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Aims/hypothesis: Diabetes distress is one of the most frequent mental health issues identified in people with type 1 and type 2 diabetes. Little is known about the role of glucose control as a potential contributor to diabetes distress and whether the subjective perception of glucose control or the objective glycaemic parameters are more important for the experience. With the emergence of continuous glucose monitoring (CGM), this is a relevant question as glucose values are now visible in real-time. We employed a precision monitoring approach to analyse the independent associations of perceived and measured glucose control with diabetes distress on a daily basis. By using n-of-1 analyses, we aimed to identify individual contributors to diabetes distress per person and analyse the associations of these individual contributors with mental health at a 3 month follow-up., Methods: In this prospective, observational study, perceived (hypoglycaemia/hyperglycaemia/glucose variability burden) and measured glucose control (time in hypoglycaemia and hyperglycaemia, CV) were assessed daily for 17 days using an ecological momentary assessment (EMA) approach with a special EMA app and CGM, respectively. Mixed-effect regression analysis was performed, with daily diabetes distress as the dependent variable and daily perceived and CGM-measured metrics of glucose control as random factors. Individual regression coefficients of daily distress with perceived and CGM-measured metrics were correlated with levels of psychosocial well-being at a 3 month follow-up., Results: Data from 379 participants were analysed (50.9% type 1 diabetes; 49.6% female). Perceived glucose variability (t=14.360; p<0.0001) and perceived hyperglycaemia (t=13.637; p<0.0001) were the strongest predictors of daily diabetes distress, while CGM-based glucose variability was not significantly associated (t=1.070; p=0.285). There was great heterogeneity between individuals in the associations of perceived and measured glucose parameters with diabetes distress. Individuals with a stronger association between perceived glucose control and daily distress had more depressive symptoms (β=0.32), diabetes distress (β=0.39) and hypoglycaemia fear (β=0.34) at follow-up (all p<0.001). Individuals with a stronger association between CGM-measured glucose control and daily distress had higher levels of psychosocial well-being at follow-up (depressive symptoms: β=-0.31; diabetes distress: β=-0.33; hypoglycaemia fear: β=-0.27; all p<0.001) but also higher HbA 1c (β=0.12; p<0.05)., Conclusions/interpretation: Overall, subjective perceptions of glucose seem to be more influential on diabetes distress than objective CGM parameters of glycaemic control. N-of-1 analyses showed that CGM-measured and perceived glucose control had differential associations with diabetes distress and psychosocial well-being 3 months later. The results highlight the need to understand the individual drivers of diabetes distress to develop personalised interventions within a precision mental health approach., (© 2024. The Author(s).)

Background: Management of type 1 diabetes (T1D) requires the use of insulin, which can cause hypoglycaemia (low blood glucose levels). While most hypoglycaemic episodes can be self-treated, all episodes can be sudden, inconvenient, challenging to prevent or manage, unpleasant and/or cause unwanted attention or embarrassment. Severe hypoglycaemic episodes, requiring assistance from others for recovery, are rare but potentially dangerous. Repeated exposure to hypoglycaemia can reduce classic warning symptoms ('awareness'), thereby increasing risk of severe episodes. Thus, fear of hypoglycaemia is common among adults with T1D and can have a negative impact on how they manage their diabetes, as well as on daily functioning, well-being and quality of life. While advances in glycaemic technologies and group-based psycho-educational programmes can reduce fear, frequency and impact of hypoglycaemia, they are not universally or freely available, nor do they fully resolve problematic hypoglycaemia or associated worries. This study aims to determine the effectiveness of a fully online, self-directed, scalable, psycho-educational intervention for reducing fear of hypoglycaemia: the Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST) programme., Methods: A 24-week, two-arm, parallel-group, hybrid type 1 randomised controlled trial, conducted remotely (online and telephone). Australian adults (≥ 18 years) with self-reported T1D and fear of hypoglycaemia will be recruited, and allocated at random (1:1) to HypoPAST or control (usual care). The primary outcome is the between-group difference in fear of hypoglycaemia (assessed using HFS-II Worry score) at 24 weeks. A sample size of N = 196 is required to detect a 9-point difference, with 90% power and allowing for 30% attrition. Multiple secondary outcomes include self-reported psychological, behavioural, biomedical, health economic, and process evaluation data. Data will be collected at baseline, 12 and 24 weeks using online surveys, 2-week ecological momentary assessments, website analytics and semi-structured interviews., Discussion: This study will provide evidence regarding the effectiveness, cost-effectiveness and acceptability of a novel, online psycho-educational programme: HypoPAST. Due to the fully online format, HypoPAST is expected to provide an inexpensive, convenient, accessible and scalable solution for reducing fear of hypoglycaemia among adults with T1D., Trial Registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000894695 (21 August 2023)., (© 2024. The Author(s).)

Introduction: To evaluate the relationship between the GRI -component of hypoglycemia (CHypo) and hyperglycemia (CHyper)- with diabetes quality of life (DQoL), diabetes-related stress (DDS), perception of hypoglycemia (Clarke Test), visual analogic scale (VAS) and diabetes-knowledge (DKQ2) in T1D., Methods: Cross-sectional study in 92 patients with T1D under intensive insulin treatment (21.7% CSII) and flash glucose monitoring (isCGM). Clinical, metabolic and glycometric parameters and quality of life/satisfaction questionnaires were analyzed., Results: 92 patients (54.3% male, BMI 25.4 ± 4.5 kg/m 2 , HbA1c 7.5 ± 1.0%, TIR 53.9 ± 15.9%) with mean age 36.1 ± 12.6years and 17.8 ± 11.3 T1D duration. The mean GRI was 60.6 ± 22.2 with a CHypo and CHyper of 5.9 ± 4.8 and 27.3 ± 14.4, respectively. 19.1% presented a pathological Clarke's test. Patients with TIR > 70% and GRI < 40 showed better VAS (8.8 ± 1.3 vs 9.3 ± 0.9, p < 0.05) and DDS (46.4 ± 22.1 vs 36.7 ± 16.6, p < 0.05) scores, showing no differences between groups. CHyper > 15 and Chypo > 3.4 were related to worse levels of DQoL (91.1 ± 23.9 vs 76.6 ± 18.6 and 94.6 ± 24.8 vs 79.8 ± 20.1, p < 0.01), DDS(49.8 ± 22.4 vs 35.7 ± 16.5 and 49.8 ± 22.4 vs 35.7 ± 16.5, p < 0.01),and DKQ2 (24.4 ± 4.3 vs 26.8 ± 5.2 and 24.1 ± 4.8 vs 26.0 ± 4.6, p < 0.05), respectively. Worse metabolic control defined by GRI correlated with worse scores in VAS (r = -0.209, p < 0.05), DQoL (r = 0.205, p < 0.05), and DDS (r = 0.205, p < 0.05). No difference was observed in knowledge´s scale. CHyper correlated with worse scores in VAS (r = -0.231, p < 0.05), DQoL (r = 0.422, p < 0.01), and DDS (r = 0.341, p < 0.01) and lower degree of knowledge DKQ2 (r = -0.231, p < 0.05). When analyzing DQoL as a dependent variable in a multiple lineal regression, only age (β = 0.747; p < 0.001) and CHyper (β = 0.717; p < 0.001) maintained statistical significance., Conclusions: Higher GRI was related to worse quality of life, diabetes-related stress and satisfaction with treatment, analogous to the TIR results.CHyper an Chypo were related to a greater decline in quality of life, diabetes-related stress, and lower satisfaction with treatment.However, in a multiple linear regression, only CHyper maintained statistical significance., (© 2024. The Author(s).)

Aims/hypothesis: The aim of this work was to examine the impact of hypoglycaemia on daily functioning among adults with type 1 diabetes or insulin-treated type 2 diabetes, using the novel Hypo-METRICS app., Methods: For 70 consecutive days, 594 adults (type 1 diabetes, n=274; type 2 diabetes, n=320) completed brief morning and evening Hypo-METRICS 'check-ins' about their experienced hypoglycaemia and daily functioning. Participants wore a blinded glucose sensor (i.e. data unavailable to the participants) for the study duration. Days and nights with or without person-reported hypoglycaemia (PRH) and/or sensor-detected hypoglycaemia (SDH) were compared using multilevel regression models., Results: Participants submitted a mean ± SD of 86.3±12.5% morning and 90.8±10.7% evening check-ins. For both types of diabetes, SDH alone had no significant associations with the changes in daily functioning scores. However, daytime and night-time PRH (with or without SDH) were significantly associated with worsening of energy levels, mood, cognitive functioning, negative affect and fear of hypoglycaemia later that day or while asleep. In addition, night-time PRH (with or without SDH) was significantly associated with worsening of sleep quality (type 1 and type 2 diabetes) and memory (type 2 diabetes). Further, daytime PRH (with or without SDH), was associated with worsening of fear of hyperglycaemia while asleep (type 1 diabetes), memory (type 1 and type 2 diabetes) and social functioning (type 2 diabetes)., Conclusions/interpretation: This prospective, real-world study reveals impact on several domains of daily functioning following PRH but not following SDH alone. These data suggest that the observed negative impact is mainly driven by subjective awareness of hypoglycaemia (i.e. PRH), through either symptoms or sensor alerts/readings and/or the need to take action to prevent or treat episodes., (© 2024. The Author(s).)

