IMPROVE-DiCE: Study to Evaluate Effect of IMB-1018972 on Cardiac Energetics in T2DM & Obesity (Pt...
Type 2 DiabetesDiabetic Cardiomyopathies1 moreThe purpose of this study is to assess the activity of IMB-1018972 on cardiac energetic reserve at rest and during stress and to assess safety and tolerability
Efficacy of Trimetazidine in Diabetic Patients
Diabetes MellitusType 21 moreSubclinical diastolic dysfunction represents the early phase of diabetic cardiomyopathy and is a common complication among type 2 diabetic patients that increases mortality rate among those patients and can progress to heart failure with preserved ejection fraction. Trimetazidine is an anti-ischemic agent widely used in the treatment of coronary artery disease and it has positive effects on energy metabolism in heart failure. Therefore, we hypothesized that trimetazidine may have potential benefit on the amelioration of the inflammatory insult and improving the clinical outcomes in patients with diabetic cardiomyopathy especially if applied in the early stages.
The DAPA-MEMRI Trial
Heart FailureDiabetic CardiomyopathiesDiabetes mellitus is among the top 10 causes of death worldwide with an increasing incidence. Patients with diabetes are at risk of developing heart failure which is characterised by significant changes in the heart muscle including scarring and thickening. Contraction of the heart involves movement of calcium across the heart muscle and disruption of this process is an early change seen in heart failure. Recently, a drug therapy (SGLT2 inhibitor therapy) in patients with diabetes was shown to benefit patients with heart failure but the mechanisms of benefit are unknown. Our hypothesis is that calcium handling is altered in patients with either type 2 diabetes mellitus (T2DM) or heart failure and that SGLT2 inhibitors can improve this in heart failure irrespective of the presence of T2DM. Scanning the heart using magnetic resonance imaging (MRI) enables detailed assessment of its structure and function by using a new contrast 'dye' containing manganese that has shown advantages over traditional contrast. We plan to further test this new dye as it has the potential to track and quantify improvements in heart function over time and detect changes in calcium handling in the heart muscle, making it an ideal measure to identify the mechanisms of benefit from SGLT2 inhibitor therapy. The study population will comprise patients with heart failure with and without type 2 diabetes, patients with type 2 diabetes without heart failure and healthy volunteers. Baseline comparisons will be made between the four groups before progressing to the randomised controlled trial with heart failure patients only. Patients will have a clinical assessment and blood tests, electrocardiogram, echocardiogram and MRI of the heart at each visit. If successful, this study will give us significant insights into mechanisms of action of SGLT2 inhibitors in heart failure and will enable us to tailor specific treatments in heart failure patients.
Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
Diabetic CardiomyopathiesThis is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure.
Mitochondrial Substrate Utilization in the Diabetic Human Heart
Heart FailureType2diabetes3 moreDiabetes can lead to heart failure independently, but the underlying causes remain incompletely understood. The main aim of this study is to identify differential regulation of mitochondrial substrate utilization and complex activity in heart failure and type 2 diabetes mellitus (T2DM). For this, we will conduct a prospective, observational study to examine myocardial mitochondrial oxidative function and related metabolic parameters, gene expression, histological markers, and inflammation in cardiac tissue from patients with heart failure or patients after heart transplantation. We will further assess cardiac function using cardiac magnetic resonance imaging with and without stress protocols and magnetic resonance spectroscopy. Glycemic control/T2DM will be characterized by oral glucose tolerance tests. The results of this project will help to better understand the cellular mechanisms of the development of diabetic cardiomyopathy and contribute to the development of early diagnostic, as well as therapeutic approaches for the prevention and treatment of diabetic cardiomyopathy.
Diabetic Cardiomyopathy and Heart Failure
Diabetic CardiomyopathiesHeart FailureThis study will demonstrate the beneficial effects of ketone bodies in type 1 diabetes (T1D) patients and will have significant translational applications to prevent serious metabolic conditions such as T1D induced diabetic cardiomyopathy (DCM).
PBMC as Biomarkers of Diabetic Cardiomyopathy
Type 2 DiabetesMetabolic Syndrome2 moreType 2 diabetes (T2D), especially when associated with metabolic syndrome (MS) is at high risk to develop heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF), and the specific impact of T2D+MS in cardiac function impairment is usually known as "diabetic cardiomyopathy" (DC). Cardiac remodelling (ie hypertrophy) and subtle myocardial dysfunction are highly prevalent in T2D+MS but not specific enough to predict further HFpEF or HFmrEF. Also, current biomarkers can identify but do not predict HFpEF or HFmrEF in T2D patients; Furthermore, specific biomarkers are needed. Peripheral blood mononuclear cells (PBMC) obtained from a peripheral blood sample can provide insights from calcic and inflammatory pathways, and may identify more specific molecular signatures shared between T2D+MS and HFpEF.
Prevalence and Determinants of Subclinical Cardiovascular Dysfunction in Adults With Type 2 Diabetes...
Diabetes MellitusType 21 moreBackground: Heart failure is a major cause of morbidity and mortality in diabetes mellitus, but its pathophysiology is poorly understood. Aim: To determine the prevalence and determinants of subclinical cardiovascular dysfunction in adults with type 2 diabetes (T2D). Plan: 518 asymptomatic adults (aged 18-75 years) with T2D will undergo comprehensive evaluation of cardiac structure and function using cardiac MRI (CMR) and spectroscopy, echocardiography, CT coronary calcium scoring, exercise tolerance testing and blood sampling. 75 controls will undergo the same evaluation. Primary hypothesis: myocardial steatosis is an independent predictor of left ventricular global longitudinal strain. Secondary hypotheses: will assess whether CMR is more sensitive to detect early cardiac dysfunction than echocardiography and BNP, and whether cardiac dysfunction is related to peak oxygen consumption. Expected value of results: This study will reveal the prevalence and determinants of cardiac dysfunction in T2D, and could provide targets for novel therapies.
CARdiomyopathy in Type 2 DIAbetes Mellitus
CardiomyopathyDiabeticThe objective of the CARDIATEAM clinical study is to assess the uniqueness of diabetic cardiomyopathy (DCM) relative to other forms of cardiomyopathy using unsupervised clustering approaches based on deep phenotyping (clinical, imaging and biological) information.
Reversal of Obese/Diabetic Cardiomyopathy After Gastric Bypass Surgery
CardiomyopathyThe overall purpose of this study is to evaluate the effect of gastric bypass surgery-induced weight loss on the heart's function and on fat deposits in the heart muscle.