Adolescent type 1 Diabetes Cardio-renal Intervention Trial (AdDIT)

Adolescent type 1 Diabetes cardio-renal Intervention Trial Research Group, M Loredana Marcovecchio, David B Dunger, R Neil Dalton, Denis Daneman, John E Deanfield, Alastair Gray, Timothy W Jones, Andrew Neil, A Toby Prevost, Carlo L Acerini, Rakesh Amin, Binu Anand, Timothy G Barrett, Timothy J Bradley, Fergus J Cameron, David S Celermajer, Timothy D Cheetham, Christopher Cooper, Jennifer Couper, Andrew M Cotterill, Elizabeth A Davis, Kim C Donaghue, Atanu Dutta, Julie A Edge, Nicholas P Mann, Christopher Moudiotis, Gerry Rayman, Julian Shield, Nandu Thalange, Tien Y Wong, Adolescent type 1 Diabetes cardio-renal Intervention Trial Research Group, M Loredana Marcovecchio, David B Dunger, R Neil Dalton, Denis Daneman, John E Deanfield, Alastair Gray, Timothy W Jones, Andrew Neil, A Toby Prevost, Carlo L Acerini, Rakesh Amin, Binu Anand, Timothy G Barrett, Timothy J Bradley, Fergus J Cameron, David S Celermajer, Timothy D Cheetham, Christopher Cooper, Jennifer Couper, Andrew M Cotterill, Elizabeth A Davis, Kim C Donaghue, Atanu Dutta, Julie A Edge, Nicholas P Mann, Christopher Moudiotis, Gerry Rayman, Julian Shield, Nandu Thalange, Tien Y Wong

Abstract

Background: The prognosis for young people diagnosed with diabetes during childhood remains poor and this is mainly related to the long-term risk of developing vascular complications.Microalbuminuria identifies subjects at risk for diabetic nephropathy (DN) and cardiovascular disease (CVD). It is often detected in adolescence but is rarely treated before the age of 18 years, as at the end of puberty albumin excretion may decline and in some subjects will return into the normal range. However, evidence indicates that subjects with both transient and persistent microalbuminuria have experienced renal damage during puberty and thus reno-protection to prevent long-term complications is warranted. In adults with diabetes and microalbuminuria, the use of angiotensin converting enzyme inhibitors (ACEI) and Statins is increasing, and in order to determine whether these agents are of value in the adolescent population a large randomized controlled clinical trial is needed.

Methods/design: The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) is a multi-center, randomized, double-blind, placebo-controlled trial of ACEI and Statin therapy in adolescents with type 1 diabetes. 500 high-risk adolescents, defined on the basis of their albumin excretion, are randomized to receive either ACEI (Quinapril) or Statins (Atorvastatin) or combination therapy or placebo for 3-4 years. There will also be a parallel open observational study, based on the follow-up of 400 low-risk non-randomized adolescents. The major endpoint of the study is the change in albumin excretion; secondary endpoints include markers of CVD, renal function, retinopathy, quality of life combined with assessment of compliance and potential health economic benefits.

Discussion: AdDIT will provide important data on the potential renal and cardiovascular protective effects of ACEI and Statins in high-risk adolescents. Long-term follow-up of the randomized subjects will provide direct evidence of disease outcomes, in addition to the data on early surrogate measures of DN and CVD. Follow-up of non-randomized low-risk subjects will determine the potential impact of intervention on DN and CVD. AdDIT will help to determine whether, in addition to encouraging young people to achieve good glycaemic control, pharmacological cardio-renal protection should also be implemented. EUDRACT NUMBER: 2007-001039-72

Trial registration number: ISRCTN91419926.

Figures

Figure 1
Figure 1
Combined study flow-chart.
Figure 2
Figure 2
Timeline and milestones.

References

    1. Bryden KS, Dunger DB, Mayou RA, Peveler RC, Neil HA. Poor prognosis of young adults with type 1 diabetes: a longitudinal study. Diabetes care. 2003;26(4):1052–1057. doi: 10.2337/diacare.26.4.1052.
    1. Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, Gatling W, Bingley PJ, Patterson CC. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia. 2003;46(6):760–765. doi: 10.1007/s00125-003-1116-6.
    1. Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for diabetes mellitus in the United States. Jama. 2003;290(14):1884–1890. doi: 10.1001/jama.290.14.1884.
