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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).)

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.)

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.)

Background: Hypoglycaemia is the most frequent complication of treatment with insulin or insulin secretagogues in people with diabetes. Severe hypoglycaemia, i.e. an event requiring external help because of cognitive dysfunction, is associated with a higher risk of adverse cardiovascular outcomes and all-cause mortality, but underlying mechanism(s) are poorly understood. There is also a gap in the understanding of the clinical, psychological and health economic impact of 'non-severe' hypoglycaemia and the glucose level below which hypoglycaemia causes harm., Aim: To increase understanding of hypoglycaemia by addressing the above issues over a 4-year period., Methods: Hypo-RESOLVE is structured across eight work packages, each with a distinct focus. We will construct a large, sustainable database including hypoglycaemia data from >100 clinical trials to examine predictors of hypoglycaemia and establish glucose threshold(s) below which hypoglycaemia constitutes a risk for adverse biomedical and psychological outcomes, and increases healthcare costs. We will also investigate the mechanism(s) underlying the antecedents and consequences of hypoglycaemia, the significance of glucose sensor-detected hypoglycaemia, the impact of hypoglycaemia in families, and the costs of hypoglycaemia for healthcare systems., Results: The outcomes of Hypo-RESOLVE will inform evidence-based definitions regarding the classification of hypoglycaemia in diabetes for use in daily clinical practice, future clinical trials and as a benchmark for comparing glucose-lowering interventions and strategies across trials. Stakeholders will be engaged to achieve broadly adopted agreement., Conclusion: Hypo-RESOLVE will advance our understanding and refine the classification of hypoglycaemia, with the ultimate aim being to alleviate the burden and consequences of hypoglycaemia in people with diabetes., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Introduction: Hypoglycaemia constitutes a significant barrier to achieving glycaemic control with insulin in both Type 1 (T1DM) and Type 2 diabetes mellitus (T2DM). The International Operations Hypoglycaemia Assessment Tool (IO HAT) study was designed to determine the incidence of hypoglycaemia in insulin-treated patients with T1DM and T2DM., Methods: The IO HAT study retrospectively and prospectively assessed the incidence of hypoglycaemia in patients with insulin-treated diabetes mellitus in nine countries. This sub-analysis included patients from Singapore with T1DM or T2DM who were aged ≥ 21 years and had completed two self-assessment questionnaires (SAQ1 and SAQ2)., Results: Of the 50 T1DM and 320 T2DM patients who completed the SAQ1, 39 T1DM and 265 T2DM patients completed SAQ2; 100% and 90.9%, respectively, experienced at least one hypoglycaemic event prospectively. The incidence rates of any hypoglycaemia were 49.5 events per patient-year (EPPY) and 16.1 EPPY for T1DM and T2DM patients, respectively, in the four-week prospective period. Hypoglycaemia rate did not differ in terms of glycated haemoglobin level. The vast majority of T1DM or T2DM patients (92.0% and 90.7%, respectively) knew the overall definition of hypoglycaemia before study participation, although over half of the patients (T1DM 54.0%, T2DM 51.9%) defined hypoglycaemia based only on symptoms., Conclusion: High proportions of insulin-treated patients with diabetes mellitus in Singapore reported hypoglycaemic events prospectively, showing that they had underreported hypoglycaemic episodes retrospectively. Patient education can help in improving hypoglycaemia awareness and its management in the region., (Copyright: © Singapore Medical Association.)

Objective: To evaluate exercise-related glucose and counterregulatory responses (CRR) in adults with type 1 diabetes with impaired awareness of hypoglycemia (IAH) using hybrid closed-loop (HCL) insulin delivery to maintain glucose homeostasis., Research Design and Methods: Twelve participants undertook 45-min high-intensity intermittent exercise (HIIE) and moderate-intensity exercise (MIE) in random order. The primary outcome was continuous glucose monitoring (CGM) time in range (70-180 mg/dL) for 24-h post-exercise commencement., Results: CGM time in range was similar for HIIE and MIE (median 79.5% [interquartile range 73.2, 87.6] vs. 76.1% [70.3, 83.9], P = 0.37), and time with levels <54mg/dL post-exercise commencement was 0%. HIIE induced greater increases in cortisol ( P = 0.002), noradrenaline ( P = 0.005), and lactate ( P = 0.002), with no differences in adrenaline, dopamine, growth hormone, or glucagon responses., Conclusions: IAH adults using HCL undertaking HIIE and MIE exhibit heterogeneity in CRR. Novel findings were a preserved cortisol response and variable catecholamine responses to HIIE., (© 2019 by the American Diabetes Association.)

Objective: People with type 2 diabetes on insulin are at risk for hypoglycemia. Recurrent hypoglycemia can cause impaired awareness of hypoglycemia (IAH), and increase the risk for severe hypoglycemia. The aim of this study was to assess the prevalence and determinants of self-reported IAH and severe hypoglycemia in a Dutch nationwide cohort of people with insulin-treated type 2 diabetes., Research Design and Methods: Observational study of The Dutch Diabetes Pearl, a cohort of people with type 2 diabetes treated in primary, secondary and tertiary diabetes care centers. The presence of IAH and the occurrence of severe hypoglycemia in the past year, defined as an event requiring external help to recover, were assessed using the validated Dutch version of the Clarke questionnaire. In addition, clinical variables were collected including age, diabetes duration, hemoglobin A1c, ethnicity and education., Results: 2350 people with type 2 diabetes on insulin were included: 59.1% men, mean age 61.1±10.4 years, mean diabetes duration 14.8±9.2 years and 79.5% on basal-bolus therapy. A total of 229 patients (9.7%) were classified as having IAH and 742 patients (31.6%) reported severe hypoglycemia. Increased odds for IAH were found with complex insulin regimens and lower odds with having a partner and body mass index ≥30 kg/m 2 . Severe hypoglycemia was associated with complex insulin regimens, non-Caucasian ethnicity and use of psychoactive drugs, and inversely with metformin use., Conclusions: In this nationwide cohort, almost one out of ten people with type 2 diabetes on insulin had IAH and >30% had a history of severe hypoglycemia in the past year., Competing Interests: Competing interests: FR has received grants from the Dutch government, during the conduct of the study. JHD has received personal fees from Novo Nordisk and Sanofi, outside the submitted work. CJT has received grants from AstraZeneca, personal fees and other from NovoNordisk and from Merck, outside the submitted work. BEDG has received grants from the Dutch Federation of University Medical Centers, during the conduct of the study and personal fees from NovoNordisk, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The HypoCOMPaSS study was designed to test the hypothesis that successful avoidance of biochemical hypoglycemia without compromising overall glycemic control would restore sufficient hypoglycemia awareness to prevent recurrent severe hypoglycemia in the majority of participants with established type 1 diabetes. Before starting the study, we planned to investigate associations between baseline characteristics and recurrent severe hypoglycemia over 2 years' follow-up., Research Design and Methods: A total of 96 adults with type 1 diabetes and impaired awareness of hypoglycemia participated in a 24-week 2 × 2 factorial randomized controlled trial comparing insulin delivery and glucose monitoring modalities, with the goal of rigorous biochemical hypoglycemia avoidance. The analysis included 71 participants who had experienced severe hypoglycemia in the 12-month prestudy with confirmed absence (complete responder) or presence (incomplete responder) of severe hypoglycemia over 24 months' follow-up., Results: There were 43 (61%) complete responders and 28 (39%) incomplete responders experiencing mean ± SD 1.5 ± 1.0 severe hypoglycemia events/person-year. At 24 months, incomplete responders spent no more time with glucose ≤3 mmol/L (1.4 ± 2.1% vs. 3.0 ± 4.8% for complete responders; P = 0.26), with lower total daily insulin dose (0.45 vs. 0.58 units/24 h; P = 0.01) and greater impairment of hypoglycemia awareness (Clarke score: 3.8 ± 2.2 vs. 2.0 ± 1.9; P = 0.01). Baseline severe hypoglycemia rate (16.9 ± 16.3 vs. 6.4 ± 10.8 events/person-year; P = 0.002) and fear of hypoglycemia were higher in incomplete responders. Peripheral neuropathy was more prevalent in incomplete responders (11 [39%] vs. 2 [4.7%]; P < 0.001) with a trend toward increased autonomic neuropathy., Conclusions: Recurrent severe hypoglycemia was associated with higher preintervention severe hypoglycemia rate, fear of hypoglycemia, and concomitant neuropathy., (© 2019 by the American Diabetes Association.)

Objective: While sodium-glucose cotransporter inhibitor (SGLTi) therapy has been evaluated in type 1 diabetes (T1D) trials, patient reactions to benefits and risks are unknown. Using established methodology, we evaluated patient preferences for different adjunct-to-insulin therapy options in T1D., Research Design and Methods: An online survey, completed by 701 respondents with T1D (231 U.S., 242 Canada, and 228 Germany), used conjoint analysis to present six hypothetical, masked, pairwise drug profile choices composed of different benefit-risk attributes and effect ranges. Data used in analyses were derived from actual phase 3 trials of a low-dose SGLTi (comparable to oral empagliflozin 2.5 mg q.d.), a high-dose SGLTi (comparable to oral sotagliflozin 400 mg q.d.), and an available adjunct-to-insulin therapy (comparable to subcutaneous pramlintide 60 μg t.i.d.)., Results: Conjoint analysis identified diabetic ketoacidosis risk as most important to patients (23% relative score; z test, P < 0.05); ranked second were HbA 1c reduction (14%), risk of severe hypoglycemia (13%), oral versus injectable treatment (12%), and risk of genital infection (12%). Next was risk of nausea (11%), followed by weight reduction (8%) and the risk of diarrhea (7%). A low-dose SGLTi drug profile was identified by conjoint analysis as the top patient preference (83% of participants; z test, P < 0.05) versus high-dose SGLTi (8%) or pramlintide (9%). Separate from conjoint analysis, when respondents were asked to choose their preferred adjunct-to-insulin therapy (masked to drug name/dose), 69%, 17%, 6%, and 9% of respondents chose low-dose SGLTi, high-dose SGLTi, pramlintide, and insulin therapy alone, respectively., Conclusions: Low-dose SGLTi profile was the favored adjunct-to-insulin therapy by persons with T1D., (© 2019 by the American Diabetes Association.)

Aims: In type 1 diabetes (T1D), treatment efficacy is limited by the unpredictability of blood glucose results and glycemic variability (GV). Fear of Hypoglycemia (FOH) remains a major brake for insulin treatment optimization. We aimed to assess the association of GV with FOH in participants with T1D in an observational cross-sectional study performed in 9 French Diabetes Centres (NCT02790060)., Methods: Participants were T1D for ≥5 years, aged 18-75 years, on stable insulin therapy for ≥3 months. The coefficient of variation (CV) of blood glucose and mean amplitude of glycemic excursions (MAGE) were used to assess GV from 7-point self-monitoring of blood glucose (SMBG). FOH was assessed using the validated French version of the Hypoglycemia Fear Survey-II (HFS-II) questionnaire., Results: Among a total of 570 recruited participants, 298 were suitable for analysis: 46% women, 58% on continuous subcutaneous insulin infusion [CSII], mean age 49 ± 16 years, HbA1c 7.5 ± 0.9%, HFS-II score 67 ± 18 and 12% with recent history of severe hypoglycemia during the previous 6 months, mean CV 39.8 ± 9.7% and MAGE 119 ± 42 mg/dL. CV and MAGE did not significantly correlate with HFS-II score (R = -0.05;P = 0.457 and R = 0.08;P = 0.170). Participants with severe hypoglycemia in the previous 6 months had higher HFS scores. Participants with higher HFS scores presented more hypoglycemias during follow-up., Conclusions: FOH as determined using the HFS-II questionnaire was not associated with 7-point SMBG variability in participants with T1D, but was associated with a positive history of severe hypoglycemia. Higher FOH was associated with higher frequency of hypoglycemia during follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hybrid closed loop (HCL) systems are designed to automate insulin delivery to improve type 1 diabetes (T1D) outcomes and reduce user burden and distress. Because the systems only automate some aspects of diabetes care, psychosocial and human factors remain an important consideration in their use. Thus, we examined whether psychosocial and human factors (i.e., distress related to diabetes management, fear of hypoglycemia, and technology attitudes) would (1) change after using the system and (2) predict glycemic outcomes during the trial., Subjects and Methods: Fourteen adults and 15 adolescents with T1D participated in a multisite clinical trial of an investigational version of the MiniMed™ 670G system (Medtronic, Northridge, CA) over 4 to 5 days in a semisupervised outpatient setting. Users completed surveys assessing psychosocial and human factors before beginning the HCL system and at the conclusion of the study. t-Tests and regression analyses were conducted to examine whether these factors changed following trial exposure to the HCL system and predicted glycemic outcomes during the trial., Results: Diabetes management distress decreased and diabetes technology attitudes became more positive over the trial period. Fear of hypoglycemia did not change over the trial period. There was a trend toward greater pretrial management distress predicting less time in range during the trial, controlling for time in range before the trial., Conclusions: Results suggest that this system is promising for enhancing technology attitudes and reducing management distress. Psychosocial factors, such as management distress, may negatively impact glycemic outcomes and should be a priority area for further investigation.

Objective: Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care., Research Design and Methods: Ninety-six adults with type 1 diabetes (29 ± 12 years' duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness., Results: Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P < 0.0001). Severe hypoglycemia rate was reduced from 8.9 ± 12.8 episodes/person-year over the 12 months prestudy to 0.4 ± 0.8 over 24 months ( P < 0.0001). HbA 1c improved (baseline 8.2 ± 3.2% [66 ± 12 mmol/mol] vs. 24 months 7.7 ± 3.1% [61 ± 10 mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of hypoglycemia were sustained. There were no significant differences between interventions at 24 months., Conclusions: Optimized insulin replacement and glucose monitoring underpinned by hypoglycemia-focused structured education should be provided to all with type 1 diabetes complicated by impaired awareness of hypoglycemia., (© 2018 by the American Diabetes Association.)

