The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator

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The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator. / Thirumathyam, Roopameera; Richter, Erik Arne; van Hall, Gerrit; Holst, Jens Juul; Fenger, Mogens; Gøtze, Jens P.; Dixen, Ulrik; Vejlstrup, Niels; Madsbad, Sten; Madsen, Per Lav; Jørgensen, Nils Bruun.

I: Cardiovascular Diabetology, Bind 23, Nr. 1, 13, 2024, s. 1-13.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Thirumathyam, R, Richter, EA, van Hall, G, Holst, JJ, Fenger, M, Gøtze, JP, Dixen, U, Vejlstrup, N, Madsbad, S, Madsen, PL & Jørgensen, NB 2024, 'The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator', Cardiovascular Diabetology, bind 23, nr. 1, 13, s. 1-13. https://doi.org/10.1186/s12933-023-02094-x

APA

Thirumathyam, R., Richter, E. A., van Hall, G., Holst, J. J., Fenger, M., Gøtze, J. P., Dixen, U., Vejlstrup, N., Madsbad, S., Madsen, P. L., & Jørgensen, N. B. (2024). The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator. Cardiovascular Diabetology, 23(1), 1-13. [13]. https://doi.org/10.1186/s12933-023-02094-x

Vancouver

Thirumathyam R, Richter EA, van Hall G, Holst JJ, Fenger M, Gøtze JP o.a. The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator. Cardiovascular Diabetology. 2024;23(1):1-13. 13. https://doi.org/10.1186/s12933-023-02094-x

Author

Thirumathyam, Roopameera ; Richter, Erik Arne ; van Hall, Gerrit ; Holst, Jens Juul ; Fenger, Mogens ; Gøtze, Jens P. ; Dixen, Ulrik ; Vejlstrup, Niels ; Madsbad, Sten ; Madsen, Per Lav ; Jørgensen, Nils Bruun. / The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator. I: Cardiovascular Diabetology. 2024 ; Bind 23, Nr. 1. s. 1-13.

Bibtex

@article{a4800d6edf024e98b76012a772b04617,
title = "The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator",
abstract = "Background: Metabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D. Methods: In a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m2, C-peptide > 500 pM. Treatments lasted 5 weeks and were preceded by 3-week washouts (WO). At the end of treatments and washouts, cardiac diastolic function was determined with magnetic resonance imaging from left ventricle early peak-filling rate and left atrial passive emptying fraction (primary and key secondary endpoints); systolic function from left ventricle ejection fraction (secondary endpoint). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E–I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students{\textquoteright} t-test or Wilcoxon signed rank test as appropriate. Results: Glucose concentrations were similar, fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: −51 ± 22 ml/s (p < 0.05); ΔE: −33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs ΔE)) and systolic function (ΔT: -3 ± 1% (p < 0.05); ΔE: −3 ± 1% (p < 0.05): ΔI: 1 ± 2 (ns, ns vs ΔE)) under chronotropic stress during empagliflozin compared to insulin treatment. Conclusions: Despite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes. Trial registration: EudraCT 2017-002101-35, August 2017.",
keywords = "Cardiac function, Hyperinsulinemia, Metabolism, Sodium-glucose linked transporter 2 inhibition, Type 2 diabetes",
author = "Roopameera Thirumathyam and Richter, {Erik Arne} and {van Hall}, Gerrit and Holst, {Jens Juul} and Mogens Fenger and G{\o}tze, {Jens P.} and Ulrik Dixen and Niels Vejlstrup and Sten Madsbad and Madsen, {Per Lav} and J{\o}rgensen, {Nils Bruun}",
note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",
year = "2024",
doi = "10.1186/s12933-023-02094-x",
language = "English",
volume = "23",
pages = "1--13",
journal = "Cardiovascular Diabetology",
issn = "1475-2840",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator

AU - Thirumathyam, Roopameera

AU - Richter, Erik Arne

AU - van Hall, Gerrit

AU - Holst, Jens Juul

AU - Fenger, Mogens

AU - Gøtze, Jens P.

AU - Dixen, Ulrik

AU - Vejlstrup, Niels

AU - Madsbad, Sten

AU - Madsen, Per Lav

AU - Jørgensen, Nils Bruun

N1 - Publisher Copyright: © 2024, The Author(s).

PY - 2024

Y1 - 2024

N2 - Background: Metabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D. Methods: In a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m2, C-peptide > 500 pM. Treatments lasted 5 weeks and were preceded by 3-week washouts (WO). At the end of treatments and washouts, cardiac diastolic function was determined with magnetic resonance imaging from left ventricle early peak-filling rate and left atrial passive emptying fraction (primary and key secondary endpoints); systolic function from left ventricle ejection fraction (secondary endpoint). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E–I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students’ t-test or Wilcoxon signed rank test as appropriate. Results: Glucose concentrations were similar, fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: −51 ± 22 ml/s (p < 0.05); ΔE: −33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs ΔE)) and systolic function (ΔT: -3 ± 1% (p < 0.05); ΔE: −3 ± 1% (p < 0.05): ΔI: 1 ± 2 (ns, ns vs ΔE)) under chronotropic stress during empagliflozin compared to insulin treatment. Conclusions: Despite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes. Trial registration: EudraCT 2017-002101-35, August 2017.

AB - Background: Metabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D. Methods: In a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m2, C-peptide > 500 pM. Treatments lasted 5 weeks and were preceded by 3-week washouts (WO). At the end of treatments and washouts, cardiac diastolic function was determined with magnetic resonance imaging from left ventricle early peak-filling rate and left atrial passive emptying fraction (primary and key secondary endpoints); systolic function from left ventricle ejection fraction (secondary endpoint). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E–I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students’ t-test or Wilcoxon signed rank test as appropriate. Results: Glucose concentrations were similar, fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: −51 ± 22 ml/s (p < 0.05); ΔE: −33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs ΔE)) and systolic function (ΔT: -3 ± 1% (p < 0.05); ΔE: −3 ± 1% (p < 0.05): ΔI: 1 ± 2 (ns, ns vs ΔE)) under chronotropic stress during empagliflozin compared to insulin treatment. Conclusions: Despite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes. Trial registration: EudraCT 2017-002101-35, August 2017.

KW - Cardiac function

KW - Hyperinsulinemia

KW - Metabolism

KW - Sodium-glucose linked transporter 2 inhibition

KW - Type 2 diabetes

U2 - 10.1186/s12933-023-02094-x

DO - 10.1186/s12933-023-02094-x

M3 - Journal article

C2 - 38184612

AN - SCOPUS:85181464935

VL - 23

SP - 1

EP - 13

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

SN - 1475-2840

IS - 1

M1 - 13

ER -

ID: 379659990