Empagliflozin's Ameliorating Effect on Plasma Triglycerides: Association with Endothelial Function Recovery in Diabetic Patients with Coronary Artery Disease

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Aim: So far, the mechanisms behind the cardiovascular benefits of sodium/glucose cotransporter 2 (SGLT2) inhibitors have not been fully clarified.

Methods: In order to evaluate the effects of SGLT2 inhibitors on systemic hemodynamics, glucose metabolism, lipid profile, and endothelial function, 50 diabetic patients with established coronary artery disease (CAD) were included in this analysis and were given empagliflozin 10 mg/d. Cookie meal testing (carbohydrates: 75 g, fats: 28.5 g), endothelial function testing using flow-mediated dilatation (FMD), and body composition evaluation were performed before and after six months of treatment. Changes in %FMD between the treatment periods and its association with metabolic biomarkers were evaluated.

Results: After six months of treatment, the body weight and body fat percentage decreased significantly, while the body muscle percentage increased significantly. The hemoglobin A1c level and fasting and postprandial plasma glucose levels were significantly decreased with treatment. Postprandial insulin secretion was also significantly suppressed and the insulin resistance index was significantly decreased. Furthermore, the fasting and postprandial triglyceride (TG) levels decreased significantly, while total ketone bodies increased significantly after the six-month treatment. While the plasma brain natriuretic peptide level was not changed, the C-reactive protein level was decreased and FMD was significantly improved after the six-month treatment. Multiple regression analysis showed that the strongest predictive factor of FMD improvement is change in the plasma TG levels.

Conclusion: SGLT2 inhibitors improve multiple metabolic parameters. Of these, a reduction in plasma TGs was strongly associated with endothelial function recovery in diabetic patients with CAD, and this reduction may be related to the cardiovascular benefits of SGLT2 inhibitors.

Related collections

Most cited references 32

Record: found
Abstract: found
Article: not found

Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications.

Hiddo J.L. Heerspink, Bruce A. Perkins, David H. Fitchett … (2016)

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and natriuretic effects contributing to plasma volume contraction, and decreases in systolic and diastolic blood pressures by 4 to 6 and 1 to 2 mm Hg, respectively, which may underlie cardiovascular and kidney benefits. SGLT2 inhibition also is associated with an acute, dose-dependent reduction in estimated glomerular filtration rate by ≈5 mL·min(-1)·1.73 m(-2) and ≈30% to 40% reduction in albuminuria. These effects mirror preclinical observations suggesting that proximal tubular natriuresis activates renal tubuloglomerular feedback through increased macula densa sodium and chloride delivery, leading to afferent vasoconstriction. On the basis of reduced glomerular filtration, glycosuric and weight loss effects are attenuated in patients with chronic kidney disease (estimated glomerular filtration rate 30% reductions in cardiovascular mortality, overall mortality, and heart failure hospitalizations associated with empagliflozin, even though, by design, the hemoglobin A1c difference between the randomized groups was marginal. Aside from an increased risk of mycotic genital infections, empagliflozin-treated patients had fewer serious adverse events, including a lower risk of acute kidney injury. In light of the EMPA-REG OUTCOME results, some diabetes clinical practice guidelines now recommend that SGLT2 inhibitors with proven cardiovascular benefit be prioritized in patients with type 2 diabetes mellitus who have not achieved glycemic targets and who have prevalent atherosclerotic cardiovascular disease. With additional cardiorenal protection trials underway, sodium-related physiological effects of SGLT2 inhibitors and clinical correlates of natriuresis, such as the impact on blood pressure, heart failure, kidney protection, and mortality, will be a major management focus.

0 comments Cited 470 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

D S Celermajer, K Sorensen, V Gooch … (1992)

Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.

0 comments Cited 302 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Close relation of endothelial function in the human coronary and peripheral circulations.

