The challenges and lessons from a formative process and value-based evaluation of the wave 1 roll-out of the all Wales Diabetes Prevention Programme.

BACKGROUND: The All Wales Diabetes Prevention Programme (AWDPP) is a Wales wide, public health initiative designed to systematically identify adults at risk of developing type 2 diabetes and offer a 30-minute person-centred lifestyle conversation focused on diet and physical activity. An independent formative process and value-based evaluation was commissioned to examine the implementation of this programme in 14 primary care cluster areas across Wales during the initial roll-out. METHODS: This evaluation was undertaken to ascertain the views on early implementation of the programme from service users, health care professionals and key stakeholders. The evaluation was informed by the Medical Research Council Framework for Process Evaluation and Wales Prudent Healthcare principles. As part of the value-based assessment, a preliminary cost-consequence analysis was conducted to understand the short-term economic impact of the implementation of the programme. RESULTS: Service users who took part in the evaluation highly valued the programme and nearly half had been previously unaware that they were at risk of developing type 2 diabetes. Delivering the programme presented challenges but there was significant enthusiasm and support from all stakeholders. Overall, the programme was being delivered as intended albeit with evidence of some variation in the application of the programme eligibility criteria. CONCLUSIONS: In Wave 1 of the AWDPP roll-out, the intent to deliver the programme in line with Prudent Healthcare was successful and promising in terms of demonstrating value. Opinions expressed by service users suggest the AWDPP matters to them; raising awareness, promoting knowledge and capacity to change behaviours and motivate and raise confidence.

Characteristics of repeat non-attenders at Diabetes Eye Screening Wales, a national community-based diabetes-related retinopathy screening service, during 2003-2018.

AIMS: To understand factors associated with repeat non-attendance at screening for diabetes-related retinopathy. METHODS: Retrospective observational study using anonymised data from Diabetic Eye Screening Wales for people with a full history of screening invitations and attendances was linked with primary and secondary care records held in the Secure Anonymised Information Linkage Databank. Repeat non-attendance was defined as no record of attendance during any 36-month period despite three cycles of annual screening invitations. The associations between repeat non-attendance and potential risk factors were examined using multivariable logistic regression analysis, stratified according to type 1 and type 2 diabetes. RESULTS: A total of 18% with type 1 diabetes (1146/6513) and 8% with type 2 diabetes (12,475/156,525) were repeat non-attenders. Participants attending their very first appointment were least likely to become repeat non-attenders [odds ratio (95% confidence interval)]: type 1 diabetes: 0.12 (0.09, 0.17) and type 2 diabetes: 0.08 (0.07, 0.09). For both types of diabetes, those of a younger age, living in areas of higher deprivation and subject to multiple house moves were at greater risk of becoming repeat non-attenders. CONCLUSION/INTERPRETATION: A more tailored approach is needed for the younger population, those living in areas of higher deprivation and/or undergoing multiple residential relocation and to ensure attendance at their initial appointment to minimise future repeat non-attendance.

Abundance of undiagnosed cardiometabolic risk within the population of a long-stay prison in the UK.

BACKGROUND: The health of people in prisons is a public health issue. It is well known that those in prison experience poorer health outcomes than those in the general community. One such example is the burden of non-communicable diseases, more specifically cardiovascular disease (CVD), stroke and type 2 diabetes (T2DM). However, there is limited evidence research on the extent of cardiometabolic risk factors in the prison environment in Wales, the wider UK or globally. METHODS: Risk assessments were performed on a representative sample of 299 men at HMP Parc, Bridgend. The risk assessments were 30 min in duration and men aged 25-84 years old and free from pre-existing CVD and T2DM were eligible. During the risk assessment, a number of demographic, anthropometric and clinical markers were obtained. The 10-year risk of CVD and T2DM was predicted using the QRISK2 algorithm and Diabetes UK Risk Score, respectively. RESULTS: The majority of the men was found to be either overweight (43.5%) or obese (37.5%) and/or demonstrated evidence of central obesity (40.1%). Cardiometabolic risk factors including systolic hypertension (25.1%), high cholesterol (29.8%), low HDL cholesterol (56.2%) and elevated total cholesterol: HDL ratios (23.1%) were observed in a considerable number of men. Ultimately, 15.4% were calculated at increased risk of CVD, and 31.8% predicted at moderate or high risk of T2DM. CONCLUSIONS: Overall, a substantial prevalence of previously undiagnosed cardiometabolic risk factors was observed and men in prison are at elevated risk of cardiometabolic disease at a younger age than current screening guidelines.

