Laura J. Gray

Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis

Aims/hypothesisSedentary (sitting) behaviours are ubiquitous in modern society. We conducted a systematic review and meta-analysis to examine the association of sedentary time with diabetes, cardiovascular disease and cardiovascular and all-cause mortality.MethodsMedline, Embase and the Cochrane Library databases were searched for terms related to sedentary time and health outcomes. Cross-sectional and prospective studies were included. RR/HR and 95% CIs were extracted by two independent reviewers. Data were adjusted for baseline event rate and pooled using a random-effects model. Bayesian predictive effects and intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future.ResultsEighteen studies (16 prospective, two cross-sectional) were included, with 794,577 participants. Fifteen of these studies were moderate to high quality. The greatest sedentary time compared with the lowest was associated with a 112% increase in the RR of diabetes (RR 2.12; 95% credible interval [CrI] 1.61, 2.78), a 147% increase in the RR of cardiovascular events (RR 2.47; 95% CI 1.44, 4.24), a 90% increase in the risk of cardiovascular mortality (HR 1.90; 95% CrI 1.36, 2.66) and a 49% increase in the risk of all-cause mortality (HR 1.49; 95% CrI 1.14, 2.03). The predictive effects and intervals were only significant for diabetes.Conclusions/interpretationSedentary time is associated with an increased risk of diabetes, cardiovascular disease and cardiovascular and all-cause mortality; the strength of the association is most consistent for diabetes.

Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis

Objective To investigate the independent effects of intake of fruit and vegetables on incidence of type 2 diabetes. Design Systematic review and meta-analysis. Data sources Medline, Embase, CINAHL, British Nursing Index (BNI), and the Cochrane library were searched for medical subject headings and keywords on diabetes, prediabetes, fruit, and vegetables. Expert opinions were sought and reference lists of relevant articles checked. Study selection Prospective cohort studies with an independent measure of intake of fruit, vegetables, or fruit and vegetables and data on incidence of type 2 diabetes. Results Six studies met the inclusion criteria; four of these studies also provided separate information on the consumption of green leafy vegetables. Summary estimates showed that greater intake of green leafy vegetables was associated with a 14% (hazard ratio 0.86, 95% confidence interval 0.77 to 0.97) reduction in risk of type 2 diabetes (P=0.01). The summary estimates showed no significant benefits of increasing the consumption of vegetables, fruit, or fruit and vegetables combined. Conclusion Increasing daily intake of green leafy vegetables could significantly reduce the risk of type 2 diabetes and should be investigated further.

Association of Sedentary Behaviour with Metabolic Syndrome: A Meta-Analysis

Background In recent years there has been a growing interest in the relationship between sedentary behaviour (sitting) and health outcomes. Only recently have there been studies assessing the association between time spent in sedentary behaviour and the metabolic syndrome. The aim of this study is to quantify the association between sedentary behaviour and the metabolic syndrome in adults using meta-analysis. Methodology/Principal Findings Medline, Embase and the Cochrane Library were searched using medical subject headings and key words related to sedentary behaviours and the metabolic syndrome. Reference lists of relevant articles and personal databases were hand searched. Inclusion criteria were: (1) cross sectional or prospective design; (2) include adults ≥18 years of age; (3) self-reported or objectively measured sedentary time; and (4) an outcome measure of metabolic syndrome. Odds Ratio (OR) and 95% confidence intervals for metabolic syndrome comparing the highest level of sedentary behaviour to the lowest were extracted for each study. Data were pooled using random effects models to take into account heterogeneity between studies. Ten cross-sectional studies (n = 21393 participants), one high, four moderate and five poor quality, were identified. Greater time spent sedentary increased the odds of metabolic syndrome by 73% (OR 1.73, 95% CI 1.55–1.94, p<0.0001). There were no differences for subgroups of sex, sedentary behaviour measure, metabolic syndrome definition, study quality or country income. There was no evidence of statistical heterogeneity (I2 = 0.0%, p = 0.61) or publication bias (Eggers test t = 1.05, p = 0.32). Conclusions People who spend higher amounts of time in sedentary behaviours have greater odds of having metabolic syndrome. Reducing sedentary behaviours is potentially important for the prevention of metabolic syndrome.

Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care

Objective To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years. Design Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level. Setting 207 general practices in 13 primary care sites in the United Kingdom. Participants 731 of the 824 participants included in the original trial were eligible for follow-up. Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants. Intervention A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care. Main outcome measures The primary outcome was glycated haemoglobin (HbA1c) levels. The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years. Results HbA1c levels at three years had decreased in both groups. After adjusting for baseline and cluster the difference was not significant (difference −0.02, 95% confidence interval −0.22 to 0.17). The groups did not differ for the other biomedical and lifestyle outcomes and drug use. The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01). Depression scores and quality of life did not differ at three years. Conclusion A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs. Trial registration Current Controlled Trials ISRCTN17844016.

The promise of N-acetylcysteine in neuropsychiatry

N-Acetylcysteine (NAC) targets a diverse array of factors germane to the pathophysiology of multiple neuropsychiatric disorders including glutamatergic transmission, the antioxidant glutathione, neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways. This review summarises the areas where the mechanisms of action of NAC overlap with known pathophysiological elements, and offers a précis of current literature regarding the use of NAC in disorders including cocaine, cannabis, and smoking addictions, Alzheimers and Parkinsons diseases, autism, compulsive and grooming disorders, schizophrenia, depression, and bipolar disorder. There are positive trials of NAC in all these disorders, and although many of these require replication and are methodologically preliminary, this makes it one of the most promising drug candidates in neuropsychiatric disorders. The efficacy pattern of NAC interestingly shows little respect for the current diagnostic systems. Its benign tolerability profile, its action on multiple operative pathways, and the emergence of positive trial data make it an important target to investigate.

Association between hormone replacement therapy and subsequent stroke: a meta analysis

Abstract Objectives To review completed trials assessing effect of hormone replacement therapy on subsequent risk of stroke, assessing stroke by pathological type, severity, and outcome. Table 1 Effect of hormone replacement therapy on stroke and its type and outcome, and transient ischaemic attack No of trials No of subjects No of events Control event rate (%) Odds ratio* (95% CI), P value Heterogeneity (P value) Stroke: 28 39 769 940 2.03 1.29 (1.13 to 1.47), 0.0002 0.56 Ischaemic 16 23 426 443 1.59 1.29 (1.06 to 1.56), 0.01 0.59 Haemorrhagic 17 23 690 63 0.25 1.07 (0.65 to 1.75), 0.79 0.75 Transient ischaemic attack 22 10 050 233 2.13 1.02 (0.78 to 1.34), 0.86 0.86 Outcome: Fatal 22 36 430 129 0.29 1.28 (0.87 to 1.88), 0.21 0.39 Non-fatal 21 36 230 710 1.72 1.23 (1.06 to 1.44), 0.007 0.45 Death or dependency 14 20 445 145 0.53 1.56 (1.11 to 2.20), 0.01 0.93 * Odds ratios calculated with random effects model. Design Systematic review of randomised controlled trials identified from the Cochrane Library, Embase, and Medline; reviews; and reference lists of relevant papers. Studies reviewed 28 trials, with 39 769 subjects, were identified. Review measures Rates for cerebrovascular events analysed with a random effects model. Sensitivity analyses for heterogeneity included phase of prevention (primary or secondary), type of hormone replacement therapy (oestrogen alone or combined with progesterone), type of oestrogen (estradiol or conjugated equine oestrogen), size of trial (< 5000 or > 5000 patients), length of follow up (£ 3 years or > 3 years), sex (women only or men only), and trial quality (high or low). Results Hormone replacement therapy was associated with significant increases in total stroke (odds ratio 1.29 (95% confidence interval 1.13 to 1.47), n = 28), non-fatal stroke (1.23 (1.06 to 1.44), n = 21), stroke leading to death or disability (1.56 (1.11 to 2.20), n = 14), ischaemic stroke (1.29 (1.06 to 1.56), n = 16), and a trend to more fatal stroke (1.28 (0.87 to 1.88), n = 22). It was not associated with haemorrhagic stroke (1.07 (0.65 to 1.75), n = 17) or transient ischaemic attack (1.02 (0.78 to 1.34), n = 22). Statistical heterogeneity was not present in any analysis. Conclusions Hormone replacement therapy was associated with an increased risk of stroke, particularly of ischaemic type. Among subjects who had a stroke, those taking hormone replacement therapy seemed to have a worse outcome. Hormone replacement therapy cannot be recommended for the primary or secondary prevention of stroke.

Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis

Aims Randomized controlled trials (RCTs) have shown that the risk of stroke and venous thromboembolism (VTE) is increased with hormone replacement therapy (HRT); the effect on coronary heart disease (CHD) remains unclear. Methods and results RCTs of HRT were identified. Event rates for cerebrovascular disease [stroke, TIA (transient ischaemic attack)], CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE (pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44 113 subjects) were identified. HRT was associated with increases in stroke (odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14–1.53) and VTE (OR 2.05, 95% CI 1.44–2.92). In contrast, CHD events were not increased (OR 1.02, 95% CI 0.90–1.11). Ordinal analyses confirmed that stroke severity was increased with HRT (OR 1.31, 95% CI 1.12–1.54). Although most trials included older subjects, age did not significantly affect risk. The addition of progesterone to oestrogen doubled the risk of VTE. Conclusion HRT is associated with an increased risk of stroke, stroke severity, and VTE, but not of CHD events. Although most trials studied older patients, increased risk was not related to age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy.

Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome –Mecp2 gene dosage effects and BDNF expression

Rett syndrome, commonly associated with mutations of the methyl CpG‐binding protein 2 (MECP2) gene, is characterised by an apparently normal early postnatal development followed by deterioration of acquired cognitive and motor coordination skills in early childhood. To evaluate whether environmental factors may influence the disease outcome of Rett syndrome, we tested the effect of environmental enrichment from 4 weeks of age on the behavioural competence of mutant mice harboring a Mecp2 tm1Tam‐null allele. Our findings show that enrichment improves motor coordination in heterozygous Mecp2 +/− females but not Mecp2 −/y males. Standard‐housed Mecp2 +/− mice had an initial motor coordination deficit on the accelerating rotarod, which improved with training then deteriorated in subsequent weeks. Enrichment resulted in a significant reduction in this coordination deficit in Mecp2 +/− mice, returning the performance to wild‐type levels. Brain‐derived neurotrophic factor (BDNF) protein levels were 75 and 85% of wild‐type controls in standard‐housed and environmentally enriched Mecp2 +/− cerebellum, respectively. Mecp2 −/y mice showed identical deficits of cerebellar BDNF (67% of wild‐type controls) irrespective of their housing environment. Our findings demonstrate a positive impact of environmental enrichment in a Rett syndrome model; this impact may be dependent on the existence of one functional copy of Mecp2.

Real-world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus: a systematic review

To identify real‐world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus.

Estrogens and experimental ischemic stroke: a systematic review

Estrogens are believed to provide females with endogenous protection against cerebrovascular events although clinical trials studying long-term hormone replacement have yielded disappointing results. In contrast, estrogens might be neuroprotective after experimental ischemia. We performed a systematic review of controlled experimental studies that administered estrogens before, or after, cerebral ischemia and measured lesion volume. Relevant studies were found from searching PubMed, Embase and Web of Science. From 161 identified publications, 27 studies using 1304 experimental subjects were analyzed using the Cochrane Review Manager software. Estrogens reduced lesion volume in a dose-dependent manner, after either transient (P < 0.001) or permanent (P < 0.001) ischemia and whether administered before or up to 4 h after ischemia onset; no studies assessed efficacy for later time periods. The effect size for estrogens decreased with increasing quality scores for studies of transient ischemia. Estrogens reduced lesion volume when administered to ovariectomized females and young adult males, but had no effect in intact females. Limited data were present for aged animals and the full dose-response relationship was not available in all experimental groups. On the basis of these data, estrogens are a candidate treatment for ischemic stroke, although further preclinical studies are also warranted.