NDLI: Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study

Content Provider	Springer Nature : BioMed Central
Author	Gaborit, B. Ancel, P. Abdullah, A. E. Maurice, F. Abdesselam, I. Calen, A. Soghomonian, A. Houssays, M. Varlet, I. Eisinger, M. Lasbleiz, A. Peiretti, F. Bornet, C. E. Lefur, Y. Pini, L. Rapacchi, S. Bernard, M. Resseguier, N. Darmon, P. Kober, F. Dutour, A.
Abstract	Background Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D). We hypothesized that empaglifozin (EMPA) could modulate ectopic fat stores and myocardial energetics in high-fat-high-sucrose (HFHS) diet mice and in type 2 diabetics (T2D). Methods C57BL/6 HFHS mice (n = 24) and T2D subjects (n = 56) were randomly assigned to 12 weeks of treatment with EMPA (30 mg/kg in mice, 10 mg/day in humans) or with placebo. A 4.7 T or 3 T MRI with 1H-MRS evaluation–myocardial fat (primary endpoint) and liver fat content (LFC)–were performed at baseline and at 12 weeks. In humans, standard cardiac MRI was coupled with myocardial energetics (PCr/ATP) measured with 31P-MRS. Subcutaneous (SAT) abdominal, visceral (VAT), epicardial and pancreatic fat were also evaluated. The primary efficacy endpoint was the change in epicardial fat volume between EMPA and placebo from baseline to 12 weeks. Secondary endpoints were the differences in PCr/ATP ratio, myocardial, liver and pancreatic fat content, SAT and VAT between groups at 12 weeks. Results In mice fed HFHS, EMPA significantly improved glucose tolerance and increased blood ketone bodies (KB) and β-hydroxybutyrate levels (p < 0.05) compared to placebo. Mice fed HFHS had increased myocardial and liver fat content compared to standard diet mice. EMPA significantly attenuated liver fat content by 55%, (p < 0.001) but had no effect on myocardial fat. In the human study, all the 56 patients had normal LV function with mean LVEF = 63.4 ± 7.9%. Compared to placebo, T2D patients treated with EMPA significantly lost weight (− 2.6 kg [− 1.2; − 3.7]) and improved their HbA1c by 0.88 ± 0.74%. Hematocrit and EPO levels were significantly increased in the EMPA group compared to placebo (p < 0.0001, p = 0.041). EMPA significantly increased glycosuria and plasma KB levels compared to placebo (p < 0.0001, p = 0.012, respectively), and significantly reduced liver fat content (− 27 ± 23 vs. − 2 ± 24%, p = 0.0005) and visceral fat (− 7.8% [− 15.3; − 5.6] vs. − 0.1% [− 1.1;6.5], p = 0.043), but had no effect on myocardial or epicardial fat. At 12 weeks, no significant change was observed in the myocardial PCr/ATP (p = 0.57 between groups). Conclusions EMPA effectively reduced liver fat in mice and humans without changing epicardial, myocardial fat or myocardial energetics, rebutting the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors. Trial registration NCT, NCT03118336. Registered 18 April 2017, https://clinicaltrials.gov/ct2/show/NCT03118336
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-021-01237-2.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-021-01237-2
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2021-03-01
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology 31P-MRS SGLT2 inhibitors Epicardial adipose tissue Ectopic fat Myocardial energetics Pcr/atp MRI
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Epicardial adipose tissue volume and myocardial ischemia in asymptomatic people living with diabetes: a cross-sectional study

SGLT2 inhibition and adipose tissue metabolism: current outlook and perspectives

Epicardial adipose tissue and severe Coronavirus Disease 19

SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart

Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus

Epicardial adipose tissue volume and coronary calcification among people living with diabetes: a cross-sectional study

Epicardial and liver fat implications in albuminuria: a retrospective study

Epicardial adipose tissue predicts incident cardiovascular disease and mortality in patients with type 2 diabetes

The effect of dapagliflozin treatment on epicardial adipose tissue volume

Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study

Similar Documents

Epicardial adipose tissue volume and myocardial ischemia in asymptomatic people living with diabetes: a cross-sectional study

SGLT2 inhibition and adipose tissue metabolism: current outlook and perspectives

Epicardial adipose tissue and severe Coronavirus Disease 19

SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart

Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus

Epicardial adipose tissue volume and coronary calcification among people living with diabetes: a cross-sectional study

Epicardial and liver fat implications in albuminuria: a retrospective study

Epicardial adipose tissue predicts incident cardiovascular disease and mortality in patients with type 2 diabetes

The effect of dapagliflozin treatment on epicardial adipose tissue volume

Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study