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes.

AIMS/HYPOTHESIS: Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. METHODS: A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. RESULTS: A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD-) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. CONCLUSIONS/INTERPRETATION: Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration.

Self-monitoring of Blood Glucose in Non-Insulin Treated Type 2 Diabetes (The SMBG Study): study protocol for a randomised controlled trial.

BACKGROUND: The benefit of Self-monitoring of Blood Glucose (SMBG) in people with non-insulin treated type 2 diabetes remains unclear with inconsistent evidence from randomised controlled trials fuelling the continued debate. Lack of a consistent finding has been attributed to variations in study population and design, including the SMBG intervention. There is a growing consensus that structured SMBG, whereby the person with diabetes and health care provider are educated to detect patterns of glycaemic abnormality and take appropriate action according to the blood glucose profiles, can prove beneficial in terms of lowering HbA1c and improving overall well-being. Despite this, many national health agencies continue to issue guidelines restricting the use of SMBG in non-insulin treated type 2 diabetes. METHODS: The SMBG Study is a 12 month, multi-centre, randomised controlled trial in people with type 2 diabetes not on insulin therapy who have poor glycaemic control (HbA1c ≥58 mmol/mol / 7.5%). The participants will be randomised into three comparative groups: Group 1 will act as a control group and receive their usual diabetes care; Group 2 will undertake structured SMBG with clinical review every 3 months; Group 3 will undertake structured SMBG with additional monthly telecare support from a trained study nurse. A total of 450 participants will be recruited from 16 primary and secondary care sites across Wales and England. The primary outcome measure will be HbA1c at 12 months with secondary measures to include weight, BMI, total cholesterol and HbA1c levels at 3, 6, 9 and 12 months. Participant well-being and attitude towards SMBG will be monitored throughout the course of the study. Recruitment began in December 2012 with the last participant visit due in September 2016. DISCUSSION: This study will attempt to answer the question of whether structured SMBG provides any benefits to people with poorly controlled type 2 diabetes who are not being treated with insulin. The data will also clarify whether the telecare support provides additional value. The overall acceptability of SMBG as a tool for self-management will be assessed. TRIAL REGISTRATION: UKCRN 12038 (Registered March 2012). ISRCTN21390608 (Retrospectively registered 15th May 2014).

Comparability Evaluation of Three Benchtop Glucose Analyzers With the Recently Withdrawn YSI 2300 Stat Plus.

BACKGROUND: We compared the performance of three currently available laboratory benchtop glucose analyzers with the outgoing YSI 2300 Stat Plus. METHODS: Plasma samples (100), across a wide glucose concentration range were analysed on the YSI 2500, Randox daytona+ (glucose oxidase) and EKF Biosen in a single laboratory and compared to the YSI 2300 Stat Plus. RESULTS: All three analyzers showed good agreement with the YSI 2300 Stat Plus, and only a small bias (≤1% YSI 2500 and Randox daytona+, 4.6% EKF Biosen) was observed for each analyzer. None of the three comparator analyzers were affected by either proportional or constant bias, thus no significant differences between the YSI 2300 Stat Plus and the comparator methods were identified. CONCLUSIONS: The results from this study suggest all could be considered as suitable reference laboratory glucose analyzers and replacements for the recently withdrawn YSI 2300 Stat Plus.

Using Artificial Intelligence to Improve the Accuracy of a Wrist-Worn, Noninvasive Glucose Monitor: A Pilot Study.

