A pragmatic and scalable strategy using mobile technology to promote sustained lifestyle changes to prevent type 2 diabetes in India and the UK: a randomised controlled trial.

AIMS/HYPOTHESIS: This randomised controlled trial was performed in India and the UK in people with prediabetes to study whether mobile phone short message service (SMS) text messages can be used to motivate and educate people to follow lifestyle modifications, to prevent type 2 diabetes. METHODS: The study was performed in people with prediabetes (n = 2062; control: n = 1031; intervention: n = 1031) defined by HbA1c ≥42 and ≤47 mmol/mol (≥6.0% and ≤6.4%). Participants were recruited from public and private sector organisations in India (men and women aged 35-55 years) and by the National Health Service (NHS) Health Checks programme in the UK (aged 40-74 years without pre-existing diabetes, cardiovascular disease or kidney disease). Allocation to the study groups was performed using a computer-generated sequence (1:1) in India and by stratified randomisation in permuted blocks in the UK. Investigators in both countries remained blinded throughout the study period. All participants received advice on a healthy lifestyle at baseline. The intervention group in addition received supportive text messages using mobile phone SMS messages 2-3 times per week. Participants were assessed at baseline and at 6, 12 and 24 months. The primary outcome was conversion to type 2 diabetes and secondary outcomes included anthropometry, biochemistry, dietary and physical activity changes, blood pressure and quality of life. RESULTS: At the 2 year follow-up (n = 2062; control: n = 1031; intervention: n = 1031), in the intention-to-treat population the HR for development of type 2 diabetes calculated using a discrete-time proportional hazards model was 0.89 (95% CI 0.74, 1.07; p = 0.22). There were no significant differences in the secondary outcomes. CONCLUSIONS/INTERPRETATION: This trial in two countries with varied ethnic and cultural backgrounds showed no significant reduction in the progression to diabetes in 2 years by lifestyle modification using SMS messaging. TRIAL REGISTRATION: The primary study was registered on www.ClinicalTrials.gov (India, NCT01570946; UK, NCT01795833). FUNDING: The study was funded jointly by the Indian Council for Medical Research and the UK Medical Research Council.

Protocol for a clinical trial of text messaging in addition to standard care versus standard care alone in prevention of type 2 diabetes through lifestyle modification in India and the UK.

BACKGROUND: Type 2 diabetes is a serious clinical problem in both India and the UK. Adoption of a healthy lifestyle through dietary and physical activity modification can help prevent type 2 diabetes. However, implementing lifestyle modification programmes to high risk groups is expensive and alternative cheaper methods are needed. We are using a short messaging service (SMS) programme in our study as a tool to provide healthy lifestyle advice and an aid to motivation. The aim of the study is to assess the efficacy and user acceptability of text messaging employed in this way for people with pre-diabetes (HbA1c 6.0% to ≤6.4%; 42-47 mmol/mol) in the UK and India. METHODS/DESIGN: This is a randomised, controlled trial with participants followed up for 2 years. After being screened and receiving a structured education programme for prediabetes, participants are randomised to a control or intervention group. In the intervention group, text messages are delivered 2-3 times weekly and contain educational, motivational and supportive content on diet, physical activity, lifestyle and smoking. The control group undergoes monitoring only. In India, the trial involves 5 visits after screening (0, 6, 12, 18 and 24 months). In the UK there are 4 visits after screening (0, 6, 12 and 24 months). Questionnaires (EQ-5D, RPAQ, Transtheoretical Model of Behavioural Change, and food frequency (UK)/24 h dietary recall (India)) and physical activity monitors (Actigraph GT3X+ accelerometers) are assessed at baseline and all follow-up visits. The SMS acceptability questionnaires are evaluated in all follow-up visits. The primary outcome is progression to type 2 diabetes as defined by an HbA1c of 6.5% or over(India) and by any WHO criterion(UK). Secondary outcomes are the changes in body weight, body mass index, waist circumference, blood pressure, fasting plasma glucose; lipids; proportion of participants achieving HbA1c ≤6.0%; HOMA-IR; HOMA-ß; acceptability of SMS; dietary parameters; physical activity and quality of life. DISCUSSION: The study is designed to assess the efficacy of tailored text messaging in addition to standard lifestyle advice to reduce the progression from prediabetes to type 2 diabetes in the two different countries. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT01570946 , 4th April 2012 (India); NCT01795833 , 21st February 2013 (UK).

