Abstract：
OBJECTIVE: 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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
目的：探讨高血糖和依帕列净对无并发症1型糖尿病(T1D)患者心肾损伤和炎症反应的影响。
方法：血清心脏（sST2，Gal-3，cTnT），肾损伤（KIM-1，NGAL），炎症（sTNFR1，sTNFR2），和血液动力学（NT-proBNP，EPO)标志物在两个单独的T1D队列中进行事后评估。血糖钳夹试验（NCT02344602）评估了正常血糖和急性高血糖条件下的49名T1D成人和27名对照。BetWEEN交叉试验（NCT02632747）在30名T1D成人患者中，与安慰剂-雷米普利4周相比，研究了empagliflozin25mg加雷米普利4周。
结果：在血糖钳夹研究中，高血糖会急剧增加NT-proBNP（p=0.0003）和sTNFR2（p=0.003）的水平。与安慰剂相比，使用empagliflozin治疗的参与者之间的NT-proBNP的亚急性升高（p=0.0147）。与血细胞比容无关。sST2和sTNFR1基线水平较高的个体收缩压降低幅度更大，肾素-血管紧张素-醛固酮系统（RAAS）介质激活幅度更大，而KIM-1和sTNFR1基线水平较高的患者的肾小球滤过率(GFR)下降较大.
结论：SGLT2抑制血压的保护机制，RAAS激活,在无并发症的T1D患者亚组中，肾脏血流动力学明显，伴有不良心肾和炎症标志物。
方法：血清心脏（sST2，Gal-3，cTnT），肾损伤（KIM-1，NGAL），炎症（sTNFR1，sTNFR2），和血液动力学（NT-proBNP，EPO)标志物在两个单独的T1D队列中进行事后评估。血糖钳夹试验（NCT02344602）评估了正常血糖和急性高血糖条件下的49名T1D成人和27名对照。BetWEEN交叉试验（NCT02632747）在30名T1D成人患者中，与安慰剂-雷米普利4周相比，研究了empagliflozin25mg加雷米普利4周。
结果：在血糖钳夹研究中，高血糖会急剧增加NT-proBNP（p=0.0003）和sTNFR2（p=0.003）的水平。与安慰剂相比，使用empagliflozin治疗的参与者之间的NT-proBNP的亚急性升高（p=0.0147）。与血细胞比容无关。sST2和sTNFR1基线水平较高的个体收缩压降低幅度更大，肾素-血管紧张素-醛固酮系统（RAAS）介质激活幅度更大，而KIM-1和sTNFR1基线水平较高的患者的肾小球滤过率(GFR)下降较大.
结论：SGLT2抑制血压的保护机制，RAAS激活,在无并发症的T1D患者亚组中，肾脏血流动力学明显，伴有不良心肾和炎症标志物。
