[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: Aims:
To investigate the association between cardiorespiratory fitness (CRF) and type 2 diabetes mellitus (T2DM) in a cohort of middle-age Finnish men and to summarise the current evidence in a meta-analysis of prospective studies.
CRF was measured at baseline in a random population-based sample of 2520 subjects by assessing oxygen uptake during maximal exercise. Cox regression analysis was used to estimate the association between CRF, expressed as metabolic equivalents (METs), and the risk of T2DM adjusted for potential confounders; this estimate was then pooled with the results of other prospective studies in a meta-analysis.
Mean (SD) baseline age and CRF were 53 (5) years and 8.7 (2.1) METs, respectively. During 23 years of follow-up, 153 (6.1%) participants developed T2DM. The hazard ratio per 1-MET higher CRF, adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, was 0.93 (95% confidence interval (CI): 0.84, 1.02; p = 0.109); further adjustment for smoking, education, and socioeconomic status did not materially change the estimate. In a random-effects meta-analysis of eight studies (92,992 participants and 8564 T2DM cases) combining maximally adjusted estimates, the pooled risk ratio of T2DM per 1-MET higher CRF level was 0.95 (95% CI: 0.93, 0.98; p = 0.003; I(2) = 81%), corresponding to 23 fewer cases per 100,000 person-years based on the assumption of a causal link between CRF and T2DM.
These data suggest that there is an inverse relationship between CRF and T2DM that is largely independent of other risk factors.
[Show abstract][Hide abstract] ABSTRACT: Screening for type 2 diabetes (T2DM) and individuals at risk of diabetes has been advocated, yet information on the response rate and diagnostic yield of different screening strategies are lacking.
Studies (from 1998 to March/2015) were identified through Medline, Embase and the Cochrane library and included if they used oral glucose tolerance test (OGTT) and WHO-1998 diagnostic criteria for screening in a community setting. Studies were one-step strategy if participants were invited directly for OGTT and two, three/four step if participants were screened at one or more levels prior to invitation to OGTT. The response rate and diagnostic yield were pooled using Bayesian random-effect meta-analyses.
47 studies (422754 participants); 29 one-step, 11 two-step and seven three/four-step were identified. Pooled response rate (95% Credible Interval) for invitation to OGTT was 65.5% (53.7, 75.6), 63.1% (44.0, 76.8), and 85.4% (76.4, 93.3) in one, two and three/four-step studies respectively. T2DM yield was 6.6% (5.3, 7.8), 13.1% (4.3, 30.9) and 27.9% (8.6, 66.3) for one, two and three/four-step strategies respectively. The number needed to invite to the OGTT to detect one case of T2DM was 15, 7.6 and 3.6 in one, two, and three/four-step strategies. In two step strategies, there was no difference between the response or yield rates whether the first step was blood test or risk-score. There was evidence of substantial heterogeneity in rates across study populations but this was not explained by the method of invitation, study location (rural versus urban) and developmental index of the country in which the study was performed.
Irrespective of the invitation method, developmental status of the countries and or rural/urban location, using a multi-step strategy increases the initial response rate to the invitation to screening for diabetes and reduces the number needed to have the final diagnostic test (OGTT in this study) for a definite diagnosis.
PLoS ONE 09/2015; 10(9):e0135702. DOI:10.1371/journal.pone.0135702 · 3.23 Impact Factor
[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 · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
We investigate differences between White and South Asian (SA) populations in levels of objectively measured and self-reported physical activity.
Leicestershire, UK, 2010-2011.
Baseline data were pooled from two diabetes prevention trials that recruited a total of 4282 participants from primary care with a high risk score for type 2 diabetes. For this study, 2843 White (age=64±8, female=37%) and 243 SA (age=58±9, female=34%) participants had complete physical activity data and were included in the analysis.
Moderate-intensity to vigorous-intensity physical activity (MVPA) and walking activity were measured using the International Physical Activity Questionnaire (IPAQ), and a combination of piezoelectric pedometer (NL-800) and accelerometer (Actigraph GT3X) were used to objectively measure physical activity.
Compared to White participants, SA participants self-reported less MVPA (30 vs 51 min/day; p<0.001) and walking activity (11 vs 17 min/day; P=0.001). However, there was no difference in objectively measured ambulatory activity (5992 steps/day vs 6157 steps/day; p=0.75) or in time spent in MVPA (18.0 vs 21.5 min/day; p=0.23). Results were largely unaffected when adjusted for age, sex and social deprivation. Compared to accelerometer data, White participants overestimated their time in MVPA by 51 min/day and SA participants by 21 min/day.
SA and White groups undertook similar levels of physical activity when measured objectively despite self-reported estimates being around 40% lower in the SA group. This emphasises the limitations of comparing self-reported lifestyle measures across different populations and ethnic groups.
Trial registration number:
Reports baseline data from: Walking Away from Type 2 Diabetes (ISRCTN31392913) and Let's Prevent Diabetes (NCT00677937).
BMJ Open 07/2015; 5(7):e006181. DOI:10.1136/bmjopen-2014-006181 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
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 · 2.26 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.