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.
Cardiovasc Diabetol
; 19(1): 72, 2020 06 03.
Article
en En
| MEDLINE
| ID: mdl-32493344
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. Cellular mechanisms of DPP4 inhibitors such as linagliptin (LG) on CVD risk, in patients with T2DM with established CKD has not been established. 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 (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) 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 (podocalyxin, 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. Trial Registration Number NCT02467478 Date of Registration 06/08/2015.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antígenos CD34
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Diabetes Mellitus Tipo 2
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Nefropatías Diabéticas
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Insuficiencia Renal Crónica
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Inhibidores de la Dipeptidil-Peptidasa IV
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Células Progenitoras Endoteliales
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Linagliptina
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Hipoglucemiantes
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Insulina
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Metformina
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Cardiovasc Diabetol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
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ENDOCRINOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos