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

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.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Product-Group Unification in Type IIB String Thoery

The product-group unification is a model of unified theories, in which masslessness of the two Higgs doublets and absence of dimension-five proton decay are guaranteed by a symmetry. It is based on SU(5) x U(N) (N=2,3) gauge group. It is known that various features of the model are explained naturally, when it is embedded in a brane world. This article describes an idea of how to accommodate all the particles of the model in Type IIB brane world. The GUT-breaking sector is realized by a D3--D7 system, and chiral quarks and leptons arise from intersection of D7-branes. The D-brane configuration can be a geometric realization of the non-parallel family structure of quarks and leptons, an idea proposed to explain the large mixing angles observed in the neutrino oscillation. The tri-linear interaction of the next-to-minimal supersymmetric standard model is obtained naturally in some cases.Comment: 33 pages, 5 figure