    1. Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G. Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Diabetologia. 2006;49(2):298–305. doi: 10.1007/s00125-005-0082-6.
    1. Orchard TJ. From diagnosis and classification to complications and therapy. DCCT. Part II? Diabetes Control and Complications Trial. Diabetes care. 1994;17(4):326–338.
    1. Borch-Johnsen K, Kreiner S. Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus. Br Med J (Clin Res Ed) 1987;294(6588):1651–1654. doi: 10.1136/bmj.294.6588.1651.
    1. Kostraba JN, Dorman JS, Orchard TJ, Becker DJ, Ohki Y, Ellis D, Doft BH, Lobes LA, LaPorte RE, Drash AL. Contribution of diabetes duration before puberty to development of microvascular complications in IDDM subjects. Diabetes care. 1989;12(10):686–693. doi: 10.2337/diacare.12.10.686.
    1. Lawson ML, Sochett EB, Chait PG, Balfe JW, Daneman D. Effect of puberty on markers of glomerular hypertrophy and hypertension in IDDM. Diabetes. 1996;45(1):51–55. doi: 10.2337/diabetes.45.1.51.
    1. Key findings about the quality of care for children and young people with diabetes in England, incorporating registrations from Wales: Report for the audit period 2004/05. National Diabetes Audit, The Information Centre. 2006.
    1. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. J Pediatr. 1994;125(2):177–188. doi: 10.1016/S0022-3476(94)70190-3.
    1. Lawson ML, Gerstein HC, Tsui E, Zinman B. Effect of intensive therapy on early macrovascular disease in young individuals with type 1 diabetes. A systematic review and meta-analysis. Diabetes care. 1999;22(Suppl 2):B35–39.
    1. Rudberg S, Dahlquist G. Determinants of progression of microalbuminuria in adolescents with IDDM. Diabetes care. 1996;19(4):369–371. doi: 10.2337/diacare.19.4.369.
    1. Schultz CJ, Konopelska-Bahu T, Dalton RN, Carroll TA, Stratton I, Gale EA, Neil A, Dunger DB. Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group. Diabetes care. 1999;22(3):495–502. doi: 10.2337/diacare.22.3.495.
    1. Gibb DM, Dunger D, Levin M, Shah V, Smith C, Barratt TM. Early markers of the renal complications of insulin dependent diabetes mellitus. Arch Dis Child. 1989;64(7):984–991. doi: 10.1136/adc.64.7.984.
    1. Mortensen HB, Marinelli K, Norgaard K, Main K, Kastrup KW, Ibsen KK, Villumsen J, Parving HH. A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood. Diabet Med. 1990;7(10):887–897. doi: 10.1111/j.1464-5491.1990.tb01324.x.
    1. Quattrin T, Waz WR, Duffy LC, Sheldon MW, Campos SP, Albini CH, Feld LG. Microalbuminuria in an adolescent cohort with insulin-dependent diabetes mellitus. Clin Pediatr (Phila) 1995;34(1):12–17. doi: 10.1177/000992289503400103.
    1. Salardi S, Cacciari E, Pascucci MG, Giambiasi E, Tacconi M, Tazzari R, Cicognani A, Boriani F, Puglioli R, Mantovani W. Microalbuminuria in diabetic children and adolescents. Relationship with puberty and growth hormone. Acta Paediatr Scand. 1990;79(4):437–443. doi: 10.1111/j.1651-2227.1990.tb11490.x.
    1. Caramori ML, Kim Y, Huang C, Fish AJ, Rich SS, Miller ME, Russell G, Mauer M. Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes. Diabetes. 2002;51(2):506–513. doi: 10.2337/diabetes.51.2.506.
    1. Schultz CJ, Amin R, Dunger DB. Markers of microvascular complications in insulin dependent diabetes. Arch Dis Child. 2002;87(1):10–12. doi: 10.1136/adc.87.1.10.
    1. Abraha A, Schultz C, Konopelska-Bahu T, James T, Watts A, Stratton IM, Matthews DR, Dunger DB. Glycaemic control and familial factors determine hyperlipidaemia in early childhood diabetes. Oxford Regional Prospective Study of Childhood Diabetes. Diabet Med. 1999;16(7):598–604. doi: 10.1046/j.1464-5491.1999.00109.x.
    1. Orchard TJ, Forrest KY, Kuller LH, Becker DJ. Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes care. 2001;24(6):1053–1059. doi: 10.2337/diacare.24.6.1053.
