Development of a new health-related quality of life measure for people with diabetes who experience hypoglycaemia: the Hypo-RESOLVE QoL.

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 (χ2=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 ).

Hypoglycaemia symptom frequency, severity, burden, and utility among adults with type 1 diabetes and impaired awareness of hypoglycaemia: Baseline and 24-week findings from the HypoCOMPaSS study.

AIMS: To determine the frequency, severity, burden, and utility of hypoglycaemia symptoms among adults with type 1 diabetes (T1D) and impaired awareness of hypoglycaemia (IAH) at baseline and week 24 following the HypoCOMPaSS awareness restoration intervention. METHODS: Adults (N = 96) with T1D (duration: 29 ± 12 years; 64% women) and IAH completed the Hypoglycaemia Burden Questionnaire (HypoB-Q), assessing experience of 20 pre-specified hypoglycaemia symptoms, at baseline and week 24. RESULTS: At baseline, 93 (97%) participants experienced at least one symptom (mean ± SD 10.6 ± 4.6 symptoms). The proportion recognising each specific symptom ranged from 15% to 83%. At 24 weeks, symptom severity and burden appear reduced, and utility increased. CONCLUSIONS: Adults with T1D and IAH experience a range of hypoglycaemia symptoms. Perceptions of symptom burden or utility are malleable. Although larger scale studies are needed to confirm, these findings suggest that changing the salience of the symptomatic response may be more important in recovering protection from hypoglycaemia through regained awareness than intensifying symptom frequency or severity.

Associations of clinical, psychological, and sociodemographic characteristics and ecological momentary assessment completion in the 10-week Hypo-METRICS study: Hypoglycaemia MEasurements ThResholds and ImpaCtS.

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.

Effectiveness of educational and behavioural interventions for reducing fear of hypoglycaemia among adults with type 1 diabetes: Systematic review and meta-analyses.

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.

Reduced heart rate variability in people with type 1 diabetes and elevated diabetes distress: Results from the longitudinal observational DIA-LINK1 study.

AIMS: People with type 1 diabetes have a higher risk for cardiovascular disease (CVD). Reduced heart rate variability (HRV) is a clinical marker for CVD. In this observational study using continuous HRV measurement across 26 days, we investigated whether psychological stressors (diabetes distress, depressive symptoms) and glycaemic parameters (hypo- and hyperglycaemic exposure, glycaemic variability and HbA1c ) are associated with lower HRV in people with type 1 diabetes. METHODS: Data from the non-interventional prospective DIA-LINK1 study were analysed. At baseline, depressive symptoms and diabetes distress were assessed. Glucose values and HRV were recorded daily for 26 days using continuous glucose monitoring (CGM) and a wrist-worn health tracker respectively. Multilevel modelling with participant as nesting factor was used to analyse associations between day-to-day HRV and diabetes distress, depressive symptoms and CGM-derived parameters. RESULTS: Data from 149 participants were analysed (age: 38.3 ± 13.1 years, HbA1c : 8.6 ± 1.9%). Participants with elevated diabetes distress had a significantly lower HRV across the 26 days compared to participants without elevated distress (ß = -0.28; p = 0.004). Elevated depressive symptoms were not significantly associated with HRV (ß = -0.18; p = 0.074). Higher daily exposure to hyperglycaemia (ß = -0.44; p = 0.044), higher average exposure to hypoglycaemia (ß = -0.18; p = 0.042) and higher HbA1c (ß = -0.20; p = 0.018) were associated with reduced HRV across the 26 days. Sensitivity analysis with HRV averaged across all days corroborated these results. CONCLUSIONS: Diabetes distress is a clinically meaningful psychosocial stressor that could play a role in the cardiovascular health of people with type 1 diabetes. These findings highlight the need for integrated psychosocial care in diabetes management.

Producing a preference-based quality of LIFE measure to quantify the impact of HYPOGLYCAEMIA on people living with diabetes: A mixed-methods research protocol.

