Adding free to total prostate-specific antigen levels in trials of prostate cancer screening

We used a nested case–control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to α-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials. © 2000 Cancer Research Campaig

The circadian syndrome predicts cardiovascular disease better than metabolic syndrome in Chinese adults

Background To compare the predictive value of the circadian syndrome (CircS) and Metabolic syndrome (MetS) for cardiovascular disease. Method We used the data of 9360 Chinese adults aged >= 40 years from the 2011 China Health and Retirement Longitudinal Study (CHARLS). Of the participants, 8253 people were followed in the 2015 survey. MetS was defined using the harmonized criteria. CircS was based on the components of the International Diabetes Federation (IDF) MetS plus short sleep and depression. The cut-off for CircS was set as >= 4. Multivariable logistic regression analysis was used to examine the associations. Results The prevalence of CircS and MetS was 39.0% and 44.7%. Both MetS and CircS were directly associated with prevalent CVD. The odds ratios for prevalent CVD comparing CircS with MetS, respectively, were 2.83 (95%CI 2.33-3.43) and 2.34 (1.93-2.83) in men, and 2.33 (1.98-2.73) and 1.79 (1.53-2.10) in women. Similar associations were found for incident CVD. The five-year incidence of CVD was 15.1% in CircS and 14.0% in MetS. The number of CircS components has a better predictive power for both prevalent and incident CVD than those of Mets components as indicated by the area under the ROC (AUC). AUC values for CVD in 2011 were higher for CircS than MetS in both men (0.659 (95%CI 0.634-0.684) vs 0.635 (95%CI 0.610-0.661)) and women (0.652 (95%CI 0.632-0.672) vs 0.619 (95%CI 0.599-0.640)). Conclusion The circadian syndrome is a strong and better predictor for CVD than the metabolic syndrome in Chinese adults.Peer reviewe

Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial

Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment. Design One year open label active treatment extension of randomised controlled trial (Hypertension in the Very Elderly Trial (HYVET)). Setting Hospital and general practice based centres mainly in eastern and western Europe, China, and Tunisia. Participants People on double blind treatment at the end of HYVET were eligible to enter the extension. Interventions Participants on active blood pressure lowering treatment continued taking active drug; those on placebo were given active blood pressure lowering treatment. The treatment regimen was as used in the main trial-indapamide SR 1.5 mg (plus perindopril 2-4 mg if required)-with the same target blood pressure of less than 150/80 mm Hg. Main outcome measures The primary outcome was all stroke; other outcomes included total mortality, cardiovascular mortality, and cardiovascular events. Results Of 1882 people eligible for entry to the extension, 1712 (91%) agreed to participate. During the extension period, 1682 patient years were accrued. By six months, the difference in blood pressure between the two groups was 1.2/0.7 mm Hg. Comparing people previously treated with active drug and those previously on placebo, no significant differences were seen for stroke (n=13; hazard ratio 1.92, 95% confidence interval 0.59 to 6.22) or cardiovascular events (n=25; 0.78, 0.36 to 1.72). Differences were seen for total mortality (47 deaths; hazard ratio 0.48, 0.26 to 0.87; P=0.02) and cardiovascular mortality (11 deaths; 0.19, 0.04 to 0.87; P=0.03). Conclusion Very elderly patients with hypertension may gain immediate benefit from treatment. Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data

Objectives To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. Methods Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. Participants Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. Intervention Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: Composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. Results One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. Conclusions ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with prediabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes

Informing patients of familial diabetes mellitus risk: How do they respond? A cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>A strong family history of type 2 diabetes mellitus (DM) confers increased DM risk. This survey analysis determined whether patients who were informed by their doctors of familial DM risk acknowledged that risk and took steps to reduce it.</p> <p>Methods</p> <p>We conducted an analysis of the National <it>Health Styles 2004 </it>mail survey. All non-diabetic participants who responded to the question of whether their doctor had or had not informed them of their familial DM risk (<it>n </it>= 3,323) were compared for their risk-reducing behaviour and attitude to DM risk.</p> <p>Results</p> <p>Forty-one percent (<it>n </it>= 616) of the question responders that had DM family histories were informed by their doctors of their familial risk; the chance of being informed increased with the number of relatives that had the disease. Members of the informed group were more likely than those in the non-informed group to report lifestyle changes to prevent DM (odds ratio [OR] 4.3, 95% confidence interval [CI] 3.5–5.2) and being tested for DM (OR 2.9, 95% CI 2.4–3.6), although no significant improvement occurred in their U.S.-recommended exercise activity (OR 0.9, 95% CI 0.7–1.1). Overall, informed responders recognised both their familial and personal DM risk; most discussed diabetes with their family (69%), though less so with friends (42%); however, 44% of them still did not consider themselves to be at risk.</p> <p>Conclusion</p> <p>Responders who were informed by their doctors of being at familial DM risk reported greater incidences of lifestyle changes, DM screening, and awareness of risk than non-informed responders. Doctors were more likely to inform patients with stronger DM family histories. Identifying this higher risk group, either in isolation or in combination with other recognised risk factors, offers doctors the opportunity to target limited health promotion resources efficiently for primary DM prevention.</p

Glycemia Determines the Effect of Type 2 Diabetes Risk Genes on Insulin Secretion

OBJECTIVE—Several single nucleotide polymorphisms (SNPs) in diabetes risk genes reduce glucose- and/or incretin-induced insulin secretion. Here, we investigated interactions between glycemia and such diabetes risk polymorphisms. RESEARCH DESIGN AND METHODS—Insulin secretion was assessed by insulinogenic index and areas under the curve of C-peptide/glucose in 1,576 subjects using an oral glucose toler-ance test (OGTT). Participants were genotyped for 10 diabetes risk SNPs associated with -cell dysfunction: rs5215 (KCNJ11), rs13266634 (SLC30A8), rs7754840 (CDKAL1), rs10811661 (CDKN2A/2B), rs10830963 (MTNR1B), rs7903146 (TCF7L2), rs10010131 (WFS1), rs7923837 (HHEX), rs151290 (KCNQ1), an

The effect of hypoxia and work intensity on insulin resistance in type 2 diabetes

Context:Hypoxia and muscle contraction stimulate glucose transport in vitro. We have previously demonstrated that exercise and hypoxia have an additive effect on insulin sensitivity in type 2 diabetics.Objectives:Our objective was to examine the effects of three different hypoxic/exercise (Hy Ex) trials on glucose metabolism and insulin resistance in the 48 h after acute hypoxia in type 2 diabetics.Design, Participants, and Interventions:Eight male type 2 diabetics completed 60 min of hypoxic [mean (sem) O(2) = ∼14.7 (0.2)%] exercise at 90% of lactate threshold [Hy Ex(60); 49 (1) W]. Patients completed an additional two hypoxic trials of equal work, lasting 40 min [Hy Ex(40); 70 (1) W] and 20 min [Hy Ex(20); 140 (12) W].Main Outcome Measures:Glucose rate of appearance and rate of disappearance were determined using the one-compartment minimal model. Homeostasis models of insulin resistance (HOMA(IR)), fasting insulin resistance index and β-cell function (HOMA(β-cell)) were calculated at 24 and 48 h after trials.Results:Peak glucose rate of appearance was highest during Hy Ex(20) [8.89 (0.56) mg/kg · min, P < 0.05]. HOMA(IR) and fasting insulin resistance index were improved in the 24 and 48 h after Hy Ex(60) and Hy Ex(40) (P < 0.05). HOMA(IR) decreased 24 h after Hy Ex(20) (P < 0.05) and returned to baseline values at 48 h.Conclusions:Moderate-intensity exercise in hypoxia (Hy Ex(60) and Hy Ex(40)) stimulates acute- and moderate-term improvements in insulin sensitivity that were less apparent in Hy Ex(20). Results suggest that exercise duration and not total work completed has a greater influence on acute and moderate-term glucose control in type 2 diabetics