Interaction of renin-angiotensin system gene polymorphisms with hypertension in Chinese patients with type 1 diabetes and retinopathy

Context: The effect of glycemic control on persisting albuminuria remains unclear. Insulin delivery and glucose variability may be important. Objective: This study aimed to investigate the effect of 1-year treatment with sensor-augmented insulin pump (SAP) or multiple daily injections (MDIs) on albuminuria. Design, Patients, and Methods: This was a randomized controlled open-label parallel trial composed of 60 patients with type 1 diabetes with a history of albuminuria and on stable renin-angiotensin system inhibition, were randomly assigned to SAP or MDI. Urine albumin creatinine ratio (UACR) was measured in three urine samples at all visits. Glucose variability and glomerular filtration rate (51Cr-EDTA-GFR) were measured at beginning and study end. Using linear mixed model, change in UACR between groups was analyzed as intention to treat. Main Outcome Measure: Change in UACR was measured. Results: Fifty-five patients (SAP, n = 26; MDI, n = 29) completed the study. Diabetes duration (mean ± SD, 33 ± 12 y), UACR (geometric mean, 99 mg/g; interquartile range, 37–233 mg/g), 51Cr-EDTA-GFR (94 ± 22 mL/min/1.73m2), glycosylated hemoglobin (HbA1c) (9.0 ± 1.1%), glucose variability (calculated as SD), 4.0 ± 1.0 mmol/l; no-group differences (P ≥ .06 for all). After 1 year, change in UACR was mean, −13%; 95% confidence interval, −39 to 22 with SAP vs mean, 30%; 95% CI, −12 to 92% on MDI treatment (unadjusted P = .051; adjusted for HbA1c, P = .04). HbA1c decreased 1.3 ± 1.0 vs 0.6 ± 1.0% (P = .013), glucose variability decreased 0.9 ± 1.1 vs 0.3 ± 1.0 mmol/L (P = .04), and 51Cr-EDTA-GFR declined 5.6 ± 9.6 vs 3.4 ± 13 mL/min/1.73m2 (P = .50) with SAP vs MDI treatment. There were no changes in blood pressure (P ≥ .27). Conclusion: SAP treatment reduced UACR in a randomized controlled trial in type 1 diabetes patients with a history of albuminuria on stable renin-angiotensin system inhibition. Significance was reached after adjustment. SAP treatment reduced HbA1c and glucose variability (calculated as SD).

Download Full-text

Inhibiting the renin‑angiotensin system in patients with type 1 diabetes: is it worth it?

Polish Archives of Internal Medicine ◽

10.20452/pamw.809 ◽

2009 ◽

Vol 119 (11) ◽

pp. 692-693

Author(s):

Irena Duka ◽

George Bakris

Keyword(s):

Type 1 Diabetes ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

Download Full-text

Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression, Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and SP-B in the Lungs of Type 1 Diabetes Rats

Endocrinology ◽

10.1210/en.2014-1685 ◽

2015 ◽

Vol 156 (10) ◽

pp. 3559-3569 ◽

Cited By ~ 64

Author(s):

Marina Romaní-Pérez ◽

Verónica Outeiriño-Iglesias ◽

Christian M. Moya ◽

Pilar Santisteban ◽

Lucas C. González-Matías ◽

...

Keyword(s):

Type 1 Diabetes ◽

Right Ventricle ◽

Rat Model ◽

Renin Angiotensin System ◽

Surfactant Protein ◽

Angiotensin System ◽

Renin Angiotensin ◽

Ventricle Hypertrophy ◽

Right Ventricle Hypertrophy

Diabetes alters microvascular function in the vascular beds of organs, including the lungs. Cardiovascular complications of pulmonary vascular affectation may be a consequence of the overactivation of the vasoconstrictive and proliferative components of the renin-angiotensin system. We previously reported that pulmonary physiology and surfactant production is improved by the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide (LIR) in a rat model of lung hypoplasia. Because we hypothesized that streptozotocin-induced diabetes rats would show deficiencies in lung function, including surfactant proteins, and develop an imbalance of the renin-angiotensin system in the lungs. This effect would in turn be prevented by long-acting agonists of the GLP-1R, such as LIR. The induction of diabetes reduced the surfactant protein A and B in the lungs and caused the vasoconstrictor component of the renin-angiotensin system to predominate, which in turn increased angiotensin II levels, and ultimately being associated with right ventricle hypertrophy. LIR restored surfactant protein levels and reversed the imbalance in the renin-angiotensin system in this type 1 diabetes mellitus rat model. Moreover, LIR provoked a strong increase in angiotensin-converting enzyme 2 expression in the lungs of both diabetic and control rats, and in the circulating angiotensin(1–7) in diabetic animals. These effects prompted complete reversion of right ventricle hypertrophy. The consequences of LIR administration were independent of glycemic control and of glucocorticoids, and they involved NK2 homeobox 1 signaling. This study demonstrates by first time that GLP-1R agonists, such as LIR, might improve the cardiopulmonary complications associated with diabetes.

Download Full-text