BACKGROUND: Assessment of patient-reported outcome measures (PROMs), including quality of life (QoL), is essential in diabetes research and care. However, a recent review concluded that current hypoglycaemia-specific PROMs have limited evidence of validity, reliability and responsiveness for assessing the impact of hypoglycaemia on QoL in people living with diabetes. None of the PROMs identified could be used directly to inform the cost-effectiveness of treatments and interventions. There is a need for a new hypoglycaemia-specific QoL PROM, which can be used directly to inform economic evaluations. AIMS: This project has three aims: (a) To develop draft PROM content for measuring the impact of hypoglycaemia on QoL in adults with diabetes. (b) To refine the draft content using cognitive debriefing interviews and psychometrics. This will result in a condition-specific PROM that can be used to quantify the impact of hypoglycaemia upon QoL. (c) To generate a preference-based measure (PBM) that will enable utility values to be calculated for economic evaluation. METHODS: A mixed-methods, three-stage design is used: (a) Qualitative interviews will inform the draft PROM content. (b) Cognitive debriefing interview data will be used to refine the draft PROM content. The PROM will be administered in a large-scale survey to enable psychometric validation. Final item selection for the PROM will be informed by psychometric performance, translatability assessment and input from stakeholder groups. (c) A classification system will be generated, comprising a reduced number of items from the PROM. A valuation survey will be conducted to derive a value set for the PBM.

Changes in quality of life following hypoglycaemia in adults with type 2 diabetes: A systematic review of longitudinal studies.

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.

Unmet support needs relating to hypoglycaemia among adults with type 1 diabetes: Results of a multi-country web-based qualitative study.

OBJECTIVE: Hypoglycaemic episodes and fear of hypoglycaemia can be burdensome for adults with type 1 diabetes. This study explored support needs relating to hypoglycaemia among adults with type 1 diabetes living in Denmark, Germany, the Netherlands and the United Kingdom. RESEARCH DESIGN AND METHODS: Respondents participated in a web-based qualitative study involving four open-ended questions that asked what they wished other people understood about hypoglycaemia and what other people could do differently to support them with hypoglycaemia. Responses were analyzed using reflexive thematic analysis. RESULTS: Participants were 219 adults with type 1 diabetes (mean ± SD age 39 ± 13 years; mean ± SD diabetes duration 20 ± 14 years). They described unmet needs relating to: (1) Clinical support, involving access to new diabetes technologies, training on hypoglycaemia prevention, personalised care and psychological support; (2) Practical support, involving family and friends better supporting them with hypoglycaemia management and prevention; (3) Education for other people, involving others becoming more informed about hypoglycaemia; and (4) An appreciation of the burden, involving others recognizing the experience and impact of episodes, and the burden of living with the risk of hypoglycaemia. CONCLUSIONS: Adults with type 1 diabetes report several unmet support needs relating to hypoglycaemia. Service delivery should be person-centred and prioritise the individual's support needs. Clinical conversations are needed to identify the individual's support needs and develop tailored support plans. People with diabetes and their family members should be offered hypoglycaemia-specific education and training.

Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol.

INTRODUCTION: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor-detected hypoglycaemia (SDH) is unclear. Hypo-METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia. METHODS: We will recruit 600 participants: 350 with insulin-treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self-detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient-reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes. ETHICS AND DISSEMINATION: The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer-reviewed journal publications and conference presentations.

The impact of hypoglycaemia in children and adolescents with type 1 diabetes on parental quality of life and related outcomes: A systematic review.

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.

The suitability of patient-reported outcome measures used to assess the impact of hypoglycaemia on quality of life in people with diabetes: a systematic review using COSMIN methods.