Fasting plasma glucose and variation in cardiometabolic risk factors in people with high-risk HbA1c-defined prediabetes: A cross-sectional multiethnic study.

AIMS: Variation in cardiometabolic risk in prediabetes and any impacts of ethnicity on such variation have been little studied. In an ethnically diverse dataset, selected according to a high-risk HbA1c-based definition of prediabetes, we have investigated relationships between glycaemia and cardiometabolic risk factors and the influence of ethnicity on these relationships. METHODS: We undertook a cross-sectional analysis of baseline data from a diabetes prevention study in the UK and a chronic care clinic in Thailand, selected for people without diabetes (fasting plasma glucose <7.0 mmol/l) with HbA1c 6.0-6.4% (42-47 mmol/mol). Thai (n=158) and UK White (n=600), South Asian (n=112), Black (n=70) and other/mixed (n=103) groups were distinguished and measurements included fasting plasma glucose (FPG), blood pressure (BP), lipids and insulin resistance-related risk factors (IRFs). RESULTS: Independently of individual characteristics including ethnicity, only systolic BP was weakly associated with FPG (beta coefficient 1.76 (95%CI 0.10-3.42), p 0.03) and only LDL-c with IFG (FPG 5.6 to <7) (adjusted -0.14 (-0.27, -0.003) p 0.04). There were no significant independent associations with cardiometabolic risk factors when categories of impaired fasting glucose (FPG ≥ 6.1 to <7.0 mmol/L) were considered. Relative to White, South Asian ethnicity was independently associated with lower systolic and diastolic BP, Black with lower triglycerides, cholesterol/HDL-c ratio and having 2 or more IRFs, and Thai with lower cholesterol/HDL-c ratio and all three non-white ethnicities with lower total and LDL cholesterol. CONCLUSION: In high-risk HbA1c-defined prediabetes additional measurement of FPG will add little to evaluation of cardiometabolic risk. Additionally, UK Whites tend to have the most adverse cardiometabolic profile of any ethnic group.

Glycemic Variability and Its Impact on Quality of Life in Adults With Type 1 Diabetes.

BACKGROUND: There is evidence suggesting that glycemic variability reduces quality of life (QoL) in people with type 2 diabetes, but this association has not been explored in type 1 diabetes. We aimed to assess whether glycemic variability has an impact on QoL in adults with established type 1 diabetes using multiple daily injections (MDI) of insulin or continuous subcutaneous insulin infusion (CSII). METHODS: Participants wore a blinded continuous glucose monitor for up to 5 days and completed the diabetes quality of life (DQOL) questionnaire. Glycemic variability measures were calculated using the EasyGV version 9.0 software. A correlation analysis was performed to assess whether there was a relationship between glycemic variability and measures of QoL. RESULTS: In all, 57 participants with type 1 diabetes (51% male, 65% on CSII, 35% on MDI, mean [SD] age 41 [13] years, duration of diabetes 21 [12] years, HbA1c 63 [12] mmol/mol [7.9% (1.1)], body mass index 25.2 [4.0] kg/m(2)) were included in the analysis. No significant associations between glycemic variability and DQOL total or subscale scores were demonstrated. The glycemic variability was significantly higher for MDI participants compared to CSII participants (P < .05 for all glycemic variability measures), but no significant difference in QoL between the 2 treatment modality groups was observed. CONCLUSIONS: Treatment with CSII is associated with lower glycemic variability compared to MDI. Despite this, and contrary to findings in type 2 diabetes, this study did not find an association between glycemic variability and QoL in adults with relatively well-controlled type 1 diabetes, irrespective of whether they are on MDI or CSII.

Feasibility study of a bio-inspired artificial pancreas in adults with type 1 diabetes.

