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Contains fulltext : 307334.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 306967.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 291035.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, 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.

01 februari 2023, Item does not contain fulltext, AIMS/HYPOTHESIS: The role of beta cell mass in the balance of glucose control and hypoglycaemic burden in people with type 1 diabetes is unclear. We applied positron emission tomography (PET) imaging with radiolabelled exendin to compare beta cell mass among people with type 1 diabetes and either low glucose variability (LGV) or high glucose variability (HGV). METHODS: All participants with either LGV (n=9) or HGV (n=7) underwent a mixed-meal tolerance test to determine beta cell function and wore a blinded continuous glucose monitor for a week. After an i.v. injection with [(68)Ga]Ga-NODAGA-exendin-4, PET images were acquired for the quantification of pancreatic uptake of radiolabelled exendin. The mean standardised uptake value (SUVmean) of the pancreas was used to determine the amount of beta cell mass. RESULTS: Participants with LGV had lower HbA(1c) (46.0 mmol/mol [44.5-52.5] [6.4% (6.3-7)] vs 80 mmol/mol [69.0-110] [9.5% (8.5-12.2)], p=0.001) and higher time in range (TIR) (75.6% [73.5-90.3] vs 38.7% [25.1-48.5], p=0.002) than those with HGV. The SUVmean of the pancreas was higher for the LGV than for the HGV group (5.1 [3.6-5.6] vs 2.9 [2.1-3.4], p=0.008). The AUC(C-peptide):AUC(glucose) ratio was numerically, but not statistically, higher in the LGV compared with the HGV group (2.7×10(-2) [6.2×10(-4)-5.3×10(-2)] vs 9.3×10(-4) [4.7×10(-4)-5.2×10(-3)], p=0.21). SUVmean correlated with the AUC(C-peptide):AUC(glucose) ratio (Pearson r=0.64, p=0.01), as well as with the TIR (r=0.64, p=0.01) and the SD of interstitial glucose levels (r=-0.66, p=0.007). CONCLUSION/INTERPRETATION: Our data show higher beta cell mass in people with type 1 diabetes and LGV than in those with HGV, independent of beta cell function.

01 april 2023, Item does not contain fulltext, AIMS: Impaired awareness of hypoglycaemia (IAH) has been reported to affect up to a third of people with type 1 diabetes. Whether the increased use of sensor technology has changed its prevalence remains unknown. The aim of this study was to investigate the current prevalence of IAH and its change over time in a cohort of individuals with type 1 diabetes. METHODS: IAH was assessed using the modified Clarke questionnaire in adults with type 1 diabetes. Participants were recruited from the diabetes outpatient clinic from February 2020 through April 2021. The scores were compared to similar data collected during previous assessments in 2006, 2010 and 2016 respectively. RESULTS: A total of 488 individuals (51.2% male) with a mean (±SD) age of 51.3 ± 15.9 years, median [Q1-Q3] diabetes duration of 30 [16-40] years and mean HbA(1c) of 60 ± 12 mmol/mol (7.7 ± 1.1%) were included. Sensors were used by 85% of the study population. IAH was present among 78 (16.0%) participants, whereas 86 (17.6%) participants had a history of severe hypoglycaemia. By comparison, the prevalence of IAH equalled 32.5% in 2006, 32.3% in 2010 and 30.1% in 2016 (p for trend <0.001), while the proportion of individuals reporting severe hypoglycaemia equalled 21.2%, 46.7% and 49.8% respectively (p for trend 0.010). Comparing sequential assessments over time, the proportion of individuals with persistent IAH decreased from 74.0% and 63.6% between 2006 and 2016 to 32.5% in 2020. CONCLUSIONS: Among individuals with type 1 diabetes and high use of sensor technology, the current prevalence of IAH was 16%, about 50% lower as compared to previous years.

Radboud University, 20 juni 2023, Promotores : Galan, B.E. de, Tack, C.J.J. Co-promotor : Stienstra, R., Item does not contain fulltext

Contains fulltext : 292525.pdf (Publisher’s version ) (Open Access), BACKGROUND: Detrimental associations of sedentary behaviour (time spent sitting) with musculoskeletal pain (MSP) conditions have been observed. However, findings on those with, or at risk of, type 2 diabetes (T2D) have not been reported. We examined the linear and non-linear associations of device-measured daily sitting time with MSP outcomes according to glucose metabolism status (GMS). METHODS: Cross-sectional data from 2827 participants aged 40-75 years in the Maastricht Study (1728 with normal glucose metabolism (NGM); 441 with prediabetes; 658 with T2D), for whom valid data were available on activPAL-derived daily sitting time, MSP [neck, shoulder, low back, and knee pain], and GMS. Associations were examined by logistic regression analyses, adjusted serially for relevant confounders, including moderate-to-vigorous intensity physical activity (MVPA) and body mass index (BMI). Restricted cubic splines were used to further examine non-linear relationships. RESULTS: The fully adjusted model (including BMI, MVPA, and history of cardiovascular disease) showed daily sitting time to be significantly associated with knee pain in the overall sample (OR = 1.07, 95%CI: 1.01-1.12) and in those with T2D (OR = 1.11, 95%CI: 1.00-1.22); this was not statistically significant in those with prediabetes (OR = 1.04, 95%CI: 0.91-1.18) or NGM (OR = 1.05, 95%CI: 0.98-1.13). There were no statistically significant associations between daily sitting time and neck, shoulder, or low back pain in any of the models. Furthermore, the non-linear relationships were statistically non-significant. CONCLUSION: Among middle-aged and older adults with T2D, daily sitting time was significantly associated with higher odds of knee pain, but not with neck, shoulder, or low back pain. No significant association was observed in those without T2D for neck, shoulder, low back, or knee pain. Future studies, preferably those utilising prospective designs, could examine additional attributes of daily sitting

01 juni 2023, Item does not contain fulltext, AIMS/HYPOTHESIS: It is generally recommended to reduce basal insulin doses after exercise to reduce the risk of post-exercise nocturnal hypoglycaemia. Based on its long t(½), it is unknown whether such adjustments are required or beneficial for insulin degludec. METHODS: The ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise test in the afternoon. All participants wore blinded continuous glucose monitors for 6 days, measuring the incidence of (nocturnal) hypoglycaemia and subsequent glucose profiles. RESULTS: We recruited 18 participants (six women, age 38 ± 13 years, HbA(1c) 56 ± 8 mmol/mol [7.3 ± 0.8%], mean ± SD). Time below range (i.e. glucose <3.9 mmol/l) the night after the exercise test was generally low and occurrence did not differ between the treatment regimens. During the subsequent whole day, time below range was lower for D40 compared with CON (median [IQR], 0 [0-23] vs 18 [0-55] min, p=0.043), without differences in the number of hypoglycaemic events. Time above range (i.e. glucose >10 mmol/l) was greater for D20-P vs CON (mean ± SEM, 584 ± 81 vs 364 ± 66 min, p=0.001) and D40 (385 ± 72 min, p=0.003). CONCLUSIONS/INTERPRETATION: Post-exercise adjustment of degludec does not mitigate the risk of subsequent nocturnal hypoglycaemia in people with type 1 diabetes. Although reducing degludec reduced next-day time below range, this did not translate into fewer hypoglycaemic events, while postponing degludec should be avoided because of increased time above range. Altogether, these data do not support degludec dose adjustment after a single exercise bout. TRIAL REGISTRATION: EudraCT number 2019-004222-22 FUNDING: The stud

01 juli 2023, Item does not contain fulltext, AIMS/HYPOTHESIS: Chronic hyperglycaemia and recurrent hypoglycaemia are independently associated with accelerated cognitive decline in type 1 diabetes. Recurrent hypoglycaemia in rodent models of chemically induced (streptozotocin [STZ]) diabetes leads to cognitive impairment in memory-related tasks associated with hippocampal oxidative damage. This study examined the hypothesis that post-hypoglycaemic hyperglycaemia in STZ-diabetes exacerbates hippocampal oxidative stress and explored potential contributory mechanisms. METHODS: The hyperinsulinaemic glucose clamp technique was used to induce equivalent hypoglycaemia and to control post-hypoglycaemic glucose levels in mice with and without STZ-diabetes and Nrf2(-/-) mice (lacking Nrf2 [also known as Nfe2l2]). Subsequently, quantitative proteomics based on stable isotope labelling by amino acids in cell culture and biochemical approaches were used to assess oxidative damage and explore contributory pathways. RESULTS: Evidence of hippocampal oxidative damage was most marked in mice with STZ-diabetes exposed to post-hypoglycaemic hyperglycaemia; these mice also showed induction of Nrf2 and the Nrf2 transcriptional targets Sod2 and Hmox-1. In this group, hypoglycaemia induced a significant upregulation of proteins involved in alternative fuel provision, reductive biosynthesis and degradation of damaged proteins, and a significant downregulation of proteins mediating the stress response. Key differences emerged between mice with and without STZ-diabetes following recovery from hypoglycaemia in proteins mediating the stress response and reductive biosynthesis. CONCLUSIONS/INTERPRETATION: There is a disruption of the cellular response to a hypoglycaemic challenge in mice with STZ-induced diabetes that is not seen in wild-type non-diabetic animals. The chronic hyperglycaemia of diabetes and post-hypoglycaemic hyperglycaemia act synergistically to induce oxidative stress and damage in the hippocampus, possibly leading to irr

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Item does not contain fulltext, 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.

Contains fulltext : 296263.pdf (Publisher’s version ) (Open Access)

01 september 2023, Contains fulltext : 295997.pdf (Publisher’s version ) (Open Access), AIMS: Impaired awareness of hypoglycaemia (IAH) has been associated with increased diabetes distress and use of sensor technology can reduce diabetes distress. The aim of this study was to examine diabetes-specific distress (emotions, cognitions, behaviours) in relation to IAH status and use of glucose sensors in people with type 1 diabetes. METHODS: Individuals with type 1 diabetes from an academic diabetes outpatient clinic completed the Clarke questionnaire (to assess hypoglycaemic awareness), Problem Areas in Diabetes (PAID-5), Hypoglycaemia Fear Survey-II (HFS-II), Attitudes to Awareness of Hypoglycaemia Survey (A2A), Nijmegen Clinical Screening Instrument Survey (NCSI) and Hyperglycaemia Avoidance Scale (HAS). RESULTS: Of the 422 participants (51.9% male, diabetes duration 30 [16-40] years, HbA(1c) 60 ± 11 mmol/mol [7.6 ± 1.0%], 351 [88.2%] used a glucose sensor; 82 [19.4%]) had IAH. Compared to individuals with normal awareness, those with IAH more often had PAID-5 scores ≥8 (35.4% vs. 21.5%, p = 0.008) and higher scores on all HFS-II subscores (total [40.2 ± 21.5 vs. 27.9 ± 17.2, p < 0.001]), HFS-II behaviour (18.5 ± 10.0 vs. 15.1 ± 8.0, p = 0.005), HFS-II worry (21.8 ± 13.5 vs. 12.7 ± 10.9, p < 0.001), HAS worries (17.5 ± 7.3 vs. 14.3 ± 7.0, p < 0.001) and NCSI hypoglycaemia items. HAS behaviour, A2A and NCSI hyperglycaemia scores did not differ between individuals with or without IAH. Restricting the analyses to individuals using a glucose sensor did not materially change the results. CONCLUSIONS: Diabetes-specific distress remains a major problem among individuals with type 1 diabetes, particularly those with IAH, despite the widespread use of (intermittently scanned) sensor technology. Further studies are needed to examine strategies to lower diabetes-specific distress in individuals with IAH.

01 juli 2023, Contains fulltext : 294782.pdf (Publisher’s version ) (Open Access), OBJECTIVE: This study aimed to evaluate the long-term effects of spinal cord stimulation (SCS) in patients with painful diabetic polyneuropathy (PDPN). MATERIALS AND METHODS: This prospective cohort study was the eight-to-ten-year follow-up of a previously performed pilot and randomized controlled trial on the effects of SCS in PDPN, initiated by the multidisciplinary pain center of Maastricht University Medical Center+. The study population consisted of a subgroup of patients who still used SCS treatment ≥ eight years after implantation (n = 19). Pain intensity scores (numeric rating scale [NRS]) during the day and night and data on secondary outcomes (ie, quality of life, depression, sleep quality) were reported during yearly follow-up consultations. Long-term efficacy of SCS was analyzed by comparing the most recently obtained data eight to ten years after implantation with those obtained at baseline. RESULTS: Pain intensity, day and night, was significantly (p < 0.01) reduced by 2.3 (NRS 6.6-4.3) and 2.2 (NRS 6.8-4.6) points, respectively, when comparing the long-term data with baseline. Moreover, for > 50% of patients, the pain reduction was > 30%, which is considered clinically meaningful. No differences were found regarding the secondary outcomes. CONCLUSION: This eight-to-ten-year follow-up study indicates that SCS can remain an effective treatment in the long term to reduce pain intensity in a subcohort of patients with PDPN who still had an SCS device implanted after eight years.

