Therapeutic targets in African-American youth with type 2 diabetes

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

This is a 3-month randomized trial in youth with type 2 diabetes with 2 intervention arms (metformin alone and metformin and liraglutide). Our project has successfully recruited participants but have experienced multiple delays in protocol initiation and recruitment related to interruptions in stable isotope supply at the NIH Clinical center as well as the COVID-19 pandemic. Due to the COVID-19 pandemic, recruitment was completely halted March 2020-July 2020 with intermittent interruptions in recruitment and protocol implementation 2020 to 2022. We have now screened 39 individuals and enrolled 24 participants with 22 completing the study that now meets our primary outcome goals. Preliminary primary data analysis is ongoing and has been presented at national meeting American Diabetes Association Scientific Sessions and International Society for Pediatric and Adolescent Diabetes 2022. Our data support improved glycemia and -cell function in youth on short-term combination therapy with metformin and liraglutide independent of changes in new glucose produced by the liver. Metformin was ineffective alone or in combination with liraglutide for lower rates of new glucose produced by the liver and further research is needed to explore therapeutics that will target this early pathological feature. . Our randomized study should be allowed to continue because our findings will provide novel insight into pathophysiology of diabetes in youth, the drugs used to treat this chronic disease and pharmacogenomic targets. We have also generated pilot data that will help decipher the metabolic (including lipoprotein), microbial, pharmacogenetic, and pharmacokinetic factors associated with metformin response in youth-onset type 2 diabetes. This year we collaborated with Dr. Sheela Magge and published a manuscript that highlights importance pathophysiological differences in the relationship between lipoproteins and insulin sensitivity in youth with obesity compared to those with dysglycemia. This work is important supporting data for our randomized controlled study described above.