Background:The Hypoglycemia Awareness Restoration Program for people with type 1 diabetes and problematic hypoglycemia with severe episodes persisting despite optimal care (HARPdoc) uniquely focusses on addressing cognitive and motivational barriers to hypoglycemia avoidance associated with impaired awareness to hypoglycemia. We aimed to compare perceptions of acceptability, feasibility, and appropriateness of HARPdoc intervention to an existing program, Blood Glucose Awareness Training (BGAT) and understand how these implementation outcomes relate to cognitive and mental health clinical outcomes. Methods:The HARPdoc trial was a hybrid randomized clinical trial delivered in the United Kingdom and United States between July 2018 and December 2019. Implementation outcomes, including perceived acceptability, appropriateness, and feasibility, were measured using published validated surveys. These surveys were completed by the people with diabetes, healthcare professionals, and relatives of participants. Clinical outcomes, including attitudes to awareness, diabetes distress, anxiety, and depression, were measured using validated self-reported questionnaires. We explored differences of perceived implementation outcomes between HARPdoc and BGAT and associations between implementation and clinical outcomes using quantile and linear regression. We also assessed whether the effect of HARPdoc on cognitive and mental health outcomes were mediated by implementation outcomes. Results:HARPdoc was perceived as more appropriate than BGAT at 12 months, with a median difference of 0.75 (95% CI 0,26,1,24) by both those involved in delivering the programs and the HARPdoc participants. All stakeholder groups also perceived HARPdoc intervention as more acceptable (MD 0.50 95% CI 0.13, 0.87), but as feasible (MD 0.00; 95% CI -0.31, 0.31) as BGAT. Each of perceived acceptability, appropriateness, and feasibility were significantly linked to improvements in clinical outcomes (feasibility- anxiety: Mean Difference: -1.07; 95% CI: -2.03, -0.10); feasibility-depression (MD: -5.25, 95% CI -9.09, -1.41)). No evidence of mediation was observed. Conclusions:HARPdoc compared to BGAT was perceived as more appropriate and acceptable and subsequently higher perceived appropriateness, acceptability and feasibility was linked to better cognitive and mental health outcomes. Our findings provide important insights for the development of an implementation blueprint and the expansion of HARPdoc and BGAT programs into routine healthcare services and highlight the need for larger, better-powered hybrid trials.

BACKGROUND:Preexisting multiple (two or more) long-term conditions (MLTCs) may negatively affect recovery after COVID-19. We investigated how preexisting MLTCs, including different categorization and patterns of MLTCs, affect 1-year health outcomes after severe COVID-19. METHODS:Adults post-hospitalization after COVID-19 were recruited during 2020-2021. We compared recovery at 1 year after discharge using adjusted multivariable logistic regression in 1:1 propensity-matched adults (for age, sex, ethnicity, social deprivation, obesity, and smoking history) with and without preexisting MLTCs. In adults with MLTCs, different categorization such as number of conditions, number and types of body systems involved (e.g. respiratory, cardiovascular), and latent class analysis-derived patterns of condition co-occurrence were assessed for their association with recovery at 1 year. RESULTS:A total of 647 adults with MLTCs were matched with 647 adults without MLTCs (n = 1294; 61.9% male, 79.6% of White ethnicity, median age 59 [interquartile range 52-67] years). The presence of MLTCs was associated with lower odds of feeling fully recovered (odds ratio 0.66 [95% confidence interval 0.51-0.85], P = 0.001). In those with MLTCs, recovery was negatively affected by number and type of body systems involved (e.g. respiratory [odds ratio 0.49 (95% confidence interval 0.34-0.69), P <0.001]) but not by the number of conditions (P >0.1). Four latent classes of MLTC co-occurrence were estimated with different risks of recovery (P <0.01). CONCLUSION:Adults with preexisting MLTCs were 34% less likely to feel fully recovered at 1 year after COVID-19 hospitalization than adults without MLTCs. We describe prognostic classifications of MLTCs, with future work needed to understand whether they have prognostication in broader post-acute infection sequalae.

AIMS:To develop a comprehensive, in-depth understanding of the impacts of hypoglycaemia on the quality of life of adults living with type 1 (T1D) or type 2 diabetes (T2D). METHODS:Thirty-one adults with T1D or T2D who experienced hypoglycaemia participated in semi-structured interviews. Participants were purposively sampled by age, sex and type/duration of diabetes. Informed by a health-related quality of life (HRQoL) framework and literature review, an interview guide explored hypoglycaemia-related impacts on quality of life. Interviews were audio-recorded, transcribed verbatim and analysed using Framework Analysis. RESULTS:Impacts were coded within three overall themes (physical, psychological and social) comprising 38 subthemes. Of the 11 physical subthemes, the most discussed were sleep, physiological symptoms, leisure and exercise, eating and drinking. Of the 18 psychological subthemes, the most discussed included: awareness; cognitive burden and planning; self management and coping; worry and anxiety; autonomy, independence and control. Of the nine social subthemes, the most discussed were impacts on others and relationship with partner. CONCLUSIONS:A novel HRQoL framework highlights a comprehensive range of impacts of hypoglycaemia on physical, psychological and social functioning of people living with diabetes. These findings offer insights for clinicians, researchers and other interested parties seeking to benefit person-centred outcomes, such as quality of life.

BACKGROUND AND AIMS:In people with insulin-treated diabetes experiencing hypoglycaemia, the multicentre Hypo-METRICS study found that 60% of sensor-detected hypoglycaemic episodes (SDH) were asymptomatic, and over 40% of person-reported hypoglycaemia (PRH) occurred at glucose levels ≥70 mg/dL (3.9 mmol/L). This subanalysis explored participants' experiences of these episodes to identify possible clinical implications. METHODS:Fifty-eight Austrian participants received a 15-item questionnaire on their experience of asymptomatic hypoglycaemia and symptoms at glucose levels ≥70 mg/dL (3.9 mmol/L). RESULTS:The response rate was 86% (n = 50). Among all participants, 56% (n = 28) reported experiencing hypoglycaemic symptoms at glucose levels ≥70 mg/dL (3.9 mmol/L) "sometimes" or "often." They attributed this to a combination of a threshold shift due to chronic hyperglycaemia, rapid glucose decline and fear of hypoglycaemia. 68% of all SDH < 70 mg/dL and 59% of those below the clinically critical level of 54 mg/dL were asymptomatic. CONCLUSION:These results demonstrate that SDH and PRH each capture different, yet equally important, dimensions of the hypoglycaemia experience. Relying on only one source of information inevitably provides an incomplete picture. By integrating the patient's voice, diabetes professionals can provide appropriate support and tailor continuous glucose monitoring (CGM) alarm settings and treatment plans to truly meet individual needs.

