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 being finalised for submission and update will be posted here once accepted somewhere.
Adolescence is a critical period in the early pathogenesis of cardiovascular disease.
This study aimed to characterise the emergence of metabolomic risk factors in adolescent T1D and investigate the impact of treatment with statins and ACE inhibitors.
Metabolomic profiles of 363 adolescents with T1D (duration 6±4 years) recruited to Adolescent Type 1 diabetes cardio-renal intervention (AdDIT) study and 81 adolescents without T1D were analysed using the Nightingale NMR platform. Comparisons of 45 metabolites encompassing lipid subfractions, amino acids, ketone bodies, fluid balance, and inflammation were made at age 14±2 years and then re-assessed again in those with T1D after 3.5yrs of intervention or observation.
At baseline, T1D was associated with widespread differences in the metabolome–most notably in HDL-related lipids, amino acids, and ketone bodies. In 3.5-year follow-up of those with T1D, numerous pro-atherogenic metabolites – particularly ApoB-related markers – were observed to increase in line with worsening glycaemic control. Statin treatment prevented rises in most lipid measures over this period, while ACE inhibitors prevented a modest decrease in HDL levels
Widespread differences in the blood metabolome are already apparent in T1D in early adolescence and worsen in line with increasing HbA1c over time. Statins and ACE inhibitors exert widespread and potentially beneficial effects on these changes, although the clinical implications of these remain to be determined.