BACKGROUND: Self-monitoring of glucose is important to the successful management of diabetes; however, existing monitoring methods require a degree of invasive measurement which can be unpleasant for users. This study investigates the accuracy of a noninvasive glucose monitoring system that analyses spectral variations in microwave signals. METHODS: An open-label, pilot design study was conducted with four cohorts (N = 5/cohort). In each session, a dial-resonating sensor (DRS) attached to the wrist automatically collected data every 60 seconds, with a novel artificial intelligence (AI) model converting signal resonance output to a glucose prediction. Plasma glucose was measured in venous blood samples every 5 minutes for Cohorts 1 to 3 and every 10 minutes for Cohort 4. Accuracy was evaluated by calculating the mean absolute relative difference (MARD) between the DRS and plasma glucose values. RESULTS: Accurate plasma glucose predictions were obtained across all four cohorts using a random sampling procedure applied to the full four-cohort data set, with an average MARD of 10.3%. A statistical analysis demonstrates the quality of these predictions, with a surveillance error grid (SEG) plot indicating no data pairs falling into the high-risk zones. CONCLUSIONS: These findings show that MARD values approaching accuracies comparable to current commercial alternatives can be obtained from a multiparticipant pilot study with the application of AI. Microwave biosensors and AI models show promise for improving the accuracy and convenience of glucose monitoring systems for people with diabetes.

Quantification of human serum insulin concentrations in clinical pharmacokinetic or bioequivalence studies: what defines the "best method"?

BACKGROUND: Historically, quantitative clinical diagnostic assays (QCDAs) have not been accepted for use in pharmacokinetic or bioequivalence studies because they do not fully comply with the US Food and Drug Administration (FDA) Guidance for Industry: Bioanalytical Method Validation (e.g., full calibration curve not generated with each analytical run). Samples from a bioequivalence study were analysed for insulin and C-peptide concentrations with QCDAs and guidance-conforming radioimmunoassays (RIAs) and the results compared across and within assays. METHODS: Serum samples (n=1913) from study MKC-TI-142 were analysed first using the Roche E170 electrochemiluminescence immunoassay (ECLIA) for insulin concentration and the Immulite 2000 chemiluminescence immunoassay (CLIA) for C-peptide, and then using the corresponding Millipore RIAs. RESULTS: The insulin assays were highly correlated: r2=0.92 excluding samples requiring dilution and R2=0.88 including all samples. There was increasing negative bias of the ECLIA compared with the RIA with increasing insulin, especially with samples that required dilution for the RIA. The ECLIA had significantly fewer below-quantifiable-limit samples, a larger dynamic analysis range without dilution, and tighter agreement within incurred sample reanalysis (ISR) as compared with the RIA. The C-peptide assays showed good agreement but the CLIA method produced ISR results that were in closer agreement with the original values. CONCLUSIONS: The science indicates that the QCDAs are appropriate for the quantification of serum insulin (ECLIA) and C-peptide (CLIA) concentrations in human pharmacokinetic and bioequivalence studies even though the calibration curve is not generated in each analytical run.

The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM.

AIMS: The two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays. MATERIALS AND METHODS: A total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis. RESULTS: The MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function. CONCLUSION: This study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution.

Evaluating the impact of a prison smoking ban on the cardiovascular health of men in a UK prison.

PURPOSE: Smoking rates are known to be higher amongst those committed to prison than the general population. Those in prison suffer from high rates of comorbidities that are likely to increase their risk of cardiovascular disease (CVD), making it more difficult to manage. In 2016, a tobacco ban began to be implemented across prisons in England and Wales, UK. This study aims to measure the effect of the tobacco ban on predicted cardiovascular risk for those quitting smoking on admission to prison. DESIGN/METHODOLOGY/APPROACH: Using data from a prevalence study of CVD in prisons, the authors have assessed the effect of the tobacco ban on cardiovascular risk, using predicted age to CVD event, ten-year CVD risk and heart age, for those who previously smoked and gave up on admission to prison. FINDINGS: The results demonstrate measurable health gains across all age groups with the greatest gains found in those aged 50 years and older and who had been heavy smokers. Quitting smoking on admission to prison led to a reduced heart age of between two and seven years for all participants. ORIGINALITY/VALUE: The data supports tobacco bans in prisons as a public health measure to reduce risk of CVD. Interventions are needed to encourage maintenance of smoking cessation on release from prison for the full health benefits to be realised.

