Altered Nutrient Uptake Causes Mitochondrial Dysfunction in Senescent CD8+ EMRA T Cells During Type 2 Diabetes.

Mitochondrial health and cellular metabolism can heavily influence the onset of senescence in T cells. CD8+ EMRA T cells exhibit mitochondrial dysfunction and alterations to oxidative phosphorylation, however, the metabolic properties of senescent CD8+ T cells from people living with type 2 diabetes (T2D) are not known. We show here that mitochondria from T2D CD8+ T cells had a higher oxidative capacity together with increased levels of mitochondrial reactive oxgen species (mtROS), compared to age-matched control cells. While fatty acid uptake was increased, fatty acid oxidation was impaired in T2D CD8+ EMRA T cells, which also showed an accumulation of lipid droplets and decreased AMPK activity. Increasing glucose and fatty acids in healthy CD8+ T cells resulted in increased p-p53 expression and a fragmented mitochondrial morphology, similar to that observed in T2D CD8+ EMRA T cells. The resulting mitochondrial changes are likely to have a profound effect on T cell function. Consequently, a better understanding of these metabolic abnormalities is crucial as metabolic manipulation of these cells may restore correct T cell function and help reduce the impact of T cell dysfunction in T2D.

Real-World Implementation of Video Outpatient Consultations at Macro, Meso, and Micro Levels: Mixed-Method Study.

BACKGROUND: There is much interest in virtual consultations using video technology. Randomized controlled trials have shown video consultations to be acceptable, safe, and effective in selected conditions and circumstances. However, this model has rarely been mainstreamed and sustained in real-world settings. OBJECTIVE: The study sought to (1) define good practice and inform implementation of video outpatient consultations and (2) generate transferable knowledge about challenges to scaling up and routinizing this service model. METHODS: A multilevel, mixed-method study of Skype video consultations (micro level) was embedded in an organizational case study (meso level), taking account of national context and wider influences (macro level). The study followed the introduction of video outpatient consultations in three clinical services (diabetes, diabetes antenatal, and cancer surgery) in a National Health Service trust (covering three hospitals) in London, United Kingdom. Data sources included 36 national-level stakeholders (exploratory and semistructured interviews), longitudinal organizational ethnography (300 hours of observations; 24 staff interviews), 30 videotaped remote consultations, 17 audiotaped face-to-face consultations, and national and local documents. Qualitative data, analyzed using sociotechnical change theories, addressed staff and patient experience and organizational and system drivers. Quantitative data, analyzed via descriptive statistics, included uptake of video consultations by staff and patients and microcategorization of different kinds of talk (using the Roter interaction analysis system). RESULTS: When clinical, technical, and practical preconditions were met, video consultations appeared safe and were popular with some patients and staff. Compared with face-to-face consultations for similar conditions, video consultations were very slightly shorter, patients did slightly more talking, and both parties sometimes needed to make explicit things that typically remained implicit in a traditional encounter. Video consultations appeared to work better when the clinician and patient already knew and trusted each other. Some clinicians used Skype adaptively to respond to patient requests for ad hoc encounters in a way that appeared to strengthen supported self-management. The reality of establishing video outpatient services in a busy and financially stretched acute hospital setting proved more complex and time-consuming than originally anticipated. By the end of this study, between 2% and 22% of consultations were being undertaken remotely by participating clinicians. In the remainder, clinicians chose not to participate, or video consultations were considered impractical, technically unachievable, or clinically inadvisable. Technical challenges were typically minor but potentially prohibitive. CONCLUSIONS: Video outpatient consultations appear safe, effective, and convenient for patients in situations where participating clinicians judge them clinically appropriate, but such situations are a fraction of the overall clinic workload. As with other technological innovations, some clinicians will adopt readily, whereas others will need incentives and support. There are complex challenges to embedding video consultation services within routine practice in organizations that are hesitant to change, especially in times of austerity.

Group clinics for young adults with diabetes in an ethnically diverse, socioeconomically deprived setting (TOGETHER study): protocol for a realist review, co-design and mixed methods, participatory evaluation of a new care model.

INTRODUCTION: Young adults with diabetes often report dissatisfaction with care and have poor diabetes-related health outcomes. As diabetes prevalence continues to rise, group-based care could provide a sustainable alternative to traditional one-to-one consultations, by engaging young people through life stage-, context- and culturally-sensitive approaches. In this study, we will co-design and evaluate a group-based care model for young adults with diabetes and complex health and social needs in socioeconomically deprived areas. METHODS AND ANALYSIS: This participatory study will include three phases. In phase 1, we will carry out a realist review to synthesise the literature on group-based care for young adults with diabetes. This theory-driven understanding will provide the basis for phase 2, where we will draw on experience-based co-design methodologies to develop a new, group-based care model for young adults (aged <25 years, under the care of adult diabetes services). In phase 3, we will use a researcher-in-residence approach to implement and evaluate the co-designed group clinic model and compare with traditional care. We will employ qualitative (observations in clinics, patient and staff interviews and document analysis) and quantitative methods (eg, biological markers, patient enablement instrument and diabetes distress scale), including a cost analysis. ETHICS AND DISSEMINATION: National Health Service ethics approval has been granted (reference 17/NI/0019). The project will directly inform service redesign to better meet the needs of young adults with diabetes in socioeconomically deprived areas and may guide a possible cluster-randomised trial, powered to clinical and cost-effectiveness outcomes. Findings from this study may be transferable to other long-term conditions and/or age groups. Project outputs will include briefing statements, summaries and academic papers, tailored for different audiences, including people living with diabetes, clinicians, policy makers and strategic decision makers. REGISTRATION DETAILS: PROSPERO (CRD42017058726).

