165-LB: Circulating Metabolomic Biomarkers of Glycemic Control in Youth with Type 2 Diabetes (T2D)

Abstract

There are few biomarkers of glycemic response among youth with T2D, despite increasing disease prevalence and suboptimal response to approved therapies. We hypothesized that plasma metabolites may predict glycemic outcomes in youth-onset T2D. We measured 480 metabolites in fasting plasma samples in the Treatment options for T2D in Adolescents and Youth (TODAY) study (n=391), in which youth with T2D aged 10-17 years were randomized to metformin alone, metformin + rosiglitazone, or metformin + intensive lifestyle intervention. Metabolite associations with loss of glycemic control (defined as HbA1c ≥8% for 6 months or need for insulin therapy) were modeled using Cox proportional hazards regression adjusted for baseline age, sex, race/ethnicity, BMI, treatment group, and fasting glucose. Loss of glycemic control was observed in 150 of 391 youth (mean 2.6 years). Baseline levels of 11 metabolites were associated with loss of glycemic control (FDR<0.05, Fig. 1A). Treatment group modified the association of hexose and xanthurenic acid levels with glycemic control. For both compounds, youth with higher baseline levels had a lower risk of treatment failure when randomized to metformin therapy alone (Fig. 1B). Thus, metabolomics provides insight into circulating analytes associated with loss of glycemic control, and may highlight different effects of specific treatments in youth with T2D. Disclosure Z. Chen: None. C. Lu: None. X. Shi: None. S. Zheng: None. D. Wolfs: None. P. Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. R. E. Gerszten: None. E. M. Isganaitis: None. Funding National Institutes of Health (K23DK127073)