BACKGROUND: This study assesses proof of concept and safety of a novel bio-inspired artificial pancreas (BiAP) system in adults with type 1 diabetes during fasting, overnight, and postprandial conditions. In contrast to existing glucose controllers in artificial pancreas systems, the BiAP uses a control algorithm based on a mathematical model of ß-cell physiology. The algorithm is implemented on a miniature silicon microchip within a portable hand-held device that interfaces the components of the artificial pancreas. MATERIALS AND METHODS: In this nonrandomized open-label study each subject attended for a 6-h fasting study followed by a 13-h overnight and post-breakfast study on a separate occasion. During both study sessions the BiAP system was used, and microboluses of insulin were recommended every 5 min by the control algorithm according to subcutaneous sensor glucose levels. The primary outcome was percentage time spent in the glucose target range (3.9-10.0 mmol/L). RESULTS: Twenty subjects (55% male; mean [SD] age, 44 [10] years; duration of diabetes, 22 [12] years; glycosylated hemoglobin, 7.4% [0.7%] [57 (7) mmol/mol]; body mass index, 25 [4] kg/m(2)) participated in the fasting study, and the median (interquartile range) percentage time in target range was 98.0% (90.8-100.0%). Seventeen of these subjects then participated in the overnight/postprandial study, where 70.7% (63.9-77.4%) of time was spent in the target range and, reassuringly, 0.0% (0.0-2.3%) of time was spent in hypoglycemia (<3.9 mmol/L). CONCLUSIONS: The BiAP achieves safe glycemic control during fasting, overnight, and postprandial conditions.

Antimicrobial treatment and clinical outcome for infections with carbapenem- and multiply-resistant Acinetobacter baumannii around London.

Carbapenem- and multiply-resistant Acinetobacter baumannii (C-MRAB) are challenging pathogens, often susceptible only to polymyxins and tigecycline. We reviewed clinical outcomes in relation to antibiotic treatment for 166 consecutive patients infected or colonised with these organisms at 18 hospitals around London, UK. Clinical data were obtained along with the isolates, which were typed by pulsed-field gel electrophoresis (PFGE). Outcomes were compared for colonised and infected patients and in relation to treatment, with associations examined by logistic regression. Most subjects (103/166; 62%) were in Intensive Care Units (ICUs) or high dependency units; 84 (50.6%) were judged to be infected and 73 (44.0%) were colonised, with 9 indeterminate. Among the 166 C-MRAB isolates, 141 belonged to OXA-23 clone 1, a European clone II lineage. Survival rates among infected and colonised patients were 68% and 67%, respectively (P > 0.05), indicating little attributable mortality. Univariate and multivariate analyses indicated poorer outcomes among ICU-infected patients and those with pulmonary infection or bacteraemia, whereas trauma patients had significantly better outcomes than the generality. Outcomes varied with hospital, even in multivariate analysis, reflecting either differences in management or case mix. There was little association between outcome and therapy with colistin and/or tigecycline except that, among patients with respiratory infection, 12/15 treated with intravenous colistin alone had poor outcome compared with 1/8 whose therapy include nebulised colistin. This difference was significant (P=0.003), although the patients receiving nebulised drug were mostly younger, included trauma cases and were at a hospital with good outcomes.

Bioprocessing of embryonic stem cells for drug discovery.

Embryonic stem cells provide a potential resource for research and drug screening. To make such a resource feasible, it is necessary to generate cells of sufficient quality and quantity. The challenge is to expand cell numbers while maintaining the fidelity of phenotype and to control and direct differentiation to produce the cell type of interest in a format that is suitable for drug screening. At present, large-scale culturing of human ES cell lines is problematic and provides substantial challenges. This article provides an overview of current bioprocessing techniques that could be used to generate cells for drug discovery applications. This will generate further technical expertise that can be applied in the production of cells for potential therapeutic applications.

Embryonic stem cells as a source of differentiated neural cells for pharmacological screens.

The process of bringing a new pharmacologically active drug to market is laborious, time consuming, and costly. From drug discovery to safety assessment, new methods are constantly sought to develop faster and more efficient procedures to eliminate drugs from further investigation because of their limited effectiveness or high toxicity. Because in vitro cell assays are an important arm of this discovery process, it is therefore somewhat unsurprising that there is an emerging contribution of embryonic stem (ES) cell technology to this area. This technology utilizes the in vitro differentiation of ES cells into somatic cell target populations that, when coupled to the use of "lineage selection" protocols, allows for the production of infinite numbers of pure populations of the desired cells for both bioactivity and toxicological screens. Unlike the use of transformed cell lines, ES-derived cells remain karyotypically normal and therefore better reflect the potential responses of cells in vivo, and when selected are more homogeneous than those obtained using primary cultures. In this chapter we discuss the use of ES cell-derived somatic cells in pharmacological screens, with particular emphasis on neural cells, and describe the methods and protocols associated with the development of ES cell-derived neural cell assays.