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The aim of this study was to develop and externally validate a score for use in dental settings to identify those at risk of undiagnosed nondiabetic hyperglycemia (NDH) or type 2 diabetes (T2D). The Studies of Health in Pomerania (SHIP) project comprises 2 representative population-based cohort studies conducted in northeast Germany. SHIP-TREND-0, 2008 to 2012 (the development data set) had 3,339 eligible participants, with 329 having undiagnosed NDH or T2D. Missing data were replaced using multiple imputation. Potential covariates were selected for inclusion in the model using backward elimination. Heuristic shrinkage was used to reduce overfitting, and the final model was adjusted for optimism. We report the full model and a simplified paper-based point-score system. External validation of the model and score employed an independent data set comprising 2,359 participants with 357 events. Predictive performance, discrimination, calibration, and clinical utility were assessed. The final model included age, sex, body mass index, smoking status, first-degree relative with diabetes, presence of a dental prosthesis, presence of mobile teeth, history of periodontal treatment, and probing pocket depths ≥5 mm as well as prespecified interaction terms. In SHIP-TREND-0, the model area under the curve (AUC) was 0.72 (95% confidence interval [CI] 0.69, 0.75), calibration in the large was -0.025. The point score AUC was 0.69 (95% CI 0.65, 0.72), with sensitivity of 77.0 (95% CI 76.8, 77.2), specificity of 51.5 (95% CI 51.4, 51.7), negative predictive value of 94.5 (95% CI 94.5, 94.6), and positive predictive value of 17.0 (95% CI 17.0, 17.1). External validation of the point score gave an AUC of 0.69 (95% CI 0.66, 0.71), sensitivity of 79.2 (95% CI 79.0, 79.4), specificity of 49.9 (95% CI 49.8, 50.00), negative predictive value 91.5 (95% CI 91.5, 91.6), and positive predictive value of 25.9 (95% CI 25.8, 26.0). A validated prediction model involving dental variables can identify NDH or undiagnosed T2DM. Further studies are required to validate the model for different European populations.

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)., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

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., (© 2020 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

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 HbA 1c , 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 HbA 1c 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., (© 2019 Diabetes UK.)

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., (© 2019 Diabetes UK.)

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 HbA 1c ≥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 HbA 1c ≥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 HbA 1c measurement, of whom 247 (7.7%) had an HbA 1c concentration ≥42 mmol/mol (6.0%). The area under the receiver-operator curve was 69.4% (95% CI 66.0-72.9) for baseline HbA 1c ≥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., (© 2017 Diabetes UK.)

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., (© 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

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., (© 2016 Diabetes UK.)

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., (© 2016 Diabetes UK.)

