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

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.

SUBMITTER: Adolescent type 1 Diabetes cardio-renal Intervention Trial Research Group

PROVIDER: S-EPMC2814806 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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

BMC pediatrics 20091217

<h4>Background</h4>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. Howe ...[more]

PMID: 20017932

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Project description:BackgroundGlycocalyx lines the inner surface of the capillary endothelium. Capillaroscopy enables visualization of the sublingual capillaries and measurement of the Perfused Boundary Region (PBR) as an estimate of the glycocalyx. Novel software enables assessment of the PBR estimated at a fixed high flow level (PBR-hf) and an overall microvascular assessment by the MicroVascular Health Score (MVHS). Damaged glycocalyx may represent microvascular damage in diabetes and assessment of its dimension might improve early cardio-renal risk stratification.AimTo assess the associations between PBR, PBR-hf and MVHS and cardio-renal risk factors in persons with type 1 diabetes (T1D); and to compare these dimensions in persons with T1D and controls.MethodsCross-sectional study including 161 persons with T1D stratified according to level of albuminuria and 50 healthy controls. The PBR, PBR-hf and MVHS were assessed by the GlycoCheck device (valid measurements were available in 136 (84.5%) with T1D and in all the controls). Higher PBR and PBR-hf indicate smaller glycocalyx width. Lower MVHS represents a worse microvascular health.ResultsThere were no associations between PBR, PBR-hf or MVHS and the cardio-renal risk factors in persons with T1D, except for higher PBR-hf and lower MVHS in females (p = 0.01 for both). There was no difference in PBR, PBR-hf or MVHS in persons with normo-, micro- or macroalbuminuria. The PBR was higher (2.20±0.30 vs. 2.03±0.18μm; p<0.001) and MVHS lower (3.15±1.25 vs. 3.53±0.86μm; p = 0.02) in persons with T1D compared to controls (p≤0.02). After adjustment for cardio-renal risk factors the difference in PBR remained significant (p = 0.001).ConclusionsThe endothelial glycocalyx dimension was impaired in persons with T1D compared to controls. We found no association between the endothelial glycocalyx dimension and the level of albuminuria or cardio-renal risk factors among persons with T1D. The use of the GlycoCheck device in T1D may not contribute to cardio-renal risk stratification.

Project description:In patients with type 2 diabetes (T2D), the excretion of glucose by the kidney with sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers glycosylated haemoglobin (HbA1c) levels, decreases body weight and visceral adiposity, as well as improving cardio-renal haemodynamics. Currently, four SGLT2 inhibitors are approved in the US and Europe to improve glycaemic control - empagliflozin, dapagliflozin, canagliflozin, and ertuglifozin. Recently, the SGLT2 inhibitor empagliflozin was approved by the FDA for the reduction of cardiovascular (CV) death in adults with T2D and CV disease (CVD). This approval was based on the findings of the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study, which was the first study to show a significant reduction of a primary CV endpoint with a glucose-lowering agent. In this study, the primary outcome (CV mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was reduced by empagliflozin (10.5%; 490/4,687) compared with placebo (12.1%; 282/2,333); hazard ratio (HR), 0.86 (95% confidence interval [CI]: 0.74, 0.99). The primary outcome was driven by a large reduction of CV mortality (relative risk reduction [RRR], 38%). Empagliflozin also reduced all-cause mortality (RRR, 32%). Furthermore, empagliflozin reduced the adjudicated outcome of heart failure (HF) hospitalisation by 35% (HR, 0.65; 95% CI: 0.50, 0.85). Other non-adjudicated measures of HF outcomes were similarly reduced including investigator reported HF, the introduction of loop diuretics and death from HF. In the analysis of renal outcomes, incident or worsening nephropathy was reduced for empagliflozin (12.7%) compared with placebo (18.8%); HR, 0.61 (95% CI: 0.53, 0.70). Empagliflozin significantly reduced the risk of progression to macroalbuminuria (38%) and doubling of creatinine (44%), as well as the need of starting renal-replacement therapy (55%). The benefits of empagliflozin for the reduction of CV death, all-cause death and hospitalisation for HF were observed across a range of baseline subgroups such as HbA1c level and renal function (down to estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m2). The rapid reduction of HF outcomes with empagliflozin is observed across the spectrum of CVD and HF risk and represents a therapeutic advance in the prevention and perhaps also in the treatment of HF, an often poorly recognised complication of T2D. This review discusses the EMPA-REG OUTCOME study and the implications for treating patients with T2D and CVD.

Project description:OBJECTIVE:(1) Evaluate feasibility and acceptability of a mindfulness-based group in adolescent girls at-risk for type 2 diabetes (T2D) with depressive symptoms, and (2) compare efficacy of a mindfulness-based versus cognitive-behavioral group for decreasing depressive symptoms and improving insulin resistance. DESIGN AND SETTING:Parallel-group, randomized controlled pilot trial conducted at a university. PARTICIPANTS:Thirty-three girls 12-17y with overweight/obesity, family history of diabetes, and elevated depressive symptoms were randomized to a six-week mindfulness-based (n=17) or cognitive-behavioral program (n=16). INTERVENTIONS:Both interventions included six, one-hour weekly group sessions. The mindfulness-based program included guided mindfulness awareness practices. The cognitive-behavioral program involved cognitive restructuring and behavioral activation. MAIN OUTCOME MEASURES:Adolescents were evaluated at baseline, post-intervention, and six-months. Feasibility/acceptability were measured by attendance and program ratings. Depressive symptoms were assessed by validated survey. Insulin resistance was determined from fasting insulin and glucose, and dual energy x-ray absorptiometry was used to assess body composition. RESULTS:Most adolescents attended ?80% sessions (mindfulness: 92% versus cognitive-behavioral: 87%, p=1.00). Acceptability ratings were strong. At post-treatment and six-months, adolescents in the mindfulness condition had greater decreases in depressive symptoms than adolescents in the cognitive-behavioral condition (ps<.05). Compared to the cognitive-behavioral condition, adolescents in the mindfulness-based intervention also had greater decreases in insulin resistance and fasting insulin at post-treatment, adjusting for fat mass and other covariates (ps<.05). CONCLUSIONS:A mindfulness-based intervention shows feasibility and acceptability in girls at-risk for T2D with depressive symptoms. Compared to a cognitive-behavioral program, after the intervention, adolescents who received mindfulness showed greater reductions in depressive symptoms and better insulin resistance. ClinicalTrials.gov identifier: NCT02218138 clinicaltrials.gov.

Project description:Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy. Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo. Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.

Project description:BACKGROUND:Rising obesity levels remain a major public health concern due to the clear link with several comorbidities such as diabetes. Diabetes now affects 6% of the UK population. Modest weight loss of 5% to 10% has been shown to be associated with significant reductions in blood sugar, lipid, and blood pressure levels. Men have been shown to be attracted to programs that do not require extensive face-to-face time commitments, illustrating the potential audience available for health behavior change via the Web. OBJECTIVE:The objective of our study was to evaluate the feasibility and acceptability of a Web-based weight loss intervention in men with type 2 diabetes. METHODS:We conducted a pilot, parallel 2-arm, individually randomized controlled trial with embedded process evaluation. Participants were randomly assigned in a one-to-one ratio to the usual care group or the 12-month Web-based weight loss intervention, including dietitian and exercise expert feedback. Face-to-face recruitment and assessment were performed by the researcher unblinded. Data collected included weight, height, body mass index (BMI), and waist circumference, together with an audit trail of eligibility, recruitment, retention, and adherence rates. A process evaluation (website use data and qualitative interviews) monitored adherence, acceptability, and feasibility of the intervention. RESULTS:General practice database searches achieved the recruitment target (n=61) for the population of men with type 2 diabetes, of whom 66% (40/61) completed 3-month follow-up measurements. By 12 months, the retention rate was 52% (32/61), with 12 of the 33 men allocated to the intervention group still active on the website. The intervention was seen as acceptable by the majority of participants. We gained insights about acceptability and use of the website from the parallel process evaluation. CONCLUSIONS:Recruitment to the Web-based weight loss intervention was successful. Results are descriptive, but there were positive indications of increased weight loss (in kilograms and as a percentage), and reduced waist circumference and BMI for the intervention group from 3 to 12 months, in comparison with control. This research adds to the evidence base in relation to incorporating a Web-based weight loss intervention within the UK National Health Service (NHS). NHS weight loss services are struggling to provide sufficient referrals. Therefore, alternative modes of delivery, with the potential to reduce health professional input and time per patient while still enabling individual and tailored care, need to be investigated to identify whether they can be effective and thus benefit the NHS. TRIAL REGISTRATION:International Standard Randomized Controlled Trial Number (ISRCTN): 48086713; http://www.isrctn.com/ISRCTN48086713 (Archived by WebCite at http://www.webcitation.org/6rO4xSlhI).

Dataset Information

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

Publications

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

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