Changes in plasma and urine metabolites associated with empagliflozin in patients with type 1 diabetes

被引：26

作者：

Liu, Hongyan ^{[1
,2
,3
]}

Sridhar, Vikas S. ^{[1
,2
,4
,5
]}

Montemayor, Daniel ^{[6
]}

Lovblom, Leif Erik ^{[7
]}

Lytvyn, Yuliya ^{[1
,4
,8
]}

Ye, Hongping ^{[6
]}

Kim, Jiwan ^{[6
]}

Ali, Mir Tariq ^{[6
]}

Scarr, Daniel ^{[7
]}

Lawler, Patrick R. ^{[9
,10
,11
,12
]}

Perkins, Bruce A. ^{[7
,13
]}

Sharma, Kumar ^{[6
]}

Cherney, David Z. I. ^{[1
,2
,3
,4
,5
,14
]}

机构：

[1] UHN, Toronto Gen Hosp Res Inst, 585 Univ Ave,8N-845, Toronto, ON M5G 2N2, Canada

[2] UHN, Dept Med, Div Nephrol, Toronto, ON, Canada

[3] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada

[4] Univ Toronto, Div Nephrol, Dept Med, Toronto, ON, Canada

[5] Banting & Best Diabet Ctr, Toronto, ON, Canada

[6] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, Ctr Renal Precis Med, 8300 Floyd Curl Dr,4th Floor,4B, San Antonio, TX 78229 USA

[7] Lunenfeld Tanenbaum Res Inst, Sinai Hlth Syst, Toronto, ON, Canada

[8] Univ Toronto, Temerty Fac Med, Toronto, ON, Canada

[9] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada

[10] Univ Toronto, Ted Rogers Ctr Heart Res, Toronto, ON, Canada

[11] Univ Toronto, Div Cardiol, Toronto, ON, Canada

[12] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada

[13] Univ Toronto, Dept Med, Div Endocrinol & Metab, Toronto, ON, Canada

[14] Univ Toronto, Dept Physiol, Toronto, ON, Canada

来源：

DIABETES OBESITY & METABOLISM | 2021年 / 23卷 / 11期

基金：

加拿大健康研究院;

关键词：

empagliflozin; metabolomics; SGLT2; inhibition; type; 1; diabetes; COTRANSPORTER; 2; INHIBITION; METABOLOMICS REVEALS; SGLT2; INHIBITORS; SHIFT; DAPAGLIFLOZIN; MECHANISM; OXIDATION; OUTCOMES; HEART;

D O I：

10.1111/dom.14489

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aim To examine the impact of the sodium-glucose co-transporter-2 inhibitor, empagliflozin, on plasma and urine metabolites in participants with type 1 diabetes. Material and Methods Participants (n = 40, 50% male, mean age 24.3 years) with type 1 diabetes and without overt evidence of diabetic kidney disease had baseline assessments performed under clamped euglycaemia and hyperglycaemia, on two consecutive days. Participants then proceeded to an 8-week, open-label treatment period with empagliflozin 25 mg/day, followed by repeat assessments under clamped euglycaemia and hyperglycaemia. Plasma and urine metabolites were first grouped into metabolic pathways using MetaboAnalyst software. Principal component analysis was performed to create a representative value for each sufficiently represented metabolic group (false discovery rate <= 0.1) for further analysis. Results Of the plasma metabolite groups, tricarboxylic acid (TCA) cycle (P < .0001), biosynthesis of unsaturated fatty acids (P = .0045), butanoate (P < .0001), propanoate (P = .0053), and alanine, aspartate and glutamate (P < .0050) metabolites were increased after empagliflozin treatment under clamped euglycaemia. Of the urine metabolite groups, only butanoate metabolites (P = .0005) were significantly increased. Empagliflozin treatment also attenuated the increase in a number of urine metabolites observed with acute hyperglycaemia. Conclusions Empagliflozin was associated with increased lipid and TCA cycle metabolites in participants with type 1 diabetes, suggesting a shift in metabolic substrate use and improved mitochondrial function. These effects result in more efficient energy production and may contribute to end-organ protection by alleviating local hypoxia and oxidative stress.

引用

页码：2466 / 2475

页数：10