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The processes occurring in the tropical tropopause layer (TTL) are of great importance for stratosphere–troposphere exchanges and the variability of the Earth's climate. Previous studies demonstrated the increasing ability of atmospheric general circulation models (AGCMs) in simulating the TTL, depending on factors such as the horizontal and vertical resolution, with the major role for physical parametrizations. In this work we assess the mean state and variability of the tropical upper troposphere and lower stratosphere simulated by 13 AGCMs of the Stratosphere–troposphere Processes And their Role in Climate Quasi‐Biennial Oscillation initiative (QBOi) for the historical period. As these models internally generate quasi‐biennial oscillations (QBOs) of the stratospheric zonal wind, we can analyse the simulated QBO influence on the TTL on interannual time‐scales. We find that model biases in temperature near the tropopause are strongly related to water vapour concentrations in the lower stratosphere. A source of intermodel spread derives from stratospheric aerosols, as the responses to eruptions differ between those models prescribing volcanic aerosol forcing. The QBO influence on the thermal structure is generally realistic in the equatorial region, but the subtropical response is weak compared with the reanalysis. This is associated with a limited downward penetration of QBO winds, generally smaller QBO meridional widths, and weaker temperature anomalies, which disappear above the tropopause for most models. We discuss the QBO impacts on tropopause pressure and precipitation, characterized by large uncertainties due to the small signal in the observational records and sampling uncertainty. Realistic QBO connection with the troposphere in some models suggests that the underlying physical processes can be correctly simulated. Overall, we find that the QBOi models have limited ability to reproduce the observed modulation of the TTL processes, which is consistent with biases in the vertical and latitudinal extent of the simulated QBOs degrading this connection. [ABSTRACT FROM AUTHOR]

Quasi‐biennial oscillations (QBOs) in thirteen atmospheric general circulation models forced with both observed and annually repeating sea surface temperatures (SSTs) are evaluated. In most models the QBO period is close to, but shorter than, the observed period of 28 months. Amplitudes are within ±20% of the observed QBO amplitude at 10 hPa, but typically about half of that observed at lower altitudes (50 and 70 hPa). For almost all models, the oscillation's amplitude profile shows an overall upward shift compared to reanalysis and its meridional extent is too narrow. Asymmetry in the duration of eastward and westward phases is reasonably well captured, though not all models replicate the observed slowing of the descending westward shear. Westward phases are generally too weak, and most models have an eastward time mean wind bias throughout the depth of the QBO. The intercycle period variability is realistic and in some models is enhanced in the experiment with observed SSTs compared to the experiment with repeated annual cycle SSTs. Mean periods are also sensitive to this difference between SSTs, but only when parametrized non‐orographic gravity wave (NOGW) sources are coupled to tropospheric parameters and not prescribed with a fixed value. Overall, however, modelled QBOs are very similar whether or not the prescribed SSTs vary interannually. A portrait of the overall ensemble performance is provided by a normalized grading of QBO metrics. To simulate a QBO, all but one model used parametrized NOGWs, which provided the majority of the total wave forcing at altitudes above 70 hPa in most models. Hence the representation of NOGWs either explicitly or through parametrization is still a major uncertainty underlying QBO simulation in these present‐day experiments. [ABSTRACT FROM AUTHOR]

Aim: Type 2 diabetes is a growing global challenge. Evidence exists demonstrating the use of primary care (non‐hospital based) dental practices to identify, through risk assessments, those who may be at increased risk of type 2 diabetes or who may already unknowingly have the condition. This review aimed to synthesize evidence associated with the use of primary care dental services for the identification of undiagnosed non‐diabetic hyperglycaemia or type 2 diabetes in adults, with particular focus on the pick‐up rate of new cases. Method: Electronic databases were searched for studies reporting the identification of non‐diabetic hyperglycaemia/type 2 diabetes in primary care dental settings. Returned articles were screened and two independent reviewers completed the data‐extraction process. A descriptive synthesis of the included articles was undertaken due to the heterogeneity of the literature returned. Results: Nine studies were identified, the majority of which utilized a two‐stage risk‐assessment process with risk score followed by a point‐of‐care capillary blood test. The main barriers cited were cost, lack of adequate insurance cover and people having previously been tested elsewhere. The pick‐up rate of new cases of type 2 diabetes and non‐diabetic hyperglycaemia varied greatly between studies, ranging from 1.7% to 24% for type 2 diabetes and from 23% to 45% for non‐diabetic hyperglycaemia, where reported. Conclusion: This review demonstrates that although it appears there may be benefit in using the dental workforce to identify undiagnosed cases of non‐diabetic hyperglycaemia and type 2 diabetes, further high‐quality research in the field is required assessing both the clinical and cost effectiveness of such practice. (Prospero Registration ID: PROSPERO 2018 CRD42018098750). What's new?: There is an established association between periodontitis and type 2 diabetes.Different populations exhibit different attendance patterns with different healthcare professionals.We found that primary care dental settings can be used to successfully identify previously undiagnosed cases of non‐diabetic hyperglycaemia and type 2 diabetes.The potential early detection of non‐diabetic hyperglycaemia/type 2 diabetes allows for instigation of either prevention strategies or earlier management, which may prove clinically and cost‐effective. [ABSTRACT FROM AUTHOR]

Background: As people with intellectual disabilities (ID) are now living longer, they are more at risk of developing non‐communicable diseases, including type 2 diabetes mellitus. However, understanding of factors associated with diabetes for targeted management and prevention strategies is limited. This study aimed to investigate prevalence of diabetes in adults (aged ≥18 years) with ID and its relationship with demographic, lifestyle, independence and health factors. Method: This was a cross‐sectional analysis of interview data from 1091 adults with ID from the Leicestershire Learning Disability Register from 1 January 2010 to 31 December 2016. Logistic regression models were used to identify factors associated with diabetes in the study population. Results: The study population did not have healthy lifestyles: just under half reported having lower physical activity levels than people without ID of a similar age; one‐quarter consumed fizzy drinks daily; and 20% consumed five or more fruit and/or vegetables per day. Prevalence of carer/self‐reported diabetes was 7.3% (95% confidence interval 5.9–9.0). After adjustment, diabetes was positively associated with South Asian ethnicity (P = 0.03) and older age groups (P < 0.001). Diabetes was less common in people living with family members (P = 0.02). We did not find a relationship between any of the lifestyle, independence and health factors investigated. Conclusions: A significant proportion of people with ID are living with diabetes. Diabetes management and prevention strategies should be tailored to individuals' complex needs and include consideration of lifestyle choices. Such strategies may want to focus on adults of South Asian ethnicity and people living in residential homes where prevalence appears to be higher. [ABSTRACT FROM AUTHOR]