Background: The effectiveness of real-time continuous glucose monitoring (rtCGM) in avoidance of hypoglycaemia among high-risk individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) is unknown. We aimed to ascertain whether the incidence and severity of hypoglycaemia can be reduced through use of rtCGM in these individuals., Methods: The HypoDE study was a 6-month, multicentre, open-label, parallel, randomised controlled trial done at 12 diabetes practices in Germany. Eligible participants had type 1 diabetes and a history of impaired hypoglycaemia awareness or severe hypoglycaemia during the previous year. All participants wore a masked rtCGM system for 28 days and were then randomly assigned to 26 weeks of unmasked rtCGM (Dexcom G5 Mobile system) or to the control group (continuing with self-monitoring of blood glucose). Block randomisation with 1:1 allocation was done centrally, with the study site as the stratifying variable. Masking of participants and study sites was not possible. Control participants wore a masked rtCGM system during the follow-up phase (weeks 22-26). The primary outcome was the baseline-adjusted number of hypoglycaemic events (defined as glucose ≤3·0 mmol/L for ≥20 min) during the follow-up phase. The full dataset analysis comprised participants who wore the rtCGM system during the baseline and follow-up phases. The intention-to-treat analysis comprised all randomised participants. This trial is registered with ClinicalTrials.gov, number NCT02671968., Findings: Between March 4, 2016, and Jan 12, 2017, 149 participants were randomly assigned (n=74 to the control group; n=75 to the rtCGM group) and 141 completed the follow-up phase (n=66 in the control group, n=75 in the rtCGM group). The mean number of hypoglycaemic events per 28 days among participants in the rtCGM group was reduced from 10·8 (SD 10·0) to 3·5 (4·7); reductions among control participants were negligible (from 14·4 [12·4] to 13·7 [11·6]). Incidence of hypoglycaemic events decreased by 72% for participants in the rtCGM group (incidence rate ratio 0·28 [95% CI 0·20-0·39], p<0·0001). 18 serious adverse events were reported: seven in the control group, ten in the rtCGM group, and one before randomisation. No event was considered to be related to the investigational device., Interpretation: Usage of rtCGM reduced the number of hypoglycaemic events in individuals with type 1 diabetes treated by MDI and with impaired hypoglycaemia awareness or severe hypoglycaemia., Funding: Dexcom Inc., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Quality of Life (QoL) of insulin-naïve people with type 2 diabetes mellitus (T2DM) improves after transition to insulin. Little is known about the role of hypoglycaemia in this context. Secondary analyses of the Study of the Psychological Impact in Real care of Initiating insulin glargine Treatment (SPIRIT) aimed to investigate the relationship between hypoglycaemia and QoL when transitioning to insulin., Methods: Insulin-naïve Dutch people with T2DM in suboptimal glycaemic control (HbA1c >53 mmol/mol; 7.0%) on maximum dose of oral glucose-lowering medications were included from 363 primary care practices (n = 911). Participants started insulin glargine and completed QoL-questionnaires (WHO-5 Well-being Index (WHO-5; emotional well-being), Hypoglycaemia Fear Survey-worry scale (HFS-w; hypoglycaemia fear) and Diabetes Symptom Checklist-revised (DSC-r; diabetes symptom distress) at baseline, 3 and 6 months follow-up. Linear GEE analyses were used to investigate the association between symptomatic, nocturnal, severe hypoglycaemia (number of episodes during 3 months prior to visit) and QoL over time., Results: 52.5% men participated, mean age 62.2 years (SD ± 10.92), and median HbA1c 67 mmol/mol (range 61-77) (8.3%). More symptomatic hypoglycaemic episodes were associated with higher HFS-w and DSC-r scores (P < 0.01). Experiencing multiple nocturnal or severe episodes was related to higher symptom distress as well, when compared to no episodes. These associations did not change significantly over time., Conclusions: Hypoglycaemia is associated with lower QoL in terms of hypoglycaemia fear and diabetes symptom distress. The transition to insulin does not affect this relationship, suggesting hypoglycaemia in itself has a detrimental effect on diabetes-related QoL independent of treatment regimen.

Aim: To further our understanding of individual use and experience of continuous glucose monitoring (CGM) in adults with Type 1 diabetes and impaired awareness of hypoglycaemia, we conducted a qualitative study supplementary to a randomized controlled trial, using semi-structured interviews., Methods: Twenty-three participants of the IN CONTROL trial were interviewed within 4 weeks after the last study visit. The interview centred around experiences of CGM, taking into account the person's expectations prior to the trial. The interview was semi-structured, using open-ended questions and, if needed, prompts were offered to elicit further responses. Using thematic analysis, the interview transcripts were coded independently by three members of the research team. The consolidated criteria for reporting qualitative research (COREQ) were followed., Results: Overall, CGM was experienced as helpful in gaining more insight into glucose variability, and temporarily improved sense of control, reduced distress and made participants less dependent on others. However, some participants experienced confrontation with CGM output as intrusive, while some reported frustration due to failing technique and difficulty trusting the device. Participants reported active and passive self-management behaviours mirroring individual differences in attitudes and coping styles., Conclusions: In adults with Type 1 diabetes at risk of recurrent hypoglycaemia due to impaired awareness of hypoglycaemia, CGM use enhances a sense of control and safety for most, but not all. Future studies should further explore differential use of CGM in this population in the context of active and passive self-management styles., (© 2017 Diabetes UK.)

Aims: Data on the impact of hypoglycaemia on patients' daily lives and diabetes self-management, particularly in developing countries, are lacking. The aim of this study was to assess fear of, and responses to, hypoglycaemia experienced by patients globally., Materials and Methods: This non-interventional, multicentre, 4-week prospective study using self-assessment questionnaires and patient diaries consisted of 27,585 patients, ≥18years, with type 1 diabetes (n=8022) or type 2 diabetes (n=19,563) treated with insulin for >12months, at 2004 sites in 24 countries worldwide., Results: Increased blood glucose monitoring (69.7%) and seeking medical assistance (62.0%) were the most common responses in the 4weeks following hypoglycaemic events for patients with type 1 diabetes and type 2 diabetes, respectively. Approximately 44% of patients with type 1 diabetes or type 2 diabetes increased calorie intake in response to a hypoglycaemic episode. Following hypoglycaemia, 3.9% (type 1 diabetes) and 6.2% (type 2 diabetes) of patients took leave from work or study. Regional differences in fear of, and responses to, hypoglycaemia were evident - in particular, a lower level of hypoglycaemic fear and utilisation of healthcare resources in Northern Europe and Canada., Conclusions: Hypoglycaemia has a major impact on patients and their behaviour. These global data for the first time reveal regional variations in response to hypoglycaemia and highlight the importance of patient education and management strategies., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic-hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia.

Aim: To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion., Methods: People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA 1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA 1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]., Results: We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P < 0.001). HFS-II scores did not differ between the two groups. Internal MHLC score was negatively associated with HbA 1c (r = -0.15, P < 0.05) and positively associated with the number of mild and severe hypoglycaemic episodes (r = 0.16, P < 0.05 and r = 0.18, P < 0.001, respectively) and with DTSQ score (r = 0.17, P < 0.05). HFS-II score was negatively associated with DTSQ score (r = -0.18, P < 0.05) and positively with number of severe hypoglycaemic episodes (r = 0.16, P < 0.5)., Conclusions: In adults with Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control., (© 2017 Diabetes UK.)

Background: While research designed to understand the concerns about hypoglycemia among patients with diabetes has been primarily focused on the investigation of fear and anxiety, recent evidence suggests a potentially important and conceptually distinct element-hypoglycemic confidence. To investigate this dimension, we developed the Hypoglycemic Confidence Scale (HCS); herein, we describe the construction and validation of the HCS and examine how key patient factors are associated with hypoglycemic confidence., Methods: Items were developed from interviews with six type 1 diabetes (T1D) adults, six insulin-using type 2 diabetes (T2D) adults, and seven diabetes healthcare professionals, resulting in nine self-report items. Separate exploratory factor analyses (EFAs) were conducted with T1D adults (N = 326), with T2D adults using both basal and prandial insulins (T2D-BP, N = 145) and with T2D adults using only basal insulin (T2D-BO, N = 82). Construct validity for the HCS was established with overall well-being (World Health Organization-5), diabetes distress (Diabetes Distress Scale), global anxiety (Generalized Anxiety Disorder), hypoglycemic fear (Hypoglycemic Fear Survey-II), and glycemic control (self-reported A1C). Hierarchical regression analyses examined the unique contribution of HCS scores, independent of hypoglycemic fear, on key psychosocial constructs and A1C., Results: EFAs of the nine HCS items yielded a single factor solution for each of the three subject samples, accounting for 50.8%, 65.1%, and 73.7% of the variance for the T1D, T2D-BP, and T2D-BO groups, respectively. Construct validity was established by significant correlations with criterion variables. The HCS was associated with well-being and diabetes distress in the T1D (in both cases, P < 0.001) and T2D-BP groups (in both cases, P < .05) and for self-reported A1C in the T2D-BP group (P < .05) independent of hypoglycemic fear., Conclusions: Hypoglycemic confidence is a unique dimension of patient experience, different from hypoglycemic fear, and is deserving of further study. The HCS is a reliable valid measure of hypoglycemic confidence for adults with T1D and insulin-using T2D.

Aim: To assess the impact on fear of hypoglycaemia and treatment satisfaction with an artificial pancreas system used for 2 consecutive months, as well as participant acceptance of the artificial pancreas system., Methods: In a randomized crossover trial patient-related outcomes associated with an evening-and-night artificial pancreas and sensor-augmented pump therapy were compared. Both intervention periods lasted 8 weeks. The artificial pancreas acceptance questionnaire (range 0-90, higher scores better), Hypoglycaemia Fear Survey II (range 0-72, higher scores worse) and Diabetes Treatment Satisfaction Questionnaire (range 0-36, higher scores better) were completed by 32 participants. Semi-structured interviews were conducted after study completion in a subset of six participants. Outcomes were compared using a repeated-measures anova model or paired t-test when appropriate., Results: The total artificial pancreas acceptance questionnaire score at the end of the artificial pancreas period was 69.1 (sd 14.7; 95% CI 63.5, 74.7), indicating a positive attitude towards the artificial pancreas. No significant differences were found among the scores at baseline, end of sensor-augmented pump therapy period or end of the artificial pancreas period with regard to fear of hypoglycaemia [28.2 (sd 17.5), 23.5 (sd 16.6) and 23.5 (sd 16.7), respectively; P = 0.099] or diabetes treatment satisfaction [29.0 (sd 3.9), 28.2 (sd 5.2) and 28.0 (sd 7.1), respectively; P = 0.43]. Themes frequently mentioned in the interviews were 'positive effects at work', 'improved blood glucose', 'fewer worries about blood glucose', but also 'frequent alarms', 'technological issues' and 'demand for an all-in-one device'., Conclusions: The psychological outcomes of artificial pancreas and sensor-augmented pump therapy were similar. Current artificial pancreas technology is promising but user concerns should be taken into account to ensure utility of these systems., (© 2016 The Authors Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Importance: The majority of individuals with type 1 diabetes do not meet recommended glycemic targets., Objective: To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections., Design, Setting, and Participants: Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5% (58 mmol/mol) treated with multiple daily insulin injections., Interventions: Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks., Main Outcomes and Measures: Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied., Results: Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA1c was 8.6% (70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92% (63 mmol/mol) during continuous glucose monitoring use and 8.35% (68 mmol/mol) during conventional treatment (mean difference, -0.43% [95% CI, -0.57% to -0.29%] or -4.7 [-6.3 to -3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia., Conclusions and Relevance: Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Further research is needed to assess clinical outcomes and longer-term adverse effects., Trial Registration: clinicaltrials.gov Identifier: NCT02092051.

Hypoglycaemia factitia means also in recent time serious diagnostic and therapeutic problem in medical clinical practice, whereby often repeating episodes of serious hypoglycaemia in patients with diabetes mellitus, but also in patients without diabetes mellitus could be very difficult do resolve. First unsuccessful diagnosis implicit from wrong chose of examination algorithm, can lead to unidentified surgical interventions as are laparotomy and pancreatectomy, respectively. Hypoglycaemia factitia is considered to be one of many manifestations of so called Münchhausen's syndrome for that is typical acting of diabetic patient with goal to intentionally making hypoglycaemia or within suicidal attempt of patient on the basis psychological disease with intention to attract attention of surrounding community to himself due to application of insulin or sulfonylurea drugs. Diagnostic and therapeutic process could be in the case of hypoglycaemia factitia extremely difficult as from time side, than from health and also from economical side and that why necessary to approach with maximum responsibility.

Background: Problematic hypoglycaemia is a significant problem among people with insulin-treated type 1 and 2 diabetes mellitus, which adversely affects quality of life and leads to high societal costs. Blood glucose awareness training (BGAT) is a psycho-educational group intervention that has shown to be effective but difficult to implement in clinical practice, due to its demanding nature. The aim of this study is to evaluate the cost-effectiveness of the HypoAware intervention that has its roots in BGAT and helps patients to effectively recognize, treat and prevent hypoglycaemia, while also focussing on the psychosocial consequences of living with the constant risk of hypoglycaemia, both for patients and their significant others., Methods/design: An economic evaluation will be conducted alongside a cluster-randomised controlled trial in eight hospitals in the Netherlands. We aim to include 154 participants who will either receive HypoAware or care as usual. HypoAware consists of three group sessions and is combined with two online modules. The primary clinical outcome is severe hypoglycaemia. Secondary outcomes include mild hypoglycaemia, hypoglycaemia awareness, fear of hypoglycaemia, diabetes distress, anxiety and depression, health-related quality of life, diabetes-specific self-efficacy and HbA1c. Utilities will be measured using the EQ-5D-5 L questionnaire. Costs will be measured from a societal perspective and include health care utilization, medication and lost productivity costs. Measurements will be performed at baseline, 2, 4, and 6 months to compare both groups, and an additional 12 months for the intervention group only. Process outcomes will be gathered after every group meeting via telephone/email contact with health care professionals and via the online environment., Discussion: HypoAware is expected to significantly reduce episodes of severe hypoglycaemia, with subsequent beneficial effects on psychosocial outcomes and health care costs. When proven cost-effective, HypoAware will be incorporated in the clinical guidelines of Dutch diabetes care., Trial Registration: Dutch Trial Register NTR4538.

Background: Hypoglycemia in children and adolescents with type 1 diabetes has diverse etiologies., Case Characteristics: We report recurrent hypoglycemia in three children with type 1 diabetes because of insulin overdose., Intervention: Hospitalization and counselling by treating team and psychologist helped in resolving the recurrent hypoglycemia., Outcome: Improvement in glycemic control was achieved., Message: Adolescents with type 1 diabetes may take extra insulin to consume more carbohydrates, or to seek attention. Parents should share the responsibility of care of adolescents during transition phase for better glycemic control.

Objectives: A study of the glycemic control, quality of life, and fear and perception of hypoglycemia by comparing continuous subcutaneous insulin infusion (CSII) group with multiple daily inyections (MDI) with bolus calculator group., Material and Methods: This is a retrospective cohort study with following up during the first 12 months that CSII group (n=30) begins the use of "bolus wizard" and the MDI-calculator (n=30) group begins the use of the bolus calculator (Accu-Chek(®) Aviva Expert)., Primary Outcome: HbA1c (3, 6 and 12 months). Questionnaires used: EsDQOL (quality of life), FH-15 (fear of hypoglycemia), and Clarke (perception of hypoglycemia)., Statistical Analysis: T Student and nonparametric tests., Results: The average reduction in HbA1c during the study was significantly higher in CSII group (-0.56±0.84%) compared with the MDI group (0.097±0.94%), P=.028. The average basal insulin dose was significantly higher in the MDI group (at baseline, 6 and 12 months). No significant differences were found between the 2 treatment groups after analyzing the EsDQOL, FH-15 and Clarke questionnaires. In the CSII group, perceived quality of life assessed by the EsDQOL questionnaire was found to be better at the end of the study than at the beginning of using the insulin pump., Conclusions: The average reduction in HbA1c was significantly higher in the CSII group. In the CSII group, perceived quality of life was better at the end of the study than at the beginning., (Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Intensive insulin therapy with multiple insulin doses in subjects with type 1 diabetes mellitus (T1D) is associated with a higher risk of hypoglycaemic episodes. Repeated hypoglycemia results in a reduced ability/failure to recognize hypoglycemia symptoms and predisposes to severe episodes. In this context is crucial to work with specific questionnaires to diagnose and address this burden. Our study aimed to perform the psychometric analysis of Spanish and Catalan versions of Clarke et al. questionnaire for hypoglycemia awareness., Patients and Method: Psychometric analysis in patients with T1D of Spanish and Catalan versions of Clarke et al. questionnaire in 3 phases: 1) translation, back-translation and cultural adaptation of the English version; 2) analysis of internal, external and test-retest validity, and 3) assessing sensitivity to change in hypoglycemia perception., Results: One-hundred and forty-four subjects with T1D answered the Clarke et al. questionnaire (mean age [SD] 36 [18] years, 46% men). We observed a Cronbach α coefficient for internal validity of 0.75, a correlation coefficient for test-retest reliability of r=0.81 and a correlation of the questionnaire score with the frequency of severe and no severe hypoglycemia events of r=0.47 and r=0.77, respectively. The analysis of 20 patients with T1D 24 months after the initiation of continuous subcutaneous insulin infusion showed a decrease in the frequency of non-severe hypoglycemia/week (from 5.40 [2.09] to 2.75 [1.74]) and in the number of severe hypoglycemic episodes/year (1.25 [0.44] to 0.05 [0.22]). This was associated with a decrease in scores of the translated versions of Clarke et al. questionnaire (from 5.45 [1.19] to 1.60 [2.03])., Conclusions: Spanish and Catalan versions of Clarke et al. questionnaire display good psychometric properties and both could be considered a useful tool for evaluating hypoglycemia awareness in patients with T1D from our area., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

Aim: To assess the effect of initiating insulin treatment on quality of life of patients with type 2 diabetes (T2DM) in the 60-week All-to-Target trial (NCT00384085)., Methods: Patient-reported outcomes from a phase IV, multicentre, randomised, open-label, parallel-group study were analysed. Participants were randomised to: insulin glargine with up to one insulin glulisine injection (G + 1); insulin glargine with stepwise addition of up to three insulin glulisine injections (G + 3); or twice-daily premixed 70/30 insulin protamine-aspart/aspart (PM-2). Patient-reported outcome questionnaires were administered at weeks 0, 6, 12, 24, 36, 48 and 60., Results: There were no between-group differences in the Psychosocial Adjustment to Illness State-Self Report (PAIS-SR) or in the EuroQoL Group Five-Dimension Self-Report Index Questionnaire (EQ-5D) from baseline to week 60; however, PAIS-SR scores improved significantly over this period in the G + 3 group (p = 0.0016) and EQ-5D scores worsened significantly in the PM-2 group (p = 0.02). Hypoglycemia Fear Survey Behaviour and Worry subscales worsened significantly for all groups, with greater deterioration being observed in the PM-2 group than in the G + 1 group (Behaviour, p = 0.0050; Worry, p = 0.0017) and G + 3 groups (Behaviour, p = 0.0105; Worry, p = 0.0016). Total scores on the Diabetes Quality of Life (DQoL) questionnaire improved more in the G + 3 group than in the PM-2 group over the study period (p = 0.0284), with all groups showing a significant improvement in DQoL score over time., Conclusion: Insulin glargine-based regimens showed advantages over premixed insulin in a number of patient-reported outcome measures. The potential impact on fear of hypoglycaemia may be of particular relevance when addressing the major barriers to early insulin treatment., (© 2014 John Wiley & Sons Ltd.)

Despite advances in treatment for type 2 diabetes in recent decades, many patients are failing to achieve adequate glycemic control. Poor glycemic control has been shown to have a detrimental effect on patients' health and well-being, and to have significant negative financial implications for both patients and healthcare systems. Insulin therapy has been proven to significantly reduce glycated hemoglobin levels; however, both patients and physicians can be reluctant to initiate insulin therapy. Research shows that both patient and provider factors contribute to a delay in initiation of insulin therapy. This review discusses the most common barriers contributing to this delay with potential solutions to overcome them., (Published by Elsevier Inc.)

Aims: Many people with type 1 diabetes do not achieve optimal treatment targets despite high patient and professional input. To investigate the reasons underlying suboptimal control we have studied clinical characteristics and self-management behaviours in adults with type 1 diabetes attending a large treatment centre., Methods: A questionnaire-based enquiry into self-care behaviours of 380 patients with type 1 diabetes (mean age: 48 (±15) years and mean duration of diabetes: 26 (±15) years), linked with validated measures of impact of treatment on perceived health and hypoglycaemia recognition (Insulin Treatment Satisfaction Questionnaire; and EuroQoL EQ-5D, Gold score) and retrospective case note review of biomedical parameters. The data were analysed using chi-square test, ANOVA, ANCOVA and post-hoc procedures (Tukey's-b) in SPSS-version 18. The minimum significance level was accepted as 0.05., Results: Sixty three percent of participants used multiple daily injections; 36% continuous subcutaneous insulin infusion. Mean HbA1c was 7.7% (±1.2) [61±-10mmol/mol]; 30% had impaired hypoglycaemia awareness (IHA). Factors significantly related to poor glycaemic control with IHA were longer duration of diabetes (p=0.01); less frequent glucose self-monitoring (p=0.05); and low level of patient-set glucose targets (p<0.001). Patients with IHA and poorer control had significantly lower insulin treatment satisfaction (p<0.001); and perceived health (p<0.001)., Conclusions: Suboptimal biomedical outcomes in adults with type 1 diabetes attending a specialist intensified insulin therapy clinic are associated with longer duration of diabetes, fewer self-management behaviours and a trend towards poorer perceived health. These data suggest a need for greater emphasis on integration of psychological and self-management support with intensive medical management of type 1 diabetes., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG)., Research Design and Methods: A 24-week 2 × 2 factorial randomized controlled trial in adults with type 1 diabetes and IAH was conducted. All received comparable education, support, and congruent therapeutic targets aimed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control. Primary end point was between-intervention difference in 24-week hypoglycemia awareness (Gold score)., Results: A total of 96 participants (mean diabetes duration 29 years) were randomized. Overall, biochemical hypoglycemia (≤3.0 mmol/L) decreased (53 ± 63 to 24 ± 56 min/24 h; P = 0.004 [t test]) without deterioration in HbA1c. Hypoglycemia awareness improved (5.1 ± 1.1 to 4.1 ± 1.6; P = 0.0001 [t test]) with decreased SH (8.9 ± 13.4 to 0.8 ± 1.8 episodes/patient-year; P = 0.0001 [t test]). At 24 weeks, there was no significant difference in awareness comparing CSII with MDI (4.1 ± 1.6 vs. 4.2 ± 1.7; difference 0.1; 95% CI -0.6 to 0.8) and RT with SMBG (4.3 ± 1.6 vs. 4.0 ± 1.7; difference -0.3; 95% CI -1.0 to 0.4). Between-group analyses demonstrated comparable reductions in SH, fear of hypoglycemia, and insulin doses with equivalent HbA1c. Treatment satisfaction was higher with CSII than MDI (32 ± 3 vs. 29 ± 6; P = 0.0003 [t test]), but comparable with SMBG and RT (30 ± 5 vs. 30 ± 5; P = 0.79 [t test])., Conclusions: Hypoglycemia awareness can be improved and recurrent SH prevented in long-standing type 1 diabetes without relaxing HbA1c. Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT, although satisfaction was higher with CSII., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims: Hypoglycaemia is a common side effect of insulin therapy in diabetes patients, with negative physical and emotional impacts. Despite this, there are few studies investigating the frequency of non-severe hypoglycaemic events from the perspective of patients in the real-world setting. We investigated self-reported NSHE frequency and levels of hypoglycaemia awareness in Germany., Methods: Respondents > 15 years with Type 1 or insulin-treated Type 2 diabetes (receiving basal only, basal-bolus or other insulin regimens) were recruited using online panels to complete ≤ 4 questionnaires. Questionnaires collected demographics, non-severe hypoglycaemic event rates and patient-reported level of hypoglycaemia awareness. Non-severe hypoglycaemic event rates are reported as respondent-week records and calculated using data from all respondents completing at least one questionnaire., Results: A total of 1,771 respondent-week records were obtained from 614 participants. Mean non-severe hypoglycaemic event rates per respondent-week were 1.6 for Type 1 and 0.6-0.8 for Type 2, with estimated annual rates of 83 and 31-42 respectively. Two-thirds of Type 1 (65%) and Type 2 (61-72%) respondents reported impaired levels of awareness or unawareness of hypoglycaemic events (inability or impaired ability to recognise the symptoms of hypoglycaemia). Respon­dents' self-reported hypoglycaemia-awareness was significantly associated with the proportion of asymptomatic non-severe hypoglycaemic events; respondents classified as being unaware of hypoglycaemia had a higher proportion of asymptomatic non-severe hypoglycaemic events than aware respondents., Conclusion: Non-severe hypoglycaemic events are common in people with Type 1 or insulin-treated Type 2 diabetes in the real-world setting in Germany but may still be underestimated due to an inability to recognise the symptoms of hypoglycaemia., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Hypoglycaemia remains an over-riding factor limiting optimal glycaemic control in type 1 diabetes. Severe hypoglycaemia is prevalent in almost half of those with long-duration diabetes and is one of the most feared diabetes-related complications. In this review, we present an overview of the increasing body of literature seeking to elucidate the underlying pathophysiology of severe hypoglycaemia and the limited evidence behind the strategies employed to prevent episodes. Drivers of severe hypoglycaemia including impaired counter-regulation, hypoglycaemia-associated autonomic failure, psychosocial and behavioural factors and neuroimaging correlates are discussed. Treatment strategies encompassing structured education, insulin analogue regimens, continuous subcutaneous insulin infusion pumps, continuous glucose sensing and beta-cell replacement therapies have been employed, yet there is little randomized controlled trial evidence demonstrating effectiveness of new technologies in reducing severe hypoglycaemia. Optimally designed interventional trials evaluating these existing technologies and using modern methods of teaching patients flexible insulin use within structured education programmes with the specific goal of preventing severe hypoglycaemia are required. Individuals at high risk need to be monitored with meticulous collection of data on awareness, as well as frequency and severity of all hypoglycaemic episodes., (Copyright © 2013 John Wiley & Sons, Ltd.)

Aim: To assess patient-reported outcomes associated with initiating insulin glargine among insulin-naïve patients with type 2 diabetes mellitus (T2DM)., Methods: This was a pooled analysis of patient-level data from Phase 3, randomized controlled trials evaluating once-daily insulin glargine vs. comparator treatment for ≥24 weeks in previously insulin-naïve adult patients with T2DM and poor glycaemic control. Eligible studies utilized strict, predefined insulin titration algorithms with weekly dose-adjustment to achieve fasting plasma glucose (FPG) levels of ≤5.6 mmol/l. Treatment satisfaction was measured using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) change (c) and status (s) versions., Results: A total of 1577 patients from four studies were included; 830 patients treated with insulin glargine and 747 with comparators. At week 24, DTSQc scores improved in both groups with a significantly higher increase in treatment satisfaction for insulin glargine vs. comparators (13.5 vs. 12.1; p < 0.0001). Multivariate regression analysis revealed that significant predictors of DTSQc improvement at week 24 were insulin glargine treatment (p < 0.0001), higher baseline DTSQs (p < 0.0001), and lower baseline body weight (p = 0.0103). Greater improvement in DTSQc at week 24 was significantly associated with decrease from baseline in glycosylated haemoglobin (p < 0.001) and FPG (p = 0.0001); a numerically more positive change in weight from baseline approached significance (p = 0.07)., Conclusion: Initiation of insulin glargine in insulin-naïve patients with T2DM is associated with greater improvements in treatment satisfaction than alternative interventions, with perceived improvements in glycaemic control and baseline weight likely to be important factors., (© 2013 John Wiley & Sons Ltd.)

Background: Regular blood glucose monitoring is important for children with type-1 diabetes; however, the relationship between maternal fear of hypoglycaemia and glycaemic control is not well understood., Purpose: The relationship between maternal beliefs about diabetes, concerns about glycaemic control and adherence to recommended blood glucose levels in young children with type-1 diabetes were examined in this study., Method: Seventy-one mothers with children under 13 were recruited, and a prospective design was used. Demographics, maternal self-reported hypoglycaemic fear and illness perceptions were measured at baseline. Self-report daily blood sugar levels were recorded over 1 week, and glycosylated haemoglobin (HbA1c) blood glucose levels were collected at baseline and 3 months later., Results: High maternal fears of hypoglycaemia were predictive of suboptimal daily glycaemic control (elevated blood glucose levels), irrespective of illness duration or age at diagnosis., Conclusion: The results suggest that mothers who worry most about hypoglycaemia compensate by maintaining their child's blood glucose levels above recommended levels. Elevated blood glucose levels have important consequences for long-term health, and further research could explore ways to target maternal fear of hypoglycaemia.

This paper presents the results of the observational program "Parameters of life quality, symptoms of hypoglycemia and treatment satisfaction in patients with type 2 diabetes mellitus on basal-bolus insulin therapy" (2012-2014). The analysis included 1000 patients. It showed that their quality of life was below that of the general population due to compromised physical, role physical, and role emotional functioning (p < 0.001). Hypoglycemia is a serious challenge to the treatment of patients with type 2 diabetes mellitus on basal-bolus insulin therapy. They are characterized by impaired physical, psychological, and social functioning compared with the patients without hypoglycemic episodes (p < 0.01). Patients experiencing mild hypoglycemic episodes were not significantly different from those without them. In patients experiencing severe hypoglycemic episodes the quality of life was much worse (ES = 0.22-0.51). The profile of hypoglycemic episodes differed in different forms of hypoglycemia. The spectrum of symptoms and problems related to hypoglycemia was broader in patients with severe and/or nocturnal hypoglycemia. Patients free from hypoglycemia were less afraid of it than those used to have hypoglycemic episodes (p < 0.001). The stronger the fear, the more pronounced disturbances in social functioning, vitality, psychic and general health (p = 0.0001). It is concluded that evaluation of quality of life and hypoglycemia-related symptoms in patients with type 2 diabetes mellitus on basal-bolus insulin therapy allows for comprehensive estimation of the effectiveness of therapy on an individual basis.

Objective: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial., Research Design and Methods: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies., Results: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation., Conclusions: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.

Objective: To evaluate the effect of continuous glucose monitoring (CGM) on the frequency of severe hypoglycemia (SH) in patients with established hypoglycemia unawareness., Research Design and Methods: We conducted a retrospective audit of 35 patients with type 1 diabetes and problematic hypoglycemia unawareness, despite optimized medical therapy (continuous subcutaneous insulin infusion/multiple daily insulin injections), who used CGM for >1 year., Results: Over a 1-year follow-up period, the median rates of SH were reduced from 4.0 (interquartile range [IQR] 0.75-7.25) episodes/patient-year to 0.0 (0.0-1.25) episodes/patient-year (P < 0.001), and the mean (±SD) rates were reduced from 8.1 ± 13 to 0.6 ± 1.2 episodes/year (P = 0.005). HbA1c was reduced from 8.1 ± 1.2% to 7.6 ± 1.0% over the year (P = 0.005). The mean Gold score, measured in 19 patients, did not change: 5.1 ± 1.5 vs. 5.2 ± 1.9 (P = 0.67)., Conclusions: In a specialist experienced insulin pump center, in carefully selected patients, CGM reduced SH while improving HbA1c but failed to restore hypoglycemia awareness.

Aims: Recurrent severe hypoglycaemia in a patient with diabetes is strongly associated with a crash risk while driving. To help ensure road safety, recent changes were made to European Union driving regulations for patients with diabetes. These included the recommendation that more than one episode of severe hypoglycaemia within 12 months would lead to the loss of a driving licence. This study has assessed the impact of this regulation if applied to patients who participated in the Diabetes Control and Complications Trial., Methods: All patients in the Diabetes Control and Complications Trial were assumed to be drivers. Repeated hypoglycaemic episodes within a year were determined during the mean 6.5 years of the study., Results: Of the 1441 patients in the Diabetes Control and Complications Trial, 439 (30%) had more than one severe hypoglycaemic episode during a 12-month period of their study participation. Amongst the study groups, 312/711 (44%) of intensively treated and 127/730 (17%) of conventionally treated patients would have lost their licence at some point during the trial. The risk of licence loss increased with lower mean HbA1c , longer duration of diabetes and younger age (all P < 0.001)., Conclusions: More than one episode of severe hypoglycaemia within a year was a frequent event in subjects in the Diabetes Control and Complications Trial, especially in intensively treated patients. If applied to current practice, improving road safety through these changes to European Union regulations could have a substantial impact on drivers who have Type 1 diabetes. This emphasizes the need to take into account the potential effects of severe hypoglycaemia in those who rely on a driving licence., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Aim: Diabetic patients often do not adjust their insulin doses using the algorithms that they have been taught. While this behavior may intuitively have a number of causes, such as the complexity of the decision or the fear of hypoglycaemia, we propose in this article a more general, "psychophysical", explanation based on behavioral economics concepts used to describe decisions made under uncertainty and risk. The concepts discussed herein may not be familiar to clinicians, who will find here an introduction to theories that may be helpful in understanding some aspects of non-adherence to medical prescriptions., Results: 1) The Prospect Theory of Kahneman and Tversky proposes that choices made in the context of risk are subject to loss aversion. 2) Decisions under uncertainty use mental short cuts called "heuristics", which can lead to biases; for instance, overestimating the probability of the risk. 3) To understand the very concept of risk, emotions must be considered with a special focus on anticipated regret. 4) Finally, selection difficulty is an important determinant of the preference for the status quo., Conclusion: These concepts may be relevant for understanding a preference for the status quo in decisions made in a context of uncertainty and risk, such as insulin dose adjustment. We suggest that these mental mechanisms may also be involved in other aspects of patients' non-adherence. As other common human behaviors, non-adherence may actually often be a consequence of biases resulting from our ways of thinking, being both cognitive and emotional, and, according to Kahneman, more often "fast" than "slow". Empirical studies are needed to support this hypothesis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aims:   Despite improvements in insulin therapy, hypoglycaemia remains an inevitable part of life for many people with Type 1 diabetes. Little attention has been paid to how individuals self-treat hypoglycaemia and their likes and dislikes of clinically recommended treatments. We explored participants' experiences of self-treating hypoglycaemia after attending a structured education programme for people with Type 1 diabetes. Our aims were: to identify treatments that are acceptable to people with Type 1 diabetes; and to provide recommendations for promoting self-treatment in line with clinical guidelines., Methods:   Thirty adults with Type 1 diabetes were recruited from the Dose Adjustment for Normal Eating (DAFNE) programme in the UK. Study participants were interviewed post-course and 6 and 12 months later, enabling their experiences to be explored over time., Results:   Study participants described a poor knowledge of how to self-treat hypoglycaemia correctly pre-course. Post-course, individuals often struggled to adhere to clinically recommended guidelines because of: panic, disorientation, hunger sensations and consequent difficulties ingesting fixed quantities of fast-acting carbohydrate; use of sweets to manage hypoglycaemia; reversion to habituated practices when cognitive impairment as a result of hypoglycaemia supervened; difficulties ingesting dextrose tablets; and other people's anxieties about under-treatment., Conclusions:   Historical experiences of hypoglycaemia and habituated practices can influence present self-treatment approaches. Professionals need to be aware of the range of difficulties individuals may experience restricting themselves to fixed quantities of fast-acting carbohydrate to manage hypoglycaemia. There may be merit in developing a more acceptable range of treatments tailored to people's own preferences, circumstances and needs., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Introduction and Objective: The ability to perceive the symptoms of hypoglycemia during the early decrease in plasma glucose concentration may be critical for the safety of T1DM patients treated with intensive insulin therapy, including those treated with continuous subcutaneous insulin infusion (CSII). In the presented observational study an attempt was made to asses clinical factors that might affect subjective awareness of hypoglycemia in CSII-treated T1DM patients, with special attention to factors specific for this mode of treatment., Materials and Methods: For the purpose of the study, data of 110 CSII-treated T1DM patients were collected (78 females and 32 males). The records were analyzed from glucose meters (200-300 measurements/download, depending on meter type) and insulin pumps (total insulin dose, basal/bolus ratio, number of boluses/day, bolus calculator and dual wave/square bolus usage, continuous glucose monitoring data) from the last 3 years., Results: It was found that the level of subjective hypoglycemia perception inversely correlated with the number of hypoglycemic episodes per 100 measurements, age, duration of diabetes, time on insulin pump, and positively correlated with mean glycemia (n = 98; r = 0.22; p = 0.0286). With respect to CSII-related factors, hypoglycemia perception inversely correlated with the percentage of basal insulin (n = 106; r = -0.20; p = 0.0354). In stepwise regression analysis, independent predictors for impaired hypoglycemia perception were: age β = -0.29 (p = 0.023), duration of diabetes β = -0.24 (p = 0.029) and number of the hypoglycemia episodes for 100 measurements β = -0.33 (p = 0.0005)., Conclusions: Risk factors for impaired hypoglycemia perception in CSII-treated patients include those identified previously for the general population of T1DM individuals. In addition, the presented results suggest that a higher basal/bolus ratio may lead to impairment of the ability to perceive early symptoms of hypoglycemia.

Aim: This study examines whether the short-term use of a continuous glucose monitor (CGM) can reduce the fear of hypoglycaemia in individuals with type 1 diabetes mellitus (T1DM)., Methods: Twelve participants with T1DM were fitted with a Guardian® REAL-Time CGM and assigned to either an alarm (low glucose alarm set at 4.5 mmol/L) or no alarm condition for 3 days, with both treatments administered following a counterbalanced study design. The participants completed the Hypoglycaemia Fear Survey on three separate occasions, before their CGM was fitted as well as following the alarm and no alarm conditions., Results: The alarm treatment reduced the incidence of hypoglycaemic episodes (CGM readings≤3.5 mmol/L; 1.1±0.5 versus 1.9±0.5; mean±SEM) and the relative time spent below this hypoglycaemic threshold (0.9±0.4% versus 2.6±1.0%) but did not alter the fear of hypoglycaemia (78.6±7.0, 75.8±5.2 and 79.3±5.8 at baseline and following the alarm and no alarm treatments, respectively; p>0.05). CGM overestimated blood glucose levels by 0.8±0.2 mmol/L for blood glucose readings less than, or equal to, 5 mmol/L., Conclusions: Short-term use of the Guardian® REAL-Time CGM has no clinically significant effect on fear of hypoglycaemia possibly due, in part, to the inaccuracies of CGMs at low blood glucose levels., (Copyright © 2011 Primary Care Diabetes Europe. All rights reserved.)

Objective: Risk of severe hypoglycaemia is increased by absence of subjective awareness of hypoglycaemia and reduced by avoidance of minor hypoglycaemia. For many, problems persist despite educational strategies that work for others. We explored psychological factors that might inhibit the efforts of an individual in hypoglycaemia avoidance., Methods: People with Type 1 diabetes and hypoglycaemia unawareness gave semi-structured interviews exploring their perceptions and experiences of their condition. Identified factors were grouped into categories and analysed to establish links and form a grounded theory in a constant comparative analysis. A questionnaire was devised from the qualitative analysis to identify patients with problematic beliefs about their hypoglycaemia., Results: Saturation (no new themes emerging) was reached with 17 patients. Responses fell into two groups: high concern and low concern regarding hypoglycaemia unawareness. Those in the first group described severe hypoglycaemia as aversive and wanted to regain awareness. The second group included three patients in whom unawareness was not associated with severe hypoglycaemia, nevertheless unhelpful attitudes which inhibited hypoglycaemia avoidance were expressed. Responses from this group fell into categories: (1) normalizing the presence of unawareness; (2) underestimating its consequences; (3) wanting to avoiding the 'sick role'; and (4) overestimating the consequences of hyperglycaemia., Conclusions: A qualitative analysis of patient interviews identified deficits in education, technology and motivation in hypoglycaemia unawareness. Interventions can therefore be tailored to target underlying problems that prevent individual patients from regaining awareness. A brief assessment tool was devised to categorize patients' hypoglycaemia unawareness accordingly. Psychological interventions should be developed to address the problems of 'low concern' regarding hypoglycaemia unawareness., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)