Contains fulltext : 299865.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 300138.pdf (Publisher’s version ) (Open Access), AIMS: Research on hypoglycaemia and quality of life (QoL) has focused mostly on severe hypoglycaemia and psychological outcomes, with less known about other aspects of hypoglycaemia (e.g., self-treated episodes) and impacts on other QoL domains (e.g., relationships). Therefore, we examined the impact of all aspects of hypoglycaemia on QoL in adults with type 1 diabetes (T1DM). METHODS: Participants completed an online survey, including assessment of hypoglycaemia-specific QoL (using the 12-item Hypoglycaemia Impact Profile). Mann-Whitney U tests examined differences in hypoglycaemia-specific QoL by hypoglycaemia frequency, severity, and awareness. Hierarchical linear regression examined associations with QoL. RESULTS: Participants were 1028 adults with T1DM (M ± SD age: 47 ± 15 years; diabetes duration: 27 ± 16 years). Severe and self-treated hypoglycaemia and impaired awareness negatively impacted on overall QoL and several QoL domains, including leisure activities, physical health, ability to keep fit/be active, sleep, emotional well-being, spontaneity, independence, work/studies, and dietary freedom. Diabetes distress was most strongly associated with hypoglycaemia-specific QoL, followed by generic emotional well-being, fear of hypoglycaemia, and confidence in managing hypoglycaemia. Hypoglycaemia frequency and awareness were no longer significantly associated with QoL once psychological factors were considered. CONCLUSIONS: Hypoglycaemia negatively impacts on several QoL domains. Psychological factors supersede the effect of hypoglycaemia frequency and awareness in accounting for this negative impact., 01 november 2023

Contains fulltext : 296933.pdf (Publisher’s version ) (Open Access), BACKGROUND: The Hypoglycaemia - MEasurement, ThResholds and ImpaCtS (Hypo-METRICS) smartphone app was developed to investigate the impact of hypoglycemia on daily functioning in adults with type 1 diabetes mellitus or insulin-treated type 2 diabetes mellitus. The app uses ecological momentary assessments, thereby minimizing recall bias and maximizing ecological validity. It was used in the Hypo-METRICS study, a European multicenter observational study wherein participants wore a blinded continuous glucose monitoring device and completed the app assessments 3 times daily for 70 days. OBJECTIVE: The 3 aims of the study were to explore the content validity of the app, the acceptability and feasibility of using the app for the duration of the Hypo-METRICS study, and suggestions for future versions of the app. METHODS: Participants who had completed the 70-day Hypo-METRICS study in the United Kingdom were invited to participate in a brief web-based survey and an interview (approximately 1h) to explore their experiences with the app during the Hypo-METRICS study. Thematic analysis of the qualitative data was conducted using both deductive and inductive methods. RESULTS: A total of 18 adults with diabetes (type 1 diabetes: n=10, 56%; 5/10, 50% female; mean age 47, SD 16 years; type 2 diabetes: n=8, 44%; 2/8, 25% female; mean age 61, SD 9 years) filled out the survey and were interviewed. In exploring content validity, participants overall described the Hypo-METRICS app as relevant, understandable, and comprehensive. In total, 3 themes were derived: hypoglycemia symptoms and experiences are idiosyncratic; it was easy to select ratings on the app, but day-to-day changes were perceived as minimal; and instructions could be improved. Participants offered suggestions for changes or additional questions and functions that could increase engagement and improve content (such as providing more examples with the questions). In exploring acceptability and feasibility, 5 themes were d

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Item does not contain fulltext, INTRODUCTION: Impaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased cerebral blood flow (CBF) during hypoglycemia appear to be involved in the pathogenesis of impaired awareness of hypoglycemia. Here we examine the effect of lactate on CBF during hypoglycemia. RESEARCH DESIGN AND METHODS: Nine people with type 1 diabetes and normal awareness of hypoglycemia underwent two hyperinsulinemic euglycemic-hypoglycemic (3.0 mmol/L) glucose clamps in a 3T MR system, once with sodium lactate infusion and once with sodium chloride infusion. Global and regional changes in CBF were determined using pseudocontinuous arterial spin labeling. RESULTS: Lactate (3.3±0.6 vs 0.9±0.2 mmol/L during lactate infusion vs placebo infusion, respectively) suppressed the counter-regulatory hormone responses to hypoglycemia. Global CBF increased considerably in response to intravenous lactate infusion but did not further increase during hypoglycemia. Lactate also blunted the hypoglycemia-induced regional redistribution of CBF towards the thalamus. CONCLUSIONS: Elevated lactate levels enhance global CBF and blunt the thalamic CBF response during hypoglycemia in patients with type 1 diabetes, mimicking observations of impaired awareness of hypoglycemia. These findings suggest that alteration of CBF associated with lactate may play a role in some aspects of the development of impaired awareness of hypoglycemia. TRIAL REGISTRATION NUMBER: NCT03730909.

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Item does not contain fulltext, INTRODUCTION: Various studies have shown a number of glycemic parameters to improve over several weeks in people with type 1 diabetes during the first surge of the COVID-19 pandemic. Whether and to what extent such improvement is sustained during following COVID-19 surges remains unknown. Therefore, the aim of this study was to investigate glycemic parameters during the first year of the COVID-19 pandemic in people with type 1 diabetes and to determine factors associated with glycemic improvement. RESEARCH DESIGN AND METHODS: This was an observational cohort study in people with type 1 diabetes, aged ≥16 years. We compared glycated hemoglobin (HbA(1c)) and flash glucose monitoring (FGM) downloads between the prelockdown period and approximately 1 year thereafter. Using logistic regression analysis, we assessed associations between an HbA(1c) reduction of at least 0.5% (~5.5 mmol/mol) with baseline clinical characteristics and self-reported changes in psychological well-being and lifestyle behavior related to COVID-19. RESULTS: A total of 437 participants were included. As compared with prepandemic data, 1 year after the start of the COVID-19 pandemic and associated lockdowns, HbA(1c) had decreased from 7.9%±1.1% (63±12 mmol/mol) to 7.5%±1.0% (59±11 mmol/mol) (p<0.001), whereas time in range increased from 55.8%±16.7% to 58.6%±16.7% (p=0.004) and time below (<3.9 mmol/L) and above (>13.9 mmol/L) range and glucose variability all decreased (all p<0.05). FGM use, higher HbA(1c) at baseline and current smoking were independently associated with an HbA(1c) decrease of at least 0.5%, whereas self-reported changes in psychological well-being and lifestyle behavior related to the first surge of the COVID-19 pandemic and associated lockdowns were not. CONCLUSIONS: The COVID-19 pandemic and related lockdown measures were associated with improvement in glucometrics, including HbA(1c) and FGM data, in individuals with type 1 diabetes, particularly in FGM users, those with highe

Item does not contain fulltext, 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.

Item does not contain fulltext, 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.

Item does not contain fulltext, 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.

Contains fulltext : 282322.pdf (Publisher’s version ) (Open Access), BACKGROUND: People with impaired awareness of hypoglycemia (IAH) are at elevated risk of severe, potentially hazardous, hypoglycemia and would benefit from a device alerting to hypoglycemia. Heart rate variability (HRV) changes with hypoglycemia due to sympathetic activity. Since IAH is associated with suppressed sympathetic activity, we investigated whether hypoglycemia elicits a measurable change in HRV in patients with T1D and IAH. METHOD: Eligible participants underwent a modified hyperinsulinemic euglycemic hypoglycemic clamp (glucose nadir, 43.1 ± 0.90 mg/dl), while HRV was measured by a VitalConnect HealthPatch. Measurements of HRV included Root Mean Square of the Successive Differences (RMSSD) and low to high frequency (LF:HF) ratio. Wilcoxon rank-sum test was used for testing within-subject HRV changes. RESULTS: We included 12 participants (8 female, mean age 57 ± 12 years, mean HbA1c 57 ± 5 mmol/mol (7.4 ± 0.4%)). Symptoms increased from 4.0 (1.5-7.0) at euglycemia to 7.5 (5.0-11.0) during hypoglycemia (P = .003). In response to hypoglycemia, the LF:HF ratio and RMSSD increased when normalized for data obtained during euglycemia (both P < .01). The LF:HF ratio increased in 6 participants (50%) and declined in one other participant (8%). The RMSSD decreased in 3 (25%) and increased in 4 (33%) participants. In 2 patients, no change in HRV could be detected in response to hypoglycemia. CONCLUSIONS: This study reveals that hypoglycemia-induced changes in HRV are retained in the majority of people with T1D and IAH, and that these changes can be detected by a wearable device. Real-time HRV seems usable for detection of hypoglycemia in patients with IAH.

Item does not contain fulltext, 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.

Contains fulltext : 251188.pdf (Publisher’s version ) (Open Access), Traditionally, clinicians consider lactate as a waste product of anaerobic glycolysis. Interestingly, research has shown that lactate may serve as an alternative fuel for the brain to protect it against harm. The increasing scientific awareness of the potential beneficial side of lactate, however, is entering the clinic rather slowly. Following this, and realizing that the application of potential novel therapeutic strategies in pediatric populations often lags behind the development in adults, this review summarizes the key data on therapeutic use of intravenous infusion of sodium lactate in humans. PubMed and clinicaltrial.gov were searched up until November 2021 focusing on interventional studies in humans. Thirty-four articles were included in this review, with protocols of lactate infusion in adults with diabetes mellitus, traumatic brain injury, Alzheimer's disease, and cardiac disease. One study on lactate infusion in children was also included. Results of our literature search show that sodium lactate can be safely administrated, without major side effects. Additionally, the present literature clearly shows the potential benefits of therapeutic lactate infusion under certain pathological circumstances, including rather common clinical conditions like traumatic brain injury. CONCLUSION: This review shows that lactate is a save, alternative energy source for the adult brain warranting studies on the potential therapeutic effects of sodium lactate infusion in children. WHAT IS KNOWN: • Lactate is generally considered a waste product of anaerobic glycolysis. However, lactate also is an alternative fuel for different organs, including the brain. • Lactate infusion is not incorporated in standard care for any patient population. WHAT IS NEW: • Thirty-four studies investigated the therapeutic use of intravenous sodium lactate in different patient populations, all with different study protocols. • Literature shows that lactate infusion may have beneficial effects in

Contains fulltext : 282348.pdf (Publisher’s version ) (Open Access), AIM/HYPOTHESIS: The physiological counterregulatory response to hypoglycaemia is reported to be organised hierarchically, with hormone responses usually preceding symptomatic awareness and autonomic responses preceding neuroglycopenic responses. To compare thresholds for activation of these responses more accurately between people with or without type 1 diabetes, we performed a systematic review on stepped hyperinsulinaemic-hypoglycaemic glucose clamps. METHODS: A literature search in PubMed and EMBASE was conducted. We included articles published between 1980 and 2018 involving hyperinsulinaemic stepped hypoglycaemic glucose clamps among people with or without type 1 diabetes. Key exclusion criteria were as follows: data were previously published; other patient population; a clamp not the primary intervention; and an inadequate clamp description. Glycaemic thresholds for counterregulatory hormone and/or symptom responses to hypoglycaemia were estimated and compared using generalised logrank test for interval-censored data, where the intervals were either extracted directly or calculated from the data provided by the study. A glycaemic threshold was defined as the glucose level at which the response exceeded the 95% CI of the mean baseline measurement or euglycaemic control clamp. Because of the use of interval-censored data, we described thresholds using median and IQR. RESULTS: A total of 63 articles were included, whereof 37 papers included participants with type 1 diabetes (n=559; 67.4% male sex, aged 32.7±10.2 years, BMI 23.8±1.4 kg/m(2)) and 51 papers included participants without diabetes (n=733; 72.4% male sex, aged 31.1±9.2 years, BMI 23.6±1.1 kg/m(2)). Compared with non-diabetic control individuals, in people with type 1 diabetes, the median (IQR) glycaemic thresholds for adrenaline (3.8 [3.2-4.2] vs 3.4 [2.8-3.9 mmol/l]), noradrenaline (3.2 [3.2-3.7] vs 3.0 [2.8-3.1] mmol/l), cortisol (3.5 [3.2-4.2]) vs 2.8 [2.8-3.4] mmol/l) and growth hormone (3.8 [3.3-3

Contains fulltext : 252731.pdf (Publisher’s version ) (Open Access), Objective: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as "level 2 hypoglycemia." In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association. Research design and methods: Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP). Results: For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c. Conclusions: IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes.

Contains fulltext : 283878.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 251188.pdf (Publisher’s version ) (Open Access), Traditionally, clinicians consider lactate as a waste product of anaerobic glycolysis. Interestingly, research has shown that lactate may serve as an alternative fuel for the brain to protect it against harm. The increasing scientific awareness of the potential beneficial side of lactate, however, is entering the clinic rather slowly. Following this, and realizing that the application of potential novel therapeutic strategies in pediatric populations often lags behind the development in adults, this review summarizes the key data on therapeutic use of intravenous infusion of sodium lactate in humans. PubMed and clinicaltrial.gov were searched up until November 2021 focusing on interventional studies in humans. Thirty-four articles were included in this review, with protocols of lactate infusion in adults with diabetes mellitus, traumatic brain injury, Alzheimer's disease, and cardiac disease. One study on lactate infusion in children was also included. Results of our literature search show that sodium lactate can be safely administrated, without major side effects. Additionally, the present literature clearly shows the potential benefits of therapeutic lactate infusion under certain pathological circumstances, including rather common clinical conditions like traumatic brain injury. CONCLUSION: This review shows that lactate is a save, alternative energy source for the adult brain warranting studies on the potential therapeutic effects of sodium lactate infusion in children. WHAT IS KNOWN: • Lactate is generally considered a waste product of anaerobic glycolysis. However, lactate also is an alternative fuel for different organs, including the brain. • Lactate infusion is not incorporated in standard care for any patient population. WHAT IS NEW: • Thirty-four studies investigated the therapeutic use of intravenous sodium lactate in different patient populations, all with different study protocols. • Literature shows that lactate infusion may have beneficial effects in

Contains fulltext : 245723.pdf (Publisher’s version ) (Open Access), OBJECTIVE: To conduct a systematic review to examine associations between hypoglycemia and quality of life (QoL) in children and adolescents with type 1 diabetes. METHODS: Four databases (Medline, Cochrane Library, CINAHL, PsycINFO) were searched systematically in November 2019 and searches were updated in September 2021. Studies were eligible if they included children and/or adolescents with type 1 diabetes, reported on the association between hypoglycemia and QoL (or related outcomes), had a quantitative design, and were published in a peer-reviewed journal after 2000. A protocol was registered the International Prospective Register of Systematic Reviews (PROSPERO; CRD42020154023). Studies were evaluated using the Joanna Briggs Institute's critical appraisal tool. A narrative synthesis was conducted by outcome and hypoglycemia severity. RESULTS: In total, 27 studies met inclusion criteria. No hypoglycemia-specific measures of QoL were identified. Evidence for an association between SH and (domains) of generic and diabetes-specific QoL was too limited to draw conclusions, due to heterogenous definitions and operationalizations of hypoglycemia and outcomes across studies. SH was associated with greater worry about hypoglycemia, but was not clearly associated with diabetes distress, depression, anxiety, disordered eating or posttraumatic stress disorder. Although limited, some evidence suggests that more recent, more frequent, or more severe episodes of hypoglycemia may be associated with adverse outcomes and that the context in which hypoglycemia takes places might be important in relation to its impact. CONCLUSIONS: There is insufficient evidence regarding the impact of hypoglycemia on QoL in children and adolescents with type 1 diabetes at this stage. There is a need for further research to examine this relationship, ideally using hypoglycemia-specific QoL measures.

Contains fulltext : 237990.pdf (Publisher’s version ) (Open Access), AIM: Impaired awareness of hypoglycaemia (IAH) affects about 25% of patients with type 1 diabetes (T1DM). IAH can be reversed by strict avoidance of hypoglycaemia for at least 3 weeks. Adjunctive treatment with sodium glucose cotransporter 2 inhibitors may reduce the risk of hypoglycaemia through reduction of glucose variability. We tested the hypothesis that short-term use of dapagliflozin may improve awareness of hypoglycaemia in people with T1DM and IAH. MATERIALS AND METHODS: Fifteen patients with T1DM and IAH were included in this randomized double-blind, placebo-controlled cross-over trial (age 49.7 ± 14.6 years, 40% men, disease duration 24.1 ± 14.2 years, glycated haemoglobin 7.5 ± 0.8% (58.6 ± 8.4 mmol/mol). They were treated with dapagliflozin 10 mg once daily or matching placebo, with a washout period of 2 weeks. At the end of each treatment period, participants underwent a modified hyperinsulinaemic normoglycaemic-hypoglycaemic glucose clamp (glucose nadir 2.5 mmol/L). Blinded continuous glucose monitors were used in the final treatment weeks. RESULTS: Treatment with dapagliflozin significantly improved glycated haemoglobin [-0.32 ± 0.10 vs. 0.22 ± 0.13% (-4.1 ± 0.9 vs. 2.3 ± 1.4 mmol/mol), dapagliflozin vs. placebo, p = .007] and glucose variability (standard deviation, 2.6 ± 0.2 vs. 3.1 ± 0.3 mmol/L, p = .029), but did not affect the frequency of hypoglycaemia. During the hypoglycaemic clamp, dapagliflozin did not affect symptom responses (8.0 ± 3.4 vs. 5.2 ± 1.6, p = .31), but significantly reduced the need for exogenous glucose to maintain hypoglycaemia (3.2 ± 0.3 vs. 4.1 ± 0.4 mg/kg/min, p = .022). CONCLUSIONS: Eight weeks of treatment with dapagliflozin did not restore hypoglycaemic awareness in people with T1DM and impaired awareness of hypoglycaemia, but ameliorated some clinical aspects.

