Ignite Creation Date:
2024-05-06 @ 7:46 PM
Last Modification Date:
2024-10-26 @ 3:13 PM
Study NCT ID:
NCT06128096
Status:
RECRUITING
Last Update Posted:
2023-11-24
First Post:
2023-11-07
Brief Title:
The Effect of SGLT-2 Inhibitors on Epicardial Adipose Tissue and Cardiac Function in T2DM Patients With CAD EpiCAD
Sponsor:
Clinical Research Centre Malaysia
Organization:
Clinical Research Centre Malaysia
Study Overview
Official Title:
The Effect of SGLT-2 Inhibitors on Epicardial Adipose Tissue and Cardiac Function in T2DM Patients With CAD EpiCAD
Status:
RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EpiCAD
Brief Summary:
Sodium-glucose contrasporter-2 SGLT-2 inhibitors make up an antidiabetic medication that promotes glycosuria They are known to have an indirect reduction in cardiovascular complications based on a series of in-depth studies However the effect of SGLT-2 inhibitors towards the thickness of epicardial adipose tissue and cardiac function in type 2 diabetes mellitus T2DM with coronary artery disease CAD patients in Malaysia has not yet been fully explored Therefore this study aims to determine the effects in epicardial adipose tissue thickness and its cardiac function in T2DM patients with CAD after the initiation of SGLT-2 inhibitors
Detailed Description:
Type 2 diabetes mellitus T2DM is a chronic metabolic disorder affecting at least 90 of the population with diabetes globally Bhupathiraju Hu 2016 T2DM is a disorder characterized insulin resistance insufficient insulin production and eventual pancreatic beta-cell failure Cantley Ashcroft 2015The global prevalence of T2DM has been increasing steadily with an estimate of 463 million individuals suffering from T2DM in 2019 and the number is projected to increase by 157 in 2030 Saeedi et al 2019 T2DM is also increasing at an alarming rate in Malaysia and as of 2019 Akhtar et al 2022 approximately 35 million 175 Malaysians were diagnosed with T2DM which doubled in number since 1996 83 Zhu et al 2019
Evidently T2DM patients are predisposed to various forms of both short and long-term complication with cardiovascular disease CVD being the main cause of death among T2DM patients Raghavan et al 2019 T2DM has been shown to decrease life expectancy by 10 years with CVD responsible for half of the mortality Einarson et al 2018 Although a close link between T2DM and CVD is established the etiology is complex and remains a significant research topic Obesity traditionally defined as excess body weight and adiposity is closely linked to the pathogenesis of T2DM Obesity associated with T2DM is linked with a cluster of metabolic and biochemical abnormalities with insulin resistance central in promoting these disturbances It could manifest itself in various pathophysiological states which includes hyperglycemia atherogenic dyslipidemia inflammation and endothelial dysfunction Galicia-Garcia et al 2020 These pathological states have been shown to exacerbate the progression of CVD and according to a global systematic review patients with T2DM had a 10 greater risk of coronary artery disease CAD approximately 50 higher risk of developing myocardial infarction MI and stroke and a staggering 112 increased risk for heart failure Einarson et al 2018
The discovery of new pharmacotherapy to reduce complications associated with T2DM has brought global attention to sodium-glucose co-transporter 2 SGLT-2 inhibitors a relatively new anti-diabetic medication SGLT-2 inhibitor exerts its hypoglycemic action by primarily blocking glucose reabsorption in the proximal convoluted tubule of the kidney which subsequently leads to glycosuria This in turn promotes the utilization of lipids for energy production in response to high glucose lost resembling prolonged fasting stateFerrannini et al 2016 Yokono et al 2014 Zaccardi et al 2016 Due to these metabolic changes SGLT-2 inhibitors reportedly induce weight loss due to its ability to reduce visceral and subcutaneous adipose tissues accumulation Bramante et al 2020 Pereira Eriksson 2019 Evidently a clinical trial conducted by Zinman et al 2016 reported remarkable reduction of cardiovascular-related mortality and decreased risk of hospitalization and re-hospitalization for heart failure in T2DM patients receiving SGLT-2 inhibitors In addition one meta-analysis conducted by Zheng et al 2018 also demonstrated that SGLT-2 inhibitors are able to reduce all-cause mortality in T2DM patients with CAD Thus emerging evidence suggested that SGLT-2 inhibitors are capable of decreasing the occurrence of cardiovascular events in T2DM patients and closely linked to their ability to reduce fat content Scheen 2014
As the indirect target of SGLT-2 inhibitors is towards reduction of adiposity adipose tissue measurements were also shown to be an important indicator of SGLT-2 inhibitors effectiveness According to Singh et al 2007 visceral adipose tissue VAT which surrounds the internal organs of body cavities could predict an undesirable metabolic and cardiovascular risk stratification For this reason epicardial adipose tissue EAT a type of visceral fat surrounding the heart supplied by major branches of coronary vessels is increasingly studied to be the measuring point for the efficacy of SGLT-2 inhibitors Sato et al 2018 Yagi et al 2017
EAT originates from splanchnopleuric mesoderm in which embryonically similar to intraabdominal adipose tissue and actively produces numerous cytokines that are essential for metabolic homeostasis Muñoz et al 2014 Physiologically normal EAT distribution is required to provide a protective physiological role to the heart Iacobellis et al 2008 Normal EAT thickness is reported to be between 45mm- 70mm Iacobellis et al 2008 Physiologically normal EAT thickness provides protective metabolic and thermogenic function towards both myocardium and coronary arteries Wu et al 2017 Iacobellis Willens 2009 EAT also produces adipokines a signaling protein that regulates lipid and glucose-insulin metabolism in the heart Talman et al 2014 Wu et al 2017 However excessive EAT depot has been hypothesized to be involved in the pathogenesis and the progression of coronary artery disease with the release of inflammatory mediators which prompt the atherosclerotic process through several paracrine mechanisms Alexopoulos et al 2010 Apart from metabolic disorders there are various determinants that can contribute to EAT thickness including age gender race and ethnicities Lima-Martínez et al 2014 Verma et al 2017 Given that the estimation of cardiovascular risk is significantly relevant with EAT as compared to other visceral fat the SGLT-2 anti-obesity effect on EAT accumulation may serve as a significant cardiovascular predictor in T2DM patients Sato et al 2018 Yagi et al 2017Evidently due its significant metabolic effect SGLT-2 inhibitors have also been shown to reduce the amount of visceral adipose tissue by caloric elimination and thereby reducing EAT in multiple pilot studies Fukuda et al 2017 Braha et al 2019 Yagi et al 2017
Given its anatomical proximity to the heart EAT is now proposed to be more relevant cardiovascular risk estimation than other visceral fat depot with multiple emerging studies have demonstrated that EAT is associated with increased coronary artery calcification Mancio et al 2017 Parallel to this our preliminary study from UMMC cardiology patients indicated that patients with CAD have significantly thicker EAT and positively correlated with BMI Given the emerging role of SGLT-2 inhibitors as treatment for obesity its effect in reducing visceral fat particularly on EAT is increasingly studied But its role specifically in T2DM and how it can be developed as a therapeutic target to reduce CVD risk among our high-risk population in our local clinical setting is less understood Therefore the aim of this study is to investigate the effect of SGLT-2 inhibitors on EAT thickness metabolic outcomes and subsequently cardiac function in T2DM patients
More significantly currently there are no existing studies which report the EAT distribution with other cardiac function parameters among Malaysian and its clinical implication in the local clinical setting Our preliminary study from UMMC cardiology patients also indicated that Malay male have significantly thicker EAT compared to other ethnicities Indeed measures of total body fat and depot-specific adiposity reveal distinct ethnic patterns which may portend different health implications Staiano et al 2013 particularly among multi-ethnics Malaysians In addition the associations between EAT thickness and cardiac function among ethnic-diverse Malaysian T2DM patients receiving SGLT-2 inhibitors are yet to be explored Thus the current study hopes to conclude the link of evidences between EAT and cardiac function in T2DM patient with CAD that were receiving SGLT-2 inhibitors
Evidently T2DM patients are predisposed to various forms of both short and long-term complication with cardiovascular disease CVD being the main cause of death among T2DM patients Raghavan et al 2019 T2DM has been shown to decrease life expectancy by 10 years with CVD responsible for half of the mortality Einarson et al 2018 Although a close link between T2DM and CVD is established the etiology is complex and remains a significant research topic Obesity traditionally defined as excess body weight and adiposity is closely linked to the pathogenesis of T2DM Obesity associated with T2DM is linked with a cluster of metabolic and biochemical abnormalities with insulin resistance central in promoting these disturbances It could manifest itself in various pathophysiological states which includes hyperglycemia atherogenic dyslipidemia inflammation and endothelial dysfunction Galicia-Garcia et al 2020 These pathological states have been shown to exacerbate the progression of CVD and according to a global systematic review patients with T2DM had a 10 greater risk of coronary artery disease CAD approximately 50 higher risk of developing myocardial infarction MI and stroke and a staggering 112 increased risk for heart failure Einarson et al 2018
