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

被引：3
作者：
Kugathasan, Luxcia [1 ,2 ,3 ]
Sridhar, Vikas S. [1 ,2 ]
Lytvyn, Yuliya [1 ,2 ]
Lovblom, Leif Erik [4 ]
Perkins, Bruce A. [5 ,6 ]
Advani, Andrew [2 ,7 ,8 ]
Cherney, David Z. I. [1 ,2 ,3 ]
机构：
[1] Univ Hlth Network, Dept Med, Div Nephrol, 585 Univ Ave, Toronto, ON M5G 2N2, Canada
[2] Univ Toronto, Temerty Fac Med, 2109 Med Sci Bldg,1 Kings Coll Cir, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Cardiovasc Sci Collaborat Specializat, POB 3C,263 McCaul St,4th Floor,Rm 413, Toronto, ON M5T 1W7, Canada
[4] Univ Hlth Network, Biostat Dept, 585 Univ Ave, Toronto, ON M5G 2N2, Canada
[5] Lunenfeld Tanenbaum Res Inst, Sinai Hlth Syst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada
[6] Univ Toronto, Dept Med, Div Endocrinol & Metab, 6 Queens Pk Crescent West,Third Floor, Toronto, ON M5S 3H2, Canada
[7] St Michaels Hosp, Keenan Res Ctr Biomed Sci, 209 Victoria St, Toronto, ON M5B 1T8, Canada
[8] St Michaels Hosp, Li Ka Shing Knowledge Inst, 209 Victoria St, Toronto, ON M5B 1T8, Canada
来源：
DIABETES RESEARCH AND CLINICAL PRACTICE | 2024年 / 213卷
基金：
加拿大健康研究院;
关键词：
SGLT2; inhibition; Hyperglycemia; Empagliflozin; Type; 1; diabetes; Cardiorenal injury; Inflammation; TNF RECEPTORS 1; CARDIOVASCULAR BIOMARKERS; KIDNEY-DISEASE; RISK; CANAGLIFLOZIN; MORTALITY; FIBROSIS; OUTCOMES; SGLT2; ERTUGLIFLOZIN;
D O I：
10.1016/j.diabres.2024.111764
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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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页数：9
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