To identify meaningful clusters of participants with shared baseline characteristics (demographic, clinical, and psychological) from a sample of adults with type 1 diabetes (T1D) completing dose adjustment for normal eating (DAFNE) structured T1D education, or the updated DAFNE plus programme. Further, to determine whether those clusters respond differently, at 6- and 12 months, to DAFNE and DAFNE plus on core outcomes: HbA1c and diabetes-specific quality of life (QoL). Latent profile analysis was conducted on the DAFNE plus randomised control trial dataset using relevant indicator variables (age; HbA1c; hypoglycaemia awareness; diabetes-specific QoL, distress, and positive well-being; fear of hypoglycaemia; satisfaction with diabetes management). Model fit indices were used to select the optimal number of clusters and multilevel linear regression models to estimate the effect of DAFNE plus (compared with DAFNE) on HbA1c and diabetes-specific QoL in each cluster. A total of n  = 363 participants were included in the analysis ( n  = 147, 40% randomised to DAFNE plus ). The final model included two clusters: the first was consistently worse off on clinical and psychological indicator variables. The multilevel analysis showed a significant adjusted mean difference, at 12 months (first cluster only), between DAFNE and DAFNE plus in diabetes-specific QoL (0.81; 95% CI: 0.19–1.43; p  = 0.01), but not at other time points or in HbA1c. This study suggests that DAFNE plus has significant added benefits in reducing the negative impact of diabetes on QoL for a subgroup of adults with T1D, but not for their HbA1c. This provides important insights for the future real-world implementation of the DAFNE plus programme.

The aim of this study was to determine whether cardiac autonomic neuropathy (CAN) is an independent risk factor for kidney function decline in type 1 diabetes mellitus over a 15 year follow-up period. Eighty seven participants with type 1 diabetes and eGFR >30 ml/min per 1.73 m2 underwent cardiovascular autonomic reflex testing at baseline. Renal data were retrieved at 4 year intervals over 15 years. Stratification of participants into Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease progression prognostic risk was done by using eGFR and urinary albumin/creatinine ratio (UACR). Longitudinal changes in eGFR and UACR were analysed using linear mixed-effects models with adjustment for potential confounders to determine whether CAN is an independent predictor of eGFR and UACR change over 15 years. At baseline, higher KDIGO risk category was associated with increased severity of CAN (r=0.38, p<0.001) and increase in UACR (p<0.001) compared with the lower risk group. Participants with established CAN at baseline exhibited greater mean (SD) eGFR decline of 14.8 (21.6) ml/min per 1.73 m2, compared with 3.1 (7.3) and 3.3 (7.4) ml/min per 1.73 m2 in the early stage and those without CAN (p=0.004). Mean (SD) increases in UACR were 0.4 (0.9), 11.3 (30.4) and 4 (8.9) mg/mmol for no CAN, early CAN and established CAN (p=0.03), respectively. After adjusting for potential confounders, baseline CAN was independently associated with both accelerated eGFR decline (p=0.018) and greater increases in UACR (p=0.002) over time. CAN is an independent predictor of both accelerated eGFR decline and increased albuminuria in type 1 diabetes. The study also explored the relationship between CAN and KDIGO prognostic risk in diabetic kidney disease, demonstrating that increased severity of CAN is associated with higher KDIGO prognostic risk.

AIMS:We investigated the proportion of sensor-detected hypoglycaemic (SDH) events progressing to level 2, and associated variables. MATERIALS AND METHODS:We used data from Hypo-METRICS, which recruited people with type 1 (pwT1D) and insulin-treated type 2 diabetes (pwT2D) with ≥ 1 hypoglycaemic event in preceding 3 months, wearing blinded continuous glucose monitoring devices (CGM), additional to usual monitoring modality, and FitBits for 10 weeks. We defined: L1: SDH < 3.9 mmol/L for ≥ 15 min but ≥ 3.0 mmol/L; L2: SDH < 3.9 mmol/L with ≥ 15 min of sensor glucose < 3.0 mmol/L; L2 ratio = L2/(L1 + L2), restricted to participants with both event types during the study period. Associations of selected variables on L2 ratio was assessed using beta regression and purposeful variable selection. RESULTS:We analysed 23 768 SDH events from 212 pwT1D and 213 pwT2D. PwT1D were predominantly female (53% vs. 42% in T2D, p = 0.023) and younger (median age 49 vs. 62 years, p < 0.001), with a higher L2 ratio (16% vs. 14%, p = 0.03). Coefficient of variation (CV), OR = 1.07, 95% CI = 1.06-1.09 (p < 0.001), and mean sensor glucose, OR = 1.13, 95% CI = 1.08-1.18 (p < 0.001) were the principal predictors in T1D and T2D respectively; mean L1-SDH duration, weekly L1-SDH frequency, personal CGM usage, impaired awareness were not. Progression was higher during sleep than wakefulness (21% vs. 11%, p < 0.001); L2 ratios during sleep did not differ by awareness status. CONCLUSIONS:Approximately one sixth of SDH events progressed to L2, with a higher proportion in T1D than T2D. The principal determinants were CV in T1D and mean glucose in T2D. Awareness status was not associated with progression risk during sleep.

Introduction and Objective: Severe hypoglycemic events (SHEs) and impaired awareness of hypoglycemia (IAH) remain major challenges for some people with type 1 diabetes (T1D), despite using continuous glucose monitoring (CGM) and insulin pumps. This study describes health status and productivity outcomes among adults with T1D using CGM and insulin pumps with recurrent SHEs and IAH. Methods: This ongoing 12-month prospective online survey enrolled adults with T1D using CGM and insulin pumps who reported recurrent SHEs (≥2 in the past year) and IAH (Clarke score ≥4). Participants were recruited through patient advocacy groups from Canada, Germany, France, Italy, UK and US. Participants reported diabetes-related complications and completed the EuroQoL Visual Analogue Scale (EQ-VAS), Diabetes Productivity Measure (DPM), and Work Productivity and Activity Impairment (WPAI) questionnaires. Baseline results are compared against US T1D and general population norms for contextualization. Results: Participants (N=137) had a mean age of 49.6 years (range: 20-75), 71.5% were female, 65.0% were from US, 59.1% worked for pay, and mean T1D duration was 34 years (range: 5-72). Health status (EQ-VAS score: 68.5, SD:19.8) was 15% lower compared to US general population norm (80.4). Diabetes-specific work and life productivity (DPM scores: 66.9 and 52.5) were 20% and 23% lower compared to US adults with diabetes (83.3 and 68.5), respectively. Generic work productivity showed 2.2 times greater work productivity loss compared to US general population norm (WPAI scores: 37% vs 17%). Conclusion: Despite using CGM and insulin pumps, adults with T1D and recurrent SHEs and IAH reported substantial burden, including sub-optimal health and productivity, highlighting continuing unmet needs. Disclosure A. Boateng-Kuffour: Employee; Current; Vertex Pharmaceuticals Incorporated. Q. Zhang: Employee; Current; Veloxis Pharmaceuticals, Inc. A. Albanese-O'Neill: Consultant; Current; Sanofi. Advisory Panel; Current; Roche Pharmaceuticals, Vertex Pharmaceuticals Incorporated. Research Support; Current; Abbott Diabetes. A. Bubeck: None. L. Green: Other - Sponsorship to my organization; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated, Sanofi. B. Hauck: None. S. Heller: Consultant; Current; Novo Nordisk. Other - DSMC chair and member; Current; Eli Lilly and Company. Advisory Panel; Current; Zucara Therapeutics, Vertex Pharmaceuticals Incorporated. W. Polonsky: Consultant; Current; Vertex Pharmaceuticals Incorporated, Dexcom, Inc., Abbott Diabetes. Research Support; Current; Abbott Diabetes, Dexcom, Inc. Consultant; Current; Lilly Diabetes, MannKind Corporation. Research Support; Current; Lilly Diabetes. Consultant; Current; Sanofi, Insulet Corporation. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. J. Speight: Advisory Panel; Current; Vertex Pharmaceuticals Incorporated. Other - AU$10k Sponsorship for PSAD 2026 conference, Geelong, Australia; Current; Sanofi. S. Tutton: Advisory Panel; Ended; Vertex Pharmaceuticals Incorporated. Other - Patient Advisory Group Participation in the T1D Multi-National PRO study; Current; Vertex Pharmaceuticals Incorporated. R. Ziegler: Advisory Panel; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Sanofi. Speaker's Bureau; Current; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Current; Roche Diabetes Care. N. Ainsworth: Consultant; Current; Vertex Pharmaceuticals Incorporated. C. Abbott: Employee; Current; Vertex Pharmaceuticals. A. Martin: Consultant; Current; Vertex Pharmaceuticals Incorporated. N. Li: Employee; Current; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. B.L. Barber: None.