Incidence of diabetic retinopathy in newly diagnosed subjects with type 2 diabetes mellitus over 5 years: Contribution of Β-cell function.

AIMS: Identifying and modulating risk factors is essential to prevent visual impairment due to diabetic retinopathy (DR). This study examines incident DR with metabolic and hormonal factors in newly-diagnosed, treatment naïve, individuals with Type2 Diabetes Mellitus (T2DM), over a 5 year period from diagnosis. METHODS: 233 T2DM subjects underwent serial DR screening using digital photography and standardised Meal Tolerance Tests at diagnosis and after 1, 2 and 5 years. Subjects (179) with no DR throughout the 5-year study period were compared with those who developed DR (54). RESULTS: Of 233 subjects, 54(23.2%) developed DR by 5 years, background DR in 50(93%) and exudative maculopathy in 4(7%) individuals. Of these subjects, 12(22%) developed DR after 1 year, 15(28%) after 2 years and 27(50%) after 5 years. At baseline, those with DR at 5 years had higher HbA1c (p = 0.017), higher fasting plasma glucose (PG) (p = 0.031) and postprandial PG (p = 0.009). They were associated with reduced basal ß-cell secretory function (M0) (p = 0.025), lower (p = 0.000) postprandial ß-cell responsiveness (M1) and ß-cell function (HOMA-B) (p = 0.044). CONCLUSIONS: There is an independent association between glycaemic control and ß-cell dysfunction at the time of diagnosis of T2DM, with incident DR over a follow-up period of 5 years.

Brief lifestyle interventions for prediabetes in primary care: a service evaluation.

BACKGROUND: The increasing number of cases of prediabetes in the UK is concerning, particularly in Wales where there is no standard programme of support. The aim of the current service evaluation was to examine the effectiveness of brief lifestyle interventions on glucose tolerance in people at risk of developing type 2 diabetes. METHODS: In this pragmatic service evaluation clinical data on people deemed at risk of developing type 2 diabetes were evaluated from two GP clusters. Patients (n = 1207) received a single 15 to 30-min, face-to-face, consultation with a health care practitioner. Interventions were assessed by changes in HbA1c and distribution across the HbA1c ranges 12 months following intervention. Statistical significance of reversion to normoglycaemia and development of diabetes were assessed through comparison with expected rates without intervention. RESULTS: Between baseline and 12-month follow-up HbA1c fell from 43.85 ± 1.57 mmol/mol (6.16 ± 0.14%) to 41.63 ± 3.84 mmol/mol (5.96 ± 0.35%), a decrease of 2.22 mmol/mol (0.20%) (95% CI 2.01 (0.18%), 2.42 (0.22%); p < 0.0001). The proportion of people with normal glucose tolerance at 12 months (0.50 95%CI 0.47, 0.52) was significantly larger than the lower (0.06 (p < 0.0001) and the upper (0.19 (p < 0.0001)) estimates based on no intervention. CONCLUSION: Results indicate significant improvement in glucose tolerance across GP clusters. The brief intervention has the potential to offer a robust and effective option to support people at risk of developing type 2 diabetes. Further research in the form of a randomised trial is needed to confirm this and identify those likely to benefit most from this intervention.

A combined insulin reduction and carbohydrate feeding strategy 30 min before running best preserves blood glucose concentration after exercise through improved fuel oxidation in type 1 diabetes mellitus.

