Effect of statins and ACE inhibitors on the metabolome in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT) cohort

Abstract

Abstract Adolescence represents a pivotal period for the development of early diabetes-related vascular complications, primarily driven by chronic hyperglycemia and associated metabolic disturbances. Metabolomics provides a promising tool to identify biomarkers reflecting these early changes. The present study compared metabolomic profiles between adolescents with and without type 1 diabetes and assessed the impact of glycemia and short-term treatment with statins and/or ACE inhibitors on metabolite trajectories. Metabolomic data were obtained via the Nightingale platform from 341 adolescents with type 1 diabetes from the AdDIT study and 81 age- and sex-matched peers without diabetes. Two hundred and forty-nine metabolites, with 45 prioritized due to well-established links with cardiovascular disease- including lipid subfractions, amino acids, ketone bodies, and markers of renal function and inflammation—were measured at a mean age of 14.0 ± 1.8 years and re-assessed after 3.5 years in those with diabetes. At baseline, significant differences were observed in glucose, ketone bodies, amino acids, and lipid classes. Over time, adolescents with diabetes showed increases in lipid subfractions, acetoacetate, and GlycA, with HbA1c positively associated with atherogenic lipidome components. Findings from the trial arm provided strong evidence that statins attenuated rises in LDL-cholesterol (1.90 [1.79, 2.01] vs. 2.38 [2.28, 2.49] mmol/l), and weaker evidence suggestive of a small effect of ACE inhibitors in preserving HDL-cholesterol (1.50 [1.45, 1.54] vs. 1.39 [1.34, 1.43] mmol/l). These findings suggest widespread glycemia-related metabolomic perturbations in adolescents with type 1 diabetes, partially mitigated by statins and ACE inhibitors, supporting their cardioprotective role. Clinical registration : ClinicalTrials.gov ID NCT01581476 (13/04/2012) https://clinicaltrials.gov/study/NCT01581476 .