The discovery of new pharmacotherapy to reduce complications associated with T2DM has brought global attention to sodium-glucose co-transporter 2 SGLT-2 inhibitors a relatively new anti-diabetic medication SGLT-2 inhibitor exerts its hypoglycemic action by primarily blocking glucose reabsorption in the proximal convoluted tubule of the kidney which subsequently leads to glycosuria This in turn promotes the utilization of lipids for energy production in response to high glucose lost resembling prolonged fasting stateFerrannini et al 2016 Yokono et al 2014 Zaccardi et al 2016 Due to these metabolic changes SGLT-2 inhibitors reportedly induce weight loss due to its ability to reduce visceral and subcutaneous adipose tissues accumulation Bramante et al 2020 Pereira Eriksson 2019 Evidently a clinical trial conducted by Zinman et al 2016 reported remarkable reduction of cardiovascular-related mortality and decreased risk of hospitalization and re-hospitalization for heart failure in T2DM patients receiving SGLT-2 inhibitors In addition one meta-analysis conducted by Zheng et al 2018 also demonstrated that SGLT-2 inhibitors are able to reduce all-cause mortality in T2DM patients with CAD Thus emerging evidence suggested that SGLT-2 inhibitors are capable of decreasing the occurrence of cardiovascular events in T2DM patients and closely linked to their ability to reduce fat content Scheen 2014
As the indirect target of SGLT-2 inhibitors is towards reduction of adiposity adipose tissue measurements were also shown to be an important indicator of SGLT-2 inhibitors effectiveness According to Singh et al 2007 visceral adipose tissue VAT which surrounds the internal organs of body cavities could predict an undesirable metabolic and cardiovascular risk stratification For this reason epicardial adipose tissue EAT a type of visceral fat surrounding the heart supplied by major branches of coronary vessels is increasingly studied to be the measuring point for the efficacy of SGLT-2 inhibitors Sato et al 2018 Yagi et al 2017
EAT originates from splanchnopleuric mesoderm in which embryonically similar to intraabdominal adipose tissue and actively produces numerous cytokines that are essential for metabolic homeostasis Muñoz et al 2014 Physiologically normal EAT distribution is required to provide a protective physiological role to the heart Iacobellis et al 2008 Normal EAT thickness is reported to be between 45mm- 70mm Iacobellis et al 2008 Physiologically normal EAT thickness provides protective metabolic and thermogenic function towards both myocardium and coronary arteries Wu et al 2017 Iacobellis Willens 2009 EAT also produces adipokines a signaling protein that regulates lipid and glucose-insulin metabolism in the heart Talman et al 2014 Wu et al 2017 However excessive EAT depot has been hypothesized to be involved in the pathogenesis and the progression of coronary artery disease with the release of inflammatory mediators which prompt the atherosclerotic process through several paracrine mechanisms Alexopoulos et al 2010 Apart from metabolic disorders there are various determinants that can contribute to EAT thickness including age gender race and ethnicities Lima-Martínez et al 2014 Verma et al 2017 Given that the estimation of cardiovascular risk is significantly relevant with EAT as compared to other visceral fat the SGLT-2 anti-obesity effect on EAT accumulation may serve as a significant cardiovascular predictor in T2DM patients Sato et al 2018 Yagi et al 2017Evidently due its significant metabolic effect SGLT-2 inhibitors have also been shown to reduce the amount of visceral adipose tissue by caloric elimination and thereby reducing EAT in multiple pilot studies Fukuda et al 2017 Braha et al 2019 Yagi et al 2017
Given its anatomical proximity to the heart EAT is now proposed to be more relevant cardiovascular risk estimation than other visceral fat depot with multiple emerging studies have demonstrated that EAT is associated with increased coronary artery calcification Mancio et al 2017 Parallel to this our preliminary study from UMMC cardiology patients indicated that patients with CAD have significantly thicker EAT and positively correlated with BMI Given the emerging role of SGLT-2 inhibitors as treatment for obesity its effect in reducing visceral fat particularly on EAT is increasingly studied But its role specifically in T2DM and how it can be developed as a therapeutic target to reduce CVD risk among our high-risk population in our local clinical setting is less understood Therefore the aim of this study is to investigate the effect of SGLT-2 inhibitors on EAT thickness metabolic outcomes and subsequently cardiac function in T2DM patients
More significantly currently there are no existing studies which report the EAT distribution with other cardiac function parameters among Malaysian and its clinical implication in the local clinical setting Our preliminary study from UMMC cardiology patients also indicated that Malay male have significantly thicker EAT compared to other ethnicities Indeed measures of total body fat and depot-specific adiposity reveal distinct ethnic patterns which may portend different health implications Staiano et al 2013 particularly among multi-ethnics Malaysians In addition the associations between EAT thickness and cardiac function among ethnic-diverse Malaysian T2DM patients receiving SGLT-2 inhibitors are yet to be explored Thus the current study hopes to conclude the link of evidences between EAT and cardiac function in T2DM patient with CAD that were receiving SGLT-2 inhibitors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None