Effect of statins and ACE inhibitors on the adolescent metabolome in type 1 diabetes: the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT)
Beatrice Prampolini, Anthony Giton, Sofia Frassineti, Paul Benitez-Aguirre, Fergus J Cameron, Maria Craig, Jennifer J Couper, Elizabeth A Davis, R Neil Dalton, Denis Daneman, John E Deanfield, Kim C Donaghue, Tim W Jones, Farid H Mahmud, Sally M Marshall, H Andrew Neil, M Loredana Marcovecchio*, and Scott T Chiesa* on behalf of the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT) Study Group
Stata code for manuscript investigating evolution of metabolomic profiles across adolescence in patients with type 1 diabetes and the impact that a four year RCT of statins and ACE inhibitors have on these outcomes. Data comes from the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT), previously reported at https://www.nejm.org/doi/full/10.1056/NEJMoa1703518.
Manuscript accepted by Scientific Reports and DOI will be posted here once published.
Adolescence represents a pivotal period for the development of early diabetes-related vascular complications, primarily driven by chronic hyperglycaemia 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 non-diabetic controls. Forty-five metabolites—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 RCT arm of the trial 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 (1.50 [1.45, 1.54] vs 1.39 [1.34, 1.43] mmol/l). These findings suggest widespread glycaemia-related metabolomic perturbations in adolescents with type 1 diabetes, partially mitigated by statins and ACE inhibitors, supporting their cardioprotective role.