AIMS/HYPOTHESIS: It is generally accepted that hypoglycaemia can negatively impact the quality of life (QoL) of people living with diabetes. However, the suitability of patient-reported outcome measures (PROMs) used to assess this impact is unclear. The aim of this systematic review was to identify PROMs used to assess the impact of hypoglycaemia on QoL and examine their quality and psychometric properties. METHODS: Systematic searches (MEDLINE, EMBASE, PsycINFO, CINAHL and The Cochrane Library databases) were undertaken to identify published articles reporting on the development or validation of hypoglycaemia-specific PROMs used to assess the impact of hypoglycaemia on QoL (or domains of QoL) in adults with diabetes. A protocol was developed and registered with PROSPERO (registration no. CRD42019125153). Studies were assessed for inclusion at title/abstract stage by one reviewer. Full-text articles were scrutinised where considered relevant or potentially relevant or where doubt existed. Twenty per cent of articles were assessed by a second reviewer. PROMS were evaluated, according to COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, and data were extracted independently by two reviewers against COSMIN criteria. Assessment of each PROM's content validity included reviewer ratings (N = 16) of relevance, comprehensiveness and comprehensibility: by researchers (n = 6); clinicians (n = 6); and adults with diabetes (n = 4). RESULTS: Of the 214 PROMs used to assess the impact of hypoglycaemia on QoL (or domains of QoL), seven hypoglycaemia-specific PROMS were identified and subjected to full evaluation: the Fear of Hypoglycemia 15-item scale; the Hypoglycemia Fear Survey; the Hypoglycemia Fear Survey version II; the Hypoglycemia Fear Survey-II short-form; the Hypoglycemic Attitudes and Behavior Scale; the Hypoglycemic Confidence Scale; and the QoLHYPO questionnaire. Content validity was rated as 'inconsistent', with most as '(very) low' quality, while structural validity was deemed 'unsatisfactory'. Other measurement properties (e.g. reliability) varied, and evidence gaps were apparent across all PROMs. None of the identified studies addressed cross-cultural validity or measurement error. Criterion validity and responsiveness were not assessed due to the lack of a 'gold standard' measure of the impact of hypoglycaemia on QoL against which to compare the PROMS. CONCLUSIONS/INTERPRETATION: None of the hypoglycaemia-specific PROMs identified had sufficient evidence to demonstrate satisfactory validity, reliability and responsiveness. All were limited in terms of content and structural validity, which restricts their utility for assessing the impact of hypoglycaemia on QoL in the clinic or research setting. Further research is needed to address the content validity of existing PROMs, or the development of new PROM(s), for the purpose of assessing the impact of hypoglycaemia on QoL. PROSPERO REGISTRATION: CRD42019125153.

The impact of hypoglycaemia on the quality of life of family members of adults with type 1 or type 2 diabetes: A qualitative systematic review.

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.

Hypoglycaemia and diabetes-specific quality of life in adolescents with type 1 diabetes.

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 HbA1c , (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 HbA1c (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 (ß 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.

The relationship between attentional bias to food and disordered eating in females with type 1 diabetes.

OBJECTIVE: Factors which may render females with type 1 diabetes mellitus (T1DM) vulnerable to disordered eating behavior or difficulties with dietary management require further investigation. Given prior associations observed between food-related attentional biases and eating behavior in groups without diabetes, this study explored the relationships between attentional bias to healthy and unhealthy pictorial food cues and disordered eating in young adult females with and without T1DM, aged 18-40yrs. METHODS: 97 participants (41 with T1DM, 56 without) completed an initial online survey assessing demographic and clinical information, and disordered eating via the Eating Disorders Examination- Questionnaire (EDE-Q). They subsequently attended an in-person session to complete a computer-based visual probe task to assess attentional bias to pictorial food cues. RESULTS: Analyses of Variance (ANOVAs) adjusting for age and body mass index showed a unique significant relationship in the group with T1DM whereby greater attentional bias scores away from unhealthy foods was associated with greater disordered eating. No relationship was observed in the group without diabetes. DISCUSSION: This study suggests that early attentional disengagement from food-related cues may be uniquely associated with eating-related outcomes for females with T1DM relative to those without diabetes. This should be further explored in future research with an aim to develop novel strategies for prevention and treatment of disordered eating behavior in this vulnerable group.

