phenotypes of CKD were as follows: proteinuric in 78% (GFR 50 ml/min/1.73 m2, UACR 62 mg/g) and non-proteinuric in 22 % (GFR 54 ml/min/1.73 m2, med UACR 5 mg/g, p&lt;0.01 for trend compared non-proteinuric). Patients with proteinuric phenotype compared to non-proteinuric were characterized by higher rate of dyslipidemia (85% vs 45%, p&lt;0.001), longer duration of HTN and DM (19.5 vs 7.5 years and 8 vs 3 years, respectively, p &lt;0.01 for trend) and lower HDL-C (1.2 vs 1.9, p=0.02). Both groups had similar office brachial SBP (156 vs 157 mmHg; p=0.48), but patients with proteinuric phenotype had higher office central SBP (147 vs 137 mmHg, p=0.007) and worse 24-h profile of central SBP (daytime 147 vs 138 mmHg, p=0.008; night-time 143 vs 130 mmHg, p=0.04). Proteinuric phenotype significantly correlated with office aortic SBP (r=0.28; p=0.01) and daytime and night-time aortic SBP (r=0.28 and 0.21 respectively, p &lt;0.05 for trend). The eGFR phenotypes were as follows: G3a in 82.2% (GFR 54 ml/min/1.73 m2, UACR 20 mg/g) and G3b in 17.8% (GFR 38 ml/min/1.73 m2, med UACR 46 mg/g, p&lt;0.01 for trend compared to G3a). Patients with worse kidney function had longer duration of HTN and DM (16 vs 11 years and 10 vs 6 years, respectively, p &lt;0.01 for trend), higher median brachial and aortic BP levels (158/90 vs 146/82 mmHg and 150/95 vs 138/80 mmHg, respectively, p&lt;0.01 for trend), worse 24-h profile of central SBP (daytime 148 vs 138 mmHg, p=0.008; night-time 146 vs 130 mmHg, p=0.006), higher central pulse pressure (56 vs 49 mmHg, p=0.007), augmentation index (33 vs 14%, p=0.007). Conclusion Hypertensive patients with T2DM and CKD G3b and proteinuria were characterized by worse 24-profile of central BP and higher arterial stiffness.

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