Objectives: Prevention of type 2 diabetes mellitus (TD2M) is a priority for healthcare systems. We estimated the cost-effectiveness compared with standard care of a structured education programme (Let's Prevent) targeting lifestyle and behaviour change to prevent progression to T2DM in people with prediabetes., Design: Cost-effectiveness analysis alongside randomised controlled trial., Setting: 44 general practices in Leicestershire, England., Participants: 880 participants with prediabetes randomised to receive either standard care or a 6-hour group structured education programme with follow-up sessions in a primary care setting., Main Outcome Measure: Incremental cost utility from the UK National Health Service (NHS) perspective. Quality of life and resource use measured from baseline and during the 36 months follow-up using the EuroQoL EQ-5D and 15D instruments and an economic questionnaire. Outcomes measured using quality-adjusted life years (QALYs) and healthcare costs calculated in 2012-2013 prices., Results: After accounting for clustering and missing data, the intervention group was found to have a net gain of 0.046 (95% CI -0.0171 to 0.109) QALYs over 3 years, adjusted for baseline utility, at an additional cost of £168 (95% CI -395 to 732) per patient compared with the standard care group. The incremental cost-effectiveness ratio is £3643/QALY with an 86% probability of being cost-effective at a willingness to pay threshold of £20 000/QALY., Conclusions: The education programme had higher costs and higher quality of life compared with the standard care group. The Let's Prevent programme is very likely to be cost-effective at a willingness to pay threshold of £20 000/QALY gained., Trial Registration Number: ISRCTN80605705., Competing Interests: An adapted version of the Let's Prevent Diabetes intervention is on the framework for the NHS Diabetes Prevention Programme. This work is led by Ingeus (main contractor), and Leicester Diabetes Centre, University Hospitals of Leicester (sub-contractor) will provide training and quality assurance for which funding will be received. MJD, KK, TY and LJG were involved in the development of this adapted programme. MJD, KK and TY were members (KK chair) of the NICE PH 38 (preventing type 2 diabetes: risk identification and interventions for individuals at high risk) Programme Development Group., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: People of South Asian origin experience higher rates of diabetes and complications of diabetes compared to white Europeans. Therefore, it is important to identify those with undiagnosed diabetes and those at high risk of developing diabetes, in order to intervene with lifestyle intervention to reduce risk and prevent complications. We conducted a study to assess the feasibility of delivering a faith centre based pathway for screening and referral to group education for high risk individuals to increase screening uptake and reduce diabetes risk., Methods: Opportunistic screening and early intervention strategy for people at risk of diabetes and cardiovascular disease in local faith centres. The screening consisted of a diabetes risk assessment tool and a near patient test for HbA1c. Participants found to be at high risk of diabetes (HbA1c 6-6.4%/42-46mmol/mol) were offered a 'Walking Away from Diabetes' group educational intervention aimed at increasing exercise levels and reducing diabetes risk., Results: 252 participants were screened during four screening events. 202 participants (80.2%) gave consent for their data to be included in the analysis. 72.4% of participants were found to have a high diabetes risk score. 32 participants (15.8%) had a HbA1c result (6-6.4%/42-46mmol/mol). Eight participants (4.0%) had a (HbA1c ⩾6.5%/⩾47mmol/mol). Of those eligible for the diabetes prevention education programme, 18 participants (56.3%) attended., Conclusions: This study confirms that screening followed by group education within faith centre settings is feasible and acceptable to participants. The strategies chosen were effective in achieving a high screening yield and high uptake of group education., (Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.)

Aims: To assess the opportunistic use in primary care of a computer risk score versus a self-assessment risk score for undiagnosed type 2 diabetes., Methods: We conducted a randomised controlled trial in 11 primary care practices in the UK. 577 patients aged 40-75years with no current diagnosis of type 2 diabetes were recruited to a computer based risk score (Leicester Practice Computer Risk Score (LPCRS)) or a patient self-assessment score (Leicester Self-Assessment Score (LSAS))., Results: The rate of self-referral blood tests was significantly higher for the LPCRS compared to the LSAS, 118.98 (95% CI: 102.85, 137.64) per 1000 high-risk patient years of follow-up compared to 92.14 (95% CI: 78.25, 108.49), p=0.022. Combined rate of diagnosis of type 2 diabetes and those at risk of developing the disease (i.e. impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)) was similar between the two arms, 15.12 (95% CI: 9.11, 25.08) per 1000 high-risk patient years for LPCRS compared to 14.72 (95% CI: 9.59, 22.57) for the LSAS, p=0.699. For the base case scenario the cost per new case of type 2 diabetes diagnosed was lower for the LPCRS compared to the LSAS, £168 (95% Credible Interval (CrI): 76, 364), and £352 (95% CrI: 109, 1148), respectively., Conclusions: Compared to a self-assessment risk score, a computer based risk score resulted in greater attendance to an initial blood test and is potentially more cost-effective., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The prevalence of type 2 diabetes (T2DM) in younger adults is growing. Compared to the late onset T2DM, it is well recognized that the disease tends to behave more aggressively in the younger age group with evidence of premature micro and macrovasular diseases and shorter life span. This increased mortality is largely attributed to cardiovascular complications. In a recent pilot study, young adults with T2DM were found to have significantly lower peak diastolic strain rate (PEDSR) on cardiac MRI (CMR), a forerunner of diabetic cardiomyopathy. Liraglutide, a glucagon like peptide-1 (GLP-1) analogue, is one of the new classes of glucose lowering therapies licensed to be used in management of T2DM. In randomised controlled trials, liraglutide improves glycaemic control by 1-1.5 % with an added benefit of weight loss of 2-3 kg. In addition, there is emerging evidence elucidating the cardioprotective effects of GLP-1 analogues independent of glycaemic control. In a small study, liraglutide has also been shown to improve cardiac function in patients with coronary ischaemia or congestive heart failure., Methods and Aims: This is a prospective, randomised, open-label, blind end-point (PROBE) active-comparator trial. A total of 90 obese eligible participants with T2DM (18-50 years) will be randomised to either liraglutide 1.8 mg once daily or sitagliptin 100 mg once daily for 26 weeks. The primary aim is to assess whether liraglutide improves diastolic function compared to sitagliptin as measured by PEDSR using CMR., Discussion: Although newer classes of GLP-1 analogues are made available in recent years, there are very few published studies demonstrating the beneficial effect of GLP-1 analogues on cardiovascular endpoints. In a recently published LEADER study, liraglutide has shown superiority to placebo in a population of type 2 diabetes with high risk of cardiovascular disease. To the best of our knowledge, there are no published studies establishing the effect of liraglutide on cardiac function in younger patients with T2DM on a larger scale. The LYDIA study will comprehensively describe changes in various parameters of cardiac structure and function in patients treated with liraglutide aiming to provide new evidence on effect of liraglutide on diastolic function in young obese people with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT02043054.

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)., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

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., (© 2015 World Obesity.)

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 (I(2)  = 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., (© 2015 John Wiley & Sons Ltd.)

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., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

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/m(2) 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., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

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 HbA1c (n = 487). None of the interventions were significantly better than the others in lowering glucose parameters. The Mediterranean diet reduced HbA1c 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., (© 2013 The British Dietetic Association Ltd.)

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/m(2)] 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., (© 2013 John Wiley & Sons Ltd.)

Aims: To externally validate the Leicester Practice Risk Score (LPRS) and the Leicester Risk Assessment score (LRAS) in a young South Asian population., Methods: South Asian participants aged 25-39 years inclusive from a population based screening study were included. The risk scores were calculated and compared to the diagnosis of type 2 diabetes mellitus (T2DM) or T2DM and Impaired Glucose Regulation (IGR, including IFG and IGT) using either an oral glucose tolerance test (OGTT) or a HbA1c (≤48mmol/mol/6.5% and ≤42mmol/mol/6.0% respectively). Measures of discrimination and calibration were calculated., Results: Of the 331 participants 8 (2.4%) had undiagnosed T2DM and 30 (9.1%) had IGR using an OGTT, 11 (3.4%) and 39 (12.1%) were found using HbA1c. Using the LPRS to detect T2DM on an OGTT gives an area under the ROC curve of 0.91 (95% CI 0.86, 0.97), including those with IGR gives an ROC of 0.72 (0.62-0.81), these values are 0.93 (0.88, 0.98) and 0.68 (0.60, 0.77) when using an HbA1c to define outcome. Acceptable levels of calibration were seen. Similar results are found for the LRAS., Conclusions: These scores can be used to identify those with undiagnosed T2DM and/or IGR in a young South Asian population. This is the first study to externally validate scores developed for prevalent undiagnosed disease in this age group using both OGTT and HbA1c., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims/hypothesis: Precise estimates of progression rates from 'prediabetes' to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals. There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA1c-defined prediabetes ranges, with some favouring 6.0-6.4% (42-46 mmol/mol). Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories., Methods: Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5.6-6.9 mmol/l], WHO-defined IFG [6.1-6.9 mmol/l], IGT (7.8-11.0 mmol/l) or raised HbA1c [6.0-6.4%/42-46 mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models., Results: Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA1c, the pooled incidence rate (95% credible interval) of diabetes was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5 [37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results were seen when the data were analysed by the criteria used to diagnose diabetes., Conclusions/interpretation: This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA1c 6.0-6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.

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., (© 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.)

Aims/hypothesis: The study aimed to examine the associations between objectively measured sedentary time, breaks in sedentary time, moderate-to-vigorous physical activity (MVPA) and total physical activity with markers of cardiometabolic health in a population with known risk factors for type 2 diabetes mellitus., Methods: This study reports data from two ongoing diabetes prevention programmes. Participants with known risk factors were recruited from primary care practices located within the East Midlands, UK, over the period 2010-2011. ActiGraph GT3X accelerometers (15 s epochs) were used to assess sedentary time (<25 counts per 15 s), MVPA (≥ 488 counts per 15 s) and total physical activity (total counts). A break was considered as any interruption in sedentary time (≥ 25 counts per 15 s). Linear regression examined the independent association of sedentary time, breaks in sedentary time, MVPA and total physical activity with markers of cardiometabolic health., Results: The sample comprised 878 participants; 153 from Project STAND (Sedentary Time And Diabetes) (age 32.9 ± 5.6 years, 28.8% male) and 725 from Walking Away from Diabetes (age 63.7 ± 7.8 years, 64.8% male). Following adjustment for various covariates, including MVPA and BMI, there were detrimental linear associations of sedentary time with 2 h plasma glucose (standardised beta coefficient) (β = 0.220, p < 0.001), triacylglycerol (β = 0.206, p = 0.001) and HDL-cholesterol (β = -0.123, p = 0.029). Breaks in sedentary time, total physical activity and MVPA were significantly inversely associated with measures of adiposity, but not with any other cardiometabolic variables after adjustment for sedentary time and BMI., Conclusions/interpretation: In adults at high risk of type 2 diabetes mellitus, time spent sedentary is strongly and adversely associated with cardiometabolic health and may be a more important indicator of poor health than MVPA.

Introduction: We compared test performance and cost per case for strategies detecting diabetes on the oral glucose tolerance test (OGTT) using either (a) glycated haemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) or (b) two HbA1c thresholds where the first cut-point 'rules out' and the second 'rules in' diabetes. HbA1c values in between the thresholds require confirmatory glucose testing for diagnosis., Materials and Methods: We conducted an analysis of adults aged 40-75 years from the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort (Leicester, UK), from 2002 to 2008, who underwent oral glucose tolerance testing (OGTT) and HbA1c testing., Results: From 8696 individuals (mean age 57.3 years, 73% white Europeans (WE) and 27% South Asians (SA)), HbA1c ≥ 6.5% produced sensitivity of 62.1% for detecting diabetes in WE and 78.9% in SA. Using two selected thresholds, HbA1c ≤ 5.8% (rule-in, 40 mmol/mol) and HbA1c ≥ 6.8% (rule-out, 51 mmol/mol) produced high sensitivity/specificity (> 91.0%) for detecting diabetes, however, 28.8% of the cohort with HbA1c 5.9%-6.7% required a subsequent glucose test. The two cut-point threshold produced a lower cost per case of diabetes detected in WE, compared to HbA1c ≥ 6.5% of £38.53 (1.89 to 86.81) per case, but was more expensive in SA by £84.50 (69.72 to 100.92) per case. Using a risk score to determine HbA1c testing, the same costs per case became £63.33 (23.33 to 113.26) in WE and £69.21 (55.60 to 82.41) in SA., Conclusion: Using a two-threshold strategy may have some benefits over a single cut-point; however, 28.8% of individuals required two blood tests.

Background: Dietary recommendations for the prevention of type 2 diabetes mellitus include the message to consume 400 g fruit and vegetables per day. Measurement of habitual diet is inherently difficult, yet errors due to self-report can be eliminated by the use of nutritional biomarkers. The aim of this study was to determine plasma vitamin C concentrations as a biomarker for fruit and vegetable intake in individuals identified at high risk of diabetes. Fruit and vegetables may confer benefit via their antioxidant capacity, thus we also measured urinary F₂-isoprostanes as a marker for oxidative stress., Subjects/methods: Participants recruited from a high-risk population as part of a diabetes prevention trial provided fasting blood samples and a spot urine sample for the quantification of plasma vitamin C and F₂-isoprostanes, respectively. We compared glycaemic parameters by the increments of the standard deviation of plasma vitamin C using multiple regression models., Results: Mean plasma vitamin C of participants was 39.3 μmol/l (s.d. 21.8). In the unadjusted model, 1 s.d. plasma vitamin C was significantly and inversely associated with HbA1c, fasting and 2 h blood glucose (P ≤ 0.0001). Relationships remained significant after adjustment for demographic variables and confounding factors. No significant association was observed between plasma vitamin C and urinary F₂-isoprostanes., Conclusion: The data adds to the evidence that small lifestyle changes may influence glucose regulation. The role that fruit and vegetables independently have should be investigated further.

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., (© 2012 Blackwell Publishing Ltd.)

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 HbA(1c) 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 HbA(1c) , 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 HbA(1c) {-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., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Aims/hypothesis: The aim of this study was to develop and validate a score for detecting the glycaemic categories of impaired glucose regulation (IGR) and type 2 diabetes using the WHO 2011 diagnostic criteria., Methods: We used data from 6,390 individuals aged 40-75 years from a multiethnic population based screening study. We developed a logistic regression model for predicting IGR and type 2 diabetes (diagnosed using OGTT or HbA(1c) ≥ 6.5% [48 mmol/mol]) from data which are routinely stored in primary care. We developed the score by summing the β coefficients. We externally validated the score using data from 3,225 participants aged 40-75 years screened as part of another study., Results: The score includes age, ethnicity, sex, family history of diabetes, antihypertensive therapy and BMI. Fifty per cent of a population would need to be invited for testing to detect type 2 diabetes mellitus on OGTT with 80% sensitivity; this is slightly raised to 54% that need to be invited if using HbA(1c). Inviting the top 10% for testing, 9% of these would have type 2 diabetes mellitus using an OGTT (positive predictive value [PPV] 8.9% [95% CI 5.8%,12.8%]), 26% would have IGR (PPV 25.9% [95% CI 20.9%, 31.4%]). Using HbA(1c) increases the PPV to 19% for type 2 diabetes mellitus (PPV 18.6% [95% CI 14.2%, 23.7%]) and 28% for an HbA(1c) between 6.0% and 6.4% (PPV 28.3% [95% CI 23.1%, 34.0%])., Conclusions: The score can be used to reliably identify those with undiagnosed IGR and type 2 diabetes in multiethnic populations. This is the first score developed taking into account HbA(1c) in the diagnosis of type 2 diabetes.

Aims: To determine whether tighter cardiovascular risk factor control with structured education in individuals with type 2 diabetes (T2DM) and microalbuminuria benefits cardiovascular risk factors., Methods: Participants from a multiethnic population, recruited from primary care and specialist clinics were randomised to intensive intervention with structured patient (DESMOND model) education (n=94) or usual care by own health professional (n=95)., Primary Outcome: change in HbA1c at 18months., Secondary Outcomes: changes in blood pressure (BP), cholesterol, albuminuria, proportion reaching risk factor targets, modelled cardiovascular risk scores., Results: Mean (SD) age and diabetes duration of participants were 61.5 (10.5) and 11.5 (9.3) years, respectively. At 18months, intensive intervention showed significant improvements in HbA1c (7.1(1.0) vs. 7.8(1.4)%, p<0.0001), systolic BP (129(16) vs. 139(17) mmHg, p<0.0001), diastolic BP (70(11) vs. 76(12) mmHg, p<0.001), total cholesterol (3.7(0.8) vs. 4.1(0.9) mmol/l, p=0.001). Moderate and severe hypoglycaemia was 11.2 vs. 29.0%; p=0.001 and 0 vs. 6.3%; p=0.07, respectively. More intensive participants achieved ≥3 risk factor targets with greater reductions in cardiovascular risk scores., Conclusions: Intensive intervention showed greater improvements in metabolic control and cardiovascular risk profile with lower rates of moderate and severe hypoglycaemia. Intensive glycaemic interventions should be underpinned by structured education promoting self-management in T2DM., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims/hypothesis: The aim of this study was to determine the frequency of undiagnosed glucose abnormalities and the burden of cardiovascular disease (CVD) risk among south Asians and white Europeans attending a systematic screening programme for type 2 diabetes (ADDITION-Leicester) and to estimate the achievable risk reduction in individuals identified with glucose disorders., Methods: Random samples of individuals (n = 66,320) from 20 general practices were invited for a 75 g OGTT and CVD risk assessment. Ten-year CVD risk among screen-detected people with diabetes or impaired glucose regulation (IGR) (impaired fasting glycaemia and/or impaired glucose tolerance [IGT]) was computed using the Framingham-based ETHRISK engine and achievable risk reduction was predicted using relative reductions for treatments extracted from published trials., Results: A total of 6,041 participants (48% male, 22% south Asian) aged 40-75 years inclusive were included. Undiagnosed glucose disorders occurred more frequently in south Asians than white Europeans; age and sex adjusted odds ratios were 1.74 (95% CI 1.42-2.13) and 2.30 (95% CI 1.68-3.16) for IGT and diabetes respectively. Prevalence of any undetected glucose disorder was 17.5% in the whole cohort. Adjusted 10-year risk was similar in screen-detected people with IGR and diabetes (18.3% vs 21.6%), and was higher in south Asians across the glucose spectrum. Absolute CVD risk reductions of up to 13% in those with screen-detected type 2 diabetes and 6% in IGR are achievable using existing cardioprotective therapies., Conclusions/interpretation: Population screening with an OGTT identifies a significant burden of modifiable CVD risk, especially within south Asian groups. Strategies enticing this population to consider screening programmes are urgently needed as significant risk reduction is possible once a glucose abnormality is identified., Trial Registration: ClinicalTrials.gov NCT00318032., Funding: The project is funded for support and treatment costs by NHS Department of Health Support for Science and project grants.

Aim: To investigate associations between anxiety and measures of glycaemia in a White European and South Asian population attending community-based diabetes screening., Methods: In total, 4688 White 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 HbA(1c) 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 HbA(1c) (r = 0.01, P = 0.40)., Conclusions: Anxiety levels at screening were greater among South Asian people. Fasting, 2-h plasma glucose and HbA(1c) 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., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Aims: Screening for Type 2 diabetes mellitus (T2DM) may improve long-term outcomes by managing cardiovascular risk at an earlier stage of the disease. The cardiovascular risk profile of screen-detected (SD) T2DM is ill defined and has not been compared to conventional newly diagnosed (CD) cases., Methods: Baseline data from SD (n=337) and CD (n=824) cohorts were compared. SD adopted mixed approaches to screening, population based (n=214) and cardiovascular-risk factor targeted (n=123). CD reflected UK primary care practice with cases referred within four weeks of diagnosis., Results: People with SD T2DM were leaner, had a lower HbA1c(%) and lower triglyceride but were more hypertensive compared to people with CD T2DM. Fewer SD were on blood pressure lowering (46% vs. 60%, p<0.0001), statin (30% vs. 41%, p<0.0001) or anti-platelet (15% vs. 27%, p<0.0001) therapies. Modelled 10 year cardiovascular disease (CVD) risk was actually greater in the SD group compared to CD (CVD: 20.8 vs. 17.2, p=0.0001)., Conclusion: Individuals with SD T2DM are at high risk of CVD as a result of untreated hyperglycaemia, hypertension and dyslipidaemia. Those prescribed antihypertensive or lipid-lowering therapies frequently still had inadequate control. Identifying vascular risk by screening for latent glucose disease provides therapeutic opportunities for earlier intervention., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Investigate levels of physical activity and their association with health in a white European (WE) and South Asian (SA) population., Methods: This study reports data from a diabetes screening programme, 2004-2007, Leicester, UK. Physical activity was measured using the International Physical Activity Questionnaire; additional outcomes included fasting and 2-h post-challenge glucose, lipid profile, body mass index (BMI) and waist circumference., Results: 1164 SA (female=48%) and 4310 WE (female=53%) were included. SAs were more likely fall below the minimum physical activity recommendations for health compared to WEs (age-adjusted OR for SA men=2.35; 95% CI=1.89-2.93, age adjusted OR for SA women=2.25; 95% CI=1.81-2.80). There were significant associations between levels of physical activity and BMI (men and women), waist circumference (men and women), 2-h glucose (women), HDL-cholesterol (men) and triglycerides (men) in WEs and waist circumference (women) and HDL-cholesterol (men) in SAs. Significant interactions between ethnicity and physical activity existed in the relationship with BMI and waist circumference in men., Conclusions: SAs are substantially less physically active than WEs. There may also be differences between SAs and WEs in the health benefits associated with higher physical activity that warrant further investigation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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.

Aims: There are calls to simplify the diagnosis of Type 2 diabetes mellitus (T2DM) to reduce the burden of undiagnosed disease. Glycated haemoglobin (HbA(1c)) 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 HbA(1c) 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 HbA(1c) results. We compared the prevalence and phenotype of subjects with T2DM based on either HbA(1c)> or =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 HbA(1c)> or =6.5%. Of those diagnosed with T2DM by OGTT, 93 (1.2%) had HbA(1c) <6.5% and therefore would not have been classified as having T2DM using proposed criteria. Using HbA(1c) 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 HbA(1c) 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 HbA(1c)> or =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.

Aims/hypothesis: Non-invasive measures of aortic stiffness reflect vascular senescence and predict outcome in diabetes. Glucose-mediated elastic artery sclerosis may play an integral role in the development of macrovascular complications. We used carotid-femoral pulse wave velocity ((cf)PWV) to quantify independent associations of fasting glucose, post-challenge glucose and derived insulin resistance (HOMA-IR) with aortic stiffness., Methods: (cf)PWV was measured using a 4 MHz continuous wave Doppler ultrasound probe within groups with newly identified age- and sex-matched normal glucose metabolism (NGM), impaired glucose regulation (IGR) and diabetes mellitus populations (n = 570, mean age 59.1, 56% male)., Results: After multivariate adjustment, IGR and diabetes were associated with significant aortic stiffening compared with NGM (adjusted (cf)PWV+/-SE: NGM, 9.15 +/- 0.12 m/s; IGR 9.76 +/- 0.11 m/s, p < 0.001; diabetes, 9.89 +/- 0.12 m/s, p < 0.001). IGR stratification indicated that impaired fasting glucose (IFG; 9.71 +/- 0.12 m/s) and post-challenge (impaired glucose tolerance; 9.82 +/- 0.24 m/s) categories had similar (cf)PWV (p = 0.83). Modelled predictors of (cf)PWV were used to assess independent metabolic associations with arterial stiffness. Fasting glucose concentration (beta = 0.10; 95% CI 0.05, 0.18; p = 0.003), 2 h post-challenge glucose (beta = 0.14; 95% CI 0.02, 0.23; p < 0.001) and HOMA-IR (beta = 0.20, 95% CI 0.05, 0.53; p < 0.001) were independently related to (cf)PWV after adjustment for age, sex, mean arterial pressure, heart rate, body mass index, renal function and antihypertensive medication., Conclusions/interpretation: IGR characterised by fasting or post-challenge hyperglycaemia is associated with significant vascular stiffening. Post-challenge glucose and HOMA-IR are the most powerful metabolic predictors of arterial stiffness, implying hyperglycaemic excursion and insulin resistance play important roles in the pathogenesis of arteriosclerosis.

Background: Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in type 2 diabetes mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of abnormal glucose tolerance and T2DM. To be effective national screening programmes must achieve good coverage across the population by identifying barriers to the detection of disease and adapting to the delivery of earlier care. Here we describe the rationale and methods of a systematic community screening programme and randomised controlled trial of cardiovascular risk management within a UK multiethnic setting (ADDITION-Leicester)., Design: A single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care., Methods: ADDITION-Leicester consists of community-based screening and intervention phases within 20 general practices coordinated from a single academic research centre. Screening adopts a universal diagnostic approach via repeated 75g-oral glucose tolerance tests within an eligible non-diabetic population of 66,320 individuals aged 40-75 years (25-75 years South Asian). Volunteers also provide detailed medical and family histories; complete health questionnaires, undergo anthropometric measures, lipid profiling and a proteinuria assessment. Primary outcome is reduction in modelled Coronary Heart Disease (UKPDS CHD) risk at five years. Seven thousand (30% of South Asian ethnic origin) volunteers over three years will be recruited to identify a screen-detected T2DM cohort (n = 285) powered to detected a 6% relative difference (80% power, alpha 0.05) between treatment groups at one year. Randomisation will occur at practice-level with newly diagnosed T2DM cases receiving either conventional (according to current national guidelines) or intensive (algorithmic target-driven multi-factorial cardiovascular risk intervention) treatments., Discussion: ADDITION-Leicester is the largest multiethnic (targeting >30% South Asian recruitment) community T2DM and vascular risk screening programme in the UK. By assessing feasibility and efficacy of T2DM screening, it will inform national disease prevention policy and contribute significantly to our understanding of the health care needs of UK South Asians., Trial Registration: Clinicaltrial.gov (NCT00318032).

Introduction: Recent meta-analyses cast doubt over purported beneficial effects of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-gamma) 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-gamma adverse effects are plausible explanations for the conflicting results of intervention trials using markers of atherosclerosis and clinical event outcomes.