This study aims to investigate the effects of metabolic bariatric surgery (MBS) on plasma proteins linked to loss of glycemic control, insulin resistance and impaired insulin secretion in youth with type 2 diabetes (T2D).We measured 7604 Aptamers in 326 plasma samples from youth with obesity, both with and without T2D, in Teen-LABS cohort, examining pre- and post-MBS changes. This analysis focused on proteins previously identified in the TODAY cohort as predictors of glycemic control loss, defined by sustained HbA1c ≥8% or insulin dependence, in youth with T2D. A mixed model evaluated proteomic changes post-MBS, maintaining a 5% false discovery rate with reported q-values. In Teen-LABS, several proteins associated with a higher glycemic control loss risk in TODAY showed notable post-surgical downregulation. Key proteins such as Fructose-bisphosphate aldolase B, Liver carboxylesterase 1, Semaphorin-6A, Interleukin-18 receptor 1, Neurofascin, and Plexin-D1 were among those most affected (Figure). These proteins participate in metabolic and immunomodulatory pathways, potentially influencing glucose homeostasis. The study identified specific proteomic changes following MBS that potentially impact metabolic and immune function relevant to glycemic regulation. Recognizing these proteins as biomarkers could tailor post-MBS care, achieving long-term glycemic control.
Y. Choi: None. N. Nguyen: None. P. Narongkiatikhun: None. K. Nash: None. K.L. Tommerdahl: None. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex. J.R. Ryder: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. L. Pyle: None.
American Diabetes Association (7-23-ICTSTDY-08); NIH/NIDDK (U01 DK61242)