    1. Schultz CJ, Neil HA, Dalton RN, Konopelska Bahu T, Dunger DB. Blood pressure does not rise before the onset of microalbuminuria in children followed from diagnosis of type 1 diabetes. Oxford Regional Prospective Study Group. Diabetes care. 2001;24(3):555–560. doi: 10.2337/diacare.24.3.555.
    1. Amin R, Turner C, van Aken S, Bahu TK, Watts A, Lindsell DR, Dalton RN, Dunger DB. The relationship between microalbuminuria and glomerular filtration rate in young type 1 diabetic subjects: The Oxford Regional Prospective Study. Kidney Int. 2005;68(4):1740–1749. doi: 10.1111/j.1523-1755.2005.00590.x.
    1. Gallego PH, Craig ME, Hing S, Donaghue KC. Role of blood pressure in development of early retinopathy in adolescents with type 1 diabetes: prospective cohort study. BMJ (Clinical research ed) 2008;337:a918. doi: 10.1136/bmj.a918.
    1. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989;32(4):219–226. doi: 10.1007/BF00285287.
    1. Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, Lehtimaki T, Ronnemaa T, Viikari J, Raitakari OT. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004;109(14):1750–1755. doi: 10.1161/01.CIR.0000124725.46165.2C.
    1. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115(4):459–467. doi: 10.1161/CIRCULATIONAHA.106.628875.
    1. Singh TP, Groehn H, Kazmers A. Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus. J Am Coll Cardiol. 2003;41(4):661–665. doi: 10.1016/S0735-1097(02)02894-2.
    1. Jarvisalo MJ, Jartti L, Nanto-Salonen K, Irjala K, Ronnemaa T, Hartiala JJ, Celermajer DS, Raitakari OT. Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children. Circulation. 2001;104(24):2943–2947. doi: 10.1161/hc4901.100522.
    1. Krantz JS, Mack WJ, Hodis HN, Liu CR, Liu CH, Kaufman FR. Early onset of subclinical atherosclerosis in young persons with type 1 diabetes. J Pediatr. 2004;145(4):452–457. doi: 10.1016/j.jpeds.2004.06.042.
    1. Peppa-Patrikiou M, Scordili M, Antoniou A, Giannaki M, Dracopoulou M, Dacou-Voutetakis C. Carotid atherosclerosis in adolescents and young adults with IDDM. Relation to urinary endothelin, albumin, free cortisol, and other factors. Diabetes care. 1998;21(6):1004–1007. doi: 10.2337/diacare.21.6.1004.
    1. Atabek ME, Pirgon O, Kurtoglu S, Imamoglu H. Evidence for an association between type 1 diabetes and premature carotid atherosclerosis in childhood. Pediatr Cardiol. 2006;27(4):428–433. doi: 10.1007/s00246-006-1199-1.
    1. Kramer H, Jacobs DR Jr, Bild D, Post W, Saad MF, Detrano R, Tracy R, Cooper R, Liu K. Urine albumin excretion and subclinical cardiovascular disease. The Multi-Ethnic Study of Atherosclerosis. Hypertension. 2005;46(1):38–43. doi: 10.1161/01.HYP.0000171189.48911.18.
    1. Smith A, Karalliedde J, De Angelis L, Goldsmith D, Viberti G. Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes. J Am Soc Nephrol. 2005;16(4):1069–1075. doi: 10.1681/ASN.2004090769.
    1. Meeking DR, Cummings MH, Thorne S, Donald A, Clarkson P, Crook JR, Watts GF, Shaw KM. Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria. Diabet Med. 1999;16(10):841–847. doi: 10.1046/j.1464-5491.1999.00158.x.
    1. Bojestig M, Arnqvist HJ, Karlberg BE, Ludvigsson J. Glycemic control and prognosis in type I diabetic patients with microalbuminuria. Diabetes care. 1996;19(4):313–317. doi: 10.2337/diacare.19.4.313.
    1. Gorman D, Sochett E, Daneman D. The natural history of microalbuminuria in adolescents with type 1 diabetes. J Pediatr. 1999;134(3):333–337. doi: 10.1016/S0022-3476(99)70459-2.
    1. Rudberg S, Persson B, Dahlquist G. Increased glomerular filtration rate as a predictor of diabetic nephropathy--an 8-year prospective study. Kidney Int. 1992;41(4):822–828. doi: 10.1038/ki.1992.126.
    1. Salardi S, Cacciari E. Is microalbuminuria progressive? Arch Dis Child. 1996;75(3):266. doi: 10.1136/adc.75.3.266-a.
    1. Shield JP, Hunt LP, Karachaliou F, Karavanaki K, Baum JD. Is microalbuminuria progressive? Arch Dis Child. 1995;73(6):512–514. doi: 10.1136/adc.73.6.512.
    1. Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, Marcovecchio L, Neil A, Dalton RN, Dunger DB. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008;336(7646):697–701. doi: 10.1136/.
    1. Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH. Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ (Clinical research ed) 2004;328(7448):1105. doi: 10.1136/bmj.38070.450891.FE.
    1. Schultz CJ, Neil HA, Dalton RN, Dunger DB. Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes. Diabetes care. 2000;23(12):1811–1815. doi: 10.2337/diacare.23.12.1811.
    1. Dunger DB, Schwarze CP, Cooper JD, Widmer B, Neil HA, Shield J, Edge JA, Jones TW, Daneman D, Dalton RN. Can we identify adolescents at high risk for nephropathy before the development of microalbuminuria? Diabet Med. 2007;24(2):131–136. doi: 10.1111/j.1464-5491.2006.02047.x.
    1. Newman DJ, Mattock MB, Dawnay AB, Kerry S, McGuire A, Yaqoob M, Hitman GA, Hawke C. Systematic review on urine albumin testing for early detection of diabetic complications. Health Technol Assess. 2005;9(30):iii–vi. xiii-163.
    1. NICE Guidance CG15 Type 1 diabetes in children and young people: full guideline. National Institute for Health and Clinical Excellence. 2004.
    1. Donaghue KC, Chiarelli F, Trotta D, Allgrove J, Dahl-Jorgensen K. Microvascular and macrovascular complications associated with diabetes in children and adolescents. Pediatric diabetes. 2009;10(Suppl 12):195–203. doi: 10.1111/j.1399-5448.2009.00576.x.
    1. Cook J, Daneman D, Spino M, Sochett E, Perlman K, Balfe JW. Angiotensin converting enzyme inhibitor therapy to decrease microalbuminuria in normotensive children with insulin-dependent diabetes mellitus. J Pediatr. 1990;117(1 Pt 1):39–45.
    1. Rudberg S, Aperia A, Freyschuss U, Persson B. Enalapril reduces microalbuminuria in young normotensive type 1 (insulin-dependent) diabetic patients irrespective of its hypotensive effect. Diabetologia. 1990;33(8):470–476. doi: 10.1007/BF00405108.
    1. Yuksel H, Darcan S, Kabasakal C, Cura A, Mir S, Mavi E. Effect of enalapril on proteinuria, phosphaturia, and calciuria in insulin-dependent diabetes. Pediatr Nephrol. 1998;12(8):648–650. doi: 10.1007/s004670050520.
    1. Drummond K, Levy-Marchal C, Laborde K, Kindermans C, Wright C, Dechaux M, Czernichow P. Enalapril does not alter renal function in normotensive, normoalbuminuric, hyperfiltering type 1 (insulin-dependent) diabetic children. Diabetologia. 1989;32(4):255–260. doi: 10.1007/BF00285294.
    1. Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data. Ann Intern Med. 2001;134(5):370–379.
    1. Rudberg S, Osterby R, Bangstad HJ, Dahlquist G, Persson B. Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus. Diabetologia. 1999;42(5):589–595. doi: 10.1007/s001250051199.
    1. Chaturvedi N, Sjolie AK, Stephenson JM, Abrahamian H, Keipes M, Castellarin A, Rogulja-Pepeonik Z, Fuller JH. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus. Lancet. 1998;351(9095):28–31. doi: 10.1016/S0140-6736(97)06209-0.
    1. Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, Drummond K, Donnelly S, Goodyer P, Gubler MC. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009;361(1):40–51. doi: 10.1056/NEJMoa0808400.
    1. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22. doi: 10.1016/S0140-6736(02)09327-3.
    1. JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart (British Cardiac Society) 2005;91(Suppl 5):v1–52.
    1. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–1278. doi: 10.1016/S0140-6736(05)67394-1.
    1. Avis HJ, Vissers MN, Stein EA, Wijburg FA, Trip MD, Kastelein JJ, Hutten BA. A systematic review and meta-analysis of statin therapy in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2007;27(8):1803–1810. doi: 10.1161/ATVBAHA.107.145151.
    1. Arambepola C, Farmer AJ, Perera R, Neil HA. Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis. Atherosclerosis. 2007;195(2):339–347. doi: 10.1016/j.atherosclerosis.2006.09.030.
    1. Dahl-Jorgensen K, Larsen JR, Hanssen KF. Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment? Diabetologia. 2005;48(8):1445–1453. doi: 10.1007/s00125-005-1832-1.
    1. Yamasaki Y, Kawamori R, Matsushima H, Nishizawa H, Kodama M, Kajimoto Y, Morishima T, Kamada T. Atherosclerosis in carotid artery of young IDDM patients monitored by ultrasound high-resolution B-mode imaging. Diabetes. 1994;43(5):634–639. doi: 10.2337/diabetes.43.5.634.
    1. Wiegman A, de Groot E, Hutten BA, Rodenburg J, Gort J, Bakker HD, Sijbrands EJ, Kastelein JJ. Arterial intima-media thickness in children heterozygous for familial hypercholesterolaemia. Lancet. 2004;363(9406):369–370. doi: 10.1016/S0140-6736(04)15467-6.
    1. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP, Karas RH, Udelson JE. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146(1):168–174. doi: 10.1016/S0002-8703(03)00094-2.
    1. Dhindsa M, Sommerlad SM, DeVan AE, Barnes JN, Sugawara J, Ley O, Tanaka H. Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity. J Appl Physiol. 2008;105(2):427–432. doi: 10.1152/japplphysiol.90431.2008.
    1. Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, Schatz DA, Earing MG, Lerman A, Mahmud FH. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatr Diabetes. 2007;8(4):193–198. doi: 10.1111/j.1399-5448.2007.00246.x.
    1. Haller MJ, Samyn M, Nichols WW, Brusko T, Wasserfall C, Schwartz RF, Atkinson M, Shuster JJ, Pierce GL, Silverstein JH. Radial artery tonometry demonstrates arterial stiffness in children with type 1 diabetes. Diabetes care. 2004;27(12):2911–2917. doi: 10.2337/diacare.27.12.2911.
    1. Wiegman A, Hutten BA, de Groot E, Rodenburg J, Bakker HD, Buller HR, Sijbrands EJ, Kastelein JJ. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. Jama. 2004;292(3):331–337. doi: 10.1001/jama.292.3.331.
    1. Keane WF, Kasiske BL, O'Donnell MP, Kim Y. The role of altered lipid metabolism in the progression of renal disease: experimental evidence. Am J Kidney Dis. 1991;17(5 Suppl 1):38–42.
    1. O'Donnell MP, Kasiske BL, Kim Y, Atluru D, Keane WF. Lovastatin inhibits proliferation of rat mesangial cells. J Clin Invest. 1993;91(1):83–87. doi: 10.1172/JCI116204.
    1. Ota T, Takamura T, Ando H, Nohara E, Yamashita H, Kobayashi K. Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model. Diabetologia. 2003;46(6):843–851. doi: 10.1007/s00125-003-1099-3.
    1. Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005–2016. doi: 10.1016/S0140-6736(03)13636-7.
    1. Athyros VG, Papageorgiou AA, Symeonidis AN, Didangelos TP, Pehlivanidis AN, Bouloukos VI, Mikhailidis DP. Early benefit from structured care with atorvastatin in patients with coronary heart disease and diabetes mellitus. Angiology. 2003;54(6):679–690. doi: 10.1177/000331970305400607.
    1. Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA. 2007;298(8):902–916. doi: 10.1001/jama.298.8.902.
    1. Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse D, Williamson E. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370(9600):1687–1697. doi: 10.1016/S0140-6736(07)61607-9.
    1. Marcovecchio ML, Dalton RN, Schwarze CP, Prevost AT, Neil HA, Acerini CL, Barrett T, Cooper JD, Edge J, Shield J. Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes. Diabetologia. 2009;52(6):1173–1181. doi: 10.1007/s00125-009-1327-6.
    1. Pocock S. Clinical Trials: A practical approach. John Wiley & Sons Ltd Chicester; 1983.
    1. Highlights of prescribing information: LIPITOR® (atorvastatin calcium) Tablets for oral administration. Pfizer Ltd. 2009.
    1. Physician Prescribing Information: Accupril® (Quinapril Hydrochloride Tablets) Pfizer Ltd. 2009.
    1. Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent patients with cystic fibrosis. J Adolesc Health. 2006;38(1):13–17. doi: 10.1016/j.jadohealth.2004.09.013.
    1. Vrijens B, Tousset E, Rode R, Bertz R, Mayer S, Urquhart J. Successful projection of the time course of drug concentration in plasma during a 1-year period from electronically compiled dosing-time data used as input to individually parameterized pharmacokinetic models. J Clin Pharmacol. 2005;45(4):461–467. doi: 10.1177/0091270004274433.
    1. Dalton RN, Booth C, Mallard B, Rigby E, Ridgen S, Turner C. SDMA is an endogenous marker of glomerular filtration rate [abstract] J Am Soc Nephrol. 2005;16:s3.
    1. Kielstein JT, Salpeter SR, Bode-Boeger SM, Cooke JP, Fliser D. Symmetric dimethylarginine (SDMA) as endogenous marker of renal function--a meta-analysis. Nephrol Dial Transplant. 2006;21(9):2446–2451. doi: 10.1093/ndt/gfl292.
    1. Bokenkamp A, Domanetzki M, Zinck R, Schumann G, Byrd D, Brodehl J. Cystatin C--a new marker of glomerular filtration rate in children independent of age and height. Pediatrics. 1998;101(5):875–881. doi: 10.1542/peds.101.5.875.
    1. Fong DS, Aiello LP, Ferris FL, Klein R. Diabetic retinopathy. Diabetes care. 2004;27(10):2540–2553. doi: 10.2337/diacare.27.10.2540.
    1. Diabetic retinopathy study. Report Number 6. Design, methods, and baseline results. Report Number 7. A modification of the Airlie House classification of diabetic retinopathy. Prepared by the Diabetic Retinopathy. Investigative ophthalmology & visual science. 1981;21(1 Pt 2):1–226.
    1. Cheung N, Donaghue KC, Liew G, Rogers SL, Wang JJ, Lim SW, Jenkins AJ, Hsu W, Li Lee M, Wong TY. Quantitative assessment of early diabetic retinopathy using fractal analysis. Diabetes care. 2009;32(1):106–110. doi: 10.2337/dc08-1233.
    1. Cheung N, Rogers SL, Donaghue KC, Jenkins AJ, Tikellis G, Wong TY. Retinal arteriolar dilation predicts retinopathy in adolescents with type 1 diabetes. Diabetes care. 2008;31(9):1842–1846. doi: 10.2337/dc08-0189.
    1. Eastman RC, Javitt JC, Herman WH, Dasbach EJ, Zbrozek AS, Dong F, Manninen D, Garfield SA, Copley-Merriman C, Maier W. Model of complications of NIDDM. I. Model construction and assumptions. Diabetes care. 1997;20(5):725–734. doi: 10.2337/diacare.20.5.725.
    1. Dong FB, Sorensen SW, Manninen DL, Thompson TJ, Narayan V, Orians CE, Gregg EW, Eastman RC, Dasbach EJ, Herman WH. Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes mellitus. Pharmacoeconomics. 2004;22(15):1015–1027. doi: 10.2165/00019053-200422150-00005.
    1. Schafer JL. Analysis of incomplete multivariate data. London: Chapman & Hall/CRC; 1997.
    1. Montgomery AA, Peters TJ, Little P. Design, analysis and presentation of factorial randomised controlled trials. BMC Med Res Methodol. 2003;3:26. doi: 10.1186/1471-2288-3-26.
    1. McAlister FA, Straus SE, Sackett DL, Altman DG. Analysis and reporting of factorial trials: a systematic review. Jama. 2003;289(19):2545–2553. doi: 10.1001/jama.289.19.2545.
    1. Dunger DB. Diabetes in puberty. Arch Dis Child. 1992;67(5):569–570. doi: 10.1136/adc.67.5.569.
    1. Silverstein J, Klingensmith G, Copeland K, Plotnick L, Kaufman F, Laffel L, Deeb L, Grey M, Anderson B, Holzmeister LA. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes care. 2005;28(1):186–212. doi: 10.2337/diacare.28.1.186.
    1. Strippoli GF, Craig M, Craig JC. Antihypertensive agents for preventing diabetic kidney disease. Cochrane Database Syst Rev. 2005. p. CD004136.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi