Dietary Intervention in Pregnant Women with Gestational Diabetes; Protocol for the DiGest Randomised Controlled Trial.
Gestational diabetes mellitus (GDM) annually affects 35,000 pregnancies in the United Kingdom, causing suboptimal health outcomes to the mother and child. Obesity and excessive gestational weight gain are risk factors for GDM. The Institute of Medicine recommends weight targets for women that are overweight and obese, however, there are no clear guidelines for women with GDM. Observational data suggest that modest weight loss (0.6-2 kg) after 28 weeks may reduce risk of caesarean section, large-for-gestational-age (LGA), and maternal postnatal glycaemia. This protocol for a multicentre randomised double-blind controlled trial aims to identify if a fully controlled reduced energy diet in GDM pregnancy improves infant birthweight and reduces maternal weight gain (primary outcomes). A total of 500 women with GDM (National Institute of Health and Care Excellence (NICE) 2015 criteria) and body mass index (BMI) ≥25 kg/m2 will be randomised to receive a standard (2000 kcal/day) or reduced energy (1200 kcal/day) diet box containing all meals and snacks from 28 weeks to delivery. Women and caregivers will be blinded to the allocations. Food diaries, continuous glucose monitoring, and anthropometry will measure dietary compliance, glucose levels, and weight changes. Women will receive standard antenatal GDM management (insulin/metformin) according to NICE guidelines. The secondary endpoints include caesarean section rates, LGA, and maternal postnatal glucose concentrations.
2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DiRECT open-label, cluster-randomised trial.
The lancet. Diabetes & endocrinology. 2020;(12):939-948
BACKGROUND The pancreas is small and irregular in shape in people with type 2 diabetes. If these abnormalities are caused by the disease state itself rather than being a predisposing factor, remission of type 2 diabetes should restore normal pancreas morphology. The objective of this study was to determine whether changes in pancreas volume and shape occurred during 2 years of remission. METHODS For this post-hoc analysis, we included a subset of adult participants of the Diabetes Remission Clinical Trial (DiRECT), who had type 2 diabetes and were randomly assigned to a weight management intervention or routine diabetes management. Intervention group participants were categorised as responders (HbA1c <6·5% [48 mmol/mol] and fasting blood glucose <7·0 mmol/L, off all anti-diabetes medication) and non-responders, who were classified as remaining diabetic. Data on pancreas volume and irregularity of pancreas border at baseline, 5 months, 12 months, and 24 months after intervention were compared between responders and non-responders; additional comparisons were made between control group participants with type 2 diabetes and a non-diabetic comparator (NDC) group, who were matched to the intervention group by age, sex, and post-weight-loss weight, to determine the extent of any normalisation. We used a mixed-effects regression model based on repeated measures ANOVA with correction for potential confounding. Magnetic resonance techniques were employed to quantify pancreas volume, the irregularity of the pancreas borders, and intrapancreatic fat content. β-cell function and biomarkers of tissue growth were also measured. FINDINGS Between July 25, 2015, and Aug 5, 2016, 90 participants with type 2 diabetes in the DiRECT subset were randomly assigned to intervention (n=64) or control (n=26) and were assessed at baseline; a further 25 non-diabetic participants were enrolled into the NDC group. At baseline, mean pancreas volume was 61·7 cm3 (SD 16·0) in all participants with type 2 diabetes and 79·8 cm3 (14·3) in the NDC group (p<0·0001). At 24 months, pancreas volume had increased by 9·4 cm3 (95% CI 6·1 to 12·8) in responders compared with 6·4 cm3 (2·5 to 10·3) in non-responders (p=0·0008). Pancreas borders at baseline were more irregular in participants with type 2 diabetes than in the NDC group (fractal dimension 1·138 [SD 0·027] vs 1·097 [0·025]; p<0·0001) and had normalised by 24 months in responders only (1·099 [0·028]). Intrapancreatic fat declined by 1·02 percentage points (95% CI 0·53 to 1·51) in 32 responders and 0·51% (-0·17 to 1·19) in 13 non-responders (p=0·23). INTERPRETATION These data show for the first time, to our knowledge, reversibility of the abnormal pancreas morphology of type 2 diabetes by weight loss-induced remission. FUNDING Diabetes UK.
Be Healthe for Your Heart: A Pilot Randomized Controlled Trial Evaluating a Web-Based Behavioral Intervention to Improve the Cardiovascular Health of Women with a History of Preeclampsia.
International journal of environmental research and public health. 2020;(16)
This pilot randomized controlled trial (RCT) aimed to determine the acceptability and preliminary efficacy of a web-based cardiovascular disease (CVD) prevention intervention for women following preeclampsia. Australian women with a recent history (≤4 years post diagnosis) of preeclampsia were randomized into two study arms: (1) Be Healthe for your Heart, a web-based behavioral intervention or; (2) Control, access to the National Heart Foundation website. Assessments were conducted at baseline, and after three months. Intervention acceptability and impact on absolute CVD 30-year risk score, CVD risk markers and health behaviors were assessed. Twenty-four of 31 (77.4%) women completed the three-month assessment. Eleven out of 13 intervention participants (84.6%) agreed/strongly agreed they were satisfied with the program, with a mean score of 4.2 ± 0.9 (maximum of five). There were no significant between or within group differences in absolute CVD risk, CVD risk markers or health behaviors from baseline to three months. Women with a history of preeclampsia were successfully recruited and retained and they reported high levels of acceptability with the Be Healthe for your Heart program. Further research is therefore needed from powered trials to determine the impact of web-based lifestyle interventions on CVD risk in this at-risk group.
Time Course of Normalization of Functional β-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes.
Diabetes care. 2020;(4):813-820
OBJECTIVE To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss. RESEARCH DESIGN AND METHODS A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA1c <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once. RESULTS During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480-811) pmol/min/m2 at baseline to 736 (542-998) pmol/min/m2 at 5 months, 942 (565-1,240) pmol/min/m2 at 12 months (P = 0.028 from baseline), and 936 (635-1,435) pmol/min/m2 at 24 months (P = 0.023 from baseline; n = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857-1,507] pmol/min/m2) by 12 (P = 0.064) and 24 (P = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4-67] to 107 [59-163] pmol/min/m2; P < 0.0001) and then remained stable at 12 and 24 months (110 [59-201] and 125 [65-166] pmol/min/m2, respectively; P < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226-429] pmol/min/m2; P < 0.0001). CONCLUSIONS A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes.
Results of the 3 Pillars Study (3PS), a relationship-based programme targeting parent-child interactions, healthy lifestyle behaviours, and the home environment in parents of preschool-aged children: A pilot randomised controlled trial.
PloS one. 2020;(9):e0238977
BACKGROUND Early childhood is a critical period for the development of obesity, with new approaches to prevent obesity in this age group needed. We designed and piloted the 3 Pillars Study (3PS), a healthy lifestyle programme informed by attachment theory for parents of preschool-aged children. METHODS A 2-arm, randomised controlled pilot study was conducted to assess the effectiveness of 3PS, a 6-week programme involving a half-day workshop plus 6-week access to a study website. The programme was designed to promote routines around healthy lifestyle behaviours, including sleep, limited screen use, and family meals, within the context of positive, reciprocal parent-child interactions. Parents (n = 54) of children aged 2-4 years who regularly exceeded screen use recommendations (≥1 hour per day), were randomised to the 3PS programme (n = 27) or a wait-list control group (n = 27). Child screen time at 6 weeks was the primary endpoint. Frequency of family meals, parent feeding practices, diet quality, sleep, Child Routine Inventory (to assess predictability of commonly occurring routines), and household chaos were also assessed. Study data were collected online at baseline, 6 weeks, and 12 weeks via REDCap. RESULTS No group differences were observed for changes from baseline in screen time (primary endpoint), feeding behaviour scores, Child Routine Inventory scores, or total night time sleep duration at 6 and 12 weeks, although all measures improved in the hypothesised direction in the 3PS group. Compared with controls, the intervention group demonstrated significant improvements from baseline in household chaos scores (i.e. a reduction in chaos) and a number of measures of sleep outcomes, indicating improved sleep continuity. The programme was highly acceptable to parents. CONCLUSIONS AND RECOMMENDATIONS A relational approach appears promising as a novel way to promote healthy lifestyle behaviours associated with the prevention of childhood obesity in children aged 2-4 years. A larger study is warranted.
