Effect of hyperglycemia and empagliflozin on markers of cardiorenal injury and inflammation in patients with type 1 diabetes

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes research and clinical practice Pub Date : 2024-07-01 DOI:10.1016/j.diabres.2024.111764

Luxcia Kugathasan , Vikas S. Sridhar , Yuliya Lytvyn , Leif Erik Lovblom , Bruce A. Perkins , Andrew Advani , David Z.I. Cherney

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Abstract

Aims

To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D).

Methods

Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions. The crossover BETWEEN trial (NCT02632747) investigated empagliflozin 25 mg plus ramipril for 4 weeks compared to placebo-ramipril for 4 weeks in 30 adults with T1D.

Results

In the glycemic clamp study, hyperglycemia acutely increased levels of NT-proBNP (p = 0.0003) and sTNFR2 (p = 0.003). BETWEEN participants treated with empagliflozin exhibited a paradoxical subacute rise in NT-proBNP (p = 0.0147) compared to placebo, independent of hematocrit. Individuals with higher baseline levels of sST2 and sTNFR1 had greater empagliflozin-associated reductions in systolic blood pressure and greater activation of renin-angiotensin-aldosterone system (RAAS) mediators, whereas those with higher baseline levels of KIM-1 and sTNFR1 had greater glomerular filtration rate (GFR) dip.

Conclusion

The protective mechanisms of SGLT2 inhibition on blood pressure, RAAS activation, and renal hemodynamics are apparent in the subset of people with uncomplicated T1D with adverse cardiorenal and inflammatory markers.

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高血糖和恩格列净对 1 型糖尿病患者心肾损伤和炎症指标的影响

目的：研究高血糖和恩格列净对无并发症1型糖尿病（T1D）患者心肾损伤和炎症的影响：在两个独立的T1D队列中对血清心脏指标（sST2、Gal-3、cTnT）、肾损伤指标（KIM-1、NGAL）、炎症指标（sTNFR1、sTNFR2）和血流动力学指标（NT-proBNP、EPO）进行了事后评估。血糖钳夹试验（NCT02344602）评估了在无糖和急性高血糖条件下的 49 名成人 T1D 患者和 27 名对照组。交叉BETWEEN试验（NCT02632747）对30名T1D成人患者进行了为期4周的empagliflozin 25 mg加雷米普利治疗与为期4周的安慰剂-雷米普利治疗的比较研究：结果：在血糖钳夹研究中，高血糖会使NT-proBNP（p = 0.0003）和sTNFR2（p = 0.003）水平急剧升高。与安慰剂相比，接受过 Empagliflozin 治疗的 BETWEEN 参与者的 NT-proBNP（p = 0.0147）呈亚急性上升，与血细胞比容无关。sST2和sTNFR1基线水平较高的患者，其收缩压的降低幅度更大，肾素-血管紧张素-醛固酮系统（RAAS）介质的激活程度更高；而KIM-1和sTNFR1基线水平较高的患者，其肾小球滤过率（GFR）的下降幅度更大：结论：SGLT2 抑制对血压、RAAS 激活和肾血流动力学的保护机制在心肾功能和炎症指标不良的无并发症 T1D 患者中显而易见。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.