Sex Differences in Coronary Microvascular Function in Individuals With Type 2 Diabetes

Abstract Background Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces risk of cardiovascular death and heart failure but the underlying mechanisms remain poorly understood. It has been suggested that a shift in fuel source in the myocardium from glucose and free fatty acids to the more energy efficient ketogenesis reduces oxidative stress involved in coronary microvascular damage, leading to improved coronary microvascular function. Purpose To test the hypothesis that treatment with the SGLT2 inhibitor empagliflozin improves non-endothelial dependent coronary microvascular function. Methods We included 26 patients with type 2 diabetes in a double blinded, placebo-controlled cross-over study. Participants were treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was change in coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Secondary endpoints were change in echocardiographic parameters of cardiac systolic function and 184 cardiovascular protein biomarkers. Results Nineteen patients completed both study periods according to protocol. There was a significant weight loss and reduction in Hba1c after empagliflozin treatment (table). We found no improvement in CFVR and parameters of cardiac systolic function. We observed a general tendency of reduction in level of cardiovascular biomarkers after empagliflozin treatment (figure) with significant difference between empagliflozin and placebo for 27 proteins, including IL18, ST2, YKL40, ACE2 and leptin. Conclusions Despite a significant weight loss and reduction in Hba1c after empagliflozin treatment, we found no effect on non-endothelial dependent coronary microvascular function in patients with type 2 diabetes mellitus. Improvement in multiple biomarkers may indicate underlying mechanisms but need confirmation in larger studies. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Council for Independent Research Table 1. Change in outcome parameters Figure 1. Change in biomarker levels

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Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes – a randomized, single-blinded, cross-over pilot study

Cardiovascular Diabetology ◽

10.1186/s12933-015-0206-3 ◽

2015 ◽

Vol 14 (1) ◽

Cited By ~ 30

Author(s):

Rebekka Faber ◽

Mette Zander ◽

Adam Pena ◽

Marie M Michelsen ◽

Naja D Mygind ◽

...

Keyword(s):

Type 2 Diabetes ◽

Pilot Study ◽

Microvascular Function ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Coronary Microvascular Function

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Mineralocorticoid Receptor Blockade Improves Coronary Microvascular Function in Individuals With Type 2 Diabetes

Diabetes ◽

10.2337/db14-0670 ◽

2014 ◽

Vol 64 (1) ◽

pp. 236-242 ◽

Cited By ~ 76

Author(s):

Rajesh Garg ◽

Ajay D. Rao ◽

Maria Baimas-George ◽

Shelley Hurwitz ◽

Courtney Foster ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mineralocorticoid Receptor ◽

Microvascular Function ◽

Receptor Blockade ◽

Coronary Microvascular Function ◽

Mineralocorticoid Receptor Blockade

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Coronary microvascular function in patients with type 2 diabetes mellitus

EuroIntervention ◽

10.4244/eijy15m03_09 ◽

2016 ◽

Vol 11 (10) ◽

pp. 1111-1117 ◽

Cited By ~ 3

Author(s):

Melissa Leung ◽

Dominic Y. Leung

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Microvascular Function ◽

Coronary Microvascular Function

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Sex Differences in Coronary Artery Disease Patients With and in Those Without Type 2 Diabetes

Diabetes ◽

10.2337/db18-1490-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1490-P

Author(s):

CHRISTOPH H. SAELY ◽

ALEXANDER VONBANK ◽

CHRISTINE HEINZLE ◽

DANIELA ZANOLIN ◽

BARBARA LARCHER ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Sex Differences ◽

Coronary Artery ◽

Artery Disease

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Non‐invasive assessment of temporal changes in myocardial microvascular function in persons with type 2 diabetes and healthy controls

Diabetic Medicine ◽

10.1111/dme.14517 ◽

2021 ◽

Author(s):

Ida K. B. Rasmussen ◽

Philip Hasbak ◽

Bernt J. Scholten ◽

Jens C. Laursen ◽

Emilie H. Zobel ◽

...

Keyword(s):

Type 2 Diabetes ◽

Temporal Changes ◽

Microvascular Function ◽

Healthy Controls ◽

Non Invasive

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Are there sex differences in the effect of type 2 diabetes in the incidence and outcomes of myocardial infarction? A matched-pair analysis using hospital discharge data

Cardiovascular Diabetology ◽

10.1186/s12933-021-01273-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Ana Lopez-de-Andres ◽

Rodrigo Jimenez-Garcia ◽

Valentin Hernández-Barrera ◽

Jose M. de Miguel-Yanes ◽

Romana Albaladejo-Vicente ◽

...

Keyword(s):

Myocardial Infarction ◽

Type 2 Diabetes ◽

Sex Differences ◽

Propensity Score ◽

Propensity Score Matching ◽

Hospital Discharge ◽

St Elevation Myocardial Infarction ◽

Men And Women ◽

St Elevation

Abstract Background To analyze incidence, use of therapeutic procedures, and in-hospital outcomes in patients with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) according to the presence of type 2 diabetes (T2DM) in Spain (2016–2018) and to investigate sex differences. Methods Using the Spanish National Hospital Discharge Database, we estimated the incidence of myocardial infarctions (MI) in men and women with and without T2DM aged ≥ 40 years. We analyzed comorbidity, procedures, and outcomes. We matched each man and woman with T2DM with a non-T2DM man and woman of identical age, MI code, and year of hospitalization. Propensity score matching was used to compare men and women with T2DM. Results MI was coded in 109,759 men and 44,589 women (30.47% with T2DM). The adjusted incidence of STEMI (IRR 2.32; 95% CI 2.28–2.36) and NSTEMI (IRR 2.91; 95% CI 2.88–2.94) was higher in T2DM than non-T2DM patients, with higher IRRs for NSTEMI in both sexes. The incidence of STEMI and NSTEMI was higher in men with T2DM than in women with T2DM. After matching, percutaneous coronary intervention (PCI) was less frequent among T2DM men than non-T2DM men who had STEMI and NSTEMI. Women with T2DM and STEMI less frequently had a code for PCI that matched that of non-T2DM women. In-hospital mortality (IHM) was higher among T2DM women with STEMI and NSTEMI than in matched non-T2DM women. In men, IHM was higher only for NSTEMI. Propensity score matching showed higher use of PCI and coronary artery bypass graft and lower IHM among men with T2DM than women with T2DM for both STEMI and NSTEMI. Conclusions T2DM is associated with a higher incidence of STEMI and NSTEMI in both sexes. Men with T2DM had higher incidence rates of STEMI and NSTEMI than women with T2DM. Having T2DM increased the risk of IHM after STEMI and NSTEMI among women and among men only for NSTEMI. PCI appears to be less frequently used in T2DM patients After STEMI and NSTEMI, women with T2DM less frequently undergo revascularization procedures and have a higher mortality risk than T2DM men.

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