AIMS:To identify meaningful clusters of participants with shared baseline characteristics (demographic, clinical, and psychological) from a sample of adults with type 1 diabetes (T1D) completing dose adjustment for normal eating (DAFNE) structured T1D education, or the updated DAFNEplus programme. Further, to determine whether those clusters respond differently, at 6- and 12 months, to DAFNE and DAFNEplus on core outcomes: HbA1c and diabetes-specific quality of life (QoL). METHODS:Latent profile analysis was conducted on the DAFNEplus randomised control trial dataset using relevant indicator variables (age; HbA1c; hypoglycaemia awareness; diabetes-specific QoL, distress, and positive well-being; fear of hypoglycaemia; satisfaction with diabetes management). Model fit indices were used to select the optimal number of clusters and multilevel linear regression models to estimate the effect of DAFNEplus (compared with DAFNE) on HbA1c and diabetes-specific QoL in each cluster. RESULTS:A total of n = 363 participants were included in the analysis (n = 147, 40% randomised to DAFNEplus). The final model included two clusters: the first was consistently worse off on clinical and psychological indicator variables. The multilevel analysis showed a significant adjusted mean difference, at 12 months (first cluster only), between DAFNE and DAFNEplus in diabetes-specific QoL (0.81; 95% CI: 0.19-1.43; p = 0.01), but not at other time points or in HbA1c. CONCLUSIONS:This study suggests that DAFNEplus has significant added benefits in reducing the negative impact of diabetes on QoL for a subgroup of adults with T1D, but not for their HbA1c. This provides important insights for the future real-world implementation of the DAFNEplus programme.

AIMS:To describe the design and examine the psychometric properties of the Hypoglycaemia Cues Questionnaire (HypoC-Q) for assessing thoughts, feelings, and behaviours related to hypoglycaemia among adults with type 1 diabetes (T1D). METHODS:The HypoC-Q was designed iteratively, informed by exploratory interviews with 17 adults with T1D with impaired awareness of hypoglycaemia and/or recurrent severe hypoglycaemia, and consultation with diabetologists. Psychometric analyses were completed on baseline data from the Hypo-METRICS study. Data from adults with T1D, reporting at least one hypoglycaemic event, were eligible if they had completed the baseline HypoC-Q. Completion rates, latent structure, internal consistency, construct and known-groups validity were examined. RESULTS:In Hypo-METRICS, 154 participants (62% females; mean ± SD age 44 ± 15 years; T1D duration: 23 ± 16 years) were eligible. All completed all 40 HypoC-Q items, demonstrating its acceptability. Exploratory factor analysis identified four scales with satisfactory internal consistency (α = 0.69-0.81): 1) low concern (7 items), 2) burnout (6 items), 3) missing cues (5 items), and 4) delaying treatment (9 items); plus eight items, treated separately. Construct validity was supported by significant moderate correlations between 'burnout' and fear of hypoglycaemia and diabetes distress, and between 'missing' and 'delay' with impaired awareness of hypoglycaemia; all three distinguished between those with intact and impaired awareness (known-groups validity); but not by history of severe hypoglycaemia. CONCLUSIONS:The HypoC-Q is an acceptable, valid, and reliable measure of thoughts, feelings, and behaviours related to hypoglycaemia among adults with T1D. It is available for informing and assessing the effect of interventions to reduce hypoglycaemia exposure and impact.