Aims: The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high‐risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer‐term outcomes at 4‐year follow‐up in these participants. Methods: Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi‐ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self‐management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c, and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. Results: Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow‐up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (−3 mmol/mol, 95% CI −4.95,−1.11; −0.4%, 95% CI −0.67,−0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (−7.3 mmHg, 95% CI −11.1, −3.5; P < 0.001), diastolic BP (−2.9 mmHg, 95% CI −5.4, −0.3; P = 0.026), cholesterol (−0.3 mmol/l, 95% CI −0.52,−0.12; P = 0.002), and 10‐year coronary heart disease (−5.3, 95% CI −8.2,−2.3; P < 0.001) and stroke risk (−4.4, 95% CI −7.5, −1.3; P < 0.001). Conclusion: Multifactorial intervention with structured diabetes self‐management education compared with usual diabetes care has benefits for cardio‐metabolic risk factor profile. There was no increase in severe hypoglycaemia and cardiovascular mortality despite intensive glycaemic control, although the study was not powered to assess these outcomes. What's new?: A complex intervention that addresses control of multiple risk factors with structured self‐management education in high‐risk individuals with type 2 diabetes shows favourable improvements in cardio‐metabolic risk compared with usual diabetes care.Structured self‐management education programmes are vital because they empower individuals to learn more about their own long‐term condition, and facilitate skills‐based learning and decision support (i.e. provide guidance for implementing evidence‐based care).A recent systematic review that studied the effects of multifaceted diabetes care in European populations showed that biomedical outcomes improved significantly in people with newly diagnosed diabetes compared with those with prevalent diabetes. Our study adds to this body of evidence and suggests that a comprehensive multifactorial care intervention with structured self‐management education is beneficial in people with established type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To compare the cardiovascular efficacy and safety of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in adults with Type 2 diabetes. Methods: Electronic databases were searched from inception to 22 October 2018 for randomized controlled trials designed to assess the cardiovascular efficacy of SGLT2 inhibitors or GLP‐1RAs with regard to a three‐point composite measure of major adverse cardiovascular events (non‐fatal stroke, non‐fatal myocardial infarction and cardiovascular mortality). Cardiovascular and safety data were synthesized using Bayesian network meta‐analyses. Results: Eight trials, including 60 082 participants, were deemed eligible for the network meta‐analysis. Both SGLT2 inhibitors [hazard ratio 0.86 (95% credible interval 0.74, 1.01]) and GLP‐1RAs [hazard ratio 0.88 (95% credible interval 0.78, 0.98)] reduced the three‐point composite measure compared to placebo, with no evidence of differences between them [GLP‐1RAs vs SGLT2 inhibitors: hazard ratio 1.02 (95% credible interval 0.83, 1.23)]. SGLT2 inhibitors reduced risk of hospital admission for heart failure compared to placebo [hazard ratio 0.67 (95% credible interval 0.53, 0.85)] and GLP‐1RAs [hazard ratio 0.71 (95% credible interval 0.53, 0.93)]. No differences were found between the two drug classes in non‐fatal stroke, non‐fatal myocardial infarction, cardiovascular mortality, all‐cause mortality or safety outcomes. Conclusions: SGLT2 inhibitors and GLP‐1RAs reduced the three‐point major adverse cardiovascular event risk compared to placebo, with no differences between them. Compared with GLP‐1RAs and placebo, SGLT2 inhibitors led to a larger reduction in hospital admission for heart failure risk. What's new?: Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are two classes of anti‐hyperglycaemic drugs with additional benefits of reducing cardiovascular risk.Comparisons between SGLT2 inhibitors and GLP‐1RAs in cardiovascular outcome trials have not yet been carried out.In the present analysis, a reduction of cardiovascular risk was observed for SGLT2 inhibitors and GLP‐1RAs compared to placebo in people with Type 2 diabetes, but few differences were observed between the two treatments.SGLT2 inhibitors reduced heart failure risk to a greater extent than GLP‐1RAs and placebo.Results from this study can aid clinicians in selecting suitable anti‐hyperglycaemic therapies for individuals with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity [two or more conditions in addition to intellectual disability (ID)] is known to be more common among people with ID. However, the relationship between multimorbidity and lifestyle factors is currently unknown. The aim of this study was to determine the prevalence of multimorbidity in a population of adults with ID. We also aimed to identify risk factors, including lifestyle factors, for multimorbidity in this population. Methods: This was a cross‐sectional analysis using data from a diabetes screening study of 920 adults aged 18–74 years with ID living in Leicestershire, UK. We described comorbidities and the prevalence of multimorbidity in this population. We explored the relationship between multimorbidity and age, gender, ethnicity, severity of ID, socio‐economic status, physical activity, sedentary behaviour, fruit and vegetable consumption and smoking status using multiple logistic regression. Results: The prevalence of multimorbidity was 61.2% (95% CI 57.7–64.7). Multimorbidity was independently associated with being female (P < 0.001) and severe/profound ID (P = 0.004). Increasing age was of borderline significance (P = 0.06). Individuals who were physically inactive or sedentary were more likely to be multimorbid, independent of ability to walk, age, gender, severity of ID, ethnicity and socio‐economic status (adjusted OR = 1.91; 95% CI 1.23–2.97; P = 0.004 and OR = 1.98; 95% CI 1.42–2.77; P < 0.001). After excluding probable life‐long conditions (autism spectrum conditions, attention deficit hyperactivity disorders, epilepsy, cerebral palsy and other paralytic syndromes) as contributing comorbidities, the effect of sedentary behaviour, but not physical activity, remained (P = 0.004). We did not observe a relationship between multimorbidity, fruit and vegetable consumption and smoking status. Conclusions: Multimorbidity presents a significant burden to people with ID. Individuals who were physically inactive or sedentary were more likely to be multimorbid, but further work is recommended to explore the relationship between multimorbidity and lifestyle factors using standardised objective measures. [ABSTRACT FROM AUTHOR]

Summary: This systematic review and meta‐analysis determined the impact of structured exercise training, and the influence of associated weight loss, on intrahepatic triglyceride (IHTG) in individuals with non‐alcoholic fatty liver disease (NAFLD). It also examined its effect on hepatic insulin sensitivity in individuals with or at increased risk of NAFLD. Analyses were restricted to studies using magnetic resonance spectroscopy or liver biopsy for the measurement of IHTG and isotope‐labelled glucose tracer for assessment of hepatic insulin sensitivity. Pooling data from 17 studies (373 exercising participants), exercise training for one to 24 weeks (mode: 12 weeks) elicits an absolute reduction in IHTG of 3.31% (95% CI: −4.41 to −2.22%). Exercise reduces IHTG independent of significant weight change (−2.16 [−2.87 to −1.44]%), but benefits are substantially greater when weight loss occurs (−4.87 [−6.64 to −3.11]%). Furthermore, meta‐regression identified a positive association between percentage weight loss and absolute reduction in IHTG (β = 0.99 [0.62 to 1.36], P < 0.001). Pooling of six studies (94 participants) suggests that exercise training also improves basal hepatic insulin sensitivity (mean change in hepatic insulin sensitivity index: 0.13 [0.05 to 0.21] mg m−2 min−1 per μU mL−1), but available evidence is limited, and the impact of exercise on insulin‐stimulated hepatic insulin sensitivity remains unclear. [ABSTRACT FROM AUTHOR]

