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

GAFA Geometric And Functional Analysis FINITE JET DETERMINATION OF LOCAL ANALYTIC CR AUTOMORPHISMS AND THEIR PARAMETRIZATION BY 2-JETS IN THE FINITE

We show that germs of local real-analytic CR automorphisms of a real-analytic hypersurface M in C 2 at a point p ∈ M are uniquely determined by their jets of some finite order at p if and only if M is not Levi-flat near p. This seems to be the first necessary and sufficient result on finite jet determination and the first result of this kind in the infinite type case. If M is of finite type at p, we prove a stronger assertion: the local real-analytic CR automorphisms of M fixing p are analytically parametrized (and hence uniquely determined) by their 2-jets at p. This result is optimal since the automorphisms of the unit sphere are not determined by their 1-jets at a point of the sphere. The finite type condition is necessary since otherwise the needed jet order can be arbitrarily high [Kow1,2], [Z2]. Moreover, we show, by an example, that determination by 2-jets fails for finite type hypersurfaces already in C3. We also give an application to the dynamics of germs of local biholomorphisms of C 2.

Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 Diabetes

OBJECTIVE This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing β-cells in subjects with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. RESULTS One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. CONCLUSIONS Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process

Depression in Chinese patients with type 2 diabetes: associations with hyperglycemia, hypoglycemia, and poor treatment adherence.

BackgroundWe hypothesize that depression in type 2 diabetes might be associated with poor glycemic control, in part due to suboptimal self-care. We tested this hypothesis by examining the associations of depression with clinical and laboratory findings in a multicenter survey of Chinese type 2 diabetic patients.Method2538 patients aged 18-75 years attending hospital-based clinics in four cities in China underwent detailed clinical-psychological-behavioral assessment during a 12-month period between 2011 and 2012. Depression was diagnosed if Patient Health Questionnaire-9 (PHQ-9) score ≥10. Diabetes self-care and medication adherence were assessed using the Summary of Diabetes Self-care Activities and the 4-item Morisky medication adherence scale respectively.ResultsIn this cross-sectional study (mean age: 56.4 ± 10.5[SD] years, 53% men), 6.1% (n = 155) had depression. After controlling for study sites, patients with depression had higher HbA(1c) (7.9 ± 2.0 vs. 7.7 ± 2.0%, P = 0.008) and were less likely to achieve HbA(1c) goal of <7.0% (36.2% vs 45.6%, P = 0.004) than those without depression. They were more likely to report hypoglycemia and to have fewer days of being adherent to their recommended diet, exercise, foot care and medication. In logistic regression, apart from young age, poor education, long disease duration, tobacco use, high body mass index, use of insulin, depression was independently associated with failure to attain HbA(1c) target (Odds Ratio [OR] = 1.56, 95%CI:1.05-2.32, P = 0.028). The association between depression and glycemic control became non-significant after inclusion of adherence to diet, exercise and medication (OR = 1.48, 95% CI 0.99-2.21, P = 0.058).ConclusionDepression in type 2 diabetes was closely associated with hyperglycemia and hypoglycemia, which might be partly mediated through poor treatment adherence

Dysglycemia and Index60 as Prediagnostic End Points for Type 1 Diabetes Prevention Trials

OBJECTIVE: We assessed dysglycemia and a T1D Diagnostic Index60 (Index60) ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants. RESEARCH DESIGN AND METHODS: Two cohorts were analyzed: 1) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and 2) baseline Index60 <1.00 OGTTs with an incident Index60 ≥1.00 OGTT. Incident dysglycemic OGTTs were divided into those with (DYS/IND+) and without (DYS/IND-) concomitant Index60 ≥1.00. Incident Index60 ≥1.00 OGTTs were divided into those with (IND/DYS+) and without (IND/DYS-) concomitant dysglycemia. RESULTS: The cumulative incidence for type 1 diabetes was greater after IND/DYS- than after DYS/IND- (P < 0.01). Within the normoglycemic cohort, the cumulative incidence of type 1 diabetes was higher after DYS/IND+ than after DYS/IND- (P < 0.001), whereas within the Index60 <1.00 cohort, the cumulative incidence after IND/DYS+ and after IND/DYS- did not differ significantly. Among nonprogressors, type 1 diabetes risk at the last OGTT was greater for IND/DYS- than for DYS/IND- (P < 0.001). Hazard ratios (HRs) of DYS/IND- with age and 30- to 0-min C-peptide were positive (P < 0.001 for both), whereas HRs of type 1 diabetes with these variables were inverse (P < 0.001 for both). In contrast, HRs of IND/DYS- and type 1 diabetes with age and 30- to 0-min C-peptide were consistent (all inverse [P < 0.01 for all]). CONCLUSIONS: The findings suggest that incident dysglycemia without Index60 ≥1.00 is a suboptimal prediagnostic end point for type 1 diabetes. Measures that include both glucose and C-peptide levels, such as Index60 ≥1.00, appear better suited as prediagnostic end points

(De)Localization in the Prime Schrodinger Operator

It is reported a combined numerical approach to study the localization properties of the one-dimensional tight-binding model with potential modulated along the prime numbers. A localization-delocalization transition was found as function of the potential intensity; it is also argued that there are delocalized states for any value of the potential intensity.Comment: 7 pages, 4 figures; to be published in J. Phys. A: Math. Ge

The cost of type 1 diabetes: a nationwide multicentre study in Brazil

Objective To determine the direct medical costs of type 1 diabetes mellitus (T1DM) to the National Brazilian Health-Care System (NBHCS) and quantify the contribution of each individual component to the total cost.Methods A retrospective, cross-sectional, nationwide multicentre study was conducted between 2008 and 2010 in 28 public clinics in 20 Brazilian cities. the study included 3180 patients with T1DM (mean age 22 year's +/- 11.8) who were surveyed while receiving health care from the NBHCS. the mean duration of their diabetes was 10.3 years (+/- 8.0). the costs of tests and medical procedures, insulin pumps, and supplies for administration, and supplies for self-monitoring of blood glucose (SMBG) were obtained from national and local health system sources for 2010-2011. Annual direct medical costs were derived by adding the costs of medications, supplies, tests, medical consultations, procedures and hospitalizations over the year preceding the interview.Findings the average annual direct medical cost per capita was 1319.15 United States dollars (US$). Treatment-related expenditure - US$ 1216.33 per patient per year represented 92.20% of total direct medical costs. Insulin administration supplies and SMBG (US$696.78 per patient per year) accounted for 52.82$ 75.64 per patient per year) of direct medical costs. Consultations accounted for 1.94% of direct medical costs (US$ 25.62 per patient per year).Conclusion Health technologies accounted for most direct medical costs of T1DM. These data can serve to reassess the distribution of resources for managing T1DM in Brazil's public health-care system.Farmanguinhos/Fundacao Oswaldo Cruz/National Health MinistryBrazilian Diabetes SocietyFundacao do Amparo a Pesquisa do Estado do Rio de JaneiroConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)State Univ Hosp Rio de Janeiro, BR-20551030 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilBauru Diabet Assoc, Bauru, BrazilJoinville Endocrinol & Diabet Inst, Joinville, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry