Danielle H. Bodicoat

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.

Breaking Up Prolonged Sitting With Standing or Walking Attenuates the Postprandial Metabolic Response in Postmenopausal Women: A Randomized Acute Study

OBJECTIVE To determine whether breaking up prolonged sitting with short bouts of standing or walking improves postprandial markers of cardiometabolic health in women at high risk of type 2 diabetes. RESEARCH DESIGN AND METHODS Twenty-two overweight/obese, dysglycemic, postmenopausal women (mean ± SD age 66.6 ± 4.7 years) each participated in two of the following treatments: prolonged, unbroken sitting (7.5 h) or prolonged sitting broken up with either standing or walking at a self-perceived light intensity (for 5 min every 30 min). Both allocation and treatment order were randomized. The incremental area under the curves (iAUCs) for glucose, insulin, nonesterified fatty acids (NEFA), and triglycerides were calculated for each treatment condition (mean ± SEM). The following day, all participants underwent the 7.5-h sitting protocol. RESULTS Compared with a prolonged bout of sitting (iAUC 5.3 ± 0.8 mmol/L ⋅ h), both standing (3.5 ± 0.8 mmol/L ⋅ h) and walking (3.8 ± 0.7 mmol/L ⋅ h) significantly reduced the glucose iAUC (both P < 0.05). When compared with prolonged sitting (548.2 ± 71.8 mU/L ⋅ h), insulin was also reduced for both activity conditions (standing, 437.2 ± 73.5 mU/L ⋅ h; walking, 347.9 ± 78.7 mU/L ⋅ h; both P < 0.05). Both standing (−1.0 ± 0.2 mmol/L ⋅ h) and walking (−0.8 ± 0.2 mmol/L ⋅ h) attenuated the suppression of NEFA compared with prolonged sitting (−1.5 ± 0.2 mmol/L ⋅ h) (both P < 0.05). There was no significant effect on triglyceride iAUC. The effects on glucose (standing and walking) and insulin (walking only) persisted into the following day. CONCLUSIONS Breaking up prolonged sitting with 5-min bouts of standing or walking at a self-perceived light intensity reduced postprandial glucose, insulin, and NEFA responses in women at high risk of type 2 diabetes. This simple, behavioral approach could inform future public health interventions aimed at improving the metabolic profile of postmenopausal, dysglycemic women.

The effect of glucagon-like peptide 1 receptor agonists on weight loss in type 2 diabetes: A systematic review and mixed treatment comparison meta-analysis

Aims 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. Methods 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. Results 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. Conclusions 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.

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.

Considerations when using the activPAL monitor in field based research with adult populations

Research indicates that high levels of sedentary behavior (sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary behavior (and patterns of sedentary time accumulation) on health is the use of objective measurement tools that collect date and time-stamped activity information. One such tool is the activPAL monitor. This thigh-worn device uses accelerometer-derived information about thigh position to determine the start and end of each period spent sitting/lying, standing, and stepping, as well as stepping speed, step counts, and postural transitions. The activPAL is increasingly being used within field-based research for its ability to measure sitting/lying via posture. We summarise key issues to consider when using the activPAL in physical activity and sedentary behavior field-based research with adult populations. It is intended that the findings and discussion points be informative for researchers who are currently using activPAL monitors or are intending to use them. Pre-data collection decisions, monitor preparation and distribution, data collection considerations, and manual and automated data processing possibilities are presented using examples from current literature and experiences from 2 research groups from the UK and Australia.

Timing of pubertal stages and breast cancer risk: the Breakthrough Generations Study

IntroductionBreast development and hormonal changes at puberty might affect breast cancer risk, but epidemiological analyses have focussed largely on age at menarche and not at other pubertal stages.MethodsWe investigated associations between the timing of pubertal stages and breast cancer risk using data from a cohort study of 104,931 women (Breakthrough Generations Study, UK, 2003–2013). Pubertal variables were reported retrospectively at baseline. Breast cancer risk was analysed using Cox regression models with breast cancer diagnosis as the outcome of interest, attained age as the underlying time variable, and adjustment for potentially confounding variables.ResultsDuring follow-up (mean = 4.1 years), 1094 breast cancers (including ductal carcinoma in situ) occurred. An increased breast cancer risk was associated with earlier thelarche (age when breast growth begins; HR [95% CI] = 1.23 [1.02, 1.48], 1 [referent] and 0.80 [0.69, 0.93] for ≤10, 11–12 and ≥13 years respectively), menarche (initiation of menses; 1.06 [0.93, 1.21], 1 [referent] and 0.78 [0.62, 0.99] for ≤12, 13–14 and ≥15 years), regular periods (0.99 [0.83, 1.18], 1 [referent] and 0.74 [0.59, 0.92] for ≤12, 13–14 and ≥15 years) and age reached adult height (1.25 [1.03, 1.52], 1 [referent] and 1.07 [0.87, 1.32] for ≤14, 15–16 and ≥17 years), and with increased time between thelarche and menarche (0.87 [0.65, 1.15], 1 [referent], 1.14 [0.96, 1.34] and 1.27 [1.04, 1.55] for <0, 0, 1 and ≥2 years), and shorter time between menarche and regular periods (1 [referent], 0.87 [0.73, 1.04] and 0.66 [0.50, 0.88] for 0, 1 and ≥2 years). These associations were generally similar when considered separately for premenopausal and postmenopausal breast cancer.ConclusionsBreast duct development may be a time of heightened susceptibility to risk of carcinogenesis, and greater attention needs to be given to the relation of breast cancer risk to the different stages of puberty.

Progressive Resistance Exercise Training in CKD: A Feasibility Study

BACKGROUND Skeletal muscle wasting in chronic kidney disease (CKD) is associated with morbidity and mortality. Resistance exercise results in muscle hypertrophy in the healthy population, but is underinvestigated in CKD. We aimed to determine the feasibility of delivering a supervised progressive resistance exercise program in CKD, with secondary aims to investigate effects on muscle size, strength, and physical functioning. STUDY DESIGN Parallel randomized controlled feasibility study. SETTING & PARTICIPANTS Patients with CKD stages 3b to 4 were randomly assigned to the exercise (n=20; 11 men; median age, 63 [IQR, 57-65] years; median estimated glomerular filtration rate, 28.5 [IQR, 19.0-32.0] mL/min/1.73 m(2)) or nonexercise control (n=18; 14 men; median age, 66 [IQR, 45-79] years; estimated glomerular filtration rate, 20.5 [IQR, 16.0-26.0] mL/min/1.73 m(2)) group. INTERVENTION Patients in the exercise group undertook an 8-week progressive resistance exercise program consisting of 3 sets of 10 to 12 leg extensions at 70% of estimated 1-repetition maximum thrice weekly. Patients in the control group continued with usual physical activity. OUTCOMES Primary outcomes were related to study feasibility: eligibility, recruitment, retention, and adherence rates. Secondary outcomes were muscle anatomical cross-sectional area, muscle volume, pennation angle, knee extensor strength, and exercise capacity. MEASUREMENTS Two- and 3-dimensional ultrasonography of skeletal muscle, dynamometry, and shuttle walk tests at baseline and 8 weeks. RESULTS Of 2,349 patients screened, 403 were identified as eligible and 38 enrolled in the study. 33 (87%) completed the study, and those in the exercise group attended 92% of training sessions. No changes were seen in controls for any parameter. Progressive resistance exercise increased muscle anatomical cross-sectional area, muscle volume, knee extensor strength, and exercise capacity. LIMITATIONS No blinded assessors, magnetic resonance imaging not used to assess muscle mass, lack of a healthy control group. CONCLUSIONS This type of exercise is well tolerated by patients with CKD and confers important clinical benefits; however, low recruitment rates suggest that a supervised outpatient-based program is not the most practical implementation strategy.

Objectively measured sedentary time and associations with insulin sensitivity: Importance of reallocating sedentary time to physical activity