Objective: A subgroup analysis of the Hypoglycemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycemia persisting despite optimized care (HARPdoc) trial was conducted to explore the impact of Blood Glucose Awareness Training (BGAT, a hypoglycemia awareness training program) and the HARPdoc (a psychoeducation addressing unhelpful hypoglycemia beliefs) in reducing severe hypoglycemia (SH) in individuals using advanced diabetes technologies (ADTs). Methods: Data from trial participants who utilized ADTs, including continuous glucose monitors or automated insulin delivery systems, were extracted. Generalized linear mixed-effects models with Poisson distribution or linear mixed-effects models were used to evaluate SH incidence, and Gold questionnaire, Attitudes to Awareness of Hypoglycemia (A2A), Problem Areas in Diabetes (PAID), Hospital Anxiety and Depress Scale (HADS)-anxiety, and HADS-depression scores as measures of hypoglycemia awareness, unhelpful hypoglycemia beliefs, diabetes distress, and anxiety and depression symptoms, respectively. Results: In the 45 participants using ADTs, the BGAT and HARPdoc interventions both reduced SH incidence by more than 50% ( P < 0.0001) and yielded improvements in hypoglycemia awareness ( P < 0.05). HARPdoc outperformed BGAT in reducing SH at month 24 ( P = 0.01). HARPdoc also mitigated unhelpful hypoglycemia beliefs ( P < 0.0001), diabetes distress ( P < 0.05), and anxiety symptoms ( P < 0.05); BGAT demonstrated no significant impacts in these respects. Neither HARPdoc nor BGAT had significant effects on depression symptoms. Conclusion: Psychoeducation (BGAT and HARPdoc) was effective in reducing SH in people using ADTs. HARPdoc may also provide greater long-term SH reduction and improves psychological well-being in this patient group.

Purpose: Hypoglycemia represents a significant source of anxiety for children with type 1 diabetes mellitus (T1DM) and their caretakers. Fear of hypoglycemia (FoH) was measured in children and adolescents with T1DM as well as in their parents using an established research instrument, the Hypoglycemia Fear Survey (HFS)., Methods: This is a two-center, cross-sectional study involving 100 children and adolescents aged 6-18 years old diagnosed with T1DM. One parent of each child also participated in the study. The participants, who were recruited from two different pediatric endocrine outpatient clinics, were asked to complete the translated Greek version of the HFS, which includes one version for children (C-HFS) and one for parents (P-HFS). The association of the questionnaire responses with subjects' characteristics, such as current age, age at diagnosis, duration of diabetes, HbA1c levels, and mode of diabetes treatment were assessed., Results: Parents exhibited significantly higher mean HFS scores than their children. No significant correlation was found between the P-HFS or the C-HFS scores and the age of the children, duration of diabetes, HbA1c, or mode of treatment., Conclusion: The finding that parents experience higher levels of FoH compared to their children emphasizes the importance of healthcare providers to screen parental FoH and focus on approaches to support them in order to reduce their psychological burden, thus optimizing children's diabetes management., (© 2024. The Author(s).)

Background: Extended glucose predictions are novel in diabetes management. Currently, there is no solution widely available. People with diabetes mellitus (DM) are offered features like trend arrows and limited predictions linked to predefined situations. Thus, the impact of extended glucose predictions on the burden of diabetes and person-reported outcomes (PROs) is unclear., Methods: In this online survey, 206 people with type 1 and type 2 diabetes (T1D and T2D), 70.9% and 29.1%, respectively, who participated in the dia·link online panel and were current continuous glucose monitoring (CGM) users, were presented with different scenarios of hypothetical extended glucose predictions. They were asked to imagine how low glucose predictions of 30 minutes and overnight as well as glucose predictions up to 2 hours would influence their diabetes management. Subsequently, they completed the Hypoglycemia Fear Survey II (HFS-II) and the T1 Diabetes Distress Scale (T1-DDS) by rating each item on a 5-point scale (-2: strong deterioration to +2: strong improvement) according to the potential change due to using glucose predictions., Results: For all glucose prediction periods, 30 minutes, up to 2 hours, and at nighttime, the surveyed participants expected moderate improvements in both fear of hypoglycemia (HFS-II: 0.57 ± 0.49) and overall diabetes distress (T1-DDS = 0.44 ± 0.49). The T1-DDS did not differ for type of therapy or diabetes., Conclusions: People with T1D and T2D would see glucose predictions as a potential improvement regarding reduced fear of hypoglycemia and diabetes distress. Therefore, glucose predictions represent a value for them in lowering the burden of diabetes and its management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.E. reports lecture fees from Roche Diabetes Care, Sanofi-Aventis, and Dexcom Germany and is an Advisory Board member of Roche Diabetes Care and Dexcom Germany. L.L. reports lecture fees from Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Merck Sharp & Dohme, Medtronic, Menarini, MOVI SpA, Mundipharma, Novo Nordisk, Roche Diabetes Care, Sanofi-Aventis, and Terumo. He is an Advisory Board member of Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly Italia, Medtronic, MOVI SpA, Novo Nordisk, Roche Diabetes Care, Sanofi-Aventis, and Terumo. L-S.P. reports lecture fees from Ypsomed. N.H. reports Advisory Board member fees from Abbott Diabetes Care and Insulet as well as honoraria for lectures from Berlin Chemie AG, Becton Dickenson, Sanofi Germany, Roche Diabetes Care, and Dexcom Germany. N.B. and T.G. are employees and stockholders of Roche Diabetes Care GmbH.

Aims/hypothesis: Valid and reliable patient-reported outcome measures are vital for assessing disease impact, responsiveness to healthcare and the cost-effectiveness of interventions. A recent review has questioned the ability of existing measures to assess hypoglycaemia-related impacts on health-related quality of life for people with diabetes. This mixed-methods project was designed to produce a novel health-related quality of life patient-reported outcome measure in hypoglycaemia: the Hypo-RESOLVE QoL., Methods: Three studies were conducted with people with diabetes who experience hypoglycaemia. In Stage 1, a comprehensive health-related quality of life framework for hypoglycaemia was elicited from semi-structured interviews (N=31). In Stage 2, the content validity and acceptability of draft measure content were tested via three waves of cognitive debriefing interviews (N=70 people with diabetes; N=14 clinicians). In Stage 3, revised measure content was administered alongside existing generic and diabetes-related measures in a large cross-sectional observational survey to assess psychometric performance (N=1246). The final measure was developed using multiple evidence sources, incorporating stakeholder engagement., Results: A novel conceptual model of hypoglycaemia-related health-related quality of life was generated, featuring 19 themes, organised by physical, social and psychological aspects. From a draft version of 76 items, a final 14-item measure was produced with satisfactory structural (χ 2 =472.27, df=74, p<0.001; comparative fit index =0.943; root mean square error of approximation =0.069) and convergent validity with related constructs (r=0.46-0.59), internal consistency (α=0.91) and test-retest reliability (intraclass correlation coefficient =0.87)., Conclusions/interpretation: The Hypo-RESOLVE QoL is a rigorously developed patient-reported outcome measure assessing the health-related quality of life impacts of hypoglycaemia. The Hypo-RESOLVE QoL has demonstrable validity and reliability and has value for use in clinical decision-making and as a clinical trial endpoint., Data Availability: All data generated or analysed during this study are included in the published article and its online supplementary files ( https://doi.org/10.15131/shef., Data: 23295284.v2 )., (© 2024. The Author(s).)

Introduction: Reporting of hypoglycaemia and its impact in clinical studies is often retrospective and subject to recall bias. We developed the Hypo-METRICS app to measure the daily physical, psychological, and social impact of hypoglycaemia in adults with type 1 and insulin-treated type 2 diabetes in real-time using ecological momentary assessment (EMA). To help assess its utility, we aimed to determine Hypo-METRICS app completion rates and factors associated with completion., Methods: Adults with diabetes recruited into the Hypo-METRICS study were given validated patient-reported outcome measures (PROMs) at baseline. Over 10 weeks, they wore a blinded continuous glucose monitor (CGM), and were asked to complete three daily EMAs about hypoglycaemia and aspects of daily functioning, and two weekly sleep and productivity PROMs on the bespoke Hypo-METRICS app. We conducted linear regression to determine factors associated with app engagement, assessed by EMA and PROM completion rates and CGM metrics., Results: In 602 participants (55% men; 54% type 2 diabetes; median(IQR) age 56 (45-66) years; diabetes duration 19 (11-27) years; HbA1c 57 (51-65) mmol/mol), median(IQR) overall app completion rate was 91 (84-96)%, ranging from 90 (81-96)%, 89 (80-94)% and 94(87-97)% for morning, afternoon and evening check-ins, respectively. Older age, routine CGM use, greater time below 3.0 mmol/L, and active sensor time were positively associated with app completion., Discussion: High app completion across all app domains and participant characteristics indicates the Hypo-METRICS app is an acceptable research tool for collecting detailed data on hypoglycaemia frequency and impact in real-time., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Emerging adulthood is a phase characterized by exploration which potentially affecting sleep quality. While many emerging adults are healthy, the effects of chronic diseases such as Type 1 Diabetes Mellitus (T1DM) on sleep may be underestimated. Considering the frequency of nocturnal glycemic alterations that cause awakenings, this study explored the perceptions of emerging adults in Andalusia on the influence of T1DM on their sleep quality. Methods: A qualitative approach was used for this study. Purposive sampling through diabetes associations was initially utilized, supplemented by snowball sampling, in order to conduct semistructured interviews with 73 emerging adults (aged 18-29) diagnosed with T1DM, to explore their perceptions of the influence of T1DM on sleep quality. Interpretative Phenomenological Analysis was used for data analysis. Results: Sleep disruptions caused by overnight hyperglycemia and hypoglycemia were identified as significant factors. However, 62% of participants did not perceive the influence of diabetes on their sleep quality, despite experiencing frequent overnight glycemic alterations (reported by 40.9%). Conclusions: Perception of the impact of T1DM on sleep quality does not always align with the frequency of disruptions. Nonetheless, promoting healthy sleep and systematically assessing sleep quality can benefit both sleep and glycemic outcomes, regardless of individual perceptions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 María-Ángeles Núñez-Baila et al.)