Aims To validate the Leicester Self-Assessment score using a representative English dataset for detecting prevalent non-diabetic hyperglycaemia or undiagnosed Type 2 diabetes (defined as HbA1c ≥6.0%) and for identifying those who may go on to develop Type 2 diabetes within 10 years. Methods Data were taken from the English Longitudinal Study of Ageing, a nationally representative dataset of people aged ≥50 years. The area under the receiver-operator curve and performance metrics for the score at the recommended score threshold (≥16), were calculated for the outcomes of HbA1c ≥42 mmol/mol (6.0%) at baseline and self-reported Type 2 diabetes within 10 years in those aged 50-75 years at baseline. Results A total of 3203 individuals had a baseline HbA1c measurement, of whom 247 (7.7%) had an HbA1c concentration ≥42 mmol/mol (6.0%). The area under the receiver-operator curve was 69.4% (95% CI 66.0-72.9) for baseline HbA1c ≥42 mmol/mol. A total of 3550 individuals had diabetes status recorded at 10 years, of whom 324 (9.1%) were diagnosed with Type 2 diabetes within this time; the area under the receiver-operator curve for this outcome was 74.9% (95% CI 72.4-77.5). The score threshold of ≥16 had a sensitivity of 89.2% (95% CI 85.3-92.4) and a specificity of 42.3% (95% CI 40.5-44.0) for Type 2 diabetes within 10 years. Conclusions The Leicester Self-Assessment score is validated for use across England to identify people with non-diabetic hyperglycaemia or undiagnosed Type 2 diabetes. Those with a high score are at high risk of developing diabetes in the future. [ABSTRACT FROM AUTHOR]

Background Adults with intellectual disabilities (ID) may be at increased risk of developing type 2 diabetes and cardiovascular disease, due to lifestyle factors, medications and other diagnosed conditions. Currently, there is lack of evidence on prevalence and prevention in this population. The aim of this study was to conduct a diabetes screening programme to determine prevalence of previously undiagnosed type 2 diabetes and impaired glucose regulation in people with ID. Methods Screening was conducted in a variety of community settings in Leicestershire, UK. Adults with ID were invited via: general practices; the Leicestershire Learning Disability Register; ID psychiatric services; and some people directly contacted the research team due to publicity about the study. Screening involved collection of anthropometric, biomedical and questionnaire data. Type 2 diabetes and impaired glucose regulation were defined according to (venous) fasting plasma glucose or HbA1c, following current World Health Organisation criteria. Results Nine hundred thirty adults (29% of those approached) participated. Mean age was 43 years, 58% were male and 16% of South Asian ethnicity. Most participants were either overweight or obese (68%). Diabetes status was successfully assessed for 675 (73%) participants: Nine (1.3%, 95% confidence interval 0.6 to 2.5) were found to have undiagnosed type 2 diabetes, and 35 (5.2%, 95% confidence interval 3.6 to 7.1) had impaired glucose regulation. Key factors associated with abnormal glucose regulation included the following: non-white ethnicity and a first degree family history of diabetes. Conclusions Results from this large multi-ethnic cohort suggest a low prevalence of screen-detected (previously undiagnosed) type 2 diabetes and impaired glucose regulation in adults with ID. However, the high levels of overweight and obesity we found emphasise the need for targeted lifestyle prevention strategies, which are specifically tailored for the needs of people with ID. [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate whether an established behavioural intervention, Walking Away from Type 2 Diabetes, is effective at promoting and sustaining increased walking activity when delivered within primary care. Methods Cluster randomized controlled trial involving 10 general practices recruited from Leicestershire, UK, in 2009-2010. Eight hundred and eight (36% female) individuals with a high risk of Type 2 diabetes mellitus, identified through a validated risk score, were included. Participants in five practices were randomized to Walking Away from Type 2 Diabetes, a pragmatic 3-h group-based structured education programme incorporating pedometer use with annual follow-on refresher sessions. The primary outcome was accelerometer assessed ambulatory activity (steps/day) at 12 months. Longer term maintenance was assessed at 24 and 36 months. Results were analysed using generalized estimating equation models, accounting for clustering. Results Complete accelerometer data for the primary outcome were available for 571 (71%) participants. Increases in ambulatory activity of 411 steps/day [95% confidence interval ( CI): 117, 704] and self-reported vigorous-intensity physical activity of 218 metabolic equivalent min/week (95% CI: 6, 425) at 12 months were observed in the intervention group compared with control; differences between groups were not sustained at 36 months. No differences between groups were observed for markers of cardiometabolic health. Replacing missing data with multiple imputation did not affect the results. Conclusions A pragmatic low-resource group-based structured education programme with pedometer use resulted in modest increases in ambulatory activity compared with control conditions after 12 months when implemented within a primary care setting to those at high risk of Type 2 diabetes mellitus; however, the results were not maintained over 36 months. [ABSTRACT FROM AUTHOR]

Aims To report contemporary regression rates from impaired glucose regulation to normal glucose tolerance, identify modifiable factors associated with early regression, and establish whether it affects subsequent diabetes risk in a population-based cohort. Methods Participants with impaired glucose regulation (impaired fasting glucose and/or impaired glucose tolerance on a 75-g oral glucose tolerance test) at baseline in the UK-based ADDITION-Leicester study had annual Type 2 diabetes re-screens for 5 years or until diabetes diagnosis. Logistic regression models investigated modifiable risk factors for regression to normal glucose tolerance at 1 year ( n = 817). Cox regression models estimated subsequent diabetes risk ( n = 630). Results At 1 year, 54% of participants had regressed to normal glucose tolerance, and 6% had progressed to diabetes. Regression to normal glucose tolerance was associated with weight loss of 0.1-3% [adjusted odds ratio 1.81 (95% CI 1.08, 3.03) compared with maintaining or gaining weight] and a waist circumference reduction of > 3 cm [adjusted odds ratio 1.78 (95% CI 1.03, 3.06) compared with maintaining or increasing waist circumference]. Those with normal glucose tolerance at 1 year subsequently had lower diabetes risk than those who remained with impaired glucose regulation [adjusted hazard ratio 0.19 (95% CI 0.10, 0.37)]. Conclusions Early regression to normal glucose tolerance was associated with reduced diabetes incidence, and might be induced by small reductions in weight or waist circumference. If confirmed in experimental research, this could be a clear and achievable target for individuals diagnosed with impaired glucose regulation. [ABSTRACT FROM AUTHOR]

Background Globally there are approximately 90 million Muslims with diabetes of which approximately 400 000 reside within the UK. The holy month of Ramadan is a fundamental practice of this religion of which fasting from sun-rise to sun-set is an integral part. This poses many potential risks for those with diabetes who wish to observe Ramadan. Methods The evidence base for best clinical management of Type 1 and Type 2 diabetes during Ramadan was reviewed. We reviewed current and previous recommendations for safe fasting during Ramadan. Results The risks associated with fasting in those with diabetes and preparing your patient for Ramadan are discussed. We have reviewed the evidence around diet-controlled diabetes and therapies including; metformin, acarbose, metglitinides, sulfonylureas, thiazolidinidiones, dipeptidyl peptidase-4 inhibitor ( DPP-4), sodium glucose co-transporter -2 ( SGLT-2) inhibitors, glucagon-like peptide -1 ( GLP-1) receptor agonists and insulin. Conclusion Up to date guidelines for the management of treatment regimes are set-out for those with Type 1 and Type 2 diabetes who wish to fast during Ramadan. [ABSTRACT FROM AUTHOR]