Background Dose Adjustment For Normal Eating is a 5-day, group-based clinical education programme for adults with type 1 diabetes, training them in the complex self-management skills, enabling them to optimise both their glycaemic management and quality of life. Although Dose Adjustment For Normal Eating is associated with improvements in many aspects of diabetes management, including psychological outcomes, it has been challenging to maintain the biomedical improvements for longer term, which have remained well above the glucose levels recommended by National Institute for Health and Care Excellence. Objectives We aimed to develop and evaluate Dose Adjustment For Normal Eating plus, an enhanced version of Dose Adjustment For Normal Eating, to enable improvements in glycaemic management (glycated haemoglobin) without compromising the quality of life. The objectives of the programme were to modify the existing Dose Adjustment For Normal Eating curriculum and evaluate it in a cluster randomised controlled trial. Design This programme comprised four workstreams. The first three workstreams focused on redevelopment of the Dose Adjustment For Normal Eating intervention to become ‘Dose Adjustment For Normal Eating plus’: involving revision of the curriculum for a 5-day, group-based programme, including relevant behaviour change techniques (workstream 1); development of a new structured, pro-active, follow-up programme to be delivered by Dose Adjustment For Normal Eating plus facilitators post course to support ongoing diabetes self-management (workstream 2); and development of a new technology interface to help glucose pattern recognition to inform improved self-management (workstream 3). We used mixed methods to review, develop and refine the Dose Adjustment For Normal Eating plus intervention (course, individual support and technological aspects). The intervention was piloted in three National Health Service specialist diabetes centres and was reviewed via two iterative waves before finalisation. Workstream 4 was a cluster randomised controlled trial using a pragmatic, parallel group (1 : 1) allocation design (Dose Adjustment For Normal Eating vs. Dose Adjustment For Normal Eating plus), with concurrent process and health economic evaluations. The primary biomedical outcome was the between-group difference in glycated haemoglobin at 12 months. The primary psychological outcome was the between-group difference in the impact of type 1 diabetes on quality of life (using Audit of Diabetes-Dependent Quality of Life-15) at 12 months. Setting The workstreams and the randomised controlled trial were undertaken in university and National Health Service specialist centres in England and Scotland. Participants Four hundred and seventy-one adults aged ≥ 18 years with confirmed diagnosis of type 1 diabetes participated in the cluster randomised controlled trial, which was 144 fewer than planned and approximately 77% of the planned sample size. Intervention Dose Adjustment For Normal Eating plus is a standardised 5-day educational course (described above), delivered 1 day per week over 5 weeks in groups, meeting face to face, followed by five individual support sessions over 12 months. An online platform supports the upload, visualisation, pattern recognition and review of glycaemic data for participants and clinicians. Trial outcome measures In the cluster randomised controlled trial, the primary biomedical outcome was glycaemia, defined as glycated haemoglobin, at 12 months. The primary psychological outcome was the impact of diabetes on quality of life (assessed using the widely recognised scale, Audit of Diabetes-Dependent Quality of Life-15). Key secondary biomedical outcomes included rates and proportions of severe hypoglycaemia and diabetic ketoacidosis. Key secondary psychological outcomes included diabetes-specific distress, diabetes-specific positive well-being and fear of hypoglycaemia. Results In the primary intention-to-treat population (309), mean glycated haemoglobin reduced from 9.1% to 8.2% (75.9–66.5 mmol/mol) in the Dose Adjustment For Normal Eating group and from 9.1% to 8.1% (75.6–65.1 mmol/mol) in the Dose Adjustment For Normal Eating plus group. The cluster randomised controlled trial showed no evidence of a between-group difference at 12 months in glycated haemoglobin {point estimate [95% confidence interval −0.014 (−0.284 to 0.255); p = 0.915]}, or diabetes-specific quality of life {point estimate [95% confidence interval 0.2 (−0.1 to 0.5); p = 0.21]}. At 12 months, significant between-group differences were observed, favouring Dose Adjustment For Normal Eating plus, in secondary psychological outcomes (diabetes-specific distress, diabetes-specific positive well-being and actions taken to avoid hypoglycaemia). Limitations Due to trial-suspension during coronavirus disease, we recruited 471 adults to the cluster randomised controlled trial, 144 fewer than planned. Although this reduced overall statistical power, we showed that the difference in glycated haemoglobin between the groups was far below that we considered a meaningful clinical difference (0.5%). Recruitment also meant that more participants were using continuous glucose monitoring, both before and during the trial than we anticipated. This may have reduced additional benefit of the Dose Adjustment For Normal Eating plus intervention on glycated haemoglobin. The pandemic probably influenced diabetes self-management during the trial in both groups. Conclusions Dose Adjustment For Normal Eating plus did not lead to greater falls in glycated haemoglobin at 12 months compared to Dose Adjustment For Normal Eating, but these falls were double those reported in previous Dose Adjustment For Normal Eating randomised controlled trials. Sixty-eight per cent of participants showed clinically relevant improved glucose levels. Those in Dose Adjustment For Normal Eating plus reported significant falls in diabetes distress, positive well-being and qualitative research reported positive experiences of Dose Adjustment For Normal Eating plus among participants and health professionals. Future work In view of major improvements in diabetes distress and positive experiences in both participants and health professionals, the Dose Adjustment For Normal Eating executives, who co-ordinate the delivery of Dose Adjustment For Normal Eating courses, are planning to include key elements of Dose Adjustment For Normal Eating plus in future courses, particularly structured support to participants following the course and key elements of the curriculum. Study registration This study is registered as IRAS: 235621 and ISRCTN: 42908016. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0514-20013) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 21. See the NIHR Funding and Awards website for further award information. Plain language summary Researchers from hospitals and universities in the United Kingdom and psychologists from Australia received money from the National Institute for Health Research to undertake research to improve an education programme. It helps adults with type 1 diabetes to self-treat their condition and improve their health and quality of life. We built on the existing (DAFNE) course by including key steps in self-treating diabetes, new technology and support after the course, calling it DAFNEplus. Adults with diabetes helped in all areas of the research. Between 2018 and 2022, 471 adults with type 1 diabetes from 13 diabetes centres across the United Kingdom took part in a trial. Centres were chosen by chance to teach either DAFNE or the new DAFNEplus course. All those involved, attended a 5-day course, but DAFNEplus added five follow-up sessions and used technology to feedback results and glucose patterns. Those taking part provided blood to measure glucose and other lab tests and questionnaires. We talked to both participants receiving and staff providing DAFNEplus and recorded their experiences. Results were collected before the course and 12 months later. The trial was badly affected by COVID-19, but enough people took part for us to collect reliable results. At 12 months, glucose levels and quality of life had improved, but there were no differences between those on the standard DAFNE and those on DAFNEplus. Glucose levels actually improved by twice the amount we had previously found in DAFNE trials in both groups. The people doing DAFNEplus also had improved levels of diabetes distress and other quality-of-life measures. The people and staff who took part in the research programme were particularly positive about the DAFNEplus approach, and we are working out how to include some parts of DAFNEplus in future DAFNE courses. Scientific summary Background Successful long-term management of type 1 diabetes (T1D) requires sustained individual engagement in complex self-management behaviours to maintain blood glucose [glycated haemoglobin (HbA1c)] levels within an optimal range. In 2002, we published a randomised controlled trial (RCT) reporting results of a 5-day training course, showing significantly improved levels of glucose and quality of life (QoL) at 12 months with no change in the control group. Although structured education programmes lead to clinically significant decreases in HbA1c, increased hypoglycaemia awareness and improved QoL, these benefits are not always sustained and glucose levels rarely reach recommended targets. The work of the Dose Adjustment For Normal Eating (DAFNE) collaborative and its associated research programmes have provided important understanding, including qualitative work, which has suggested roles in therapeutic interventions for: ongoing structured long-term support, including behaviour change science to support initial and ongoing learning and technology, facilitating links between professionals and a person with diabetes. Objectives The overall aim of Dose Adjustment For Normal Eating plus (DAFNEplus) was to refine the existing DAFNE curriculum, embedding behavioural science frameworks in all aspects of the intervention, addressing ‘ongoing support’, and including technological support, to aid long-term maintenance of HbA1c within an acceptable clinical range with no negative effects on participant’s QoL. Methods and results Workstream 1 The specific aims of this workstream (WS) were to: specify behaviours involved in T1D self-management and barriers and enablers to sustaining these behaviours specify behaviour change techniques (BCTs) included in the existing DAFNE intervention and examine whether they target the identified barriers/enablers identify additional BCTs with the potential to address barriers/enablers not currently targeted generate recommendations for revising the existing DAFNE curricula via stakeholder consultation and consensus integrate recommendations into a coproduced DAFNEplus intervention, pilot and refine the intervention ahead of the trial. This WS applied behavioural science to refine the existing DAFNE structured education programme into DAFNEplus. We identified underlying behaviours and influencing factors contributing to T1D self-management, and we identified 51 unique BCTs to address these. This enabled co-design of the DAFNEplus intervention which was piloted and refined in three centres and then taken forward for the evaluation of effectiveness and cost-effectiveness in a cluster RCT (cRCT) (WS4), and a parallel process evaluation was performed to explore the mechanisms of action, acceptability and fidelity (WS4). Workstream 2 The aims were to explore participants’ self-management after attending structured T1D education and their unmet need(s) for support to sustain improvements in glycaemic management and then to develop an evidence-informed model to guide effective follow-up support following DAFNEplus. To inform the design of effective follow-up support, we undertook a meta-ethnography of qualitative studies focusing on self-management of T1D, following structured education. We expressed the synthesis as a logic model: Follow-Up Support for Effective T1D Self-management (FUSED). The FUSED model provided an explanation of why people find it difficult to maintain T1D self-management following structured education, and it outlined the elements required for effective follow-up support. Following on from this activity, we undertook a further systematic review to identify the most effective type of education programme to support sustained improvements in glycaemia. Workstream 3 Workstream 3 aimed to develop technological resources to support learning and understanding of individual glycaemic control. The Glucollector web-based platform is supported by the WithCare+ device for data acquisition and by developed bespoke tools for modelling, decision support and visual representation and interpretation. It incorporates functionalities to support shared visualisation for patients and clinicians based on collected data from various monitoring devices, automated feedback, goal setting and self-care facilitation. The WithCare+ device transmits data securely on self-care behaviours like blood glucose measurements [including both capillary glucose readings and continuous glucose monitoring (CGM) from Libre flash monitoring], carbohydrate intake and insulin doses. It supports linking to activity tracking devices and prompts users to contextualise abnormal readings. Clinician versions are available for in-clinic use. Pilot and feasibility trial We undertook a pilot study to assess the feasibility and best approach to developing the logistics of the cRCT. We considered recruitment, intervention delivery, participant engagement and data collection methods, with the intention of refining the prototype DAFNEplus programme to optimise the intervention prior to the trial. The prototype DAFNEplus programme was piloted in two waves, at three DAFNE centres, at: Sheffield Teaching Hospitals NHS Foundation Trust King’s College Hospital NHS Foundation Trust Norfolk and Norwich University Hospitals NHS Foundation Trust This was a non-randomised feasibility pilot where all participants received the intervention. The pilot intervention was delivered by practising DAFNE educators (diabetes specialist nurses, dietitians and physicians) at each participating site, who had undertaken training in DAFNEplus. We anticipated that the DAFNEplus programme could be optimised with participants from eight courses across the three centres. The number of courses was selected to enable all centres to complete at least two DAFNEplus courses during the pilot. Eight DAFNEplus courses involving 54 patient participants were completed. The collaborative working group We developed a novel structured collaborative working group (CWG) process to use findings from the embedded qualitative work and feedback from other stakeholders (e.g. individuals involved in designing and delivering the intervention) to make iterative refinements to the intervention prior to the RCT. Pilot study components Pilot study process evaluation Glucollector/Withcare+ user testing Collection of outcome measures Pilot study key outcomes We piloted and iteratively amended the DAFNEplus curriculum via two waves of pilot courses. All eight DAFNEplus cohorts in the pilot study were given access to the technology and structured follow-up support as part of the intervention. In line with the work developing and refining the curriculum, the CWG used the same approach to optimising the structured support and technology. The qualitative research with DAFNEplus participants and facilitators enabled the identification of key barriers and facilitators to delivery and receipt of the intervention in real time. In addition, we were able, through the CWG, to mobilise the knowledge generated through both the pilot study and patient and public involvement feedback, to iteratively develop the intervention and address any identified shortcomings. The Your Self-management And You study advised on the primary and other psychological-related, patient-reported outcome measures. The health economists completed an evaluation of the potential cost-effectiveness of DAFNEplus compared to standard DAFNE in an NHS setting. This is detailed within the health economic evaluation. Workstream 4 cluster randomised trial Introduction A cRCT was conducted to examine the effectiveness of the intervention (DAFNEplus) compared with standard DAFNE. Concurrent health economic and process evaluations were undertaken. The aim of this superiority cRCT was to investigate whether DAFNEplus enabled improved and sustained diabetes self-management behaviours, leading to better glucose management (i.e. reduced mean HbA1c by minimum clinically significant difference of 0.5%) at 12 months than achieved with standard DAFNE, without compromising QoL [Coates E, Amiel S, Baird W, Benaissa M, Brennan A, Campbell MJ, et al.; DAFNEplus group. Protocol for a cluster randomised controlled trial of the DAFNEplus (Dose Adjustment For Normal Eating) intervention compared with 5x1 DAFNE: a lifelong approach to promote effective self-management in adults with type 1 diabetes. BMJ Open 2021;11:e040438]. Objectives The primary objective was to compare the effect of DAFNEplus to standard DAFNE on glycaemia (HbA1c) at 12 months (primary biomedical outcome). The secondary objectives were: to compare the effects of DAFNEplus to standard DAFNE on: diabetes-specific QoL at 12 months (primary psychological outcome) glycaemia (HbA1c) at 6 months (medium-term outcome) other biomedical outcomes, including severe hypoglycaemic episodes, diabetic ketoacidosis (DKA), weight, body mass index, blood pressure and lipids secondary psychological outcomes, including diabetes distress, diabetes-specific positive well-being and fear of hypoglycaemia to undertake a mixed-methods process evaluation to aid understanding of the cRCT findings and inform decision-making about the implementation of DAFNEplus in clinical care post trial to assess the fidelity of delivery of DAFNEplus to undertake a health economic analysis to determine the cost-effectiveness of DAFNEplus versus standard DAFNE. Design The trial used a pragmatic, parallel group, superiority cluster randomised (1 : 1 allocation) controlled design involving 14 NHS specialist diabetes centres. Centre randomisation was implemented rather than individual participants, as contamination of the control arm may have occurred if educators were trained in DAFNEplus (intervention) and still were required to deliver standard DAFNE (control). Cluster randomised controlled trial methods Participants Participants were considered eligible if they were ≥ 18 years of age, had a diagnosis of T1D for at least 6 months (or post honeymoon), were prepared to undertake multiple daily injection therapy and frequent self-monitoring of blood glucose, could attend all sessions as part of the intervention and the principal investigator was confident that they could adhere to the protocol requirements. Those currently using continuous subcutaneous insulin infusion pump therapy or who had attended a DAFNE course within the last 5 years were ineligible. Intervention DAFNEplus was facilitated by practising DAFNE educators (diabetes nurses, dietitians and physicians) in the NHS, all of whom had previous experience in DAFNE training. An extensive training package was undertaken by all intervention staff. Randomisation All participating centres were randomised on a 1 : 1 basis to control (standard DAFNE course) or the intervention arm (DAFNEplus programme). End points The primary biomedical outcome was HbA1c at 12 months. The study was powered for this single, primary end point. All additional analyses were performed to further inform this primary end point and should be interpreted accordingly. The number of participants achieving glycaemic control [defined as either a HbA1c < 7.5% (58 mmol/mol) or a decrease in HbA1c of ≥ 0.5% (≥ 5.5 mmol/mol)] were calculated at both 6 and 12 months post course. Other secondary biomedical outcomes included: severe hypoglycaemia, as defined by the American Diabetes Association, both rates and proportion of those affected; DKA, both rates and proportion of those affected. Participant safety was assessed by way of adverse and serious adverse reporting. All participants were included in safety summaries. We also collected and will analyse 24-month outcome data (HbA1c and severe hypoglycaemic episodes) after the main study has been reported. The primary psychological outcome was diabetes-specific QoL at 12 months, measured using the Audit of Diabetes-Dependent Quality of Life-15 (ADDQoL-15). Secondary psychological outcomes included: diabetes-specific QoL (Diabetes Attitudes Wishes and Needs Impact of Diabetes Profile); diabetes distress [Problem Areas in Diabetes scale-11 (PAID)-11)]; diabetes-specific positive well-being [4-item subscale of the Well-Being Questionnaire (28 items)]; and fear of hypoglycaemia (HFS-II short-form). Statistical analysis Three analyses populations were defined: Primary intention-to-treat (ITT) population composed of consented participants with baseline HbA1c > 7.5%, analysed as per their randomisation allocation, regardless of treatment adherence and protocol non-compliances. Full ITT population composed of consented participants, analysed as per their randomisation allocation, regardless of treatment adherence and protocol non-compliances. Per-protocol population composed of the subset of the primary ITT population who adhered to their assigned intervention. For all analysis populations, participants recruited in 2020, who did not attend at least one session of the initial DAFNE course, were excluded. This was due to courses not running during the COVID-19 pandemic. Cluster randomised controlled trial results Key findings: biomedical outcomes Four hundred and seventy-one people were recruited from 13 sites over 4 years, which was 144 fewer than planned (approximately, 77% of the planned sample size, which was planned to recruit over 3 years). In the primary ITT population, mean HbA1c reduced from 9.1% to 8.2% (75.9–66.5 mmol/mol) in the DAFNE group and from 9.1% to 8.1% (75.6–65.1 mmol/mol) in the DAFNEplus group. There was no evidence of a between-arm difference in HbA1c at 12 months {point estimate [95% confidence interval (CI) −0.014 (−0.284 to 0.255); p = 0.915]} in the primary ITT population. This was consistent with sensitivity analyses, including those adjusting for adherence, and varying assumptions about missing data. In the full ITT population (245 DAFNE, 178 DAFNEplus) of those we have baseline and 12-month HbA1c paired measurements, around 70% improved their glucose levels during the trial; either HbA1c < 7.5%, fall in HbA1c, or both measures at 12 months. No evidence of between-group difference was found for any of the secondary end points. In the full ITT population (423, DAFNE 245, DAFNEplus 178), number of adverse events reported was low. During follow-up, at least one episode of severe hypoglycaemia was experienced by 3% in the DAFNEplus arm (vs. 7% in the DAFNE arm) in the full as-randomised population. Key findings: psychological outcomes In the ITT analyses, the adjusted mean difference in the impact of diabetes on QoL [i.e. the ADDQoL-15 average weighted impact score at 12 months (primary psychological outcome)] was 0.2 (95% CI −0.1 to 0.5; p = 0.21), equivalent to a standardised effect size of d= 0.1 (95% CI −0.1 to 0.4). For the secondary psychological outcomes, at 12 months, there was a statistically significant difference in diabetes distress (PAID: adjusted mean difference −3.3, p = 0.001 and d = −0.4) and hypoglycaemia avoidance (HFS-II behaviour subscale: adjusted mean difference −1.1, p = 0.002 and d = −0.3), and diabetes-specific positive well-being (4-item subscale of the WBQ-28: adjusted mean difference 0.9, p = 0.004 and d= 0.4), favouring the DAFNEplus intervention. The economic evaluation alongside the trial showed that DAFNEplus had an incremental cost of £611 versus DAFNE, an incremental quality-adjusted life-year (QALY) of + 0.008 and an incremental cost-effectiveness ratio (ICER) of £78,147 per QALY gained, considerably above National Institute for Health and Care Excellence’s (NICE’s) typical maximum acceptable ICER of £20,000–£30,000 per QALY gained. All our scenario analyses, including complete-case analysis and conducting a long-term extrapolation model of biomedical outcomes had ICERs above £20,000 per QALY gained. NICE’s typical range for a maximum acceptable ICER is £20,000–30,000 per QALY gained, and the ICER for DAFNEplus versus DAFNE is highly likely to exceed this range. Limitations Due to trial-suspension during the pandemic, we recruited 471 adults to the cRCT, 144 fewer than planned. Although this reduced overall statistical power, our results showed that differences in HbA1c between the two groups was close to zero and far below that we considered a meaningful clinical difference (0.5%). Delays in recruitment also meant that more participants were using CGM, both before and during the trial than we anticipated. This may have reduced additional benefit of the DAFNEplus intervention on HbA1c. The pandemic probably influenced diabetes self-management during the trial in both groups. Conclusions The DAFNEplus did not lead to greater falls in HbA1c at 12 months compared to DAFNE, but these falls were double those reported in previous DAFNE RCTs. Sixty-eight per cent of participants showed clinically relevant improved glucose levels. Those in DAFNEplus (compared with DAFNE) reported significant falls in diabetes distress, positive well-being, and qualitative research reported positive experiences of DAFNEplus among participants and health professionals. Study registration This study is registered as IRAS: 235621 and ISRCTN: 42908016. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0514-20013) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 21. See the NIHR Funding and Awards website for further award information.

Introduction and Objective: The health and psychosocial impacts of recurrent severe hypoglycemic events (SHEs) and impaired awareness of hypoglycemia (IAH) in adults with type 1 diabetes (T1D) who use continuous glucose monitors (CGM) and insulin pumps remain poorly understood. This study describes the health and psychosocial burden of adults with T1D using CGM and insulin pumps with recurrent SHEs and IAH. Methods: This ongoing 12-month prospective online survey enrolled adults with T1D using CGM and insulin pumps with recurrent SHEs (≥2 SHEs in the past year) and IAH (Clarke score ≥4). Participants were recruited through patient advocacy groups from Canada, Germany, France, Italy, UK, and US. Participants reported diabetes-related complications and completed the Hypoglycemia Fear Survey-II (HFS-II) and the 17-item Diabetes Distress Scale (DDS-17). Baseline results are presented and compared against US T1D and general population norms for contextualization. Results: Participants (N=137) had a mean age of 49.6 years (range: 20-75), 71.5% were female, 65.0% were from the US, and mean T1D duration was 34 years (range: 5-72). Participants reported a mean of 5.7 SHEs (SD: 8.0) in the past year. The most frequently reported diabetes-related complications included mental health problems (79.6%), vision problems (58.4%), heart and circulation problems (50.4%), and nerve complications (46.7%). Participants reported high psychosocial burden: fear of hypoglycemia score (mean HFS-II total score 58.0, SD: 24.9) was 32% higher compared to the US T1D population norm (44.1). Diabetes distress was substantial (mean DDS-17 total score: 2.67, SD: 1.10), with 64.2% indicating moderate-to-high diabetes distress (DDS-17 score≥2), which warrants clinical support. Conclusion: Despite using CGM and insulin pumps, adults living with T1D and recurrent SHEs and IAH reported substantial health and psychosocial burden, highlighting continuing unmet needs. Disclosure A. Boateng-Kuffour: Employee; Current; Vertex Pharmaceuticals Incorporated. Q. Zhang: Employee; Current; Veloxis Pharmaceuticals, Inc. A. Albanese-O'Neill: Consultant; Current; Sanofi. Advisory Panel; Current; Roche Pharmaceuticals, Vertex Pharmaceuticals Incorporated. Research Support; Current; Abbott Diabetes. A. Bubeck: None. L. Green: Other - Sponsorship to my organization; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated, Sanofi. B. Hauck: None. S. Heller: Consultant; Current; Novo Nordisk. Other - DSMC chair and member; Current; Eli Lilly and Company. Advisory Panel; Current; Zucara Therapeutics, Vertex Pharmaceuticals Incorporated. W. Polonsky: Consultant; Current; Vertex Pharmaceuticals Incorporated, Dexcom, Inc., Abbott Diabetes. Research Support; Current; Abbott Diabetes, Dexcom, Inc. Consultant; Current; Lilly Diabetes, MannKind Corporation. Research Support; Current; Lilly Diabetes. Consultant; Current; Sanofi, Insulet Corporation. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. J. Speight: Advisory Panel; Current; Vertex Pharmaceuticals Incorporated. Other - AU$10k Sponsorship for PSAD 2026 conference, Geelong, Australia; Current; Sanofi. S. Tutton: Advisory Panel; Ended; Vertex Pharmaceuticals Incorporated. Other - Patient Advisory Group Participation in the T1D Multi-National PRO study; Current; Vertex Pharmaceuticals Incorporated. R. Ziegler: Advisory Panel; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Sanofi. Speaker's Bureau; Current; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Current; Roche Diabetes Care. N. Ainsworth: Consultant; Current; Vertex Pharmaceuticals Incorporated. C. Abbott: Employee; Current; Vertex Pharmaceuticals. A. Martin: Consultant; Current; Vertex Pharmaceuticals Incorporated. N. Li: Employee; Current; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. B.L. Barber: None.