Objective: To assess the clinical impact of flash glucose monitoring (FGM) systems on fear of hypoglycemia (FoH) and quality of life in adults with type 1 diabetes mellitus (T1DM). Methods: Prospective quasi-experimental study with a 12-month follow-up. People with T1DM (18-80 years old) and self-monitoring by blood capillary glycemia controls were included. The FH15 questionnaire, a survey validated in Spanish in a comparable study population, was used to diagnose FoH with a cutoff point of 28 points. Results: A total of 181 participants were included, with a FoH prevalence of 69% ( n  = 123). A mean reduction in FH15 score of -4 points (95% confidence interval [-5.5 to -3]; P  < 0.001) was observed, along with an improvement in quality of life (EsDQOL-test (Diabetes Quality of Life, Spanish version), -7 points [-10; -4], P  < 0.001) and satisfaction with treatment (Diabetes Treatment Satisfaction questionnaire, self-reported version [DTSQ-s] test, +4.5 points [4; 5.5], P  < 0.001). At the end of the follow-up, 64.2% of the participants saw an improved FoH intensity, compared to 35.8% who scored the same or higher. This improvement in FoH status was associated with a higher time-in-range at the end of the follow-up ( P  = 0.003), as well as a lower time spent in hyperglycemia ( P  = 0.005). In addition, it was linked to participants with a high baseline FoH levels ( P  < 0.001) and those who were university degree holders ( P  = 0.07). Conclusions: FGM is associated with an overall reduction of FoH in adults with T1DM and with an increase in their quality of life. Nevertheless, a significant percentage of patients may experience an increase of this phenomenon leading to clinical repercussions and a profound impact on quality of life.

Aims: To describe the development of a novel, conceptually sound instrument with contemporary content for assessing diabetes distress (DD) among adults with type 1 diabetes., Methods: Qualitative interviews with 15 adults and 7 clinicians were used to develop Core (intensity of DD emotional burden) and primary Source (key DD contributors) items. These were administered to a national sample recruited from the TCOYD Research Registry, T1D Exchange and our previous studies. Exploratory and confirmatory factor analyses were undertaken, along with reliability and construct validity studies, and cut-point analyses to determine elevated DD., Results: Analyses based on 650 respondents yielded an 8-item Core DD scale (α = 0.95) and 10 2- or 3-item DD Source Scales (α range = 0.53-0.88): Financial Worries, Interpersonal Challenges, Management Difficulties, Shame, Hypoglycemia Concerns, Healthcare Quality, Lack of Diabetes Resources, Technology Challenges, Burden to Others and Worries about Complications. Core and Source scores were significantly associated with criterion variables: Higher DD scores were significantly linked with higher HbA 1C , more frequent episodes of severe hypoglycaemia, missed boluses, and poorer quality of life (p > 0.001). A ≥2.0 scale cut-point to define elevated DD is suggested., Conclusions: The new T1-Diabetes Distress Assessment System demonstrated good reliability and validity, and with measures of both Core emotional burden and Sources of DD, it provides a contemporary, flexible and practical approach to assessing DD that can be used seamlessly to inform intervention for clinicians and researchers., (© 2024 Diabetes UK.)

The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70-180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8-12 years) and parents; the Quality of Life for Youth scale for adolescents (13-18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients' HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients' PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months.  Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D. What is Known: • Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements. • Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D. • Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context. What is New: • First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients. • Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life., (© 2024. The Author(s).)

Objective: Our aim in this study was to examine the potential impact of a 3-pronged digital health pilot intervention (TRIFECTA) on diabetes distress and depressive symptoms among adults with type 1 diabetes (T1D) in British Columbia., Methods: We recruited 60 adults with T1D (mean age 38.9±15.1 years, 75% female, 77% Caucasian) who participated in the 6-month pilot intervention involving 3 digital health platforms: monthly, provider-led, group-based sessions over Zoom (virtual huddles); a WhatsApp peer texting group; and a web-based "Ask-the-expert" portal. Assessments were conducted at baseline and 6 months and measured diabetes distress (T1D Diabetes Distress Scale), depressive symptoms (9-item Personal Health Questionnaire), and TRIFECTA engagement metrics., Results: Participation in TRIFECTA was associated with significant reductions in Overall Distress (p=0.011) and 4 distress subscales: Powerlessness (p=0.006), Management Distress (p=0.001), Hypoglycemia Distress (p=0.029), and Eating Distress (p<0.001). A higher number of virtual huddles attended predicted lower Overall Distress (p=0.019) and Family/Friends Distress (p=0.023). A higher number of "Ask-the-expert" posts viewed predicted lower Overall Distress (p=0.046), whereas a higher number of WhatsApp messages posted predicted lower Management Distress (p=0.006). Furthermore, engagement in all 3 metrics was a predictor for lower Negative Social Perceptions Distress (p<0.05). No associations were seen in other distress subscales or for depressive symptoms., Conclusions: Participation in TRIFECTA was linked to reduced diabetes distress levels, but not depressive symptoms, in a platform-dependent manner. This study provides promising pilot data for a subsequent large-scale and fully powered randomized controlled trial., (Copyright © 2023 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Hypoglycemia is a limiting adverse effect of glucose-lowering medications and particularly insulin replacement therapy. This review provides insights into the burden of hypoglycemia in the management of diabetes and outlines strategies available to reduce the risk of hypoglycemia and improve patients' well-being. People with type 1 diabetes are primarily affected by hypoglycemic episodes which are associated with direct physical harms like injuries and cardiac events as well as indirect psychosocial consequences including constant anxiety, absenteeism, increased healthcare costs and overall poorer quality of life. These complications are more prominent amongst individuals with hypoglycemia unawareness or overnight hypoglycemia and could even extend to caregivers such as parents of children with diabetes. Patients experiencing frequent or severe hypoglycemic events might also develop a pathological fear of hypoglycemia and adopt aberrant behaviors intending to maintain higher blood glucose levels. Modern pharmaceutical options with a safer profile in terms of hypoglycemia are available including novel basal insulins with lower rates of nocturnal hypoglycemia along with ultra-rapid-acting insulin analogs with a shorter duration of action that might avert late post-meal hypoglycemia. Continuous glucose monitoring and sensor-augmented insulin pump therapy with low glucose suspend technology can also prevent hypoglycemia, although concerns about cost and patient satisfaction remain. Advancements in insulin therapy and technological modalities should be coupled with ongoing education and support for patients to become co-managers of their disease and reduce the risk of hypoglycemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Youth with type 1 diabetes (T1D) and parents experience reduced quality of life and sleep quality due to nocturnal monitoring, hypoglycemia fear, and diabetes-related disruptions. This study examined the sleep and quality of life impact of advanced technology., Methods: Thirty-nine youth with T1D, aged 2-17 years, starting an advanced hybrid closed-loop (HCL) system and a parent participated in an observational study. Surveys, actigraphy, sleep diaries, and glycemic data (youth) were captured prior to HCL, at one week, 3 months, and 6 months. Outcomes were modeled using linear mixed effects models with random intercepts to account for within-subject correlation, with least-squares means at each timepoint compared to baseline., Results: Parents and youth reported improvements in health-related quality of life and fear of hypoglycemia after HCL initiation. Concurrently, nocturnal glycemia improved. Actigraphy-derived sleep outcomes showed improved 6 month adolescent efficiency and 3 and 6 month parent wake after sleep onset. Additionally, parents reported improved subjective sleep quality and child sleep-related impairment at 3 months., Conclusions: With nocturnal glycemic improvements in youth using HCL technology, some aspects of parent and youth sleep and quality of life improved. This may reflect decreased parental monitoring and worry and highlights benefits for youth beyond glycemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hypoglycemia is a common adverse reaction to glucose-lowering treatment. Diabetes mellitus (DM) combined with recurrent nonsevere hypoglycemia (RH) can accelerate cognitive decline. Currently, the metabolic pattern changes in cognition-related brain regions caused by this combined effect of DM and RH (DR) remain unclear. In this study, we first characterized the metabolic profiles of the hippocampus in mice exposed to DR using non-targeted metabolomic platforms. Our results showed that DR induced a unique metabolic pattern in the hippocampus, and several significant differences in metabolite levels belonging to the histidine metabolism pathway were discovered. Based on these findings, in the follow-up experiment, we found that histidine treatment could attenuate the cognitive impairment and rescue the neuronal and synaptic damage induced by DR in the hippocampus, which are closely related to ameliorated mitochondrial injury. These findings provide new insights into the metabolic mechanisms of the hippocampus in the progression of DR, and l-histidine supplementation may be a potential metabolic therapy in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Research on hypoglycaemia and quality of life (QoL) has focused mostly on severe hypoglycaemia and psychological outcomes, with less known about other aspects of hypoglycaemia (e.g., self-treated episodes) and impacts on other QoL domains (e.g., relationships). Therefore, we examined the impact of all aspects of hypoglycaemia on QoL in adults with type 1 diabetes (T1DM)., Methods: Participants completed an online survey, including assessment of hypoglycaemia-specific QoL (using the 12-item Hypoglycaemia Impact Profile). Mann-Whitney U tests examined differences in hypoglycaemia-specific QoL by hypoglycaemia frequency, severity, and awareness. Hierarchical linear regression examined associations with QoL., Results: Participants were 1028 adults with T1DM (M ± SD age: 47 ± 15 years; diabetes duration: 27 ± 16 years). Severe and self-treated hypoglycaemia and impaired awareness negatively impacted on overall QoL and several QoL domains, including leisure activities, physical health, ability to keep fit/be active, sleep, emotional well-being, spontaneity, independence, work/studies, and dietary freedom. Diabetes distress was most strongly associated with hypoglycaemia-specific QoL, followed by generic emotional well-being, fear of hypoglycaemia, and confidence in managing hypoglycaemia. Hypoglycaemia frequency and awareness were no longer significantly associated with QoL once psychological factors were considered., Conclusions: Hypoglycaemia negatively impacts on several QoL domains. Psychological factors supersede the effect of hypoglycaemia frequency and awareness in accounting for this negative impact., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: This study examined the psychosocial impact of Loop, an open-source automated insulin dosing system that has emerged from the diabetes technology "Do-It-Yourself" (DIY) movement., Methods: Subsamples of 239 adults, 115 children, and 243 parents completed data collection at the time of Loop initiation and 3 and 6 months later. Surveys collected demographic and clinical information, percent time-in-range, HbA1c, and validated psychosocial measures. Analyses included paired t tests and McNemar's tests to compare psychosocial functioning at 3 and 6 months and regression models to assess baseline predictors of psychosocial outcomes at 6 months., Results: Adults reported significant improvements in diabetes distress ( t = -7.20 P < .001; t = -8.01, P < .001), sleep quality ( t = 6.81, P < .001; t = 2.98, P = .003), fear of hypoglycemia ( t = -4.42, P < .001; t = -4.97, P < .001), and hypoglycemia confidence ( t = 8.68, P < .001; t = 7.96 P < .001) from baseline to 3 months and 6 months, respectively. Significant improvements in parents' and children's sleep quality and parents' fear of hypoglycemia were also observed. Several baseline characteristics were associated with psychosocial outcomes at 6 months., Conclusions: The current findings support the broad and sustained benefits of Loop across multiple aspects of psychosocial well-being. Advancement and dissemination of such technologies has the potential to improve mental and physiological health among people living with type 1 diabetes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: To examine the impact of real-time continuous glucose monitoring (rtCGM) on psychosocial outcomes in adults with insulin-using type 2 diabetes (T2D)., Methods: A total of 174 insulin-using adults with T2D completed questionnaires assessing diabetes distress, hypoglycemic confidence, hypoglycemic fear, device-related emotional burden, and device-related trust before and after a six-month trial of rtCGM. Hemoglobin A1c (HbA1c) was assessed at the same time points; impaired hypoglycemic awareness (IAH) was assessed at baseline. Change in psychosocial outcomes was examined with t tests, then modeled as a function of baseline HbA1c and IAH and simultaneous change in HbA1c in multiple regression analyses., Results: Respondents were predominantly male (57.5%) and non-Hispanic white (67.8%). Significant improvement over the trial was observed in hypoglycemic fear ( P = .031), hypoglycemic confidence ( P < .001), diabetes distress ( P < .001), and device-related emotional burden ( P < .001). Impaired hypoglycemic awareness at baseline predicted greater improvement in hypoglycemic fear ( P = .002), hypoglycemic confidence ( P = .003), diabetes distress ( P = .013), and device-related emotional burden ( P < .001). Higher baseline HbA1c was linked with greater improvement in hypoglycemic fear ( P = .030); HbA1c change over the trial was positively associated with change in diabetes distress ( P = .010) and device-related emotional burden ( P = .003)., Conclusions: Introduction of rtCGM in adults with insulin-using T2D was associated with significant improvements in diabetes-related psychosocial outcomes over six months. Gains were significantly greater among participants reporting IAH and those with higher HbA1c at baseline, thus providing the first evidence regarding which users might more likely benefit., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.H.P. has served as a consultant for Dexcom and Abbott Diabetes Care.

Aim: To pilot-test an intervention, co-designed with people with type 1 diabetes (T1DM) and diabetes specialist nurses, to reduce diabetes distress (DD) in adults with T1DM and moderate-to-severe DD., Methods: A group-based programme to reduce DD in people with T1DM and moderate-to-severe DD (REDUCE) was pilot-tested in four groups with five bi-weekly two and a half-hour meetings facilitated by two trained diabetes specialist nurses. Data collection included baseline and post-intervention questionnaires measuring DD and psychosocial outcomes and semi-structured interviews with participants post-intervention (n = 18). Data were analysed using descriptive statistics and systematic text condensation., Results: Twenty-five adults with T1DM participated in the study. The median age and diabetes duration of participants were 50 (IQR: 32;57.5) years and 26 (IQR: 18;45) years, respectively. Seventeen (68%) were women. The pilot study showed a significant reduction in DD (measured by Type 1 Diabetes Distress Scale) between baseline and post-intervention from 2.6 ± 0.7 to 1.9 ± 0.6 (mean ± SD) (p < 0.001). The largest reductions were seen on the subscales: powerlessness 1.2 ± 1.1, eating distress 0.9 ± 1.2 and fear of hypoglycaemia 0.8 ± 1.0 (mean ± SD). Significant improvements were also seen for quality of life, diabetes empowerment and emotion regulation. Qualitative data showed that REDUCE supported participants in verbalizing emotions and seeing worries in a more constructive perspective. Acknowledgement of negative diabetes experiences eased negative self-judgments. Sharing experiences among peers increased relatedness and reduced loneliness., Conclusion: Participation in REDUCE was associated with significant reduction in DD and significant increase in quality of life. Larger scale studies are planned to determine sustained effectiveness of REDUCE., (© 2023 Diabetes UK.)

