Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT): Urinary screening and baseline biochemical and cardiovascular assessments

  1. on behalf of the AdDIT Investigators.
  1. 1Department of Paediatrics, MRL Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre and the Cambridge Clinical Trial Unit, University of Cambridge, Cambridge, UK
  2. 2Institute of Child Health, University College London, London, UK
  3. 3Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
  4. 4Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
  5. 5Centre for Diabetes, Endocrinology& Metabolism, University of Oxford, Oxford, UK
  6. 6Department of Public Health Sciences, Kings College, London, UK
  7. 7WellChild Laboratory, Evelina Children’s Hospital, St Thomas’ Hospital London, London, UK
  1. Corresponding author: David B Dunger, Email: dbd25{at}cam.ac.uk
  1. denotes equal contribution

Abstract

Objective To assess the association between early increases in albumin excretion and cardiovascular (CV) and renal markers in a large cohort of young people with type 1 diabetes.

Research Design and Methods As part of preliminary screening for a multicentre, randomized controlled trial of statins/ACE inhibitors, we measured albumin-creatinine ratio (ACR) in 6 early morning urine samples from 3,353 adolescents (10-16 years) and calculated tertiles based on an established algorithm. From those subjects deemed to be at higher risk (upper ACR tertile) we recruited 400 into the intervention study (Trial cohort). From those subjects deemed to be at lower risk (middle-lower ACR tertiles) we recruited 329 to the Observation cohort. At baseline vascular measurements (carotid intima-media thickness, pulse wave velocity (PWV), flow-mediated dilatation, digital pulse amplitude tonometry), renal (symmetric dimethylarginine, cystatin C, creatinine) and CVD markers (lipids and apolipoproteins (Apo)A-1 and B, C-Reactive Protein, asymmetric dimethylarginine) were assessed.

Results Age- and sex-adjusted PWV was higher in the Trial than in the Observational cohort (5.00±0.84 vs 4.86±0.70m/s, p=0.021). Similarly, non-HDL-cholesterol (2.95±0.83 vs 2.81±0.78mmol/l, p=0.02) and ApoB/ApoA-1 ratio (0.50±0.14 vs 0.47±0.11, p=0.04) were higher in the Trial cohort. Cystatin C and creatinine were decreased (0.88±0.13 vs 0.90±0.13ng/ml, p=0.04; 51.81±10.45 vs 55.35±11.05mmol/l, p<0.001) and eGFR (137.05±23.89 vs 129.31±22.41ml/min/1.73m2, p<0.001) increased in the Trial compared to the Observational cohort.

Conclusions Our data demonstrate that in adolescents with type 1 diabetes, the group with the highest tertile of albumin excretion showed more evidence of early renal and CV disease than those in the lower tertiles.

Footnotes

  • * Joint first authors

  • Received July 11, 2013.
  • Accepted October 10, 2013.

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