BACKGROUND AND AIMS:People with diabetes and chronic kidney disease (CKD) may be at increased risk of iatrogenic hypoglycaemia. We compared rates of sensor-detected (SDH) and person-reported hypoglycaemia (PRH) in people with insulin-treated Type 2 diabetes (T2D) with and without CKD in the Hypo-METRICS study. MATERIALS AND METHOD:Insulin-treated T2D patients with > 1 hypoglycaemic episode within the last 3 months wore a blinded continuous glucose monitor (CGM) and recorded PRH on the bespoke Hypo-METRICS app for 10 weeks. SDH was defined as per consensus guidelines. The participants were grouped based on estimated glomerular filtration rate (eGFR), that is CKD 1 (eGFR ≥ 90 mL/min; n = 117), CKD 2 (eGFR 60-89 mL/min; n = 140), and CKD 3 (eGFR 30-59 mL/min; n = 56). We used descriptive statistics, Kruskal-Wallis rank sum tests, and a negative binomial models to control for confounders. RESULTS:In total, 313 participants with T2DM were included. Median age increased with declining eGFR (p < 0.001). Median (IQR) events per week for SDH < 3.9 mmol/L were 1.72 (0.66-3.43) in CKD 1, 2.12 (0.85-4.55) in CKD 2, and 2.22 (1.09-4.57) in CKD 3 (p = 0.12). For SDH < 3.0 mmol/L, these rates were 0.20 (0.00-0.50), 0.21 (0.10-0.61), and 0.20 (0.00-0.71), respectively (p = 0.88). PRH events had medians of 1.05 (0.40-2.12), 1.31 (0.61-2.42), and 1.28 (0.68-2.25) for CKD 1, CKD 2, and CKD 3 (p = 0.24). CONCLUSION:In people with insulin-treated T2DM and CKD stages 2 or 3, the rates of SDH and PRH do not significantly differ from those in people without CKD. TRIAL REGISTRATION:ClinicalTRials.gov: NCT04304963.

AIMS:Gold and Clarke questionnaires are used to identify impaired awareness of hypoglycaemia (IAH) and severe hypoglycaemic event (SHE) risk in people with diabetes (pwD). We explored their overlap, including Clarke's Hypoglycaemia Awareness Status (Clarke-HAS) subfactor, and subsection differences in SHE incidence (Gold, Clarke, overlap). MATERIALS AND METHODS:This post hoc analysis of the Hypo-METRICS study recruited pwD on insulin (type 1: T1D; type 2: T2D) with ≥ 1 hypoglycaemic event in the previous 3 months. IAH was defined as Gold ≥ 4, Clarke ≥ 4, Clarke-HAS ≥ 2. RESULTS:Gold and Clarke were completed by 232 pwT1D and 285 pwT2D (age: 47 vs. 62 years, p < 0.001; HbA1c: 56 mmol/mol (7.3%) vs. 57 mmol/mol (7.4%), p = 0.03). IAH prevalence in T1D vs. T2D was 21% vs. 26% (p = 0.1), 14% vs. 18% (p = 0.2), and 41% vs. 48% (p = 0.2) according to Gold, Clarke and Clarke-HAS. The overlap between Gold ≥ 4, Clarke ≥ 4 was 40% (T1D: 45%; T2D: 37%); between Gold ≥ 4, Clarke-HAS ≥ 2 it was 45% (T1D: 43%; T2D: 47%). The overlap between Gold ≥ 4, Clarke ≥ 4 was 41% vs. 39% in CGM vs. non-CGM users (T1D: 50% vs. 35%; T2D: 32% vs. 40%); between Gold ≥ 4, Clarke-HAS ≥ 2 it was 39% vs. 53% (T1D: 38% vs. 54%; T2D: 40% vs. 53%). In the IAH sample, SHE rate was lower in people found with IAH by Gold vs. Clarke, 9% vs. 53%, and in those assessed by Gold-Clarke overlap vs. Clarke, 20% vs. 53% (all p < 0.001). CONCLUSIONS:Gold and Clarke show moderate consistency (37%-54%) in identifying IAH in insulin-treated diabetes, with/without CGM use, each associated with different SHE rates, indicating the two questionnaires measure different, independent aspects of IAH.

Physical activity increases the risk of hypoglycaemia in individuals with type 2 diabetes when basal or basal-bolus insulin therapy is administered. Once-weekly basal insulins may elevate the risk of physical activity-attributed hypoglycaemia compared with other basal insulins because the administered levels cannot be reduced in anticipation of increased physical activity. This post hoc analysis of five separate randomised trials (ONWARDS 1–5) aimed to examine physical activity-attributed hypoglycaemic episodes in adults with type 2 diabetes receiving either once-weekly basal insulin icodec (herein referred to as ‘icodec’) or once-daily basal insulins. The ONWARDS 1–5 Phase 3a randomised controlled trials compared the efficacy and safety of once-weekly basal icodec vs once-daily basal insulin in insulin-naive (ONWARDS 1, 3 and 5) and insulin-experienced (ONWARDS 2 and 4) adults with type 2 diabetes. Participants self-monitored their blood glucose levels using a blood glucose meter and a digital diary. In each trial, suspected hypoglycaemia symptoms triggered additional self-measured blood glucose readings, and values indicative of hypoglycaemia were recorded in the participants’ digital diary. Participants who experienced hypoglycaemic episodes were instructed to note any relation of each episode to physical activity. Hypoglycaemic episodes were classified as alert value (level 1: blood glucose <3.9 but ≥3.0 mmol/l), clinically significant (level 2: blood glucose <3.0 mmol/l) or severe (level 3: cognitive impairment requiring external assistance). The proportions of hypoglycaemic episodes that were attributed to physical activity and the ORs of having a physical activity-attributed hypoglycaemic episode were calculated for the two basal insulin types (once-weekly vs once-daily) for each of the five trials. Across all trials, there were no consistent differences between icodec and the once-daily insulin comparators in the proportions of hypoglycaemic episodes that were attributed to physical activity; these episodes were mainly alert value or clinically significant hypoglycaemic episodes. In both insulin-naive and insulin-experienced participants, the incidence of physical activity-attributed clinically significant or severe hypoglycaemic episodes was consistently ≤3.0

This article consists of a citation of a published article describing research funded by the Health and Social Care Delivery Research programme under project number 16/48/07, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1186/s12913-023-10002-y The National Health Service Diabetes Prevention Programme (NHS DPP) was commissioned by NHS England in 2016 and rolled out in three ‘waves’ across the whole of England. It aims to help people with raised blood glucose levels reduce their risk of developing type 2 diabetes through behaviour change techniques (e.g., weight loss, dietary changes and exercise). An independent, longitudinal, mixed methods evaluation of the NHS DPP was undertaken. We report the findings from the implementation work package: a qualitative interview study with designated local leads, responsible for the local commissioning and implementation of the programme. The aim of the study was to explore how local implementation processes were enacted and adapted over time. We conducted a telephone interview study across two time-points. Twenty-four semi-structured interviews with local leads across 19 sampled case sites were undertaken between October 2019 and January 2020 and 13 interviews with local leads across 13 sampled case sites were conducted between July 2020 and August 2020. Interviews aimed to reflect on the experience of implementation and explore how things changed over time. We identified four overarching themes to show how implementation was locally enacted and adapted across the sampled case sites: 1. Adapting to provider change; 2. Identification and referral; 3. Enhancing uptake in underserved populations; and 4. Digital and remote service options. This paper reports how designated local leads, responsible for local implementation of the NHS DPP, adapted implementation efforts over the course of a changing national diabetes prevention programme, including how local leads adapted implementation during the COVID-19 pandemic. This paper highlights three main factors that influence implementation: the importance of facilitation, the ability (or not) to tailor interventions to local needs and the role of context in implementation. This publication was funded by the Health and Social Care Delivery Research programme as a part of award number 16/48/07. https://doi.org/10.1186/s12913-023-10002-y This article reports on one component of the research award Evaluating the NHS Diabetes Prevention Programme (NHS DPP): the DIPLOMA research programme (Diabetes Prevention Long term Multimethod Assessment). For more information about this research please view the award page [https://fundingawards.nihr.ac.uk/award/16/48/07]

This article consists of a citation of a published article describing research funded by the Health and Social Care Delivery Research programme under project number 16/48/07, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1186/s12913-023-09195-z The prevention of type 2 diabetes (T2DM) is a major concern for health services around the world. The English NHS Diabetes Prevention Programme (NHS-DPP) offers a group face-to-face behaviour change intervention, based around exercise and diet, to adults with non-diabetic hyperglycaemia (NDH), referred from primary care. Previous analysis of the first 100,000 referrals revealed just over half of those referred to the NHS-DPP took up a place. This study aimed to identify the demographic, health and psychosocial factors associated with NHS-DPP uptake to help inform the development of interventions to improve uptake and address inequities between population groups. Drawing on the Behavioral Model of Health Services Utilization we developed a survey questionnaire to collect data on a wide range of demographic, health and psychosocial factors that might influence uptake of the NHS-DPP. We distributed this questionnaire to a cross-sectional random sample of 597 patients referred to the NHS-DPP across 17 general practices, chosen for variation. Multivariable regression analysis was used to identify factors associated with NHS-DPP uptake. 325 out of 597 questionnaires were completed (54%). Only a third of responders took up the offer of a place. The best performing model for uptake (AUC=0.78) consisted of four factors: older age; beliefs concerning personal vulnerability to T2DM; self-efficacy for reducing T2DM risk; and the efficacy of the NHS-DPP. After accounting for these, demographic and health-related factors played only a minor role. Unlike fixed demographic characteristics, psychosocial perceptions may be amenable to change. NHS-DPP uptake rates may be improved by targeting the beliefs of patients about their risk of developing T2DM, their ability to carry out and sustain behaviours to reduce this risk, and the efficacy of the NHS-DPP in providing the necessary understanding and skills required. The recently introduced digital version of the NHS DPP could help address the even lower uptake amongst younger adults. Such changes could facilitate proportional access from across different demographic strata. This publication was funded by the Health and Social Care Delivery Research programme as a part of award number 16/48/07. https://doi.org/10.1186/s12913-023-09195-z This article reports on one component of the research award Evaluating the NHS Diabetes Prevention Programme (NHS DPP): the DIPLOMA research programme (Diabetes Prevention Long term Multimethod Assessment). For more information about this research please view the award page https://fundingawards.nihr.ac.uk/award/16/48/07