Aims: To summarize and critically appraise evidence regarding the effectiveness of educational and/or behavioural interventions in reducing fear of hypoglycaemia among adults with type 1 diabetes., Methods: Systematic searches of medical and psychology databases were conducted. Risk-of-bias was assessed using the Joanna Briggs Institute Critical Appraisal Tools. Data were synthesized using random-effects meta-analyses for randomized controlled trials (RCTs) and narrative synthesis for observational studies., Results: Five RCTs (N = 682) and seven observational studies (N = 1519) met the inclusion criteria, reporting on behavioural, structured education and cognitive-behavioural therapy (CBT) interventions. Most studies assessed fear of hypoglycaemia using the Hypoglycaemia Fear Survey Worry (HFS-W) and Behaviour (HFS-B) subscales. Mean fear of hypoglycaemia at baseline was relatively low across studies. Meta-analyses showed a significant effect of interventions on HFS-W (SMD = -0.17, p = 0.032) but not on HFS-B scores (SMD = -0.34, p = 0.113). Across RCTs, Blood Glucose Awareness Training (BGAT) had the largest effect on HFS-W and HFS-B scores, and one CBT-based program was as effective as BGAT in reducing HFS-B scores. Observational studies showed that Dose Adjustment for Normal Eating (DAFNE) was associated with significant fear of hypoglycaemia reductions., Conclusions: Current evidence suggests that educational and behavioural interventions can reduce fear of hypoglycaemia. However, no study to date has examined these interventions among people with high fear of hypoglycaemia., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Introduction: The aim of this study was to determine the acceptability and psychometric properties of the Hypo-METRICS (Hypoglycemia MEasurement, ThResholds and ImpaCtS) application (app): a novel tool designed to assess the direct impact of symptomatic and asymptomatic hypoglycemia on daily functioning in people with insulin-treated diabetes., Materials and Methods: 100 adults with type 1 diabetes mellitus (T1DM, n = 64) or insulin-treated type 2 diabetes mellitus (T2DM, n = 36) completed three daily 'check-ins' (morning, afternoon and evening) via the Hypo-METRICs app across 10 weeks, to respond to 29 unique questions about their subjective daily functioning. Questions addressed sleep quality, energy level, mood, affect, cognitive functioning, fear of hypoglycemia and hyperglycemia, social functioning, and work/productivity. Completion rates, structural validity, internal consistency, and test-retest reliability were explored. App responses were correlated with validated person-reported outcome measures to investigate convergent (rs>±0.3) and divergent (rs<±0.3) validity., Results: Participants' mean±SD age was 54±16 years, diabetes duration was 23±13 years, and most recent HbA1c was 56.6±9.8 mmol/mol. Participants submitted mean±SD 191±16 out of 210 possible 'check-ins' (91%). Structural validity was confirmed with multi-level confirmatory factor analysis showing good model fit on the adjusted model (Comparative Fit Index >0.95, Root-Mean-Square Error of Approximation <0.06, Standardized Root-Mean-square Residual<0.08). Scales had satisfactory internal consistency (all ω≥0.5), and high test-retest reliability (rs≥0.7). Convergent and divergent validity were demonstrated for most scales., Conclusion: High completion rates and satisfactory psychometric properties demonstrated that the Hypo-METRICS app is acceptable to adults with T1DM and T2DM, and a reliable and valid tool to explore the daily impact of hypoglycemia., Competing Interests: US works for Novo Nordisk A/S (the work for this manuscript was undertaken prior to this employment). UPB has served on advisory boards and received lecture fees from for Novo Nordisk and Sanofi. BDG has received research support from Novo Nordisk. SAA has served on advisory boards for Novo Nordisk and Medtronic and have spoken at educational events sponsored by Novo Nordisk and Sanofi. JKM is a member on the advisory board of Abbott Diabetes Care, Boehringer Ingelheim, Becton-Dickinson, Eli Lilly, Medtronic, Novo Nordisk A/S, Prediktor A/S, Roche Diabetes Care, Sanofi-Aventis and received speaker honoraria from Abbott Diabetes Care, AstraZeneca, Becton-Dickinson, Dexcom, Eli Lilly, MSD, Novo Nordisk A/S, Roche Diabetes Care, Sanofi, and Servier. JKM is a shareholder of decide Clinical Software GmbH. FP has received unrestricted funding for research from Novo Nordisk, Eli Lilly and Sanofi. PC has received personal fees from Abbott, Insulet, Medtronic, Novo Nordisk, Eli Lilly, Sanofi and Dexcom. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The data underlying the results presented in the study are available from the Hypo-RESOLVE data repository for researchers who meet the criteria for access. Please contact Hypo-RESOLVE (chair of the publication committee Professor Stephanie Amiel or principal investigator Professor Pratik Choudhary) for further details: https://hypo-resolve.eu/contact, (Copyright: © 2023 Søholm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Maternal diabetes mellitus in pregnancy is associated with impairments in memory functions of the offspring in childhood and adolescence but has not been studied in adulthood. The association of perinatal hypoglycemia with memory has not been studied in adulthood either. The combined sequelae of these two risk factors have not been directly compared. We studied general cognitive ability and memory functions in a prospective follow-up of a cohort born in 1971 to 1974. The sample included participants exposed to prenatal hyperglycemia ( n = 24), perinatal hypoglycemia ( n = 19), or both ( n = 7). It also included controls with no early risks ( n = 82). We assessed the participants' Intelligence quotient (IQ), working memory, and immediate and delayed recall of both verbal and visual material at the age of 40. We did not find significant differences in IQ or the memory tests between the groups. We did identify an interaction ( p = 0.03) of the early risk with the type of digit span task: compared to the controls, the participants exposed to perinatal hypoglycemia had a larger difference between the forward digit span, a measure of attention, and the backward digit span, a measure of working memory processing ( p = 0.022). The interaction remained significant when birth weight was controlled for ( p = 0.026). Thus, in this small cohort, prenatal hyperglycemia, perinatal hypoglycemia, and their combination appeared relatively benign disorders. The association of these conditions with neurocognitive impairments in adulthood remains unconfirmed. The significance of the working memory difference needs to be verified with a larger sample., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Järvinen, Launes, Lipsanen, Virta, Vanninen, Lehto, Schiavone, Tuulio-Henriksson and Hokkanen.)

Background: Continuous glucose monitoring (CGM) decreases fear of hypoglycemia (FOH) and improves glycemic control among those affected by type 1 diabetes (T1D). No studies to date have examined the impact of using do-it-yourself real-time continuous glucose monitoring (DIY RT-CGM) on psychological and glycemic outcomes., Methods: Child-parent dyads were recruited for a multicentre randomized crossover trial. Children with T1D were current intermittently scanned CGM (isCGM) users and aged 2-13 years. Families received either 6 weeks of DIY RT-CGM with parental remote monitoring (intervention) or 6 weeks of isCGM plus usual diabetes care (control), followed by a 4-week washout period, then crossed over. The primary outcome was parental FOH. Secondary outcomes were glycemic control using traditional CGM metrics, as well as a range of other psychosocial measures., Findings: Fifty five child-parent dyads were recruited. The child mean age was 9.1 ± 2.8 years. Although, there was no effect on parental FOH, -0.1 (95%CI: -0.3, 0.1, p = 0.4), time-in-range (TIR) (%3.9-10 mmol/L) was significantly higher with DIY RT-CGM over isCGM (54.3% ± 13.7 vs. 48.1% ± 13.6), mean difference, 5.7% (95%CI 1.8, 9.6, p <0.004). There was no difference for time spent in hypoglycemia. Parent diabetes treatment satisfaction was significantly higher following DIY RT-CGM compared to isCGM, mean difference 5.3 (95%CI: 2.3, 8.2, p <0.001)., Conclusion: The use of DIY RT-CGM versus isCGM did not improve parental FOH; however, TIR and parental satisfaction with diabetes treatment were significantly improved. This suggests in the short term, DIY RT-CGM appears safe and may offer families some clinically important advantages over isCGM., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

This systematic review aims to summarize and critically evaluate the current evidence regarding the impact of hypoglycaemia in children and adolescents with type 1 diabetes on parental quality of life. MEDLINE, PsycINFO, CINAHL, and the Cochrane Library were searched. Inclusion criteria were: 1) quantitative design, 2) included parents of children or adolescents with type 1 diabetes, 3) assessment of hypoglycemia in children/adolescents with type 1 diabetes, 4) assessment of parent quality of life (or related domains of life), and 5) analysis of the relationship(s) between the child's hypoglycaemia and parents' quality of life. The data were summarised in accordance with Synthesis Without Meta-Analysis Guidelines. Twelve studies were included, reporting data from 1895 parents across six countries. Ten studies were cross-sectional; two included prospective data. Evidence suggested that greater frequency and severity of hypoglycemia was associated with greater parental fear of hypoglycemia, emotional distress and family burden. Children's hypoglycaemia has a negative impact on the well-being of parents, but there is an absence of evidence regarding the impact on their overall quality of life. Research into the hypoglycaemia-specific quality of life of parents is needed to explore the impact on various areas, such as social and physical dimensions., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Purpose of Review: The purpose of this paper is to describe rescue glucagon types, safety, efficacy, and preferences, as well as to review articles regarding emergency glucagon usage, severe hypoglycemia, and the emotions of both phenomena. We conducted a review of current literature on glucagon usage and the emotional impact of severe hypoglycemia on people with diabetes (PwD) and the caregivers of people with type 1 diabetes (T1D)., Recent Findings: Minimal research exists pertaining to glucagon and severe hypoglycemic experiences in PwD, which is troubling considering the severity of risks and possible side effects. Recent articles described negative emotions such as fear, anxiety, stress, helplessness, shame, embarrassment, loneliness, frustration, hopefulness, and uncertainty surrounding glucagon usage. There is scarce research regarding PwD's emotions surrounding severe hypoglycemia and rescue glucagon use. Additional research is needed to investigate the emotions and feelings people with T1D and their caregivers' experience pertaining to severe hypoglycemia and emergency glucagon use., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Currently, Italian versions of the Hypoglycemia Fear Survey for Children (CHFS) and for Parents (PHFS) quantifying Fear of Hypoglycemia (FoH) in pediatric diabetes are not available., Objective: To validate the Italian version of the CHFS and PHFS., Subjects and Methods: One hundred and seventy-four children with type 1 diabetes aged 6-18 and 178 parents completed the CHFS and PHFS, the PedsQL 3.0 Diabetes module and the KIDSCREEN-10. Internal consistency was good (α = 0.85 for CHFS, α = 0.88 for PHFS); validity was supported by correlations of CHFS total score (CHFS-T r = -0.50; p < 0.001, CI = -0.62 to -0.35) and Worry subscale (CHFS-W r = -0.49; p < 0.001, CI = -0.62 to -0.32) with measures of health-related quality of life (QoL), which were not related to PHFS scores. Factor analyses justified the structure and the separate scoring of Behavior and Worry subscales. Children's age was negatively correlated with CHFS-T (r = -0.16; p = 0.03, CI = -0.36 to 0.00), CHFS-W (r = -0.29; p = 0.02, CI = -0.39 to -0.07), PHFS-T (r = -0.20; p = 0.006, CI = -0.35 to -0.04), PHFS-B (r = -0.30; p = 0.001, CI = -0.43 to -0.17). Mean (SD) item scores of CHFS-T (1.47 ± 0.56 vs. 1.27 ± 0.57; p < 0.05) and CHFS-W (1.20 ± 0.73 vs. 0.96 ± 0.68; p < 0.05) were higher in children with HbA1c ≥7.5%. Higher levels of distress for upsetting hypoglycemia were associated with lower child's QoL scores as perceived by children (Peds-QL: 72.6 ± 12.8 vs. 80.4 ± 11.9; p < 0.001) and parents (Peds-QL: 70.6 ± 13.8 vs. 75.8 ± 12.9; p < 0.05)., Conclusion: The Italian version of CHFS and PHFS appears to be a valid measure to assess FoH in clinical practice and factor analysis supports separate scoring for the Worry and Behavior subscales., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The objective of the CRASH (Conversations and Reactions Around Severe Hypoglycemia) survey was to further our understanding of the characteristics, experience, behavior and conversations with healthcare professionals (HCPs) of people with diabetes (PWD) receiving insulin, and of caregivers (CGs) caring for such people, concerning hypoglycemia requiring external assistance (severe hypoglycemic events [SHEs])., Methods: CRASH was an online cross-sectional survey conducted across eight countries. PWD with self-reported type 1 (T1D) or insulin-treated type 2 (T2D) diabetes were aged≥18 years and had experienced one or more SHEs in the past 3 years; CGs were non-medical professionals aged ≥18 years, caring for PWD meeting all the above criteria except for PWD age (≥4 rather than ≥18 years). The present report is a descriptive analysis of data from France., Results: Among PWD who had ever discussed SHEs with an HCP, 38.9% of T1D PWD and 50.0% of T2D PWD reported that SHEs were discussed at every consultation; 26.3% and 8.8%, respectively, had not discussed the most recent SHE with an HCP. In total, 35.7% of T1D PWD and 53.8% of T2D PWD reported that glucagon was not available to them at the time of their most recent SHE. Only 16.9% of T1D PWD and 6.5% of T2D PWD who had discussed their most recent SHE with an HCP reported that the HCP recommended obtaining a glucagon kit or asked them to confirm that they already had one. High proportions of PWD and CGs reported that the most recent SHE had made them feel unprepared, scared and helpless and had affected mood, emotional state and activities., Conclusion: CRASH survey data from France identify a need for greater discussion about SHEs between HCPs and PWD and the CGs of such people, and reveal gaps in the diabetes education of PWDs and CGs., (Copyright © 2021 Eli Lilly and Company. Published by Elsevier Masson SAS.. All rights reserved.)

Aims: To develop an updated, more theoretically sound system for describing and assessing diabetes-related emotional distress (DD) in adults with type 2 diabetes (T2D)., Methods: Items were developed from qualitative interviews with 11 adults with T2D and 6 clinicians, then categorized as reflecting a core emotional experience of DD or a primary source of DD. Items were then administered to a national sample of TCOYD Registry participants. Data were analyzed using both exploratory (EFA) and confirmatory (CFA) factor analyses. Reliability (alpha) and construct validity also were assessed., Results: EFAs with 599 adults (258 insulin users, 341 non-insulin users) yielded a coherent DD Core scale and 7 DD Source scales (management demands, healthcare provider, hypoglycemia, long-term health, interpersonal issues, shame/stigma, healthcare access), which were confirmed by CFA. All alphas were >0.65. DD Core and DD Source scales were associated with criterion variables (all p < .001). Higher DD Core scores were linked to higher HbA 1c , BMI, more frequent severe hypoglycemia, and poorer self-management (all p < .001)., Conclusions: Good reliability and validity were found for this two-part T2DD Assessment System. It reflects a more contemporary and actionable approach to DD assessment that distinguishes between its key emotional dimension and its underlying contributors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To conduct a systematic review of published studies reporting on the longitudinal impacts of hypoglycaemia on quality of life (QoL) in adults with type 2 diabetes., Method: Database searches with no restrictions by language or date were conducted in MEDLINE, Cochrane Library, CINAHL and PsycINFO. Studies were included for review if they used a longitudinal design (e.g. cohort studies, randomised controlled trials) and reported on the association between hypoglycaemia and changes over time in patient-reported outcomes related to QoL., Results: In all, 20 longitudinal studies published between 1998 and 2020, representing 50,429 adults with type 2 diabetes, were selected for review. A descriptive synthesis following Synthesis Without Meta-analysis guidelines indicated that self-treated symptomatic hypoglycaemia was followed by impairments in daily functioning along with elevated symptoms of generalised anxiety, diabetes distress and fear of hypoglycaemia. Severe hypoglycaemic events were associated with reduced confidence in diabetes self-management and lower ratings of perceived health over time. Frequent hypoglycaemia was followed by reduced energy levels and diminished emotional well-being. There was insufficient evidence, however, to conclude that hypoglycaemia impacted sleep quality, depressive symptoms, general mood, social support or overall diabetes-specific QoL., Conclusions: Longitudinal evidence in this review suggests hypoglycaemia is a common occurrence among adults with type 2 diabetes that impacts key facets in the physical and psychological domains of QoL. Nonetheless, additional longitudinal research is needed-in particular, studies targeting diverse forms of hypoglycaemia, more varied facets of QoL and outcomes assessed using hypoglycaemia-specific measures., (© 2021 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Objective: To conduct a systematic review to examine associations between hypoglycemia and quality of life (QoL) in children and adolescents with type 1 diabetes., Methods: Four databases (Medline, Cochrane Library, CINAHL, PsycINFO) were searched systematically in November 2019 and searches were updated in September 2021. Studies were eligible if they included children and/or adolescents with type 1 diabetes, reported on the association between hypoglycemia and QoL (or related outcomes), had a quantitative design, and were published in a peer-reviewed journal after 2000. A protocol was registered the International Prospective Register of Systematic Reviews (PROSPERO; CRD42020154023). Studies were evaluated using the Joanna Briggs Institute's critical appraisal tool. A narrative synthesis was conducted by outcome and hypoglycemia severity., Results: In total, 27 studies met inclusion criteria. No hypoglycemia-specific measures of QoL were identified. Evidence for an association between SH and (domains) of generic and diabetes-specific QoL was too limited to draw conclusions, due to heterogenous definitions and operationalizations of hypoglycemia and outcomes across studies. SH was associated with greater worry about hypoglycemia, but was not clearly associated with diabetes distress, depression, anxiety, disordered eating or posttraumatic stress disorder. Although limited, some evidence suggests that more recent, more frequent, or more severe episodes of hypoglycemia may be associated with adverse outcomes and that the context in which hypoglycemia takes places might be important in relation to its impact., Conclusions: There is insufficient evidence regarding the impact of hypoglycemia on QoL in children and adolescents with type 1 diabetes at this stage. There is a need for further research to examine this relationship, ideally using hypoglycemia-specific QoL measures., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The aim of this study was to evaluate the feasibility, acceptability and preliminary efficacy of a theory-driven group education intervention designed to reduce fear of hypoglycemia (FoH) as a barrier to physical activity (PA) in adults with type 1 diabetes (T1D)., Methods: This study was a single-blinded, pilot randomized controlled trial of adults aged 18 to 65 years and living with T1D in Western Australia. Participants were randomized (1:1) to standard care or intervention with self-management education. Primary outcomes were feasibility and acceptability of the study procedures, and change to barriers to PA and FoH. Secondary outcomes were change to attitudes and intentions toward PA, self-reported participation in PA, self-efficacy, diabetes distress and well-being. To calculate effect sizes, we used a Bayesian comparison of the between-group difference scores (i.e. [score t2  - score t1 ] TREATMENT vs [score t2  - score t1 ] CONTROL )., Results: We randomized 117 participants with T1D, 86 (74%) of whom provided baseline data and attended initial workshops. Of these participants, 81% attended the booster workshop 4 weeks later. They were 45±12 years of age, reported high levels of activity and had been living with T1D for 20±14 years. Small-to-moderate effect sizes [ESs] in favour of the intervention were observed at 12 weeks for overall barriers to PA (ES, -0.38; highest density interval, -0.92 to 0.17), self-efficacy for blood glucose management after PA (ES, 0.45; highest density interval, 0 to 0.91), diabetes distress (ES, -0.29; highest density interval, -0.77 to 0.15) and well-being (ES, 0.36; highest density interval, -0.12 to 0.8)., Conclusions: Quantitative findings indicate study procedures were acceptable to participants and feasible to deliver. A future definitive trial is justified to replicate preliminary efficacy and to determine the utility of the intervention for improving PA participation., (Copyright © 2021 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Aim: To summarize and critically appraise the recent qualitative evidence regarding the impact of hypoglycaemia on the quality of life of family members of adults with type 1 or type 2 diabetes., Methods: Four databases were searched systematically (MEDLINE, PsycINFO, CINAHL and Cochrane Library), and results were screened for eligibility. Article quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Data were extracted, coded and analysed using thematic analysis. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Enhancing transparency in reporting of qualitative research (ENTREQ) guidelines., Results: Eight qualitative studies were included in the final review. The majority of participants were partners or spouses of adults with type 1 diabetes. Thematic synthesis resulted in six analytical themes: 'Hypoglycaemia alters everyday life, reducing freedoms and increasing disruptions', 'Hypoglycaemia has an adverse impact on sleep', 'Hypoglycaemia negatively changes the relationship with the person with diabetes', 'Hypoglycaemia negatively impacts emotional well-being', 'The detection, prevention, and treatment of hypoglycaemia consumes time and energy' and 'Family members have unmet needs for informational and emotional support regarding hypoglycaemia'. Across the six analytical themes, family members described how hypoglycaemia has a severe negative impact on different aspects of their lives, including daily living, personal relationships and emotional well-being., Conclusions: Family members experience the impact of hypoglycaemia as a major recurrent challenge in their lives. The unmet needs of family members need further attention in research and clinical practice., (© 2021 Diabetes UK.)

Background: Type 1 diabetes in young children is a heavy parental burden. As part of pilot phase of the KIDSAP01 study, we conducted a baseline assessment in parents to study the association between hypoglycemia fear, parental well-being and child behavior., Methods: All parents were invited to fill in baseline questionnaires: hypoglycemia fear survey (HFS), WHO-5, Epworth Sleepiness Scale and Strength and Difficulties Questionnaire (SDQ)., Results: 24 children (median age: 5-year, range 1-7 years, 63% male, mean diabetes duration: 3 ± 1.7 years) participated. 23/24 parents filled out the questionnaires. We found a higher score for the hypoglycemia fear behavior 33.9 ± 5.6 compared to hypoglycemia worry 34.6 ± 12.2. Median WHO-5 score was 16 (8 - 22) with poor well-being in two parents. Median daytime sleepiness score was high in five parents (>10). For six children a high total behavioral difficulty score (>16) was reported. Pro social behavior score was lower than normal in six children (<6). Parental well-being was negatively associated with HFS total ( r = - 0.50, p <.05) and subscale scores ( r = - 0.44, p <.05 for HFS-Worry and HFS-Behavior), child behavior ( r = - 0.45, p = .05) and positively with child age and diabetes duration ( r = 0.58, p <.01, r = 0.6, p <.01). HFS, parental well-being nor daytime sleepiness are associated with the HbA1c., Conclusion: Regular screening of parental well-being, hypoglycemia fear and child behavior should be part of routine care to target early intervention., Competing Interests: MT reports having received speaker honoraria from Minimed Medtronic and Novo Nordisk. MFr has received speaker honoraria from Minimed Medtronic and has served on advisory boards for Eli Lilly. JM is a member in the advisory board of Becton-Dickinson, Boehringer Ingelheim, Eli Lilly, Medtronic and Sanofi, and has received speaker honoraria from ABBOTT Diabetes Care, Astra Zeneca, Eli Lilly, Nintamed, Novo Nordisk, Roche Diabetes Care, Sanofi, Servier and Takeda. MW has received license fees from Becton Dickinson and has served as a consultant to Beckton Dickinson. SH declares speaker honoraria from Eli Lilly and Sanofi. EF-R reports having received speaker honoraria from Minimed Medtronic and Eli Lilly, serving on advisory boards for Eli Lilly. TK has received speaker honoraria from Minimed Medtronic, Roche and Eli Lilly and is member of an advisory board for ABBOTTt Diabetes Care. CdB has received speaker honoraria from Minimed Medtronic and is member of their European Psychology Advisory Board. FC does attend Advisory Boards and obtain speaking fees for ABBOTTt, Medtronic, Lilly, and NovoNordisk. BR-M reports having received speaker honoraria from Minimed Medtronic, Eli Lilly, Roche, Menarini and Novo Nordisk, serving on advisory boards for Eli Lilly. RH reports having received speaker honoraria from Eli Lilly, Dexcom and Novo Nordisk, receiving license fees from Medtronic, and being director at CamDiab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Beaufort, Pit-ten Cate, Schierloh, Cohen, Boughton, Tauschmann, Allen, Nagl, Fritsch, Yong, Metcalfe, Schaeffer, Fichelle, Thiele, Abt, Faninger, Mader, Slegtenhorst, Ashcroft, Wilinska, Sibayan, Kollman, Hofer, Fröhlich-Reiterer, Kapellen, Acerini, Campbell, Rami-Merhar and Hovorka.)

Aims: To examine whether frequency, perceived severity and fear of hypoglycaemia are independently associated with diabetes-specific quality of life in adolescents with type 1 diabetes., Methods: Cross-sectional self-reported data on demographics, frequency and perceived severity of both self-treated and severe hypoglycaemia, fear of hypoglycaemia (Hypoglycaemia Fear Survey-Child version) and diabetes-specific quality of life (Pediatric Quality of Life Diabetes Module; PedsQL-DM) were obtained from the project 'Whose diabetes is it anyway?'. Hierarchical regression analyses were performed for the total scale and recommended summary scores of the PedsQL-DM as dependent variables; independent variables were entered in the following steps: (1) age, gender and HbA 1c , (2) frequency of hypoglycaemia, (3) perceived severity of hypoglycaemia and (4) fear of hypoglycaemia., Results: Adolescents (12-18 years; n = 96) completed questionnaires. In the first three steps, female gender (p < 0.05), higher HbA 1c (p < 0.05), higher frequency of severe hypoglycaemia (p < 0.05) and higher perceived severity of severe (p < 0.05) and self-treated hypoglycaemia (p < 0.001) were significantly associated with lower diabetes-specific quality of life (β ranging from 0.20 to 0.35). However, in the final model only fear of hypoglycaemia was significantly associated with QoL (p < 0.001). Adolescents with greater fear reported lower diabetes-specific quality of life, with 52% explained variance. This pattern was observed across subdomains of diabetes-specific quality of life., Conclusions: Fear of hypoglycaemia was the only factor independently associated with diabetes-specific quality of life, whereas frequency and perceived severity of hypoglycaemia were not. These findings highlight the importance of awareness and assessment of fear of hypoglycaemia in clinical practice., (© 2021 Diabetes UK.)

Objectives: Hypoglycemia is the most common acute complication of type 1 diabetes (T1D), and the potential short- and long-term sequelae can cause children and parents to develop significant fear of hypoglycemia (FOH). FOH and associated anxiety can be disruptive to activities of daily living and lead to reduced quality of life. We sought to determine the extent of FOH among parents of children with T1D within our clinic and to identify factors associated with greater FOH., Methods: Two hundred sixty-four parents of youth (2 to 18 years of age; mean ± standard deviation, 12.4±3.5 years) with T1D completed a survey that included demographic and disease-specific questions, the Spielberger State-Trait Anxiety Inventory and the Hypoglycemia Fear Survey---Parent version (HFS-P)., Results: Of the 264 participants, 207 completed the full HFS-P, with a mean score of 67±19 (range, 31 to 119). The most frequent worries related to the child being hypoglycemic while alone or asleep. Higher HFS-P scores were also associated with more frequent and severe hypoglycemic episodes, higher state-trait anxiety scores, use of a continuous glucose monitor and more frequent blood glucose checks. Higher HFS-P scores were also associated with worse parental sleep quality and less parental engagement with treatment plans., Conclusions: Parents of children with T1D experience FOH, especially during times of high vulnerability. Moreover, FOH could potentially impact clinical care (with parents being reluctant to administer suggested insulin doses) and quality of life (due to parental/child sleep disruption). Further studies are needed to develop and evaluate interventions aimed at reducing FOH in parents of youth with T1D., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18 F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated., (© 2021 by the American Diabetes Association.)

Purpose: Five quality of life (QoL) domains are particularly important to patients with type 2 diabetes (T2D) using basal insulin-sense of physical well-being, sense of safety regarding hypoglycemia, sense of diabetes as burdensome, feelings of freedom and flexibility, and sleep quality., Methods: An online survey assessed these QoL domains in adult patients with T2D in the USA who had switched from a previous basal insulin to insulin degludec (IDeg): modified versions of the World Health Organization (Five) Well-Being Index (WHO-5), Hypoglycemia Attitudes and Behavior Scale (HABS; confidence and anxiety subscales only), and Diabetes Distress Scale (DDS; emotional burden and regimen-related distress subscales only); three items assessing feelings of freedom and flexibility; and one item assessing sleep quality (hours of restful sleep). Patients rated each item for their previous basal insulin and currently while using IDeg. Correlations between sleep quality and the other QoL scales were also assessed., Results: In total, 152 patients completed the survey and were included in the study sample. Patients reported significantly improved scores while using IDeg on all WHO-5, DDS, HABS, feelings of freedom and flexibility item scores, and total raw/mean subscale scores (P < 0.0001). Patients also reported a significantly greater number of hours of restful sleep [mean (SD) 6.6 (2.0) vs. 5.5 (1.8); P < 0.0001]. Better sleep quality statistically significantly correlated with improved QoL in all other domains assessed., Conclusions: Treatment with IDeg after switching from a previous basal insulin was associated with statistically significant improvements in all QoL domains assessed.

Hypoglycaemia (blood glucose concentration below the normal range) has been recognised as a complication of insulin treatment from the very first days of the discovery of insulin, and remains a major concern for people with diabetes, their families and healthcare professionals today. Acute hypoglycaemia stimulates a stress response that acts to restore circulating glucose, but plasma glucose concentrations can still fall too low to sustain normal brain function and cardiac rhythm. There are long-term consequences of recurrent hypoglycaemia, which are still not fully understood. This paper reviews our current understanding of the acute and cumulative consequences of hypoglycaemia in insulin-treated diabetes.

The discovery of insulin and its subsequent mass manufacture transformed the lives of people with type 1 and 2 diabetes. Insulin, however, was a drug with a 'dark side'. It brought with it the risk of iatrogenic hypoglycaemia. In this short review, the cellular consequences of recurrent hypoglycaemia, with a particular focus on the brain, are discussed. Using the ventromedial hypothalamus as an exemplar, this review highlights how recurrent hypoglycaemia has an impact on the specialised cells in the brain that are critical to the regulation of glucose homeostasis and the counterregulatory response to hypoglycaemia. In these cells, recurrent hypoglycaemia initiates a series of adaptations that ensure that they are more resilient to subsequent hypoglycaemia, but this leads to impaired hypoglycaemia awareness and a paradoxical increased risk of severe hypoglycaemia. This review also highlights how hypoglycaemia, as an oxidative stressor, may also exacerbate chronic hyperglycaemia-induced increases in oxidative stress and inflammation, leading to damage to vulnerable brain regions (and other end organs) and accelerating cognitive decline. Pre-clinical research indicates that glucose recovery following hypoglycaemia is considered a period where reactive oxygen species generation and oxidative stress are pronounced and can exacerbate the longer-term consequence of chronic hypoglycaemia. It is proposed that prior glycaemic control, hypoglycaemia and the degree of rebound hyperglycaemia interact synergistically to accelerate oxidative stress and inflammation, which may explain why increased glycaemic variability is now increasingly considered a risk factor for the complications of diabetes.

