Alison J. Dunkley

Diabetes Prevention in the Real World: Effectiveness of Pragmatic Lifestyle Interventions for the Prevention of Type 2 Diabetes and of the Impact of Adherence to Guideline Recommendations: A Systematic Review and Meta-analysis

OBJECTIVE To summarize the evidence on effectiveness of translational diabetes prevention programs, based on promoting lifestyle change to prevent type 2 diabetes in real-world settings and to examine whether adherence to international guideline recommendations is associated with effectiveness. RESEARCH DESIGN AND METHODS Bibliographic databases were searched up to July 2012. Included studies had a follow-up of ≥12 months and outcomes comparing change in body composition, glycemic control, or progression to diabetes. Lifestyle interventions aimed to translate evidence from previous efficacy trials of diabetes prevention into real-world intervention programs. Data were combined using random-effects meta-analysis and meta-regression considering the relationship between intervention effectiveness and adherence to guidelines. RESULTS Twenty-five studies met the inclusion criteria. The primary meta-analysis included 22 studies (24 study groups) with outcome data for weight loss at 12 months. The pooled result of the direct pairwise meta-analysis shows that lifestyle interventions resulted in a mean weight loss of 2.32 kg (95% CI −2.92 to −1.72; I2 = 93.3%). Adherence to guidelines was significantly associated with a greater weight loss (an increase of 0.4 kg per point increase on a 12-point guideline-adherence scale). CONCLUSIONS Evidence suggests that pragmatic diabetes prevention programs are effective. Effectiveness varies substantially between programs but can be improved by maximizing guideline adherence. However, more research is needed to establish optimal strategies for maximizing both cost-effectiveness and longer-term maintenance of weight loss and diabetes prevention effects.

Effectiveness of interventions for reducing diabetes and cardiovascular disease risk in people with metabolic syndrome: systematic review and mixed treatment comparison meta-analysis

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.

What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review.

BACKGROUND Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise. OBJECTIVE To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients. DATA SOURCES Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature. REVIEW METHODS A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin. RESULTS Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY. LIMITATIONS The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses. CONCLUSION The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Prevalence and Incidence of Hypoglycaemia in 532,542 People with Type 2 Diabetes on Oral Therapies and Insulin: A Systematic Review and Meta-Analysis of Population Based Studies.

Objective To collate and evaluate the current literature reporting the prevalence and incidence of hypoglycaemia in population based studies of type 2 diabetes. Research Design and Methods 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. Results 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. Conclusions 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.

Waist circumference measurement: knowledge, attitudes and barriers in patients and practitioners in a multi-ethnic population

BACKGROUND Currently, body mass index (BMI) is widely used to identify health risk due to overweight or obesity. However, waist circumference is considered by many to be a better indicator of health risk than BMI. The primary health care team are ideally suited to screen for people at high risk of glucose intolerance and increased cardiovascular risk using waist circumference measurement (WCM). OBJECTIVES To determine the knowledge and attitudes of patients and primary care practitioners concerning WCM, with particular reference to exploring barriers in a multi-ethnic setting. METHODS A qualitative study using purposive sampling, semi-structured interviews and thematic analysis was conducted. Nine general practices were selected from Leicestershire, UK. The participants were 10 practitioners (four practice nurses, six general practitioners) and 18 patients (six south Asians). RESULTS Two overarching themes were identified from patient and practitioner interviews: understanding of waist size measurement to assess or monitor risk and attitudes related to perceived barriers and facilitators to waist measurement. A few practitioners felt uncomfortable about carrying out WCM and some perceived that patients might feel embarrassed. Practical barriers raised by professionals included lack of time, extra workload and financial implications. In contrast, patients generally raised few barriers to WCM. Being given an explanation appeared to be what was most important to them. No clear differences emerged when comparing views of patients from different ethnic groups or general practitioners and practice nurses. CONCLUSIONS This study adds to our understanding of views on WCM in a multi-ethnic setting, highlighting factors for consideration if WCM is to be facilitated in routine practice.

The association between body mass index and health‐related quality of life: influence of ethnicity on this relationship

The association between obesity and a poorer health‐related quality of life (HRQL) has previously been explored. The influence of ethnicity on this relationship has less frequently been considered. We aimed to explore the relationship between body mass index (BMI) and HRQL in a mixed population of White European (WE) and South Asian (SA) ethnicity.

