Hot off the presses! Jul 15 Lancet

The Jul 15 issue of the Lancet is now up on Pubget (About Lancet): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• The diabetes pandemic
  - Lancet 378(9786):99 (2011)
  
• The assault on reproductive rights
  - Lancet 378(9786):100 (2011)
  
• Inspiring young scientists: a Nobel cause
  - Lancet 378(9786):100 (2011)
  
• Diet and exercise for new-onset type 2 diabetes?
  - Lancet 378(9786):101-102 (2011)
  
• Glycaemia and heart failure in diabetes types 1 and 2
  - Lancet 378(9786):103-104 (2011)
  
• HbA1c and blood glucose for the diagnosis of diabetes
  - Lancet 378(9786):104-106 (2011)
  
• The case for diabetes screening: ADDITION-Europe
  - Lancet 378(9786):106-108 (2011)
  
• IDF's view of bariatric surgery in type 2 diabetes
  - Lancet 378(9786):108-110 (2011)
  
• The medium-secure project and criminal justice mental health
  - Lancet 378(9786):110-111 (2011)
  
• Offline: What about the people?
  - Lancet 378(9786):112 (2011)
  
• The long Avandia endgame
  - Lancet 378(9786):113 (2011)
  
• NHS reform: take two
  - Lancet 378(9786):114-115 (2011)
  
• Report criticises antipsychotic use in US nursing homes
  - Lancet 378(9786):116 (2011)
  
• The Lancet Technology: July, 2011
  - Lancet 378(9786):117 (2011)
  
• Tien Yin Wong: tackling the rising burden of diabetic retinopathy
  - Lancet 378(9786):118 (2011)
  
• Medha Munshi: tailoring diabetes care for older patients
  - Lancet 378(9786):119 (2011)
  
• The substance of the brand
  - Lancet 378(9786):120-121 (2011)
  
• Rosalyn Sussman Yalow
  - Lancet 378(9786):122 (2011)
  
• GOSH consultants express alarm
  - Lancet 378(9786):123 (2011)
  
• Response to Offline about Great Ormond Street Hospital
  - Lancet 378(9786):123-124 (2011)
  
• Effects of the 2008 recession on health: a first look at European data
  - Lancet 378(9786):124-125 (2011)
  
• Phentermine plus topiramate in the treatment of obesity
  - Lancet 378(9786):125-126 (2011)
  
• Phentermine plus topiramate in the treatment of obesity
  - Lancet 378(9786):126 (2011)
  
• Phentermine plus topiramate in the treatment of obesity – Authors' reply
  - Lancet 378(9786):126-127 (2011)
  
• Safety of medicines and the use of animals in research
  - Lancet 378(9786):127-128 (2011)
  
• Safety of medicines and the use of animals in research
  - Lancet 378(9786):128 (2011)
  
• Department of Error
  - Lancet 378(9786):128 (2011)
  
• Department of Error
  - Lancet 378(9786):128 (2011)
  
• Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial
  - Lancet 378(9786):129-139 (2011)
  Background Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus, but no large trials have compared interventions. We investigated the effects of diet and physical activity on blood pressure and glucose concentrations. Methods We did a randomised, controlled trial in southwest England in adults aged 30–80 years in whom type 2 diabetes had been diagnosed 5–8 months previously. Participants were assigned usual care (initial dietary consultation and follow-up every 6 months; control group), an intensive diet intervention (dietary consultation every 3 months with monthly nurse support), or the latter plus a pedometer-based activity programme, in a 2:5:5 ratio. The primary endpoint was improvement in glycated haemoglobin A1c(HbA1c) concentration and blood pressure at 6 months. Analysis was done by intention to treat. This study is registered, number ISRCTN92162869. Findings Of 593 eligible individuals, 99 were assigned usual care, 248 the diet regimen, and 246 diet plus activity. Outcome data were available for 587 (99%) and 579 (98%) participants at 6 and 12 months, respectively. At 6 months, glycaemic control had worsened in the control group (mean baseline HbA1c percentage 6·72, SD 1·02, and at 6 months 6·86, 1·02) but improved in the diet group (baseline-adjusted difference in percentage of HbA1c −0·28%, 95% CI −0·46 to −0·10; p=0·005) and diet plus activity group (−0·33%, −0·51 to −0·14; p<0·001). These differences persisted to 12 months, despite less use of diabetes drugs. Improvements were also seen in bodyweight and insulin resistance between the intervention and control groups. Blood pressure was similar in all groups. Interpretation An intensive diet intervention soon after diagnosis can improve glycaemic control. The addition of an activity intervention conferred no additional benefit. Funding Diabetes UK and the UK Department of Health.
• Glycaemic control and incidence of heart failure in 20 985 patients with type 1 diabetes: an observational study
  - Lancet 378(9786):140-146 (2011)
  Background Poor glycaemic control is associated with microvascular and macrovascular complications in type 1 diabetes, but whether glycaemic control is associated with heart failure in such patients is not known. We aimed to assess this association in a large cohort of patients with type 1 diabetes identified from the Swedish national diabetes registry. Methods We identified all patients (aged ≥18 years) with type 1 diabetes and no known heart failure who were registered in the national diabetes registry between January, 1998, and December, 2003. These patients were followed up until hospital admission for heart failure, death, or end of follow-up on Dec 31, 2009. We calculated incidence categorised by glycated haemoglobin A1c (HbA1c) values, and we assessed the association between patients' characteristics, including HbA1c, and heart failure. Findings In a cohort of 20 985 patients with mean age of 38·6 years (SD 13·3) at baseline, 635 patients (3%) were admitted to hospital with a primary or secondary diagnosis of heart failure during a median follow-up of 9·0 years (IQR 7·3–11·0), with an incidence of 3·38 events per 1000 patient-years (95% CI 3·12–3·65). Incidence increased monotonically with HbA1c, with a range of 1·42–5·20 per 1000 patient-years between patients in the lowest (<6·5%) and highest (≥10·5%) categories of HbA1c. In a Cox regression analysis, with adjustment for age, sex, duration of diabetes, cardiovascular risk factors, and baseline or intervening acute myocardial infarction and other comorbidities, the hazard ratio for development of heart failure was 3·98 (95% CI 2·23–7·14) in patients with HbA1c of 10·5% or higher compared with a reference group of patients with HbA1c of less than 6·5%. Risk of heart failure increased with age and duration of diabetes. Other modifiable facto rs associated with increased risk of heart failure were smoking, high systolic blood pressure, and raised body-mass index. In a subgroup of 18 281 patients (87%) with data for blood lipids, higher HDL cholesterol was associated with lower risk of heart failure, but there was no association with LDL cholesterol. Interpretation The positive association between HbA1c and risk of heart failure in fairly young patients with type 1 diabetes indicates a potential for prevention of heart failure with improved glycaemic control. Funding AstraZeneca, Novo Nordisk Scandinavia, Swedish Heart and Lung Foundation, and Swedish Research Council.
• HbA1c 5·7–6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study
  - Lancet 378(9786):147-155 (2011)
  Background The clinical relevance of the diagnostic criteria for prediabetes to prediction of progression to diabetes has been little studied. We aimed to compare the prevalence of prediabetes when assessed by the new glycated haemoglobin A1c (HbA1c) 5·7–6·4% criterion or by impaired fasting glucose, and assessed differences in progression rate to diabetes between these two criteria for prediabetes in a Japanese population. Methods Our longitudinal cohort study included 4670 men and 1571 women aged 24–82 years without diabetes at baseline (diabetes was defined as fasting plasma glucose ≥7·0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA1c ≥6·5%) who attended Toranomon Hospital (Tokyo, Japan) for a routine health check between 1997 and 2003. Participants with a baseline diagnosis of prediabetes according to impaired fasting glucose (fasting plasma glucose 5·6–6·9 mmol/L) or HbA1c 5·7–6·4%, or both, were divided into four groups on the basis of baseline diagnosis of prediabetes. Rate of progression to diabetes was assessed annually. Findings Mean follow-up was 4·7 (SD 0·7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA1c 5·7–6·4% criterion. Screening by HbA1c alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA1c 5·7–6·4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA1c or impaired fasting glucose alone (incidence was 7% for HbA1c alone [n=412 individuals and 30 incident cases] and 9% for impaired fasting glucose alone [n=1270, 108 cases]; log-rank test, p=0·3317). Multivariate-adjusted hazard ratios for incident diabetes were 6·16 (95% CI 4·33–8·77) for those diagnosed with prediabetes by impaired fasting glucose alone and 6·00 (3·76–9·56) for diagnosis by HbA1c alone, and were substantially increased to 31·9 (22·6–45·0) for diagnosis by both impaired fasting glucose and HbA1c compared with normoglycaemic individuals. Interpretation Diagnosis of prediabetes by both the new HbA1c criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA1c criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA1c 5·7–6·4% was similar to that assessed by impaired fasting glucose alone. The two tests used together could efficiently target people who are most likely to develop diabetes and allow for early intervention. Funding Japan Society for the Promotion of Science; Ministry of Health Labor and Welfare, Japan.
• Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial
  - Lancet 378(9786):156-167 (2011)
  Background Intensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening. Methods In a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40–69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non-traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practice's study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549. Findings Primary endpoint data were available for 3055 (99·9%) of 3057 screen-detected patients. The mean age was 60·3 (SD 6·9) years and the mean duration of follow-up was 5·3 (SD 1·6) years. Improvements in cardiovascular risk factors (HbA1c and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7·2% (13·5 per 1000 person-years) in the intensive treatment group and 8·5% (15·9 per 1000 person-years) in the routine care group (hazard ratio 0·83, 95% CI 0·65–1·05), and of all-cause mortality 6·2% (11·6 per 1000 person-years) and 6·7% (12·5 per 1000 person-years; 0·91, 0·69–1·21), respectively. Interpretation An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death. Funding National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Wellcome Trust, UK Medical Research Council, UK NIHR Health Technology Assessment Programme, UK National Health Service R&D, UK National Institute for Health Research, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Novo Nordisk, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Merck.
• Spontaneous aneurysm of the superficial temporal artery
  - Lancet 378(9786):168 (2011)
  
• Type 2 diabetes across generations: from pathophysiology to prevention and management
  - Lancet 378(9786):169-181 (2011)
  Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet β-cell and adipose-tissue responses to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing β cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues such as the heart. Reversal of overnutrition, healing of the β cells, and lessen ing of adipose tissue defects should be treatment priorities.
• Management of type 2 diabetes: new and future developments in treatment
  - Lancet 378(9786):182-197 (2011)
  The increasing prevalence, variable pathogenesis, progressive natural history, and complications of type 2 diabetes emphasise the urgent need for new treatment strategies. Longacting (eg, once weekly) agonists of the glucagon-like-peptide-1 receptor are advanced in development, and they improve prandial insulin secretion, reduce excess glucagon production, and promote satiety. Trials of inhibitors of dipeptidyl peptidase 4, which enhance the effect of endogenous incretin hormones, are also nearing completion. Novel approaches to glycaemic regulation include use of inhibitors of the sodium–glucose cotransporter 2, which increase renal glucose elimination, and inhibitors of 11β-hydroxysteroid dehydrogenase 1, which reduce the glucocorticoid effects in liver and fat. Insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery.
• Papular-purpuric gloves and socks syndrome
  - Lancet 378(9786):198 (2011)