T. Anderson, A Uehata, M Gerhard … (1995)

The relation between endothelium-dependent vasodilator function in the brachial and coronary arteries was determined in the same subjects. Coronary artery endothelial dysfunction precedes the development of overt atherosclerosis and is important in its pathogenesis. A noninvasive assessment of endothelial function in a peripheral conduit vessel, the brachial artery, was recently described, but the relation between brachial artery function and coronary artery vasodilator function has not been explored. In 50 patients referred to the catheterization laboratory for the evaluation of coronary artery disease (mean age +/- SD 56 +/- 10 years), the coronary vasomotor response to serial intracoronary infusions of the endothelium-dependent agonist acetylcholine (10(-8) to 10(-6) mol/liter), was studied. Endothelium-dependent vasodilation was also assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia. Patients with coronary artery endothelial dysfunction manifested as vasoconstriction in response to acetylcholine had significantly impaired flow-mediated vasodilation in the brachial artery compared with that of patients with normal coronary endothelial function (4.8 +/- 5.5% vs. 10.8 +/- 7.6%, p < 0.01). Patients with coronary artery disease also had an attenuated brachial artery vasodilator response compared with that of patients with angiographically smooth coronary arteries (4.5 +/- 4.6% vs. 9.7 +/- 8.1%, p < 0.02). By multivariate analysis, the strongest predictors of reduced brachial dilator responses to flow were baseline brachial artery diameter (p < 0.001), coronary endothelial dysfunction (p = 0.003), the presence of coronary artery disease (p = 0.007) and cigarette smoking (p = 0.016). The brachial artery vasodilator response to sublingual nitroglycerin was independent of coronary endothelial responses or the presence of coronary artery disease. The positive predictive value of abnormal brachial dilation ( < 3%) in predicting coronary endothelial dysfunction is 95%. This study demonstrated a close relation between coronary artery endothelium-dependent vasomotor responses to acetylcholine and flow-mediated vasodilation in the brachial artery. This noninvasive method may become a useful surrogate in assessing the predisposition to atherosclerosis in patients with cardiac risk factors.

0 comments Cited 249 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Atheroscler Thromb

Journal ID (iso-abbrev): J. Atheroscler. Thromb

Journal ID (publisher-id): jat

Journal ID (hwp): jat

Title: Journal of Atherosclerosis and Thrombosis

Publisher: Japan Atherosclerosis Society

ISSN (Print): 1340-3478

ISSN (Electronic): 1880-3873

Publication date (Print): 1 July 2020

Volume: 27

Issue: 7

Pages: 644-656

Affiliations

[1 ] Hyogo Prefectural Himeji Cardiovascular Center, Division of Cardiovascular Medicine, Hyogo, Japan

[2 ] Hyogo Prefectural Himeji Cardiovascular Center, Division of Diabetes and Endocrinology, Hyogo, Japan

Author notes

Address for correspondence: Takahiro Sawada, Hyogo Prefectural Himeji Cardiovascular Center, Division of Cardiovascular Medicine Department of Internal Medicine 520, Saisho-Kou, Himeji, Hyogo, 670-0981, Japan E-mail: taktak319@ 123456yahoo.co.jp

Article

DOI: 10.5551/jat.50807

PMC ID: 7406405

PubMed ID: 31631099

SO-VID: eeb85054-103d-4cd3-b774-9625c57d783d

License:

This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License. http://creativecommons.org/licenses/by-nc-sa/3.0/

History

Date received : 13 May 2019

Date accepted : 11 September 2019

Page count

Figures: 1, Tables: 4, References: 41, Pages: 13

Comments

Comment on this article

scite_

Cited by 11

See all cited by

Most referenced authors 666

See all reference authors

Empagliflozin's Ameliorating Effect on Plasma Triglycerides: Association with Endothelial Function Recovery in Diabetic Patients with Coronary Artery Disease

Read this article at

Abstract

Related collections

Probing cerebral hemodynamics with BOLD fMRI

Most cited references 32

Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications.

Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

Close relation of endothelial function in the human coronary and peripheral circulations.

Author and article information

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 108

Cited by 11

Most referenced authors 666