A study at Vall d'Hebron has identified that 60% of patients with controlled type 2 diabetes have insulin resistance in the myocardium, i.e. their heart muscle cells do not respond to this hormone to incorporate glucose into the cells. For the first time, it has been possible to determine in vivo insulin resistance in the myocardium and to observe that these patients also have structural changes in the heart and calcifications in the coronary arteries that make them more susceptible to cardiovascular complications. These are the results of a pilot clinical trial carried out by the Molecular Medical Imaging group, led by Dr. J Raul Herance and Dr. Santiago Aguadé, and the Diabetes and Metabolism group led by Dr. Rafael Simó.

Type 2 diabetes affects more than 450 million people worldwide and its incidence is increasing every year. It is a disease characterized by high blood glucose levels caused by the dysfunction of the cells that produce insulin in the pancreas and by the lack of response to insulin in the cells of key organs such as the muscle or the heart. Insulin is a hormone that is produced when glucose is present in the blood and allows it to enter the cells so that they can obtain energy. If the cells do not respond to insulin, they are resistant to this hormone and they will not be able to incorporate glucose into their interior. Therefore, it generates serious physiological dysfunctions in these cells.

The study carried out by Vall d'Hebron researchers and published in the Journal of Personalized Medicine aimed to study insulin resistance in one of the organs most commonly affected in type 2 diabetes, the heart, and its relationship with cardiovascular risk. Specifically, they were able to quantify insulin sensitivity or resistance in the myocardium using an innovative methodology they have developed. This involves positron emission tomography/computed tomography (PET/CT), which in this case uses ¹⁸F-FDG to study glucose metabolism, incorporated into a hyperinsulinemic-euglycemic clamp. This allows assessment of myocardial glucose uptake during fasting (low insulin stimulus) and after maximal insulin stimulation of glucose uptake.

The study found two subtypes of patients depending on whether or not glucose was taken up by myocardial cells. Specifically, 40% of patients were insulin-sensitive and, in contrast, 60% had insulin-resistant myocardium.

The study identified, for the first time, that the subgroup of patients with insulin-resistant myocardium had structural changes in the heart, as well as an increased number of calcifications in the coronary arteries. "Calcifications in the coronary arteries are one of the main risk factors for cardiovascular complications, which is why we believe that patients with the myocardial insulin resistance phenotype would be more likely to suffer this type of event," says Dr. J Raul Herance, head of the Molecular Medical Imaging group at Vall d'Hebron Research. Identifying those people who have a higher risk of cardiovascular pathologies, the main cause of mortality in patients with type 2 diabetes, will allow more appropriate screening and more exhaustive follow-up to try to prevent these complications.

Currently, and with the aim of transferring these results to clinical practice, researchers are working to find biomarkers that are accessible, safe and minimally invasive to identify and monitor patients with insulin resistance in the myocardium, as well as its causes.

The study has been possible thanks to funding from the Instituto de Salud Carlos III and the European Regional Development Fund (PI20/01588; PI16/02064) and AGAUR (2017SGR1303).