To investigate the fear of hypoglycaemia in patients with type 2 diabetes mellitus (T2DM), to identify factors related to this fear, and thus to provide evidence for clinical assessment. A total of 385 patients with T2DM who were admitted to the departments of endocrinology in five tertiary grade-A hospitals in Chongqing, China were included in this study. A questionnaire for general information and a Chinese version of Hypoglycemia Fear Survey (HFS) were used to collect the data. The average total score on the HFS was 71.67 ± 17.06 (HFS-W was 38.15 ± 10.57; HFS-B was 33.52 ± 9.54).The three items with the highest average score for HFS-W were not recognising low blood glucose (BG), not having food available, experiencing a hypoglycaemic episode alone, and for HFS-B were eating large amount of snacks, measuring BG six or more times per day, and keeping BG > 150 mmol/L. Regressions showed that number of hospitalisations for T2DM, receiving health education on diabetes, age and hypoglycaemia history because of T2DM were associated with fear of hypoglycaemia (all p < 0.05). Fear of hypoglycaemia in hospitalised patients with T2DM was strongly associated with diabetes health education, hospitalisation for diabetes, age, and hypoglycaemia history. Medical professionals should attach importance to the specific psychological interventions, health education on diabetes and the early prevention of hypoglycaemia or diabetic complications for patients with T2DM to reduce the fear of hypoglycaemia and improve their health status.

Hypoglycaemia is a common barrier to optimal glycaemic management and often feared among adults with type 1 diabetes. The aim of this systematic review was to summarize current evidence regarding the impact of hypoglycaemia on quality of life (QoL) and related outcomes. Electronic searches of MEDLINE, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were conducted. Peer-reviewed empirical studies investigating the relationship between hypoglycaemia and QoL were eligible for inclusion. Thirty studies met the inclusion criteria. Extracted data was summarized in a narrative synthesis according to Synthesis Without Meta-Analysis guidelines. None of the studies examined the impact of hypoglycaemia on general QoL. There was no association between hypoglycaemia and diabetes-specific QoL in four of the 30 studies. Severe hypoglycaemia was associated with greater fear of hypoglycaemia and diabetes distress, and lower general emotional well-being, but not with depression, anxiety, or health status. Self-treated hypoglycaemia was associated with greater fear of hypoglycaemia. With the exception of fear of hypoglycaemia, this review shows mixed associations between hypoglycaemia and psychological outcomes. Further research is needed to investigate the impact of hypoglycaemia on other domains of QoL., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims/hypothesis: The aim of this work was to assess the effect of spontaneous nocturnal hypoglycaemia on quality of life and mood during subsequent days in type 1 diabetes., Methods: A total of 153 people with type 1 diabetes participated in 6 days of blinded continuous glucose monitoring while documenting hypoglycaemic symptoms, quality of life and mood, daily. Hypoglycaemia was defined by interstitial glucose ≤3.9 mmol/l (IG 3.9 ) and ≤ 3.0 mmol/l (IG 3.0 ) for ≥15 min and was classified as asymptomatic if no hypoglycaemic symptoms were reported., Results: Self-estimated quality of life assessed by the EQ-5D VAS (but not by the WHO Well-Being Index) was higher the day after asymptomatic (but not after symptomatic) hypoglycaemic nights, as compared with non-hypoglycaemic nights (IG 3.9 , p = 0.021; IG 3.0 , p = 0.048). The effect increased with lower glucose nadir and longer duration of nocturnal hypoglycaemia (IG 3.9 , p = 0.03). The finding was confined to participants with impaired hypoglycaemia awareness. There was no effect of nocturnal hypoglycaemia on mood or self-estimated effectiveness at work the following day., Conclusions/interpretation: Individuals with type 1 diabetes and impaired hypoglycaemia awareness reported higher quality of life on days preceded by nights with asymptomatic (but not symptomatic) hypoglycaemia. The effect was amplified by lower glucose nadir and longer duration of the episodes and may help explain resistance to implementation of interventions to reduce hypoglycaemia in many people with impaired hypoglycaemia awareness.

To determine if pump therapy with continuous glucose monitoring offering low glucose suspend (LGS) decreases fear of hypoglycemia among children with type 1 diabetes and their parents. The CGM TIME trial is a multicenter randomized controlled trial that enrolled 144 children with type 1 diabetes for at least 1 year (mean duration 3.4 ± 3.1 years) starting pump therapy (MiniMed™ Veo™, Medtronic Canada). CGM (MiniMed™ Enlite™ sensor) offering LGS was introduced simultaneously or delayed for 6 months. Hypoglycemia Fear Scale (HFS) was completed by children ≥10 years old and all parents, at study entry and 12 months later. Simultaneous and Delayed Group participants were combined for all analyses. Subscale scores were compared with paired t-tests, and individual items with paired Wilcoxon tests. Linear regression examined association with CGM adherence. 121/140 parents and 91/99 children ≥10 years had complete data. Mean Behavior subscale score decreased from 21.1 (SD 5.9) to 17.2 (SD 6.1) (p < .001) for children, and 20.7 (SD 7.5) to 17.4 (7.4) (p < .001) for parents. Mean Worry subscale score decreased from 17.9 (SD 11.9) to 11.9 (SD 11.4) (p < .001) for children, and 23.1 (SD 13.2) to 17.6 (SD 10.4) (p < .001) for parents. Median scores for 10/25 child items and 12/25 parent items were significantly lower at 12 months (p < .001). Linear regression found no association between HFS scores and CGM adherence. Insulin pump therapy with CGM offering LGS significantly reduced fear of hypoglycemia not related to CGM adherence in children with type 1 diabetes and their parents., (© 2020 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Context: Type 1 diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycemia (SH) and impaired awareness of hypoglycemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI)., Objective: To investigate whether there are structural brain differences in a group of T1D patients with IAH compared with normal awareness of hypoglycemia (NAH)., Design: General practice, population-based, cross-sectional study (July 2018 to July 2019)., Setting: Endocrinology Department, Hospital Santa Creu i Sant Pau., Participants: A total of 40 T1D patients (20 each with IAH and NAH) matched for age, sex, T1D duration, and education level., Main Outcome Measures: Using different neuroimaging techniques, we compared whole-brain gray matter (GM) and white matter (WM) differences. We used voxel-based morphometry and cortical surface area analysis methods to assess GM differences, and fractional anisotropy (FA) to assess WM differences., Results: Compared with patients with T1D-NAH, patients with T1D-IAH had reduced GM volumes and cortical surface areas, especially in frontal and parietal regions (P < 0.05 corrected), and also showed reduced FA values in major WM tracts. The observed MRI differences correlated with both SH frequency and IAH severity., Conclusions: MRI for patients with T1D show that IAH is associated with brain changes involving both GM and WM. Further research is needed to elucidate whether the observed differences are a consequence of increased SH episode frequency and increased IAH severity., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: In recent years, a growing number of people with type 1 diabetes gained access to real-time continuous glucose monitoring (rtCGM). Long-term benefits of rtCGM are unclear because of a lack of large studies of long duration. We evaluated whether real-world rtCGM use up to 24 months offered benefits, particularly in those living with impaired awareness of hypoglycemia (IAH)., Research Design and Methods: This 24-month, prospective, observational cohort study followed 441 adults with insulin pumps receiving full reimbursement for rtCGM. Forty-two percent had IAH. The primary end point was evolution of HbA 1c , with secondary end points change in acute hypoglycemia complications, diabetes-related work absenteeism, and quality of life scores. Additionally, we evaluated whether people could achieve glycemic consensus targets during follow-up., Results: After 24 months, HbA 1c remained significantly lower compared with baseline (7.64% [60 mmol/mol] vs. 7.37% [57 mmol/mol], P < 0.0001). Sustained benefits were also observed for the score on the hypoglycemia fear survey and hypoglycemia-related acute complications irrespective of hypoglycemia awareness level. People with IAH had the strongest improvement, especially for severe hypoglycemia (862 events in the year before vs. 119 events per 100 patient-years in the 2nd year, P < 0.0001). Over 24 months, more people were able to meet hypoglycemia consensus targets at the expense of slightly fewer people achieving hyperglycemia consensus targets. Furthermore, the number of people with HbA 1c <7% (<53 mmol/mol) without severe hypoglycemia events more than doubled (11.0% vs. 25.4%, P < 0.0001)., Conclusions: Use of rtCGM led to sustained improvements in hypoglycemia-related glucose control over 24 months. Lower fear of hypoglycemia, fewer acute hypoglycemia-related events, and fewer diabetes-related days off from work were observed, particularly in those with IAH., (© 2020 by the American Diabetes Association.)

Objective: This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors., Research Design and Methods: We prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled., Results: Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, P < 0.001), item-color recall (β = -0.08, P = 0.010), and forward digit span (β = -0.06, P = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, P = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA 1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA 1c was associated with lower item-color recall (β = -0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for., Conclusions: A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia., (© 2020 by the American Diabetes Association.)

Background: Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA., Objectives: To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA., Methods: A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI., Results: Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (β (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA., Conclusions: In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)