[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the effect of delay in treatment intensification (IT; clinical inertia) in conjunction with glycaemic burden on the risk of macrovascular events (CVE) in type 2 diabetes (T2DM) patients.
A retrospective cohort study was carried out using United Kingdom Clinical Practice Research Datalink, including T2DM patients diagnosed from 1990 with follow-up data available until 2012.
In the cohort of 105,477 patients mean HbA1c was 8.1% (65 mmol/mol) at diagnosis, 11% had a history of cardiovascular disease, and 7.1% experienced at least one CVE during 5.3 years of median follow-up. In patients with HbA1c consistently above 7/7.5% (53/58 mmol/mol, n = 23,101/11,281) during 2 years post diagnosis, 26/22% never received any IT. Compared to patients with HbA1c <7% (<53 mmol/mol), in patients with HbA1c ≥7% (≥53 mmol/mol), a 1 year delay in receiving IT was associated with significantly increased risk of MI, stroke, HF and composite CVE by 67% (HR CI: 1.39, 2.01), 51% (HR CI: 1.25, 1.83), 64% (HR CI: 1.40, 1.91) and 62% (HR CI: 1.46, 1.80) respectively. One year delay in IT in interaction with HbA1c above 7.5% (58 mmol/mol) was also associated with similar increased risk of CVE.
Among patients with newly diagnosed T2DM, 22% remained under poor glycaemic control over 2 years, and 26% never received IT. Delay in IT by 1 year in conjunction with poor glycaemic control significantly increased the risk of MI, HF, stroke and composite CVE.
[Show abstract][Hide abstract] ABSTRACT: 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 to control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based on 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 to both CON & CT, (HIIT vs. CON: standardised mean difference (SMD)=-0.49, confidence intervals (CI) -0.87 to -0.12, p=0.009; CT: SMD=-0.35, -0.68 to -0.02, p=0.036). Compared to CON, HbA1c decreased by 0.19% (-0.36 to -0.03, p=0.021) and body weight decreased by 1.3kg (-1.9 to -0.7, p<0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants with or at risk of Type 2 diabetes experienced reductions in fasting glucose (-0.92mmol.L-1, -1.22 to -0.62, p<0.001) compared to CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with Type 2 diabetes. Larger randomised controlled trials of longer duration than those included in this meta-analysis are required to confirm these results.
[Show abstract][Hide abstract] ABSTRACT: IntroductionThe 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.AimTo 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.ResultsA 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 [(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 6.5 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)This article is protected by copyright. All rights reserved.
Diabetic Medicine 08/2015; DOI:10.1111/dme.12885 · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevention of type 2 diabetes is recognised as a health care priority. Lifestyle change has proven effective at reducing the risk of type 2 diabetes, but limitations in the current evidence have been identified in: the promotion of physical activity; availability of interventions that are suitable for commissioning and implementation; availability of evidence-based interventions using new technologies; and physical activity promotion among ethnic minorities. We aim to investigate whether a structured education programme with differing levels of ongoing support, including text-messaging, can increase physical activity over a 4 year period in a multi-ethnic population at high risk of diabetes.
A multi-centre randomised controlled trial, with follow-up at 12 and 48 months. The primary outcome is change in ambulatory activity at 48 months. Secondary outcomes include changes to markers of metabolic, cardiovascular, anthropometric and psychological health along with cost-effectiveness. Participants aged 40-74 years for White European, or 25-74 years for South Asians, with an HbA1c value of between 6.0 and < 6.4 % (42 and 47 mmol/mol) or with a previously recorded plasma glucose level or HbA1c value within the high risk (prediabetes) range within the last five years, are invited to take part in the trial. Participants are identified through primary care, using an automated diabetes risk score within their practice database, or from a database of previous research participants. Participants are randomly assigned to either: 1) the control group who receive a detailed advice leaflet; 2) the Walking Away group, who receive the same leaflet and attend a 3 hour structured education programme with annual maintenance sessions delivered in groups; or 3) the Walking Away Plus group, who receive the leaflet, attend the structured education programme with annual maintenance sessions, plus receive follow-on support through highly-tailored text-messaging and telephone calls to help to aid pedometer use and behaviour change.
This study will provide new evidence for the long-term effectiveness of a structured education programme focused on physical activity, conducted within routine care in a multi-ethnic population in the UK. It will also investigate the impact of different levels of ongoing support and the cost-effectiveness of each intervention.
ISRCTN83465245 Trial registration date: 14/06/2012.
[Show abstract][Hide abstract] ABSTRACT: To determine the effects of glucagon-like peptide-1 receptor agonists compared with placebo and other anti-diabetic agents on weight loss in overweight or obese patients with type 2 diabetes mellitus.
Electronic searches were conducted for randomised controlled trials that compared a glucagon-like peptide-1 receptor agonist therapy at a clinically relevant dose with a comparator treatment (other type 2 diabetes treatment or placebo) in adults with type 2 diabetes and a mean body mass index ≥ 25kg/m2. Pair-wise meta-analyses and mixed treatment comparisons were conducted to examine the difference in weight change at six months between the glucagon-like peptide-1 receptor agonists and each comparator.
In the mixed treatment comparison (27 trials), the glucagon-like peptide-1 receptor agonists were the most successful in terms of weight loss; exenatide 2mg/week: -1.62kg (95% CrI: -2.95kg, -0.30kg), exenatide 20μg: -1.37kg (95% CI: -222kg, -0.52kg), liraglutide 1.2mg: -1.01kg (95%CrI: -2.41kg, 0.38kg) and liraglutide 1.8mg: -1.51 kg (95% CI: -2.67kg, -0.37kg) compared with placebo. There were no differences between the GLP-1 receptor agonists in terms of weight loss.
This review provides evidence that glucagon-like peptide-1 receptor agonist therapies are associated with weight loss in overweight or obese patients with type 2 diabetes with no difference in weight loss seen between the different types of GLP-1 receptor agonists assessed.
PLoS ONE 06/2015; 10(6):e0126769. DOI:10.1371/journal.pone.0126769 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To collate and evaluate the current literature reporting the prevalence and incidence of hypoglycaemia in population based studies of type 2 diabetes.
Medline, Embase and Cochrane were searched up to February 2014 to identify population based studies reporting the proportion of people with type 2 diabetes experiencing hypoglycaemia or rate of events experienced. Two reviewers independently screened studies for eligibility and extracted data for included studies. Random effects meta-analyses were carried out to calculate the prevalence and incidence of hypoglycaemia.
46 studies (n = 532,542) met the inclusion criteria. Prevalence of hypoglycaemia was 45% (95%CI 0.34,0.57) for mild/moderate and 6% (95%CI, 0.05,0.07) for severe. Incidence of hypoglycaemic episodes per person-year for mild/moderate and for severe was 19 (95%CI 0.00, 51.08) and 0.80 (95%CI 0.00,2.15), respectively. Hypoglycaemia was prevalent amongst those on insulin; for mild/moderate episodes the prevalence was 50% and incidence 23 events per person-year, and for severe episodes the prevalence was 21% and incidence 1 event per person-year. For treatment regimes that included a sulphonylurea, mild/moderate prevalence was 30% and incidence 2 events per person-year, and severe prevalence was 5% and incidence 0.01 events per person-year. A similar prevalence of 5% was found for treatment regimes that did not include sulphonylureas.
Current evidence shows hypoglycaemia is considerably prevalent amongst people with type 2 diabetes, particularly for those on insulin, yet still fairly common for other treatment regimens. This highlights the subsequent need for educational interventions and individualisation of therapies to reduce the risk of hypoglycaemia.
PLoS ONE 06/2015; 10(6):e0126427. DOI:10.1371/journal.pone.0126427 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Despite the health benefits of physical activity, data from the UK suggest that a large proportion of adolescents do not meet the recommended levels of moderate-to-vigorous physical activity (MVPA). This is particularly evident in girls, who are less active than boys across all ages and may display a faster rate of decline in physical activity throughout adolescence. The ‘Girls Active’ intervention has been designed by the Youth Sport Trust to target the lower participation rates observed in adolescent girls. ‘Girls Active’ uses peer leadership and marketing to empower girls to influence decision making in their school, develop as role models and promote physical activity to other girls. Schools are provided with training and resources to review their physical activity, sport and PE provision, culture and practices to ensure they are relevant and attractive to adolescent girls.
This study is a two-arm cluster randomised controlled trial (RCT) aiming to recruit 20 secondary schools. Clusters will be randomised at the school level (stratified by school size and proportion of Black and Minority Ethnic (BME) pupils) to receive either the ‘Girls Active’ intervention or carry on with usual practice (1:1). The 20 secondary schools will be recruited from state secondary schools within the Midlands area. We aim to recruit 80 girls aged 11–14 years in each school. Data will be collected at three time points; baseline and seven and 14 months after baseline. Our primary aim is to investigate whether ‘Girls Active’ leads to higher objectively measured (GENEActiv) moderate-to-vigorous physical activity in adolescent girls at 14 months after baseline assessment compared to the control group. Secondary outcomes include other objectively measured physical activity variables, adiposity, physical activity-related psychological factors and the cost-effectiveness of the ‘Girls Active’ intervention. A thorough process evaluation will be conducted during the course of the intervention delivery.
The findings of this study will provide valuable information on whether this type of school-based approach to increasing physical activity in adolescent girls is both effective and cost-effective in the UK.
ISRCTN10688342. Registered 12 January 2015.
BMC Public Health 06/2015; 15(1). DOI:10.1186/s12889-015-1886-z · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In nondiabetic individuals, low values of fasting plasma glucose (FPG) have been associated with an increased risk of cardiovascular events. Identification of the potential mechanisms behind this association could help to elucidate the relationship between glycaemia and cardiovascular disease. We aimed to determine the association between FPG and ventricular arrhythmias.
FPG and other cardiometabolic risk factors were measured in a population-based cohort of 2,482 men without a known history of type 2 diabetes mellitus at baseline. Associations between FPG levels and incident cases of ventricular arrhythmias (ventricular tachycardia or fibrillation events ascertained using the National Hospital Discharge Register) were estimated using Cox regression analysis adjusted for potential confounders.
During a median follow-up of 23.3 (interquartile range 18.5-25.3) years, 74 (2.9%) incident events were recorded. In a multivariable analysis adjusted for age, systolic BP, smoking status, LDL- and HDL-cholesterol, and C-reactive protein, the HR for ventricular arrhythmia per 1 mmol/l higher baseline FPG was 0.58 (95% CI 0.34, 0.98); this estimate did not materially change after further adjustment for BMI, alcohol consumption, triacylglycerols and history of ischaemic heart disease (0.50 [95% CI 0.28, 0.89]).
In this nondiabetic male population, FPG was inversely associated with incident risk of ventricular arrhythmias. While our results could help clarify the relationship between low glucose levels and cardiovascular risk, further studies are required to confirm these findings in other populations.
[Show abstract][Hide abstract] ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPARγ) is an important regulator of metabolic health and a common polymorphism in the PPAR-γ2 gene (PPARG2) may modify associations between lifestyle behaviour and health.
To investigate whether the PPARG2 Pro12Ala genotype modifies the associations of sedentary behaviour and moderate-to-vigorous intensity physical activity (MVPA) with common measures of insulin sensitivity.
Participants with a high risk of impaired glucose regulation were recruited, United Kingdom, 2010-2011. Sedentary and MVPA time were objectively measured using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were assessed; insulin sensitivity was calculated using Matsuda-ISI and HOMA-IS. DNA was extracted from whole blood. Linear regression examined associations of sedentary time and MVPA with insulin sensitivity and examined interactions by PPARG2 Pro12Ala genotype.
541 subjects were included (average age = 65 years, female = 33%); 18% carried the Ala12 allele. Both sedentary time and MVPA were strongly associated with HOMA-IS and Matsuda-ISI after adjustment for age, sex, ethnicity, medication, smoking status and accelerometer wear time. After further adjustment for each other and BMI, only associations with Matsuda-ISI were maintained. Every 30 minute difference in sedentary time was inversely associated with a 4% (0, 8%; p = 0.043) difference in Matsuda-ISI, whereas every 30 minutes in MVPA was positively associated with a 13% (0, 26%; p = 0.048) difference. The association of MVPA with Matsuda-ISI was modified by genotype (p = 0.005) and only maintained in Ala12 allele carriers. Conversely, sedentary time was not modified by genotype and remained inversely associated with insulin sensitivity in Pro12 allele homozygotes.
The association of MVPA with Matsuda-ISI was modified by PPARG2 Pro12Ala genotype with significant associations only observed in the 18% of the population who carried the Ala12 allele, whereas associations with sedentary time were unaffected.
PLoS ONE 05/2015; 10(5):e0124062. DOI:10.1371/journal.pone.0124062 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An estimated 850,000 people have diabetes without knowing it and as many as 7 million more are at high risk of developing it. Within the NHS Health Checks programme, blood glucose testing can be undertaken using a fasting plasma glucose (FPG) or a glycated haemoglobin (HbA1c) test but the relative cost-effectiveness of these is unknown.
To estimate and compare the cost-effectiveness of screening for type 2 diabetes using a HbA1c test versus a FPG test. In addition, to compare the use of a random capillary glucose (RCG) test versus a non-invasive risk score to prioritise individuals who should undertake a HbA1c or FPG test.
Cost-effectiveness analysis using the Sheffield Type 2 Diabetes Model to model lifetime incidence of complications, costs and health benefits of screening.
England; population in the 40-74-years age range eligible for a NHS health check.
The Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) data set was used to analyse prevalence and screening outcomes for a multiethnic population. Alternative prevalence rates were obtained from the literature or through personal communication.
(1) Modelling of screening pathways to determine the cost per case detected followed by long-term modelling of glucose progression and complications associated with hyperglycaemia; and (2) calculation of the costs and health-related quality of life arising from complications and calculation of overall cost per quality-adjusted life-year (QALY), net monetary benefit and the likelihood of cost-effectiveness.
Based on the LEADER data set from a multiethnic population, the results indicate that screening using a HbA1c test is more cost-effective than using a FPG. For National Institute for Health and Care Excellence (NICE)-recommended screening strategies, HbA1c leads to a cost saving of £12 and a QALY gain of 0.0220 per person when a risk score is used as a prescreen. With no prescreen, the cost saving is £30 with a QALY gain of 0.0224. Probabilistic sensitivity analysis indicates that the likelihood of HbA1c being more cost-effective than FPG is 98% and 95% with and without a risk score, respectively. One-way sensitivity analyses indicate that the results based on prevalence in the LEADER data set are insensitive to a variety of alternative assumptions. However, where a region of the country has a very different joint HbA1c and FPG distribution from the LEADER data set such that a FPG test yields a much higher prevalence of high-risk cases relative to HbA1c, FPG may be more cost-effective. The degree to which the FPG-based prevalence would have to be higher depends very much on the uncertain relative uptake rates of the two tests. Using a risk score such as the Leicester Practice Database Score (LPDS) appears to be more cost-effective than using a RCG test to identify individuals with the highest risk of diabetes who should undergo blood testing.
We did not include rescreening because there was an absence of required relevant evidence.
Based on the multiethnic LEADER population, among individuals currently attending NHS Health Checks, it is more cost-effective to screen for diabetes using a HbA1c test than using a FPG test. However, in some localities, the prevalence of diabetes and high risk of diabetes may be higher for FPG relative to HbA1c than in the LEADER cohort. In such cases, whether or not it still holds that HbA1c is likely to be more cost-effective than FPG depends on the relative uptake rates for HbA1c and FPG. Use of the LPDS appears to be more cost-effective than a RCG test for prescreening.
The National Institute for Health Research Health Technology Assessment programme.
[Show abstract][Hide abstract] ABSTRACT: The cardiovascular and mortality risk in patients with incident type 2 diabetes in relation to smoking status and concurrent use of metformin is not well known. The risks of myocardial infarction (MI), stroke and mortality in incident type 2 diabetes patients were evaluated in relation to their smoking status with and without concurrent use of metformin.
Cohort study in 82205 incident type 2 diabetes patients from the United Kingdom Clinical Practice Research Datalink.
During 5.4 years of median follow-up, among patients without cardiovascular disease (CVD) history before diagnosis of diabetes (n=63166), compared to non-smokers without metformin treatment, current smokers with and without metformin had 8% (HR: 1.08; 95% CI: 0.81, 1.45) and 32% (HR: 1.32; 95% CI: 1.07, 1.65) increased risk of MI or stroke respectively. The respective HR (95% CI) for mortality in these patients were 0.96 (0.83, 1.11) and 1.86 (1.68, 2.07). The HR for mortality among ex-smokers with and without concurrent metformin treatment were 0.92 (0.83, 1.11) and 1.19 (1.10, 1.30) respectively. Ex-smokers did not have elevated risk of MI or stroke, irrespective of metformin treatment. Similar beneficial modifiable effects of metformin among ex- and current smokers were observed in patients with cardiovascular disease before diagnosis of diabetes (n=19039).
In type 2 diabetes patients, concurrent treatment with metformin attenuates the observed higher cardiovascular and mortality risk in ex- and current smokers. In addition to smoking cessation support, treatment with metformin, particularly in ex- and current smokers, should be encouraged.
This article is protected by copyright. All rights reserved.
Journal of Diabetes 04/2015; DOI:10.1111/1753-0407.12302 · 2.35 Impact Factor