Evidence map›Paper›PMID 29091568›Full record

Trial reportThe New England journal of medicine2017

ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes.

M Loredana Marcovecchio, Scott T Chiesa, Simon Bond, Denis Daneman, Sarah Dawson, Kim C Donaghue, Timothy W Jones, Farid H Mahmud, Sally M Marshall, H Andrew W Neil and 4 more

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01581476. Cited by 62 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 5 pooled it
9.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01581476 phase3completed

Randomised, Double Blind, Placebo Controlled Trial of Angiotensin Converting Enzyme Inhibitors and Statins in the Prevention of Long Term Complications in Young People With Type 1 Diabetes

Ran2009Enrolled443Registered outcomes5Posted comparisons0ConditionsType 1 DiabetesArmsACE inhibitor, Combination therapy, Placebo, Statin
PMID 20017932PMID 22416821PMID 17257274PMID 18349042other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 5 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Blood pressure control for diabetic retinopathy.The Cochrane database of systematic reviews · 2023
    Pooled it
  3. Pooled it
  4. Guideline
  5. Guideline
  6. Trial
  7. Trial
  8. Article
  9. Review
  10. Review
  11. Beyond HbAFrontiers in endocrinology · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 11 institutions in 3 countries.

M Loredana MarcovecchioFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Scott T ChiesaFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Simon BondFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Denis DanemanFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Sarah DawsonFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Kim C DonaghueFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Timothy W JonesFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Farid H MahmudFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
Sally M MarshallFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
H Andrew W NeilFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
R Neil DaltonFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
John DeanfieldFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
David B DungerFrom the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust-Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children's Hospital, St. Thomas' Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) - all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) - both in Australia.
AdDIT Study Group
Cambridge University Hospitals NHS Foundation Trust · GBUniversity College London · GBNewcastle University · GBOxford Centre for Diabetes, Endocrinology and Metabolism · GBSickKids Foundation · CASt. Thomas Hospital · CAUniversity of Cambridge · GBUniversity of Sydney · AUUniversity of Toronto · CAUniversity of Western Australia · AUWellcome/MRC Institute of Metabolic Science · GB

Funding

Medical Research Council G0600717
6 · The paper itself

Abstract

backgroundAmong adolescents with type 1 diabetes, rapid increases in albumin excretion during puberty precede the development of microalbuminuria and macroalbuminuria, long-term risk factors for renal and cardiovascular disease. We hypothesized that adolescents with high levels of albumin excretion might benefit from angiotensin-converting-enzyme (ACE) inhibitors and statins, drugs that have not been fully evaluated in adolescents.

methodsWe screened 4407 adolescents with type 1 diabetes between the ages of 10 and 16 years of age and identified 1287 with values in the upper third of the albumin-to-creatinine ratios; 443 were randomly assigned in a placebo-controlled trial of an ACE inhibitor and a statin with the use of a 2-by-2 factorial design minimizing differences in baseline characteristics such as age, sex, and duration of diabetes. The primary outcome for both interventions was the change in albumin excretion, assessed according to the albumin-to-creatinine ratio calculated from three early-morning urine samples obtained every 6 months over 2 to 4 years, and expressed as the area under the curve. Key secondary outcomes included the development of microalbuminuria, progression of retinopathy, changes in the glomerular filtration rate, lipid levels, and measures of cardiovascular risk (carotid intima-media thickness and levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine).

resultsThe primary outcome was not affected by ACE inhibitor therapy, statin therapy, or the combination of the two. The use of an ACE inhibitor was associated with a lower incidence of microalbuminuria than the use of placebo; in the context of negative findings for the primary outcome and statistical analysis plan, this lower incidence was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35 to 0.94). Statin use resulted in significant reductions in total, low-density lipoprotein, and non-high-density lipoprotein cholesterol levels, in triglyceride levels, and in the ratio of apolipoprotein B to apolipoprotein A1, whereas neither drug had significant effects on carotid intima-media thickness, other cardiovascular markers, the glomerular filtration rate, or progression of retinopathy. Overall adherence to the drug regimen was 75%, and serious adverse events were similar across the groups.

conclusionsThe use of an ACE inhibitor and a statin did not change the albumin-to-creatinine ratio over time. (Funded by the Juvenile Diabetes Research Foundation and others; AdDIT ClinicalTrials.gov number, NCT01581476 .).

Indexed as

AdolescentAlbuminuriaAngiotensin-Converting Enzyme InhibitorsArea Under CurveChildCreatinineDiabetes Mellitus, Type 1Double-Blind MethodDrug Therapy, CombinationFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLipidsMaleMedication AdherenceAngiotensin-Converting Enzyme InhibitorsCreatinineHydroxymethylglutaryl-CoA Reductase InhibitorsLipids

Identifiers

PMID29091568
OpenAlexW2734964899

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.