In this study, we examined the glycaemic and fuel oxidation responses to alterations in the timing of a low glycaemic index carbohydrate and 75% reduced insulin dose, prior to running, in type 1 diabetes individuals. After carbohydrate (75 g isomaltulose) and insulin administration, the seven participants rested for 30 min, 60 min, 90 min or 120 min (conditions 30MIN, 60MIN, 90MIN, and 120MIN, respectively) before completing 45 min of running at 70% peak oxygen uptake. Carbohydrate and lipid oxidation rates were monitored during exercise and blood glucose and insulin were measured before and for 3 h after exercise. Data were analysed using repeated-measures analysis of variance. Pre-exercise blood glucose concentrations were lower for 30MIN compared with 120MIN (P < 0.05), but insulin concentrations were similar. Exercising carbohydrate and lipid oxidation rates were lower and greater, respectively, for 30MIN compared with 120MIN (P < 0.05). The drop in blood glucose during exercise was less for 30MIN (3.7 mmol · l(-1), s(x) = 0.4) compared with 120MIN (6.4 mmol · l(-1), s(x) = 0.3) (P = 0.02). For 60 min post-exercise, blood glucose concentrations were higher for 30MIN compared with 120MIN (P < 0.05). There were no cases of hypoglycaemia in the 30MIN condition, one case in the 60MIN condition, two in the 90MIN condition, and five in the 120MIN condition. In conclusion, a low glycaemic index carbohydrate and reduced insulin dose administered 30 min before running improves pre- and post-exercise blood glucose responses in type 1 diabetes.

Risk factors for having diabetic retinopathy at first screening in persons with type 1 diabetes diagnosed under 18 years of age.

OBJECTIVE: To determine the risk factors for having diabetic retinopathy (DR) in children and young people (CYP) with type 1 diabetes (T1DM) at first screening. METHODS: Records from the Diabetes Eye Screening Wales (DESW) service for people in Wales, UK, with T1DM diagnosed under age 18 years were combined with other electronic health record (EHR) data in the Secure Anonymised Information Linkage (SAIL) Databank. Data close to the screening date were collected, and risk factors derived from multivariate, multinomial logistic regression modelling. RESULTS: Data from 4172 persons, with median (lower quartile, upper quartile) age 16.3 (13.0, 22.3) years and duration of diabetes 6.6 (2.3, 12.3) years were analysed. 62.6% (n = 2613) had no DR, 26.7% (n = 1112) background DR, and 10.7% (n = 447) had referable DR (RDR). No RDR was observed under 19 years of age. Factors associated with an increased risk of DR were diabetes duration, elevated HbA1c, and diastolic blood pressure. People diagnosed with T1DM at 12 years or older had an additional risk for each year they had diabetes compared to those diagnosed before age 12 controlling for the diabetes duration (odds ratios 1.23 and 1.34, respectively). CONCLUSIONS: This study found that 37.4% of the study cohort had DR at first screening, the risk being greater the longer the duration of diabetes or higher the HbA1c and diastolic blood pressure. In addition, people diagnosed at 12 years of age or over were more likely to have DR with each additional year with diabetes.

Estimating the burden of type 2 diabetes in the UK prison environment for the next decade.

Although limited, global evidence suggests that the cardiometabolic health of those in prison is poorer than their community peers. Type 2 diabetes (T2DM) is a public health challenge and community rates are continuing to rise. Given that cardiometabolic risk factors are prevalent amongst younger individuals within the prison population, it is reasonable to assume that the prison environment will also experience an increase in new cases of T2DM. Therefore, the aim of this study was, to predict in a current prison population, how many potential new cases of T2DM could develop in the next 10 years. This study used health data collected from a prison sample (n = 299) aged 25-84 years in HMP Parc, UK, and the Diabetes UK Risk Score was used to predict T2DM risk. In terms of projecting new cases, it was estimated that in the next decade 6.4 individuals per 100 would develop T2DM, and this value increased to 16.4 individuals per 100 in those aged 50 years and older. The development of new cases across all age groups is a concern, and it appears that the prison community are a 'target population' for prevention opportunities.

A retrospective epidemiological study of type 1 diabetes mellitus in wales, UK between 2008 and 2018.