Protocol for an implementation study of an evidence-based home cardiac rehabilitation programme for people with heart failure and their caregivers in Scotland (SCOT:REACH-HF).
BMJ open. 2020;(12):e040771
INTRODUCTION Despite evidence that cardiac rehabilitation (CR) is an essential component of care for people with heart failure, uptake is low. A centre-based format is a known barrier, suggesting that home-based programmes might improve accessibility. The aim of SCOT Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) is to assess the implementation of the REACH-HF home-based CR intervention in the context of the National Health Service (NHS) in Scotland.This paper presents the design and protocol for this observational implementation study. Specific objectives of SCOTREACH-HF are to: (1) assess service-level facilitators and barriers to the implementation of REACH-HF; (2) compare real-world patient and caregiver outcomes to those seen in a prior clinical trial; and (3) estimate the economic (health and social) impact of implementing REACH-HF in Scotland. METHODS AND ANALYSIS The REACH-HF intervention will be delivered in partnership with four 'Beacon sites' across six NHS Scotland Health Boards, covering rural and urban areas. Health professionals from each site will be trained to facilitate delivery of the 12-week programme to 140 people with heart failure and their caregivers. Patient and caregiver outcomes will be assessed at baseline and 4-month follow-up. Assessments include the Minnesota Living with Heart Failure Questionnaire (MLHFQ), five-dimension EuroQol 5L, Hospital Anxiety and Depression Scale, and the Caregiver Burden Questionnaire. Qualitative interviews will be conducted with up to 20 health professionals involved in programme delivery (eg, cardiac nurses, physiotherapists). 65 facilitator-patient consultations will be audio recorded and assessed for fidelity. Integrative analysis will address key research questions on fidelity, context and CR participant-related outcomes. The SCOTREACH-HF findings will inform the future potential roll-out of REACH-HF in Scotland. ETHICS AND DISSEMINATION The study has been given ethical approval by the West of Scotland Research Ethics Service (reference 20/WS/0038, approved 25 March 2020). Written informed consent will be obtained from all participants. The study is listed on the ISRCTN registry with study ID ISRCTN53784122. The research team will ensure that the study is conducted in accordance with both General Data Protection Regulations and the University of Glasgow's Research Governance Framework. Findings will be reported to the funder and shared with Beacon Sites, to facilitate service evaluation, planning and good practice. To broaden interest in, and understanding of REACH-HF, we will seek to publish in peer-reviewed scientific journals and present at stakeholder events, national and international conferences.
Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss.
Cell metabolism. 2020;(2):233-249.e4
The role of hepatic lipoprotein metabolism in diet-induced remission of type 2 diabetes is currently unclear. Here, we determined the contributions of hepatic VLDL1-triglyceride production rate and VLDL1-palmitic acid content to changes in intra-pancreatic fat and return of first phase insulin response in a subgroup of the Diabetes Remission Clinical Trial. Liver fat, VLDL1-triglyceride production, and intra-pancreatic fat decreased after weight loss and remained normalized after 24 months of remission. First-phase insulin response remained increased only in those maintaining diabetes remission. Compared with those in remission at 24 months, individuals who relapsed after initial remission had a greater rise in the content of VLDL1-triglyceride and VLDL1-palmitic acid, re-accumulated intra-pancreatic fat, and lost first-phase response by 24 months. Thus, we observed temporal relationships between VLDL1-triglyceride production, hepatic palmitic acid flux, intra-pancreatic fat, and β-cell function. Weight-related disordered fat metabolism appears to drive development and reversal of type 2 diabetes.
Efficacy of a compulsory homework programme for increasing physical activity and improving nutrition in children: a cluster randomised controlled trial.
