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

The effect of aggressive versus standard lipid lowering by atorvastatin on diabetic dyslipidemia. The DALI Study: a double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes and diabetic dyslipidemia

WSTĘP. Jak dotąd nie wykazano, aby intensywna kontrola glikemii u chorych na cukrzycę typu 2, która skutecznie zapobiega rozwojowi mikroangiopatii, miała równie jednoznaczny korzystny wpływ na występowanie chorób układu sercowo-naczyniowego. U chorych na cukrzycę stwierdza się charakterystyczne zaburzenia lipidowe (wysokie stężenie triglicerydów, niskie stężenie cholesterolu frakcji HDL). Intensywne obniżanie stężenia triglicerydów może okazać się skuteczną metodą zmniejszania ryzyka chorób układu sercowo-naczyniowego. MATERIAŁ I METODY. Badanie przeprowadzono metodą podwójnie ślepej próby kontrolowanej placebo. Do badania losowo wybrano 217 chorych na cukrzycę typu 2, ze stężeniem triglicerydów na czczo 1,5&#8211;6,0 mmol/l, aby ocenić wpływ 30-tygodniowego podawania 10 i 80 mg atorwastatyny na stężenie triglicerydów w osoczu. WYNIKI. Podawanie 10 i 80 mg atorwastatyny spowodowało wyraźne obniżenie (odpowiednio o 25 i 35%) stężenia triglicerydów w osoczu (w obu przypadkach p 0,5). Atorwastatyna przyjmowana w dawce 10 mg wywoływała wyraźne obniżenie w stosunku do wartości wyjściowych stężenia cholesterolu całkowitego (-30%, p < 0,001), cholesterolu frakcji LDL (-40%, p < 0,001) i apolipoproteiny B (-31%, p < 0,001) oraz wyraźnie zwiększała stężenie cholesterolu frakcji HDL - o 6% w stosunku do jego wartości wyjściowych (p < 0,005). Atorwastatyna w dawce 80 mg wywierała podobny wpływ na stężenie cholesterolu frakcji HDL (+5,2%, p < 0,005), jednak znacznie bardziej niż atorwastatyna w dawce 10 mg (p < 0,005) obniżała stężenie cholesterolu całkowitego (&#8211;40%, p < 0,001), cholesterolu frakcji LDL (&#8211;52%, p < 0,001) oraz apolipoproteiny B (&#8211;40%, p < 0,001). Działania niepożądane były podobne w grupie przyjmującej atorwastatynę w dawce 10 i 80 mg i nie różniły się od obserwowanych w grupie otrzymującej placebo. WNIOSKI. Podawanie chorym na cukrzycę typu 2 atorwastatyny w dawkach 10 i 80 mg powoduje zbliżone, wyraźne obniżenie stężenia triglicerydów w stosunku do wartości wyjściowych. Duże dawki atorwastatyny korzystnie wpływają na stężenie cholesterolu. Obie dawki były dobrze tolerowane w tej grupie chorych.INTRODUCTION. In patients with type 2 diabetes, intensive glucose regulation, although effective for microangiopathy, has not been shown to have unambiguous preventive effects on the occurrence of cardiovascular disease. Patients with diabetes show a characteristic dyslipidemia (high triglyceride level, low HDL cholesterol level). Aggressive reduction of triglycerides might be an effective method to reduce the cardiovascular risk in these patients. MATERIAL AND METHODS. A double-blind, placebocontrolled, randomized study to assess the effect of 30 weeks of administration of atorvastatin 10 and 80 mg on plasma triglyceride levels in 217 patients with type 2 diabetes and fasting triglyceride levels between 1.5 and 6.0 mmol/l. RESULTS. Administration of atorvastatin 10 and 80 mg resulted in significant reductions (25 and 35%, respectively) of plasma triglyceride levels (both P 0.5). Atorvastatin 10 mg provided significant reductions from baseline in total cholesterol (&#8211;30%, P < 0.001), LDL cholesterol (&#8211;40%, P < 0.001), and apolipoprotein B (&#8211;31%, P < 0.001), and significantly increased HDL cholesterol from baseline by 6% (P < 0.005). Atorvastatin 80 mg had a similar effect on HDL cholesterol (+5.2%, P < 0.005) but significantly decreased total cholesterol (&#8211;40%, P < 0.001), LDL cholesterol (&#8211;52%, P < 0.001), and apolipoprotein B (&#8211;40%, P < 0.001) more than atorvastatin 10 mg (P < 0.005). The side effects of atorvastatin 10 and 80 mg were similar and did not differ from the patients receiving placebo. CONCLUSIONS. Administration of 10- and 80-mg doses of atorvastatin provides similar, significant reductions from baseline in triglyceride levels in patients with type 2 diabetes. A higher dose of atorvastatin improves cholesterol-related parameters. Both doses were well tolerated in this patient population

Susceptibility to Neurodegeneration in a Glaucoma Is Modified by Bax Gene Dosage

In glaucoma, harmful intraocular pressure often contributes to retinal ganglion cell death. It is not clear, however, if intraocular pressure directly insults the retinal ganglion cell axon, the soma, or both. The pathways that mediate pressure-induced retinal ganglion cell death are poorly defined, and no molecules are known to be required. DBA/2J mice deficient in the proapoptotic molecule BCL2-associated X protein (BAX) were used to investigate the roles of BAX-mediated cell death pathways in glaucoma. Both Bax (+/−) and Bax (−/−) mice were protected from retinal ganglion cell death. In contrast, axonal degeneration was not prevented in either Bax (+/−) or Bax (−/−) mice. While BAX deficiency did not prevent axonal degeneration, it did slow axonal loss. Additionally, we compared the effects of BAX deficiency on the glaucoma to its effects on retinal ganglion cell death due to two insults that are proposed to participate in glaucoma. As in the glaucoma, BAX deficiency protected retinal ganglion cells after axon injury by optic nerve crush. However, it did not protect retinal ganglion cells from N-methyl-D-aspartate (NMDA)-induced excitotoxicity. BAX is required for retinal ganglion cell death in an inherited glaucoma; however, it is not required for retinal ganglion cell axon degeneration. This indicates that distinct somal and axonal degeneration pathways are active in this glaucoma. Finally, our data support a role for optic nerve injury but not for NMDA receptor-mediated excitotoxicity in this glaucoma. These findings indicate a need to understand axon-specific degeneration pathways in glaucoma, and they suggest that distinct somal and axonal degeneration pathways may need to be targeted to save vision

Collective action, collective impact: New Hampshire\u27s strategy for reducing the misuse of alcohol and other drugs and promoting recovery 2013-2017

Provides information on how to reduce the misuse of alcohol and other drugs in New Hampshire

Call to action: responding to New Hampshire\u27s prescription drug abuse epidemic

Report of prescription drug abueuse in New Hampshire

Stroke following percutaneous coronary intervention : type-specific incidence, outcomes and determinants seen by the British Cardiovascular Intervention Society 2007-12

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: [email protected] reviewedPostprin

Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial.

Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (β) 0.33) and negatively associated with eGFR (β -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g