The effect of antiobesity drugs on waist circumference: a mixed treatment comparison.

To use meta‐analytic techniques to quantitatively evaluate the efficacy of orlistat and lorcaserin in the treatment of people who are overweight and obese.

Is having a family history of type 2 diabetes or cardiovascular disease a predictive factor for metabolic syndrome

AIMS To determine whether a first degree family history (FH) of diabetes and/or a first degree FH of cardiovascular disease (CVD), can predict prevalent cases of metabolic syndrome (MetS). Also, to establish if the association is different for South Asians compared to White Europeans, and for obese compared to non-obese individuals. METHODS Cross-sectional data were analysed for a mixed-ethnic cohort of 3094 at-risk individuals, aged 40-75 years (29% South Asian), who were screened in Leicestershire (UK) for undiagnosed type 2 diabetes using an oral glucose tolerance test. Logistic regression was used to assess the relationship between FH and prevalent MetS, including adjustment for potential confounders. RESULTS Prevalence of MetS was 39%. Adjusted odds ratios (OR) showed that only a FH of CVD (OR 1.41, 95%CI: 1.18-1.68, p<0.001) was significantly associated with prevalent MetS. Interaction analysis showed no effect modification for obesity and ethnicity. We did not find any association for a FH of diabetes. CONCLUSIONS These findings suggest that a first degree FH of CVD predicts prevalent cases of MetS in a mixed-ethnic population. Evidence of an association may help to identify individuals who should be targeted for screening and early prevention of type 2 diabetes and CVD.

The Reversal Intervention for Metabolic Syndrome (TRIMS) study: rationale, design, and baseline data.

BackgroundRecent attention has focused on strategies to combat the forecast epidemic of type-2 diabetes (T2DM) and its major vascular sequelae. Metabolic syndrome (MetS) comprises a constellation of factors that increase the risk of cardiovascular disease (CVD) and T2DM. Our study aims to develop a structured self-management education programme for people with MetS, which includes management of cardiovascular and diabetes risk factors, and to determine its impact. This paper describes the rationale and design of the TRIMS study, including intervention development, and presents baseline data.MethodsSubjects recruited from a mixed-ethnic population with MetS were randomised to intervention or control arms. The intervention arm received structured group education based on robust psychological theories and current evidence. The control group received routine care. Follow-up data will be collected at 6 and 12 months. The primary outcome measure will be reversal of metabolic syndrome in the intervention group subjects compared to controls at 12 months follow-up.Results82 participants (44% male, 22% South Asian) were recruited between November 2009 and July 2010. Baseline characteristics were similar for both the intervention (n = 42) and control groups (n = 40). Median age was 63 years (IQR 57 - 67), mean waist size 106 cm (SD ± 11), and prescribing of statins and anti-hypertensives was 51% in each case.ConclusionResults will provide information on changes in diabetes and CVD risk factors and help to inform primary prevention strategies in people with MetS from varied ethnic backgrounds who are at high risk of developing T2DM and CVD. Information gathered in relation to the programmes acceptability and effectiveness in a multi-ethnic population would ensure that our results are widely applicable.Trial registrationThe study is registered at ClinicalTrials.gov, study identifier: NCT01043770.

A cross sectional survey of secondary prevention measures in patients with peripheral arterial disease in primary care.

Background: The National Service Framework for coronary heart disease (CHD) defines standards for the secondary prevention of cardiovascular disease in at risk individuals, including those with peripheral arterial disease (PAD). Aim: To assess current standards of secondary prevention and health monitoring in patients with PAD following a vascular procedure, and additionally compare care in patients with and without diagnosed CHD. Methods: Indicators for this cross sectional survey were identified from national recommendations and evidence. A retrospective review was conducted of general practitioner records, for patients who were treated in hospital for PAD. Results: Data were collected for 103 patients from 42 practices. Overall, prescribing was well achieved for antiplatelets but poor for statins. Standards of assessment of blood pressure, smoking status, and smoking cessation advice were high. However, approximately only half of the patients received advice about exercise or had their body mass index checked. Furthermore, for all indicators, standards of care for patients who additionally had a diagnosis of CHD were better than for patients without CHD. Conclusion: The cross sectional survey suggested the treatment received by some patients with established PAD is substandard. There is considerable potential to increase secondary prevention of CHD in patients with PAD disease in primary care.