INTRODUCTION: Studies of prevalence and the demographic profile of type 1 diabetes are challenging because of the relative rarity of the condition, however, these outcomes can be determined using routine healthcare data repositories. Understanding the epidemiology of type 1 diabetes allows for targeted interventions and care of this life-affecting condition. OBJECTIVES: To describe the prevalence, incidence and demographics of persons with type 1 diabetes diagnosed in Wales, UK, using the Secure Anonymised Information Linkage (SAIL) Databank. METHODS: Data derived from primary and secondary care throughout Wales available in the SAIL Databank were used to identify people with type 1 diabetes to determine the prevalence and incidence of type 1 diabetes over a 10 year period (2008-18) and describe the demographic and clinical characteristics of this population by age, socioeconomic deprivation and settlement type. The seasonal variation in incidence rates was also examined. RESULTS: The prevalence of type 1 diabetes in 2018 was 0.32% in the whole population, being greater in men compared to women (0.35% vs 0.28% respectively); highest in those aged 15-29 years (0.52%) and living in the most socioeconomically deprived areas (0.38%). The incidence of type 1 diabetes over 10 years was 14.0 cases/100,000 people/year for the whole population of Wales. It was highest in children aged 0-14 years (33.6 cases/100,000 people/year) and areas of high socioeconomic deprivation (16.8 cases/100,000 people/year) and least in those aged 45-60 years (6.5 cases/100,000 people/year) and in areas of low socioeconomic deprivation (11.63 cases/100,000 people/year). A seasonal trend in the diagnoses of type 1 diabetes was observed with higher incidence in winter months. CONCLUSION: This nation-wide retrospective epidemiological study using routine data revealed that the incidence of type 1 diabetes in Wales was greatest in those aged 0-14 years with a higher incidence and prevalence in the most deprived areas. These findings illustrate the need for health-related policies targeted at high deprivation areas to include type 1 diabetes in their remit.

Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol.

INTRODUCTION: Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%-20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis. METHODS AND ANALYSIS: This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12-18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work. ETHICS AND DISSEMINATION: This trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN14274380.

The impact of structured self-monitoring of blood glucose on glycaemic variability in non-insulin treated type 2 diabetes: The SMBG study, a 12-month randomised controlled trial.

BACKGROUND AND AIMS: There is inconsistent evidence supporting the self-monitoring of blood glucose (SMBG) in people with non-insulin treated type 2 diabetes (T2D). Structured SMBG protocols have a greater impact on glycaemic control than unstructured SMBG and may improve measures of glycaemic variability (GV), though few previous studies have reported on specific GV outcomes. Our aim was to determine the impact of structured SMBG on simple measures of GV in people with T2D. METHODS: Participants undertook structured SMBG over 12 months, with HbA1c recorded at baseline and at 3-monthly follow-up. For each participant, the mean blood glucose (MBG), fasting blood glucose (FBG), standard deviation BG (SD-BG), coefficient of variation of BG (CV-BG), mean absolute glucose change (MAG) and HbA1c were determined for each 3-month period. Responders were participants with an improvement in HbA1c of ≥5 mmol/mol (0.5%) over 12 months. RESULTS: Data from two hundred and thirty-one participants were included for analysis. Participants had a baseline median [interquartile range] HbA1c 68.0 [61.5-75.5] mmol/mol (8.4%). Participants demonstrated significant improvements in the MBG (-1.25 mmol/L), FBG (-0.97 mmol/L), SD-BG (-0.44 mmol/L), CV-BG (-1.43%), MAG (-0.97 mmol/L), and HbA1c (-7.0 mmol/mol) (all p < 0.001) at 12 months compared to these measures collected within the first 3 months of SMBG. Responders had a significantly higher baseline median [interquartile range] HbA1c of 70.0 [63.0-78.0] mmol/mol compared to 61.0 [56.5-66.0] mmol/mol in non-responders (P < 0.001). CONCLUSIONS: Structured SMBG improved all the observed measures of GV. These results support the use of structured SMBG in people with non-insulin treated T2D.

Prevalence of admission plasma glucose in 'diabetes' or 'at risk' ranges in hospital emergencies with no prior diagnosis of diabetes by gender, age and ethnicity.