The international journal of behavioral nutrition and physical activity. 2019;(1):80
BACKGROUND Most physical activity interventions in children focus on the school setting; however, children typically engage in more sedentary activities and spend more time eating when at home. The primary aim of this cluster randomised controlled trial was to investigate the effects of a compulsory, health-related homework programme on physical activity, dietary patterns, and body size in primary school-aged children. METHODS A total of 675 children aged 7-10 years from 16 New Zealand primary schools participated in the Healthy Homework study. Schools were randomised into intervention and control groups (1:1 allocation). Intervention schools implemented an 8-week applied homework and in-class teaching module designed to increase physical activity and improve dietary patterns. Physical activity was the primary outcome measure, and was assessed using two sealed pedometers that monitored school- and home-based activity separately. Secondary outcome measures included screen-based sedentary time and selected dietary patterns assessed via parental proxy questionnaire. In addition, height, weight, and waist circumference were measured to obtain body mass index (BMI) and waist-to-height ratio (WHtR). All measurements were taken at baseline (T0), immediately post-intervention (T1), and 6-months post-intervention (T2). Changes in outcome measures over time were estimated using generalised linear mixed models (GLMMs) that adjusted for fixed (group, age, sex, group x time) and random (subjects nested within schools) effects. Intervention effects were also quantified using GLMMs adjusted for baseline values. RESULTS Significant intervention effects were observed for weekday physical activity at home (T1 [P < 0.001] and T2 [P = 0.019]), weekend physical activity (T1 [P < 0.001] and T2 [P < 0.001]), BMI (T2 only [P = 0.020]) and fruit consumption (T1 only [P = 0.036]). Additional analyses revealed that the greatest improvements in physical activity occurred in children from the most socioeconomically deprived schools. No consistent effects on sedentary time, WHtR, or other dietary patterns were observed. CONCLUSIONS A compulsory health-related homework programme resulted in substantial and consistent increases in children's physical activity - particularly outside of school and on weekends - with limited effects on body size and fruit consumption. Overall, our findings support the integration of compulsory home-focused strategies for improving health behaviours into primary education curricula. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry, ACTRN12618000590268 . Registered 17 April 2018.
Home-based rehabilitation for heart failure with reduced ejection fraction: mixed methods process evaluation of the REACH-HF multicentre randomised controlled trial.
BMJ open. 2019;(8):e026039
OBJECTIVE To identify and explore change processes explaining the effects of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention taking account of reach, amount of intervention received, delivery fidelity and patient and caregiver perspectives. DESIGN Mixed methods process evaluation parallel to a randomised controlled trial using data from the intervention group (REACH-HF plus usual care). SETTING Four centres in the UK (Birmingham, Cornwall, Gwent and York). PARTICIPANTS People with heart failure with reduced ejection fraction (HFrEF) and their caregivers. METHODS The REACH-HF intervention consisted of a self-help manual for patients with HFrEF and caregivers facilitated over 12 weeks by trained healthcare professionals. The process evaluation used multimodal mixed methods analysis. Data consisted of audio recorded intervention sessions; demographic data; intervention fidelity scores for intervention group participants (107 patients and 53 caregivers); qualitative interviews at 4 and 12 months with a sample of 19 patients and 17 caregivers. OUTCOME MEASURES Quantitative data: intervention fidelity and number, frequency and duration of intervention sessions received. Qualitative data: experiences and perspectives of intervention participants and caregivers. RESULTS Intervention session attendance with facilitators was high. Fidelity scores were indicative of adequate quality of REACH-HF intervention delivery, although indicating scope for improvement in several areas. Intervention effectiveness was contingent on matching the intervention implementation to the concerns, beliefs and goals of participants. Behaviour change was sustained when shared meaning was established. Respondents' comorbidities, socio-economic circumstances and existing networks of support also affected changes in health-related quality of life. CONCLUSIONS By combining longitudinal mixed methods data, the essential ingredients of complex interventions can be better identified, interrogated and tested. This can maximise the clinical application of research findings and enhance the capacity of multidisciplinary and multisite teams to implement the intervention. TRIAL REGISTRATION NUMBER ISRCTN25032672; Pre-results.
Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: Assessment of Causal Relations.
Plain language summary
It is generally accepted that certain diet and lifestyle choices contribute to a person’s risk of developing type 2 diabetes (T2D). In this meta-analysis, researchers set out to review previous studies and assess whether there is any evidence that the amount and type of carbohydrate (measured by Glycaemic Index (GI) and Glycaemic Load (GL)) in a person’s diet has a direct influence on their risk of developing T2D. The authors concluded with a high level of confidence that eating high GI and GL foods can lead to a higher risk of developing T2D. They suggest that nutrition advice that favours low GI and GL foods could produce significant cost savings for public healthcare.
While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.