Project 467193

Diabetes mellitus is one of the fastest growing public health crises worldwide and accounts for 6% of global prevalence. Chronic high blood glucose, a hallmark of diabetes, stems from impaired insulin release or action, defined as type 1 diabetes (T1D) or type 2 diabetes (T2D) respectively, and can implicate a myriad of complications. Namely, diabetes is one of the leading causes of chronic kidney disease (CKD) and is a prime risk factor for cardiovascular disease (CVD). Until recently, the most effective treatment plan for diabetes-associated CVD and CKD was to monitor blood pressure and glucose. This shifted when sodium-glucose cotransporter 2 (SGLT2) inhibitors revolutionized clinical practice for people with T2D. The anti-diabetic agents act on kidney tubules to block glucose reabsorption, thereby decreasing blood sugar. Intriguingly, SGLT2 inhibitors were also reported to display protective effects against CVD and CKD progression. Since this discovery was serendipitous, the mechanisms that underpin these observed clinical benefits remain unclear. Addedly, as SGLT2 inhibitors have mainly been studied as a T2D therapeutic, the potential benefits in T1D are incompletely understood. In my study, I will advance our current state of knowledge by investigating how SGLT2 inhibitors elicit protection against CKD and CVD risk in T1D patients. To investigate this, I will (1) contrast the expression of molecular markers between T1D patients at high and low risk of CVD or CKD and (2) examine whether intervention modifies the T1D-specific marker profile. By exploring mechanisms of SGLT2 inhibitors, health research can expand treatment options for additional patient groups, including those with T1D, CKD, and CVD, in hopes of reducing diabetes-related complications and mortality.