Pharmaco-epidemiology of diabetes in patients with end-stage kidney disease

Project Summary Diabetes is a leading cause of end-stage kidney disease (ESKD), with about 55-600% of patients on dialysis having diabetes. Glucose management in the context of dialysis is challenging. In recent studies, we reported that patients with diabetes and ESKD have increased risk of severe hypoglycaemia and hyperglycemic crises. However, there is lack of contemporary, nationwide data about how diabetes is managed among these patients, and how each treatment regimen may impact the risks of acute preventable complications (e.g., severe hypoglycaemia and hyperglycemia) and health outcomes (e.g., readmissions, mortality). Similarly, it is unknown whether there is a relationship between specific anti-diabetic agents or insulin formulations and the rates of diabetes crises among minority groups, such as African Americans and Hispanics, which are disproportionately affected by diabetes and ESKD. In this observational study, we propose to use the most comprehensive database of patients with ESKD, the United States Renal Data System to (aim 1) characterize contemporary, real-world patterns of glucose-lowering therapy and diabetes technologies in this population, which may diverge from what is recommended in clinical guideless or explicitly studied in clinical trials. We will also (aim 2) examine health-related outcomes, specifically all-cause and cause-specific (i.e., for hypoglycemia, hyperglycemia) hospitalizations, readmissions, and mortality, as a function of glucose-lowering regimens (e.g., human and analog insulin, GLP-1 receptor agonist, DPP-4 inhibitor). Our analyses will also evaluate for differences by diabetes type and for disparities based on patient’s race/ethnicity and sex. We anticipate identifying the most vulnerable subgroups and treatment agents associated with higher risk of acute glycemic complications, which will have downstream impacts such as translational research trials and management recommendations. With support from a K23 grant (5-K23DK123384-04), Dr. Galindo is currently assessing if (aim 1) a novel, factory-calibrated, continuous glucose monitoring (CGM) system can provide better assessment of glycemic excursions compared to the standard-of-care using capillary glucose testing, and (aim 2) if using real-time CGM will prevent hypoglycemic events among patients with diabetes and ESKD on dialysis using insulin therapy, and provide better overall glycemic control. Findings from this study R03 study, coupled with findings from my K23 prospective study, will have strong clinical and translational impact, and will be used to design randomized trials focusing on de-escalating or tailoring patient-centered efficacious and safer anti- diabetic regimens, using an improved glycemic monitoring systems (e.g., CGM) for this high-risk group in subsequent R01 applications.