A Systematic Review and Meta-analysis of Executive Function Performance in Type 1 Diabetes Mellitus.

OBJECTIVE: The aims of the study were to examine the current evidence for executive function (EF) performance differences between groups with type 1 diabetes mellitus (T1DM) and nondiabetic control groups during adolescence and early adulthood and to explore the relationships between EF and diabetes-related risk factors. METHODS: A systematic review of the literature examining EF performance in groups with T1DM was conducted according to the PRISMA guidelines. Electronic database searches for published and unpublished literature yielded a final set of 26 articles after application of inclusion and exclusion criteria. A meta-analysis was conducted on a subset of these articles (n = 17) comparing EF performance in T1DM and control groups, across a total sample size of 1619. RESULTS: Sixteen of 26 studies found significantly lower EF on at least one task in groups with T1DM. Meta-analyses of the performance difference between T1DM groups and control groups without diabetes showed that inhibition (g = -0.28, p < .001), working memory (g = -0.34, p < .001), set-shifting (g = -0.31, p = .012), and overall EF performance across these domains (g = -0.42, p < .001) were all significantly lower in groups with T1DM. Performance on specific EF domains also seemed to be differentially associated with early age of diabetes onset, chronic hyperglycemia and its complications, and severe hypoglycemia. CONCLUSIONS: T1DM and its associated risk factors are related to subtle impairments across the inhibition, working memory, and set-shifting domains of EF. Lower EF may be a key factor contributing to behavioral and clinical problems experienced by individuals with T1DM.

Associations Between Hypoglycemia Awareness Status and Symptoms of Hypoglycemia Among Adults with Type 1 or Insulin-Treated Type 2 Diabetes Using the Hypo-METRICS Smartphone Application.

Introduction: This study examined associations between hypoglycemia awareness status and hypoglycemia symptoms reported in real-time using the novel Hypoglycaemia-MEasurement, ThResholds and ImpaCtS (Hypo-METRICS) smartphone application (app) among adults with insulin-treated type 1 (T1D) or type 2 diabetes (T2D). Methods: Adults who experienced at least one hypoglycemic episode in the previous 3 months were recruited to the Hypo-METRICS study. They prospectively reported hypoglycemia episodes using the app for 10 weeks. Any of eight hypoglycemia symptoms were considered present if intensity was rated between "A little bit" to "Very much" and absent if rated "Not at all." Associations between hypoglycemia awareness (as defined by Gold score) and hypoglycemia symptoms were modeled using mixed-effects binary logistic regression, adjusting for glucose monitoring method and diabetes duration. Results: Of 531 participants (48% T1D, 52% T2D), 45% were women, 91% white, and 59% used Flash or continuous glucose monitoring. Impaired awareness of hypoglycemia (IAH) was associated with lower odds of reporting autonomic symptoms than normal awareness of hypoglycemia (NAH) (T1D odds ratio [OR] 0.43 [95% confidence interval {CI} 0.25-0.73], P = 0.002); T2D OR 0.51 [95% CI 0.26-0.99], P = 0.048), with no differences in neuroglycopenic symptoms. In T1D, relative to NAH, IAH was associated with higher odds of reporting autonomic symptoms at a glucose concentration <54 than >70 mg/dL (OR 2.18 [95% CI 1.21-3.94], P = 0.010). Conclusion: The Hypo-METRICS app is sensitive to differences in hypoglycemia symptoms according to hypoglycemia awareness in both diabetes types. Given its high ecological validity and low recall bias, the app may be a useful tool in research and clinical settings. The clinical trial registration number is NCT04304963.

A Comparison of the Rates of Clock-Based Nocturnal Hypoglycemia and Hypoglycemia While Asleep Among People Living with Diabetes: Findings from the Hypo-METRICS Study.