The 11-year solar cycle signal in December-January-February (DJF) averaged mean-sea-level pressure (SLP) and Atlantic/European blocking frequency is examined using multilinear regression with indices to represent variability associated with the solar cycle, volcanic eruptions, the El Niño-Southern Oscillation (ENSO) and the Atlantic Multidecadal Oscillation (AMO). Results from a previous 11-year solar cycle signal study of the period 1870-2010 (140 years; ∼13 solar cycles) that suggested a 3-4 year lagged signal in SLP over the Atlantic are confirmed by analysis of a much longer reconstructed dataset for the period 1660-2010 (350 years; ∼32 solar cycles). Apparent discrepancies between earlier studies are resolved and stem primarily from the lagged nature of the response and differences between early- and late-winter responses. Analysis of the separate winter months provide supporting evidence for two mechanisms of influence, one operating via the atmosphere that maximises in late winter at 0-2 year lags and one via the mixed-layer ocean that maximises in early winter at 3-4 year lags. Corresponding analysis of DJF-averaged Atlantic/European blocking frequency shows a highly statistically significant signal at ∼1-year lag that originates primarily from the late winter response. The 11-year solar signal in DJF blocking frequency is compared with other known influences from ENSO and the AMO and found to be as large in amplitude and have a larger region of statistical significance. [ABSTRACT FROM AUTHOR]

Introduction The effect of intensive glycaemic control alone or as part of a multifactorial intervention on cardiovascular and mortality outcomes is not fully understood. In addition, the interaction of duration of diabetes diagnosis on cardiovascular and mortality outcomes is unclear. Aim To quantify the effect of intensive treatment (i.e. intensive glucose lowering either alone or as part of a multifactorial intervention) on non-fatal myocardial infarction ( MI), non-fatal stroke, cardiovascular disease ( CV) mortality and all-cause mortality in patients with Type 2 diabetes. A secondary objective was to investigate the association between the treatment effect and trial-level characteristics such as average age, duration of Type 2 diabetes, the percentage male and the baseline event rate. Methods We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials without language restrictions from inception to 13 May 2015. We included randomized controlled trials ( RCTs) that evaluated intensive treatment in adult patients with Type 2 diabetes. The review was registered on PROSPERO (registration number 42014013860). We pooled rates across studies using random effects meta-analysis and investigated study-level covariate associations using Bayesian meta-regression. Results A total of 19 RCTs were included: 16 examined non-fatal MI ( n = 79 595), 14 non-fatal stroke ( n = 78 568), 18 cardiovascular mortality ( n = 83 938) and 18 all-cause mortality ( n = 84 266). There was evidence to suggest that compared with standard care, intensive treatment reduced the risk of non-fatal MI [risk ratio ( RR) 0.90, 95% confidence interval ( CI) 0.83-0.96], but not non-fatal stroke ( RR 0.96, 95% CI 0.86-1.07), CV mortality ( RR 1.00, 95% CI 0.90-1.11) or all-cause mortality ( RR 1.00, 95% CI 0.94-1.06). Compared with standard care, multifactorial interventions alone reduced non-fatal stroke ( RR 0.53, 95% CI 0.32-0.0.87) but not non-fatal MI ( RR 0.66, 95% CI 0.38-1.03), CV mortality ( RR 0.72, 95% CI 0.46-1.14) or all-cause mortality ( RR 0.82, 95% CI 0.64-1.05). There was no evidence to suggest that the effect of intensive treatment on cardiovascular and mortality outcomes was associated with mean age, mean duration of Type 2 diabetes and percentage of male patients across trials. There was evidence to suggest that the effectiveness of intensive treatment to reduce mortality outcomes increases as the baseline incidence of cardiovascular mortality [ratio of hazard = 0.82, 95% credible interval (CrI) 0.65-0.99] increased across trials, but not baseline incidence of non-fatal MI, non-fatal stroke and all-cause mortality. Intensive glucose-lowering and multifactorial interventions are predicted to have the desired beneficial effect of reducing CVD mortality in populations where the incidence rate is greater than about 6.3 CVD deaths per 1000 person-years or an average 10-year CVD risk of 6.3%. Conclusions Apart from non-fatal MIs, there was no evidence that intensive glucose-lowering and multifactorial interventions reduced or increased the risk of cardiovascular and mortality outcomes. Intensive glucose-lowering and multifactorial interventions are likely to be beneficial in populations with a higher baseline incidence of CV mortality, but there was no evidence of an association with the mean duration of Type 2 diabetes. Multifactorial interventions had a much greater impact on non-fatal MI and non-fatal strokes. ( PROSPERO registration no.: 42014013860) [ABSTRACT FROM AUTHOR]

The surface response to the 11 year solar cycle is assessed in ensemble simulations of the twentieth century climate performed in the framework of the fifth phase of the Coupled Model Inter-Comparison Project (CMIP5). A lead/lag multiple linear regression analysis identifies a multi-model mean (MMM) global mean surface warming of about 0.07K, lagging the solar cycle by 1-2 years on average. The anomalous warming penetrates to approximately the first 80-100m depth in the ocean. Solar signals in the troposphere show a similar time lag of 1-2 years and the strongest MMM warming is simulated in the Tropics above 300 hPa. At the surface, the MMM response in a subset of models that show statistically significant global mean warming (CMIP5-SIG95) is characterized by an anomalous warming in the west equatorial Pacific Ocean and the Arctic, at 1-2 years after solar maximum. The Arctic warming is twice as strong as the global mean response and appears in the winter months only. The surface warming in the equatorial Pacific Ocean is related to dynamical/thermodynamical processes. Different increase rates of global mean precipitation and atmospheric water vapour in response to a warmer surface lead to a weakerWalker circulation and anomalous westerly winds over the equatorial Pacific in the years following the solar maximum. Owing to atmosphere--ocean coupling, the anomalous westerly winds cool the subsurface and warm the surface in the western equatorial Pacific by ~0.14 K. The CMIP5-SIG95 MMM surface warming in the equatorial Pacific and Arctic is weak but qualitatively similar compared with solar signals in the HadCRUT4 dataset. [ABSTRACT FROM AUTHOR]

The aim of this meta-analysis was to quantify the effects of high-intensity interval training ( HIIT) on markers of glucose regulation and insulin resistance compared with control conditions ( CON) or continuous training ( CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT ( HIIT vs. CON: standardized mean difference [ SMD] = −0.49, confidence intervals [ CIs] −0.87 to −0.12, P = 0.009; CT: SMD = −0.35, −0.68 to −0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (−0.36 to −0.03, P = 0.021) and body weight decreased by 1.3 kg (−1.9 to −0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (−0.92 mmol L−1, −1.22 to −0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results. [ABSTRACT FROM AUTHOR]

A multiple linear regression statistical method is applied to model data taken from the Coupled Model Intercomparison Project, phase 5 (CMIP-5) to estimate the 11-year solar cycle responses of stratospheric ozone, temperature, and zonal wind during the 1979-2005 period. The analysis is limited to the six CMIP-5 models which resolve the stratosphere (high-top models) and which include interactive ozone chemistry. All simulations assumed a conservative 11-year solar spectral irradiance (SSI) variation based on the Naval Research Laboratory model. These model responses are then compared to corresponding observational estimates derived from two independent satellite ozone profile datasets and from ERA-Interim reanalysis meteorological data. The models exhibit a range of 11-year responses with three models (CESM1-WACCM, MIROC-ESM-CHEM and MRI-ESM1) yielding substantial solar-induced ozone changes in the upper stratosphere which compare favourably with available observations. The remaining three models do not, apparently because of differences in the details of their radiation and photolysis rate codes. During winter in both hemispheres, the three models with stronger upper-stratospheric ozone responses produce relatively strong latitudinal gradients of ozone and temperature in the upper stratosphere which are associated with accelerations of the polar night jet under solar maximum conditions. This behaviour is similar to that found in the satellite ozone and ERA-Interim data, except that the latitudinal gradients tend to occur at somewhat higher latitudes in the models. The sharp ozone gradients are dynamical in origin and assist in radiatively enhancing the temperature gradients, leading to a stronger zonal wind response. These results suggest that simulation of a realistic solar-induced variation of upper-stratospheric ozone, temperature and zonal wind in winter is possible for at least some coupled climate models even if a conservative SSI variation is adopted. [ABSTRACT FROM AUTHOR]

Amultiple linear regression analysis of nine different reanalysis datasets has been performed to test the robustness of variability associated with volcanic eruptions, the El Niño Southern Oscillation, the Quasi-Biennial Oscillation and with a specific focus on the 11-year solar cycle. The analysis covers both the stratosphere and troposphere and extends over the period 1979-2009. The characteristic signals of all four sources of variability are remarkably consistent between the datasets and confirm the responses seen in previous analyses. In general, the solar signatures reported are primarily due to the assimilation of observations, rather than the underlying forecast model used in the reanalysis system. Analysis of the 11-year solar response in the lower stratosphere confirms the existence of the equatorial temperature maximum, although there is less consistency in the upper stratosphere, probably reflecting the reduced level of assimilated data there. The solar modulation of the polar jet oscillation is also evident, but only significant during February. In the troposphere, vertically banded anomalies in zonal mean zonal winds are seen in all the reanalyses, with easterly anomalies at 30°N and 30°S suggesting a weaker and possibly broader Hadley circulation under solar maximum conditions. This structure is present in the annual signal and is particularly evident in NH wintertime. As well as the 'top-down' solar contribution to Northern Annular Mode variability, we show the potential contribution from the surface conditions allowing for a 'bottom-up' pathway. Finally, the reanalyses are compared with both observed global-mean temperatures from the Stratospheric Sounding Unit (SSU) and from the latest general circulation models from CMIP-5. The SSU samples the stratosphere over three different altitudes, and the 11-year solar cycle fingerprint is identified in these observations using detection and attribution techniques. [ABSTRACT FROM AUTHOR]

The 11 year solar-cycle component of climate variability is assessed in historical simulations of models taken from the Coupled Model Intercomparison Project, phase 5 (CMIP-5). Multiple linear regression is applied to estimate the zonal temperature, wind and annular mode responses to a typical solar cycle, with a focus on both the stratosphere and the stratospheric influence on the surface over the period ~1850-2005. The analysis is performed on all CMIP-5 models but focuses on the 13 CMIP-5 models that resolve the stratosphere (high-top models) and compares the simulated solar cycle signature with reanalysis data. The 11 year solar cycle component of climate variability is found to be weaker in terms of magnitude and latitudinal gradient around the stratopause in the models than in the reanalysis. The peak in temperature in the lower equatorial stratosphere (~70 hPa) reported in some studies is found in the models to depend on the length of the analysis period, with the last 30 years yielding the strongest response. A modification of the Polar Jet Oscillation (PJO) in response to the 11 year solar cycle is not robust across all models, but is more apparent in models with high spectral resolution in the short-wave region. The PJO evolution is slower in these models, leading to a stronger response during February, whereas observations indicate it to be weaker. In early winter, the magnitude of the modelled response is more consistent with observations when only data from 1979-2005 are considered. The observed North Pacific high-pressure surface response during the solar maximum is only simulated in some models, for which there are no distinguishing model characteristics. The lagged North Atlantic surface response is reproduced in both high- and low-top models, but is more prevalent in the former. In both cases, the magnitude of the response is generally lower than in observations. [ABSTRACT FROM AUTHOR]

Aim To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan. Methods Electronic databases were searched for randomized controlled trials ( RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin ( HbA1c) change were included. Data were pooled using random effects models. Results A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 ( DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio ( RR) 0.48, 95% confidence interval ( CI) 0.36, 0.64; p > 0.0001]. This was not replicated in the RCTs of vildagliptin, but a significant reduction was found in the observational studies ( RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high heterogeneity ( I2 = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (−1.81 kg, 95% CI −2.91, −0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001). Conclusions The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide ( GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines. [ABSTRACT FROM AUTHOR]

Aim To develop and test a format of delivery of diabetes self-management education by paired professional and lay educators. Methods We conducted an equivalence trial with non-randomized participant allocation to a Diabetes Education and Self Management for Ongoing and Newly Diagnosed Type 2 diabetes (DESMOND) course, delivered in the standard format by two trained healthcare professional educators (to the control group) or by one trained lay educator and one professional educator (to the intervention group). A total of 260 people with Type 2 diabetes diagnosed within the previous 12 months were referred for self-management education as part of routine care and attended either a control or intervention format DESMOND course. The primary outcome measure was change in illness coherence score (derived from the Diabetes Illness Perception Questionnaire-Revised) between baseline and 4 months after attending education sessions. Secondary outcome measures included change in HbA1c level. The trial was conducted in four primary care organizations across England and Scotland. Results The 95% CI for the between-group difference in positive change in coherence scores was within the pre-set limits of equivalence (difference = 0.22, 95% CI 1.07 to 1.52). Equivalent changes related to secondary outcome measures were also observed, including equivalent reductions in HbA1c levels. Conclusion Diabetes education delivered jointly by a trained lay person and a healthcare professional educator with the same educator role can provide equivalent patient benefits. This could provide a method that increases capacity, maintains quality and is cost-effective, while increasing access to self-management education. [ABSTRACT FROM AUTHOR]

Aim A pilot study to phenotype young adults (< 40 years) with Type 2 diabetes mellitus. Methods Twenty people with Type 2 diabetes (aged 18-40 years), 10 lean and 10 obese control subjects underwent detailed assessment, including tagged cardiac magnetic resonance imaging, inflammatory proteins, lipids, vitamin D and maximal oxygen uptake. Outcomes were compared between the group with Type 2 diabetes and the control group. Results Mean (standard deviation) age, Type 2 diabetes duration and BMI in the group with Type 2 diabetes were 31.8 (6.6) years, 4.7 (4.0) years and 33.9 (5.8) kg/m2 respectively. Compared with lean control subjects, those with Type 2 diabetes had more deleterious profiles of hyperlipidaemia, vitamin D deficiency, inflammation and maximal oxygen uptake relative to body mass. However, there was no difference between the group with Type 2 diabetes and the obese control group. The group with Type 2 diabetes had a higher left ventricular mass and a trend towards concentric remodelling compared with the lean control group ( P = 0.002, P = 0.052) but not the obese control group ( P > 0.05). Peak early diastolic strain rate was reduced in the group with Type 2 diabetes [1.51 (0.24)/s] compared with the lean control [1.97 (0.34)/s, P = 0.001] and obese control [1.78 (0.39)/s, P = 0.042] group. Conclusions Young adults with Type 2 diabetes and those with obesity have similar adverse cardiovascular risk profiles, higher left ventricular mass and a trend towards left ventricular concentric remodelling. In addition, those with Type 2 diabetes demonstrate diastolic dysfunction, a known risk marker for future heart failure and mortality. [ABSTRACT FROM AUTHOR]

Background Overweight or obese individuals with type 2 diabetes are encouraged to lose weight for optimal glucose management, yet many find this difficult. Determining whether alterations in dietary patterns irrespective of weight loss can aid glucose control has not been fully investigated. Methods We conducted a systematic review and meta-analysis aiming to determine the effects of a Mediterranean diet compared to other dietary interventions on glycaemic control irrespective of weight loss. Electronic databases were searched for controlled trials that included a Mediterranean diet intervention. The interventions included all major components of the Mediterranean diet and were carried out in free-living individuals at high risk or diagnosed with type 2 diabetes. Network meta-analysis compared all interventions with one another at the same time as maintaining randomisation. Analyses were conducted within a Bayesian framework. Results Eight studies met the inclusion criteria, seven examined fasting blood glucose ( n = 972), six examined fasting insulin ( n = 1330) and three examined Hb A1c ( n = 487). None of the interventions were significantly better than the others in lowering glucose parameters. The Mediterranean diet reduced Hb A1c significantly compared to usual care but not compared to the Palaeolithic diet. Conclusions The effect of alterations in dietary practice irrespective of weight loss on glycaemic control cannot be concluded from the present review. The need for further research in this area is apparent because no firm conclusions about relative effectiveness of interventions could be drawn as a result of the paucity of the evidence. [ABSTRACT FROM AUTHOR]

Aims To compare a sulphonylurea with the glucagon like peptide-1 ( GLP-1) receptor agonist liraglutide in combination with metformin in patients on mono/dual oral therapy with established type 2 diabetes fasting during Ramadan. Methods Ninety-nine adults intending to fast during Ramadan [50% male, mean age 52 years, body mass index ( BMI) 32 kg/m2] were randomized from two UK sites. Baseline data were collected ≥14 days prior to Ramadan and at 3 and 12 weeks after Ramadan. Results At 12 weeks, more patients in the liraglutide compared with the sulphonylurea group achieved a composite endpoint of haemoglobin A1c ( HbA1c) < 7%, no weight gain and no severe hypoglycaemia but this did not reach statistical significance [odds ratio ( OR) 4.08, 95% confidence interval ( CI) 0.97, 17.22, p = 0.06]. From a baseline of 7.7% there was no change in HbA1c at 12 weeks in the sulphonylurea (+0.02%) compared with a 0.3% reduction in the liraglutide group (adjusted coefficient −0.41, 95% CI −0.83, 0.01, p = 0.05). Significant reductions were also observed in weight and diastolic blood pressure ( BP) in the liraglutide compared with the sulphonylurea group. Treatment satisfaction was comparable across the treatment groups. There were no episodes of severe hypoglycaemia in either group, however, self-recorded episodes of blood glucose ≤3.9 mmol/l were significantly lower with liraglutide (incidence rate ratio 0.29, 95% CI 0.19, 0.41, p < 0.0001). Conclusions Liraglutide compared with sulphonylurea is well tolerated and maybe an effective therapy in combination with metformin during Ramadan with more patients able to achieve target HbA1c, lose or maintain weight with no severe hypoglycaemia. This was achieved with a high level of treatment satisfaction. [ABSTRACT FROM AUTHOR]

Aim To use meta-analytic techniques to quantitatively evaluate the efficacy of orlistat and lorcaserin in the treatment of people who are overweight and obese. Methods We identified publications from searches of electronic databases and extracted data from studies that compared orlistat or lorcaserin to lifestyle advice (standard care), placebo, sibutramine, rimonabant or metformin and collected information on waist circumference change or withdrawals due to adverse events (AEs). A mixed treatment comparison (MTC) meta-analysis was performed on the data extracted. Results Orlistat was found to be significantly better than placebo and standard care in reducing waist circumference at 6 and 12 months; orlistat reduced waist circumference by −6.96 cm [95% credible interval ( CrI): −8.93, −4.96 cm] compared to standard care at 6 months. The results suggested that lorcaserin reduced waist circumference by a greater amount than all other interventions at 12 months, for example, lorcaserin lead to a greater reduction of −2.45 cm (95% CrI: −4.99, 0.08 cm) in comparison to placebo, although these differences were not statistically significant. Although data were very limited, metformin reduced waist circumference by a greater amount (−2.11 cm, 95% CI: −1.00, −3.22 cm) than orlistat at 6 months. On average, 6.5% of patients on orlistat and 5.4% of those on lorcaserin discontinued their treatment due to AEs at 12 months. Conclusions Orlistat should be considered as an addition to lifestyle interventions in the treatment of obesity. Lorcaserin has recently been approved by the US Food and Drug Administration ( FDA) and these results suggest that it is similar in both efficacy and safety compared to orlistat. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the effectiveness of smart-phone applications (apps) for assessing the risk of type 2 diabetes. It carried out a literature review and found no studies describing the development, validation and implementation of these apps. It concluded that the evidence base for the existing apps for assessing type 2 diabetes risk is lacking; however, it suggested that smart-phone apps may increase the uptake to screening and may motivate behaviour change.

Aims To identify real-world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus. Methods A literature search was conducted in PubMed and EMBASE in November 2011 to identify studies reporting factors associated with adherence/non-adherence to insulin therapy in adults with Type 1 or Type 2 diabetes. Results Seventeen studies were identified; six used self-reported measures and 11 used calculated measures of adherence. Most (13/17) were conducted exclusively in the USA. Four categories of factors associated with non-adherence were identified: predictive factors for non-adherence, patient-perceived barriers to adherence, type of delivery device and cost of medication. For predictive factors and patient-perceived barriers, only age, female sex and travelling were associated with non-adherence in more than one study. Fear of injections and embarrassment of injecting in public were also cited as reasons for non-adherence. Conversely, adherence was improved by initiating therapy with, or switching to, a pen device (in four studies), and by changing to an insurance scheme that lowered the financial burden on patients (in two studies). Conclusions Adherence to insulin therapy is generally poor. Few factors or patient-perceived barriers were consistently identified as predictive for non-adherence, although findings collectively suggest that a more flexible regimen may improve adherence. Switching to a pen device and reducing patient co-payments appear to improve adherence. Further real-world studies are warranted, especially in countries other than the USA, to identify factors associated with non-adherence and enable development of strategies to improve adherence to insulin therapy. [ABSTRACT FROM AUTHOR]

The structure of the Arctic stratospheric polar vortex in three chemistry-climate models (CCMs) taken from the CCMVal-2 intercomparison is examined using zonal mean and geometric-based methods. The geometric methods are employed by taking 2D moments of potential vorticity fields that are representative of the polar vortices in each of the models. This allows the vortex area, centroid location and ellipticity to be determined, as well as a measure of vortex filamentation. The first part of the study uses these diagnostics to examine how well the mean state, variability and extreme variability of the polar vortices are represented in CCMs compared to ERA-40 reanalysis data, and in particular for the UMUKCA-METO, NIWA-SOCOL and CCSR/NIES models. The second part of the study assesses how the vortices are predicted to change in terms of the frequency of sudden stratospheric warmings and their general structure over the period 1960-2100. In general, it is found that the vortices are climatologically too far poleward in the CCMs and produce too few large-scale filamentation events. Only a small increase is observed in the frequency of sudden stratospheric warming events from the mean of the CCMVal-2 models, but the distribution of extreme variability throughout the winter period is shown to change towards the end of the twentyfirst century. Copyright © 2012 Royal Meteorological Society and British Crown Copyright, the Met Office [ABSTRACT FROM AUTHOR]

Aims: To review the evidence on interventions for reversing metabolic syndrome or preventing development of type 2 diabetes and cardiovascular disease in people with metabolic syndrome. Methods: A systematic review and Bayesian mixed treatment comparison meta-analysis was conducted. Relevant electronic bibliographic databases were searched up to January 2010. Included studies were randomized controlled trials with a follow-up of ≥24 weeks and outcomes comparing incidence of diabetes and/or cardiovascular disease, or reversal of metabolic syndrome. Results: A total of 16 studies met the inclusion criteria. Thirteen studies with outcome data for reversal of metabolic syndrome, involving 3907 participants, were included in the meta-analysis. Insufficient trials reported cardiovascular events/mortality, or incidence of type 2 diabetes, to conduct a meta-analysis for these outcomes. Interventions, alone or in combination, included lifestyle (diet and/or exercise) and pharmacological therapy. Using random-effect models, both lifestyle (odds ratio, OR 3.81; 95% confidence interval, CI 2.47-5.88) and pharmacological interventions (OR 1.59; 95% CI 1.04-2.45) were statistically superior compared with control for reversing metabolic syndrome. Using mixed treatment comparison methods, the probability that lifestyle interventions were the most clinically effective was 87%. Conclusions: Evidence suggests that both lifestyle and pharmacological interventions can reverse metabolic syndrome. However, there is a lack of data on whether these benefits are sustained and translate into longer term prevention of diabetes and/or cardiovascular disease. [ABSTRACT FROM AUTHOR]

The study aims to compare anti-obesity interventions in a single evidence synthesis framework. Electronic databases were searched for randomized controlled trials of orlistat, rimonabant or sibutramine reporting weight or body mass index (BMI) change from baseline at 3, 6 or 12 months. A mixed treatment comparison was used to combine direct and indirect trial evidence. Ninety-four studies involving 24,808 individuals were included; 83 trials included data on weight change and 41 on BMI change. All results are in comparison with placebo. The active drugs were all effective at reducing weight and BMI. At 3 months, orlistat reduced weight by −2.65 kg (95% credibility interval −4.00 kg, −1.31 kg). For sibutramine, 15 mg gave a greater reduction than 10 mg at 12 months, −6.35 kg versus −5.42 kg, respectively. Rimonabant reduced weight by −11.23 kg at 3 months and −4.55 kg at 12 months. Lifestyle advice alone also reduced weight at 6 and 12 months, but was less effective than the pharmacological interventions. In conclusion, modest weight reductions were seen for all pharmacological interventions. Those interventions which have now been withdrawn from use (sibutramine and rimonabant) seem to be the most effective, implying that there may be a place in clinical practice for similar drugs if side effects could be avoided. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 531-540 (2012) Abstract Aims To compare the effects of intensive multifactorial cardiovascular risk intervention with standard care in screen-detected Type 2 diabetes. Methods Twenty general practices randomly invited 30 950 adults without diagnosed diabetes for screening (World Health Organization, 1999). In a cluster randomized controlled trial, screen-detected cases were assigned by practice allocation to receive intensive protocol-driven cardiovascular risk management ( n = 146) or standard care ( n = 199) according to local guidelines. Intensive intervention was designed to achieve an HbA1c of 48 mmol/mol (6.5%), blood pressure < 130/80 mmHg and total cholesterol < 3.5 mmol/l. Primary outcome was modelled 5-year coronary heart disease risk (UKPDS-CHD). Analysis was via intention to treat. Results After 1.1 years 339 (98%) individuals were still participating. There were significant reductions in HbA1c, blood pressure and total cholesterol from baseline in both groups [mean change for total study population −27.7 mmol/mol (−0.62%), −11.64/10.01 mmHg, −1.11 mmol/l]. After adjustment for baseline and clustering, significant inter-group differences were observed in mean changes from baseline for HbA1c{−28.5 mmol/mol [−0.7% (1.4)] vs. −27.5 mmol/mol [−0.6% (1.6)], P = 0.001}, blood pressure [systolic −16.2 (19.6) vs. −8.4 (18.6) mmHg, P < 0.001], total cholesterol [−1.3 (1.3) vs. −1.0 (1.2) mmol/l, P < 0.001] and weight [−3.8 (5.5) vs. −2.2 (5.5) kg, P = 0.01] in favour of intensive treatment. UKPDS 5-year coronary heart disease risk was reduced by 3.2% and 2.3%, respectively ( P < 0.0001). Intensive intervention was associated with more lipid-lowering and anti-hypertensive but not hypoglycaemic medication use [odds ratios 2.5 (1.4-4.4), 5.5 (2.4-11.5), 1.6 (0.8-2.3); compared with standard care, P < 0.001, P = 0.003, P = 0.65]. Treatment satisfaction responses were superior with intensive intervention, with no increase in self-reported hypoglycaemia. Conclusion Intensive intervention in patients with diabetes identified through systematic non-risk-factor-based screening significantly reduces modelled coronary heart disease risk. This is achieved predominantly with lipid-lowering and anti-hypertensive treatments with no adverse effect on quality of life or hypoglycaemia. [ABSTRACT FROM AUTHOR]

Aim To investigate associations between anxiety and measures of glycaemia in a White European and SouthAsian population attending community-based diabetes screening. Methods In total, 4688White European and 1353 South Asian participants (aged 40-75 years) without a previous diagnosis of Type 2 diabetes underwent an oral glucose tolerance test and HbA1c measurement, detailed history, anthropometric measurements and completed the short-form Spielberger State Trait Anxiety Inventory. Results Anxiety was significantly higher in South Asian participants (mean 34.1; sd 0.37) compared with White European participants (mean 29.8; sd 0.13). Significant correlations were not identified between anxiety and fasting (r = )0.01, P = 0.75), 2-h glucose (r = )0.10, P = 0.24) or HbA1c (r = 0.01, P = 0.40). Conclusions Anxiety levels at screening were greater among South Asian people. Fasting, 2-h plasma glucose and HbA1c are not affected by anxiety during screening tests for diabetes. Current and proposed screening methods for diagnosis of diabetes are not affected by anxiety at screening. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 887–895 (2010) Aims Risk assessment scores identify those at high risk of impaired glucose regulation and Type 2 diabetes mellitus. To date no risk assessment scores that can be completed by a lay person have been developed and validated specifically for multiethnic populations in the UK. Methods We used data on 6186 subjects aged 40–75 years from a multiethnic UK screening study (73% white European, 22% South Asian). All participants were given a 75 g oral glucose tolerance test. We developed logistic regression models for predicting current impaired glucose regulation (impaired fasting glycaemia/impaired glucose tolerance) or Type 2 diabetes mellitus using data from anthropometric measurements and self-reported questionnaires. Using the best-fitting model, we developed the Leicester Risk Assessment score. We externally validated the score using data from 3171 subjects aged 40–75 years from a separate screening study. Results The components of the final model are age, ethnicity [white European vs. other (predominantly South Asian)], sex, first degree family history of diabetes, antihypertensive therapy or history of hypertension, waist circumference and body mass index. The score ranges from 0 to 47. Validating this model using the data from the second screening study gave an area under the receiver operator characteristic curve of 72% (95% confidence interval, 69–74%). A cut point of 16 had a sensitivity of 81% and a specificity of 45%. Conclusions The Leicester Risk Assessment score can be used to identify those at high risk of impaired glucose regulation and Type 2 diabetes mellitus in UK multiethnic populations. The score is simple (seven questions) and non-invasive. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 762–769 (2010) Aims There are calls to simplify the diagnosis of Type 2 diabetes mellitus (T2DM) to reduce the burden of undiagnosed disease. Glycated haemoglobin (HbA1c) is therefore being considered as a preferred diagnostic tool to replace the need for an oral glucose tolerance test (OGTT), considered by many as cumbersome and inconvenient. The aim of this study was to examine the potential impact of the preferred use of HbA1c as a diagnostic tool on the prevalence and phenotype of T2DM. Methods Analysis of the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort for previously undiagnosed individuals between 40 and 75 years of age who had OGTT, repeated if within the diabetes range, and HbA1c results. We compared the prevalence and phenotype of subjects with T2DM based on either HbA1c≥6.5% or OGTT using 1999 World Health Organization criteria. Results From the total population of 8696, we detected 291 (3.3%) with T2DM from using an OGTT, and 502 (5.8%) had HbA1c≥6.5%. Of those diagnosed with T2DM by OGTT, 93 (1.2%) had HbA1c <6.5% and therefore would not have been classified as having T2DM using proposed criteria. Using HbA1c criteria resulted in 304 (3.5%) additional cases of T2DM, approximately doubling the prevalence. Of these 304 additional people, 172 (56.7%) had impaired glucose tolerance/impaired fasting glycaemia according to 1999 World Health Organization criteria. Using HbA1c criteria there was an increase of 2.2- and 1.4-fold in south Asians and white Europeans detected, respectively. Conclusions Within this multi-ethnic cohort, we found that introducing HbA1c≥6.5% as the preferred diagnostic test to diagnose T2DM significantly increased numbers detected with T2DM; however, some people were no longer detected as having T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Recent meta-analyses cast doubt over purported beneficial effects of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) receptor agonists. Thiazolidinedione (TZD) trials using surrogate outcomes to postulate an antiatherogenic paradigm have been criticised as misinformative. We conducted an independent systematic review and meta-analysis of controlled TZD studies incorporating carotid intima-media thickness (CIMT) or pulse wave velocity (PWV) as primary outcome measures. The aim was to provide an evidence-based overview of TZD intervention studies using markers prospectively linked to vascular outcome in type 2 diabetes. Methods: Systematic search of known databases for TZD intervention trials using mean thickness CIMT(n = 9) and ankle-brachial PWV(n = 6) as primary outcome measures was performed. CIMT and PWV pooled weighted mean difference was calculated using a random effects model accounting for heterogeneity and publication bias. An indirect meta-analysis provided a comparison of rosiglitazone and pioglitazone effects. Results: A composite of combined placebo and comparator controlled trials demonstrated a significant weighted mean difference of–0.06 mm for CIMT (95% CI–0.09 to–0.02, p = 0.001) and–0.72 ms−1 for PWV (95% CI–1.28 to–0.16, p = 0.011) in favour of thiazolidiendione treatment. No TZD intraclass variation in CIMT (p = 0.96) or PWV (p = 0.33) change was observed. Conclusion: TZDs exhibit significant beneficial effects on aorto-carotid atherosclerosis when assessed using prospectively validated non-invasive techniques. Inferring clinical benefit in the absence of confirmatory outcome trials is questionable and caution should be exercised when interpreting intervention data with surrogate endpoints. TZD-induced congestive cardiac failure or other unknown PPAR-γ adverse effects are plausible explanations for the conflicting results of intervention trials using markers of atherosclerosis and clinical event outcomes. [ABSTRACT FROM AUTHOR]

Background and Purpose: Disodium 2,4-disulphophenyl-N-tert-butylnitrone (NXY-059) was neuroprotective in experimental stroke models but ineffective in a large clinical trial. This first-ever individual animal meta-analysis was used to assess the preclinical studies.Experimental Approach: Studies were obtained from AstraZeneca and PubMed searches. Data for each animal were obtained from the lead author of each study and/or AstraZeneca. Published summary data were used if individual data were not available. Infarct volume and motor impairment were standardized to reflect different species and scales. Standardized mean difference (SMD), coefficients from multilevel models and 95% confidence intervals (95% CI) are presented.Key Results: Fifteen studies (26 conditions, 12 laboratories) involving rats (544), mice (9) and marmosets (32) were identified (NXY-059: 332, control: 253) with individual data for 442 animals. Four studies were unpublished. Studies variably used randomization (40%), blinding of surgeon (53%) and outcome assessor (67%). NXY-059 reduced total (SMD -1.17, 95% CI -1.50 to -0.84), cortical (SMD -2.17, 95% CI -2.99 to -1.34) and subcortical (-1.43, 95% CI -2.20 to -0.86) lesion volume; efficacy was seen in transient, permanent and thrombotic ischaemia, up to 180 min post occlusion. NXY-059 reduced motor impairment (SMD -1.66, 95% CI -2.18 to -1.14) and neglect. Evidence for performance, attrition and publication bias was present.Conclusions and Implications: NXY-059 was neuroprotective in experimental stroke although bias may have resulted in efficacy being overestimated. Efficacy in young, healthy, male animals is a poor predictor of clinical outcome. We suggest the use of preclinical meta-analysis before initiation of future clinical trials. [ABSTRACT FROM AUTHOR]