AIMS: To establish the prevalence of admission plasma glucose in 'diabetes' and 'at risk' ranges in emergency hospital admissions with no prior diagnosis of diabetes; characteristics of people with hyperglycaemia; and factors influencing glucose measurement. METHODS: Electronic patient records for 113 097 hospital admissions over 1 year from 2014 to 2015 included 43 201 emergencies with glucose available for 31 927 (74%) admissions, comprising 22 045 people. Data are presented for 18 965 people with no prior diagnosis of diabetes and glucose available on first attendance. RESULTS: Three quarters (14 214) were White Europeans aged 62 (43-78) years, median (IQ range); 12% (2241) South Asians 46 (32-64) years; 9% (1726) Unknown/Other ethnicities 43 (29-61) years; and 4% (784) Afro-Caribbeans 49 (33-63) years, P < .001. Overall, 5% (1003) had glucose in the 'diabetes' range (≥11.1 mmol/L) higher at 8% (175) for South Asians; 16% (3042) were 'at risk' (7.8-11.0 mmol/L), that is 17% (2379) White Europeans, 15% (338) South Asians, 14% (236) Unknown/Others and 11% (89) Afro-Caribbeans, P < .001. The prevalence for South Asians aged <30 years was 2.1% and 5.2%, respectively, 2.6% and 8.6% for Afro-Caribbeans <30 years, and 2.0% and 8.4% for White Europeans <40 years. Glucose increased with age and was more often in the 'diabetes' range for South Asians than White Europeans with South Asian men particularly affected. One third of all emergency admissions were for <24 hours with 58% of these having glucose measured compared to 82% with duration >24 hours. CONCLUSIONS: Hyperglycaemia was evident in 21% of adults admitted as an emergency; various aspects related to follow-up and initial testing, age and ethnicity need to be considered by professional bodies addressing undiagnosed diabetes in hospital admissions.

Cost-effectiveness of biennial screening for diabetes related retinopathy in people with type 1 and type 2 diabetes compared to annual screening.

OBJECTIVE: Examine the health and economic impact of extending screening intervals in people with Type 2 diabetes (T2DM) and Type 1 diabetes (T1DM) without diabetes-related retinopathy (DR). SETTING: Diabetic Eye Screening Wales (DESW). STUDY DESIGN: Retrospective observational study with cost-utility analysis (CUA) and Decremental Cost-Effectiveness Ratios (DCER) study. INTERVENTION: Biennial screening versus usual care (annual screening). INPUTS: Anonymised data from DESW were linked to primary care data for people with two prior screening events with no DR. Transition probabilities for progression to DR were estimated based on a subset of 26,812 and 1232 people with T2DM and T1DM, respectively. DCER above £20,000 per QALY was considered cost-effective. RESULTS: The base case analysis DCER results of £71,243 and £23,446 per QALY for T2DM and T1DM respectively at a 3.5% discount rate and £56,822 and £14,221 respectively when discounted at 1.5%. Diabetes management represented by the mean HbA1c was 7.5% for those with T2DM and 8.7% for T1DM. SENSITIVITY ANALYSIS: Extending screening to biennial based on HbA1c, being the strongest predictor of progression of DR, at three levels of HbA1c 6.5%, 8.0% and 9.5% lost one QALY saving the NHS £106,075; £58,653 and £31,626 respectively for T2DM and £94,696, £37,646 and £11,089 respectively for T1DM. In addition, extending screening to biennial based on the duration of diabetes > 6 years for T2DM per QALY lost, saving the NHS £54,106 and for 6-12 and > 12 years for T1DM saving £83,856, £23,446 and £13,340 respectively. CONCLUSIONS: Base case and sensitivity analyses indicate biennial screening to be cost-effective for T2DM irrespective of HbA1c and duration of diabetes. However, the uncertainty around the DCER indicates that annual screening should be maintained for those with T1DM especially when the HbA1c exceeds 80 mmol/mol (9.5%) and duration of diabetes is greater than 12 years.