Research Description
HFpEF and obesity represent two intermingling epidemics driving perhaps the greatest unmet health problem in cardiovascular medicine in the 21st century. Recent evidence has changed our thinking about the contribution of obesity to HFpEF: from being a mechanical cause of exercise intolerance, to the primary, direct cause of HFpEF. Increased visceral and epicardial adiposity promotes inflammation, induces cardiac fibrosis and limits ventricular distensibility, all of which are hallmarks of HFpEF and contribute to its pathophysiology. Increased adiposity in the liver is associated with elevated mortality in these patients. HFpEF also has disproportionally increased adipose infiltration in the muscle and worse skeletal muscle function compared with other forms of HF. Both cardiac and skeletal muscle abnormalities contribute to severe exercise intolerance in HFpEF. We have previously demonstrated that SGLT2 inhibition reduce body weight, cut the volume of epicardial adipose tissue and improves cardiac function in HF with reduced ejection fraction (HFrEF). Given that adiposity plays even a more important role in the pathophysiology of HFpEF compared with HFrEF, a positive effect with SGLT1-2i is also expected in patients with preserved EF. Not much evidence is available. To address this knowledge gap, we have designed the SOTA-P-CARDIA CLINICAL TRIAL (NCT05562063) in HFpEF. Our hypothesis is that SGLT1-2i with sotagliflozin reduces adiposity, while improving cardiac and skeletal muscle and ultimately, exercise tolerance. We will study the effect of SGLT1-2i on cardiac and skeletal muscle structure and function, epicardial, visceral and liver adiposity, systemic inflammation and exercise capacity.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?My research project will focus on the study of SGLT2 inhibitors, a novel group of antidiabetic drugs that work by preventing the kidneys from reabsorbing glucose and releasing it into the blood. There is an increasing recognition of potential additional benefits beyond its ability to help manage blood glucose: SGLT2 inhibitors have been shown to protect heart and kidney function, reduce body weight and mitigate inflammation, thus improving overall cardiometabolic health. We are currently investigating these broader cardiometabolic effects, whether this weight reduction is attributed to a particular effect on body fat and examining how various fat deposits in the body respond to SGLT2 inhibitors.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Having diabetes can be like a puzzle where pieces connect to other health concerns. Diabetes frequently goes hand in hand with obesity, kidney problems and heart disease. Sadly, cardiovascular disease is the leading cause of serious complications and even mortality in diabetic patients. Newer antidiabetic SGLT2 inhibitors exhibit additional benefits beyond just keeping your blood glucose in check – it might also make your heart and arteries healthier, protect your kidney function and reduce body fat. By addressing multiple aspects of your health, we expect to make a real difference in preventing future complications.
Why important for you, personally, to become involved in diabetes research? What role will this award play?Patients with cardiovascular diseases frequently have diabetes and the presence of diabetes significantly worsens the prognosis. At the same time, patients with diabetes have cardiovascular disease as the leading cause of death and serious complications. I am fascinated about studying an antidiabetic medication that has demonstrated a reduction in cardiovascular events and provides cardiovascular benefits beyond glucose control. This promising aspect suggests a broader impact on cardiometabolic health, and I am eager to delve into the research to better understand the mechanisms behind the cardiovascular benefits of the SGLT2 inhibitors. Furthermore, this opportunity will help me to expand my work, forge new partnerships and collaborate with other researchers in the field of diabetes and cardio-metabolism.
In what direction do you see the future of diabetes research going?The future of diabetes holds great promise, particularly as we shift from a glucose-centric approach to a more comprehensive perspective on metabolic health. We are currently studying medications that go beyond mere glycemic control, aiming to improve overall metabolic health. This shift in paradigm reflects a broader understanding of diabetes, cardiovascular disease and obesity as multifaceted, interconnected conditions with common inflammatory, adipogenic and metabolic implications.