Grant: Team Grant: Diabetes Mechanisms and Translational Solutions - LOI - General

Colchicine is an anti-inflammatory medication and is one of the oldest remedies still commonly in use today as a treatment for gout. Recently, we have shown in the COLCOT study that colchicine reduced the risk of cardiovascular events in patients with a recent heart attack. In the precision medicine study of COLCOT, we found genetic biomarkers that may determine which patients benefit more from colchicine, and which patients are at risk of gastrointestinal discomfort with colchicine. Our team will soon launch a new study, COLCOT-T2D, to determine if colchicine will reduce major cardiovascular events in 10,000 patients with type 2 diabetes. The present Team Grant application proposes a precision medicine study using data collected from participants to COLCOT-T2D. We will collect DNA and blood samples and we will use the techniques of genomics (to measure DNA variation) and proteomics (variation in protein levels), we will measure drug metabolites in circulation in the blood of patients, and we will use clinical information including the patients' medical history and complications of diabetes. The study will allow for the validation of the COLCOT findings to determine which patients may benefit more or less from colchicine. We will also study the role of sex and gender on diabetes and drug response and on study participation. Precision medicine has the potential to identify who benefits more from diabetes medication. Such risk stratification is particularly important as there are increasing therapeutic options for patients with diabetes, with equipoise between several treatment options. Given the huge burden of diabetes, the vast choice of therapies, and the potential costs of treatment, there are critical societal and economic needs to identify which patients should be treated with which drug for optimal outcome. Our Team Grant will provide valuable evidence toward better prevention strategies and treatment options for patients with diabetes.