Virtual online consultations: advantages and limitations (VOCAL) study.

INTRODUCTION: Remote video consultations between clinician and patient are technically possible and increasingly acceptable. They are being introduced in some settings alongside (and occasionally replacing) face-to-face or telephone consultations. METHODS: To explore the advantages and limitations of video consultations, we will conduct in-depth qualitative studies of real consultations (microlevel) embedded in an organisational case study (mesolevel), taking account of national context (macrolevel). The study is based in 2 contrasting clinical settings (diabetes and cancer) in a National Health Service (NHS) acute trust in London, UK. Main data sources are: microlevel--audio, video and screen capture to produce rich multimodal data on 45 remote consultations; mesolevel--interviews, ethnographic observations and analysis of documents within the trust; macrolevel--key informant interviews of national-level stakeholders and document analysis. Data will be analysed and synthesised using a sociotechnical framework developed from structuration theory. ETHICS APPROVAL: City Road and Hampstead NHS Research Ethics Committee, 9 December 2014, reference 14/LO/1883. PLANNED OUTPUTS: We plan outputs for 5 main audiences: (1) academics: research publications and conference presentations; (2) service providers: standard operating procedures, provisional operational guidance and key safety issues; (3) professional bodies and defence societies: summary of relevant findings to inform guidance to members; (4) policymakers: summary of key findings; (5) patients and carers: 'what to expect in your virtual consultation'. DISCUSSION: The research literature on video consultations is sparse. Such consultations offer potential advantages to patients (who are spared the cost and inconvenience of travel) and the healthcare system (eg, they may be more cost-effective), but fears have been expressed that they may be clinically risky and/or less acceptable to patients or staff, and they bring significant technical, logistical and regulatory challenges. We anticipate that this study will contribute to a balanced assessment of when, how and in what circumstances this model might be introduced.

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach.

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made.

New models of self-management education for minority ethnic groups: pilot randomized trial of a story-sharing intervention.

OBJECTIVE: no model of self-management education or peer support has yet achieved widespread reach and acceptability with minority ethnic groups. We sought to refine and test a new complex intervention in diabetes education: informal story-sharing groups facilitated by bilingual health advocates. METHODS: pilot randomized trial with in-depth process evaluation in a socioeconomically deprived area. 157 people referred for diabetes education were randomized by concealed allocation to an intervention (story-sharing group in their own language) or control ('usual care' self-management education, through an interpreter if necessary) arm. Story-sharing groups were held in five ethnic languages and English (for African Caribbeans), and ran fortnightly for six months. Primary outcome was UKPDS (UK Prospective Diabetes Study) risk score. Secondary outcomes included attendance, HbA1c, well-being and enablement. Process measures included ethnographic observation, and qualitative interviews with staff and patients. RESULTS: some follow-up data were obtained on 87% of participants. There was no significant difference between intervention and control arms in biomedical outcomes. Attendance was 79% in the story-sharing arm and 35% in the control arm (p < 0.0001), and patient enablement scores were significantly higher (8.3 compared to 5.9, p < 0.005). The model was very popular with clinicians, managers and patients, which helped overcome numerous challenges to its successful embedding in a busy public sector diabetes service. CONCLUSION: people from minority ethnic groups in a socioeconomically deprived area were keen to attend informal story-sharing groups and felt empowered by them, but clinical outcomes were no better than with conventional education. Further research is needed to maximize the potential and evaluate the place of this appealing service model before it is introduced as a part of mainstream diabetes services.

Storylines of self-management: narratives of people with diabetes from a multiethnic inner city population.

OBJECTIVES: to analyse the narratives of people with diabetes to inform the design of culturally congruent self-management education programmes. METHODS: the study was based on quasi-naturalistic story-gathering; i.e. making real-time field notes of stories shared spontaneously in diabetes self-management education groups in a socioeconomically deprived London borough. Eighty-two adults aged 25-86, from six minority ethnic groups who were in the intervention arm of a randomized controlled trial of story-sharing, participated. Stories were translated in real time by the facilitator or group members. Ethnographic field notes were transcribed, and analysed thematically (to identify self-management domains raised by participants) and interpretively for over-arching storylines (i.e. considering how self-management domains were contextualized and made meaningful in personal narratives). Analysis was informed by both biomedical and sociological theories of self-management. RESULTS: people with diabetes identified seven self-management domains: knowledge; diet; exercise; medication; foot care; self-monitoring; and attending check-ups. Interpretive analysis revealed eight illness storylines within which these practical issues acquired social meaning and moral worth: becoming sick; rebuilding spoiled identity; becoming a practitioner of self-management; living a disciplined and balanced life; mobilizing a care network; navigating and negotiating in the health care system; managing the micro-morality of self-management 'choices'; and taking collective action. CONCLUSION: living with diabetes involves both medically recommended behaviours and complex biographical work to make sense of and cope with illness. Self-management education programmes should take closer account of over-arching storylines that pattern experience of chronic illness and recognize that some elements of self-management knowledge cannot be pre-specified in a structured curriculum.