OBJECTIVE The aim of this study is to quantify associations between objectively measured sedentary time and markers of insulin sensitivity by considering allocation into light-intensity physical activity or moderate- to vigorous-intensity physical activity (MVPA). METHODS Participants with an increased risk of impaired glucose regulation (IGR) were recruited (Leicestershire, United Kingdom, 2010-2011). Sedentary, light-intensity physical activity and MVPA time were measured using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were assessed; insulin sensitivity was calculated by HOMA-IS and Matsuda-ISI. Isotemporal substitution regression models were used. Data were analysed in 2014. RESULTS 508 participants were included (average age=65years, female=34%). Reallocating 30min of sedentary time into light-intensity physical activity was associated a 5% (95% CI 1, 9%; p=0.024) difference in Matsuda-ISI after adjustment for measured confounding variables. Reallocation into MVPA was associated with a 15% (7, 25%; p<0.001) difference in HOMA-IS and 18% (8, 28%; p<0.001) difference in Matsuda-ISI. Results for light-intensity physical activity were modified by IGR status with stronger associations seen in those with IGR. CONCLUSIONS Reallocating sedentary time into light-intensity physical activity or MVPA was associated with differences in insulin sensitivity, with stronger and more consistent associations seen for MVPA.

The association between neighbourhood greenspace and type 2 diabetes in a large cross-sectional study

Objective To investigate the relationship between neighbourhood greenspace and type 2 diabetes. Design Cross-sectional. Setting 3 diabetes screening studies conducted in Leicestershire, UK in 2004–2011. The percentage of greenspace in the participants home neighbourhood (3 km radius around home postcode) was obtained from a Land Cover Map. Demographic and biomedical variables were measured at screening. Participants 10 476 individuals (6200 from general population; 4276 from high-risk population) aged 20–75 years (mean 59 years); 47% female; 21% non-white ethnicity. Main outcome measure Screen-detected type 2 diabetes (WHO 2011 criteria). Results Increased neighbourhood greenspace was associated with significantly lower levels of screen-detected type 2 diabetes. The ORs (95% CI) for screen-detected type 2 diabetes were 0.97 (0.80 to 1.17), 0.78 (0.62 to 0.98) and 0.67 (0.49 to 0.93) for increasing quartiles of neighbourhood greenspace compared with the lowest quartile after adjusting for ethnicity, age, sex, area social deprivation score and urban/rural status (Ptrend=0.01). This association remained on further adjustment for body mass index, physical activity, fasting glucose, 2 h glucose and cholesterol (OR (95% CI) for highest vs lowest quartile: 0.53 (0.35 to 0.82); Ptrend=0.01). Conclusions Neighbourhood greenspace was inversely associated with screen-detected type 2 diabetes, highlighting a potential area for targeted screening as well as a possible public health area for diabetes prevention. However, none of the risk factors that we considered appeared to explain this association, and thus further research is required to elicit underlying mechanisms. Trial registration number This study uses data from three studies (NCT00318032, NCT00677937, NCT00941954).

Body Mass Index and Waist Circumference Cut-Points in Multi-Ethnic Populations from the UK and India: The ADDITION-Leicester, Jaipur Heart Watch and New Delhi Cross-Sectional Studies

Aims To derive cut-points for body mass index (BMI) and waist circumference (WC) for minority ethnic groups that are risk equivalent based on endogenous glucose levels to cut-points for white Europeans (BMI 30 kg/m2; WC men 102 cm; WC women 88 cm). Materials and Methods Cross-sectional data from participants aged 40–75 years: 4,672 white and 1,348 migrant South Asian participants from ADDITION-Leicester (UK) and 985 indigenous South Asians from Jaipur Heart Watch/New Delhi studies (India). Cut-points were derived using fractional polynomial models with fasting and 2-hour glucose as outcomes, and ethnicity, objectively-measured BMI/WC, their interaction and age as covariates. Results Based on fasting glucose, obesity cut-points were 25 kg/m2 (95% Confidence Interval: 24, 26) for migrant South Asian, and 18 kg/m2 (16, 20) for indigenous South Asian populations. For men, WC cut-points were 90 cm (85, 95) for migrant South Asian, and 87 cm (82, 91) for indigenous South Asian populations. For women, WC cut-points were 77 cm (71, 82) for migrant South Asian, and 54 cm (20, 63) for indigenous South Asian populations. Cut-points based on 2-hour glucose were lower than these. Conclusions These findings strengthen evidence that health interventions are required at a lower BMI and WC for South Asian individuals. Based on our data and the existing literature, we suggest an obesity threshold of 25 kg/m2 for South Asian individuals, and a very high WC threshold of 90 cm for South Asian men and 77 cm for South Asian women. Further work is required to determine whether lower cut-points are required for indigenous, than migrant, South Asians.