Introduction: Nocturnal hypoglycemia is generally calculated between 00:00 and 06:00. However, those hours may not accurately reflect sleeping patterns and it is unknown whether this leads to bias. We therefore compared hypoglycemia rates while asleep with those of clock-based nocturnal hypoglycemia in adults with type 1 diabetes (T1D) or insulin-treated type 2 diabetes (T2D). Methods: Participants from the Hypo-METRICS study wore a blinded continuous glucose monitor and a Fitbit Charge 4 activity monitor for 10 weeks. They recorded details of episodes of hypoglycemia using a smartphone app. Sensor-detected hypoglycemia (SDH) and person-reported hypoglycemia (PRH) were categorized as nocturnal (00:00-06:00 h) versus diurnal and while asleep versus awake defined by Fitbit sleeping intervals. Paired-sample Wilcoxon tests were used to examine the differences in hypoglycemia rates. Results: A total of 574 participants [47% T1D, 45% women, 89% white, median (interquartile range) age 56 (45-66) years, and hemoglobin A1c 7.3% (6.8-8.0)] were included. Median sleep duration was 6.1 h (5.2-6.8), bedtime and waking time ∼23:30 and 07:30, respectively. There were higher median weekly rates of SDH and PRH while asleep than clock-based nocturnal SDH and PRH among people with T1D, especially for SDH <70 mg/dL (1.7 vs. 1.4, P < 0.001). Higher weekly rates of SDH while asleep than nocturnal SDH were found among people with T2D, especially for SDH <70 mg/dL (0.8 vs. 0.7, P < 0.001). Conclusion: Using 00:00 to 06:00 as a proxy for sleeping hours may underestimate hypoglycemia while asleep. Future hypoglycemia research should consider the use of sleep trackers to record sleep and reflect hypoglycemia while asleep more accurately. The trial registration number is NCT04304963.

Associations between disordered eating behaviors and HbA1c in young people with type 1 diabetes: a systematic review and meta-analysis.

BACKGROUND: In type 1 diabetes, disordered eating behaviors (DEBs) can adversely impact HbA1c. Diabetes-adapted DEB questionnaires assess intentional insulin omission, whereas generic questionnaires do not. Given the number of studies describing DEB-HbA1c associations published over the past decade, an updated systematic review is warranted. OBJECTIVE: The study aimed to examine the associations between disordered eating behaviors (DEBs) assessed by generic and diabetes-adapted questionnaires (and subscales) and HbA1c among young people (<29 years) with type 1 diabetes. METHODS: A systematic search was conducted in PubMed, Embase, PsycInfo, and CINAHL databases. Observational studies examining associations between DEB as assessed by questionnaires and HbA1c were included. Publication information, DEB and HbA1c characteristics, and DEB-HbA1c associations were extracted. Hedges' g was calculated for mean HbA1c differences between groups with and without DEB. RESULTS: The systematic search yielded 733 reports, of which 39 reports representing 35 unique studies met the inclusion criteria. Nineteen studies assessing DEB by diabetes-adapted questionnaires (n=5,795) and seven using generic questionnaires (n=2,162) provided data for meta-analysis. For diabetes-adapted questionnaires, DEB was associated with higher HbA1c (g=0.62 CI=0.52; 0.73) with a similar effect size when restricted to validated questionnaires (g=0.61; CI=0.50; 0.73). DEB was not associated with HbA1c for generic questionnaires (g=0.19; CI=-0.17; 0.55), but significantly associated with higher HbA1c for validated generic questionnaires (g=0.32; 95% CI=0.16-0.48). Participant and HbA1c collection characteristics were often inadequately described. CONCLUSION: Diabetes-adapted DEB questionnaires should be used in youth with type 1 diabetes because they capture intentional insulin omission and are more strongly associated with HbA1c than generic DEB questionnaires.