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

Contains fulltext : 235311.pdf (Publisher’s version ) (Open Access), BACKGROUND: Closed-loop insulin delivery systems, which integrate continuous glucose monitoring (CGM) and algorithms that continuously guide insulin dosing, have been shown to improve glycaemic control. The ability to predict future glucose values can further optimize such devices. In this study, we used machine learning to train models in predicting future glucose levels based on prior CGM and accelerometry data. METHODS: We used data from The Maastricht Study, an observational population-based cohort that comprises individuals with normal glucose metabolism, prediabetes, or type 2 diabetes. We included individuals who underwent >48h of CGM (n = 851), most of whom (n = 540) simultaneously wore an accelerometer to assess physical activity. A random subset of individuals was used to train models in predicting glucose levels at 15- and 60-minute intervals based on either CGM data or both CGM and accelerometer data. In the remaining individuals, model performance was evaluated with root-mean-square error (RMSE), Spearman's correlation coefficient (rho) and surveillance error grid. For a proof-of-concept translation, CGM-based prediction models were optimized and validated with the use of data from individuals with type 1 diabetes (OhioT1DM Dataset, n = 6). RESULTS: Models trained with CGM data were able to accurately predict glucose values at 15 (RMSE: 0.19mmol/L; rho: 0.96) and 60 minutes (RMSE: 0.59mmol/L, rho: 0.72). Model performance was comparable in individuals with type 2 diabetes. Incorporation of accelerometer data only slightly improved prediction. The error grid results indicated that model predictions were clinically safe (15 min: >99%, 60 min >98%). Our prediction models translated well to individuals with type 1 diabetes, which is reflected by high accuracy (RMSEs for 15 and 60 minutes of 0.43 and 1.73 mmol/L, respectively) and clinical safety (15 min: >99%, 60 min: >91%). CONCLUSIONS: Machine learning-based models are able to accurately and safely predic

Item does not contain fulltext, AIMS/HYPOTHESIS: Recurrent hypoglycaemia in people with diabetes leads to progressive suppression of counterregulatory hormonal responses to subsequent hypoglycaemia. Recently it has been proposed that the mechanism underpinning this is a form of adaptive memory referred to as habituation. To test this hypothesis, we use two different durations of cold exposure to examine whether rodents exposed to recurrent hypoglycaemia exhibit two characteristic features of habituation, namely stimulus generalisation and dishabituation. METHODS: In the first study (stimulus generalisation study), hyperinsulinaemic-hypoglycaemic (2.8 mmol/l) glucose clamps were performed in non-diabetic rodents exposed to prior moderate-duration cold (4°C for 3 h) or control conditions. In the second study (dishabituation study), rodents exposed to prior recurrent hypoglycaemia or saline (154 mmol/l NaCl) injections over 4 weeks underwent a longer-duration cold (4°C for 4.5 h) exposure followed 24 h later by a hyperinsulinaemic-hypoglycaemic (2.8 mmol/l) glucose clamp. Output measures were counterregulatory hormone responses during experimental hypoglycaemia. RESULTS: Moderate-duration cold exposure blunted the adrenaline (epinephrine) response (15,266 ± 1920 vs 7981 ± 1258 pmol/l, Control vs Cold; p < 0.05) to next day hypoglycaemia in healthy non-diabetic rodents. In contrast, the suppressed adrenaline response (Control 5912 ± 1417 vs recurrent hypoglycaemia 1836 ± 736 pmol/l; p < 0.05) that is associated with recurrent hypoglycaemia was restored following longer-duration cold exposure (recurrent hypoglycaemia + Cold 4756 ± 826 pmol/l; not significant vs Control). CONCLUSIONS/INTERPRETATION: Non-diabetic rodents exhibit two cardinal features of habituation, namely stimulus generalisation and dishabituation. These findings provide further support for the hypothesis that suppressed counterregulatory responses following exposure to recurrent hypoglycaemia in diabetes result from habituation.

Contains fulltext : 236713.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 232448.pdf (Publisher’s version ) (Open Access), AIMS/HYPOTHESIS: The hyperinsulinaemic-hypoglycaemic glucose clamp technique has been developed and applied to assess effects of and responses to hypoglycaemia under standardised conditions. However, the degree to which the methodology of clamp studies is standardised is unclear. This systematic review examines how hyperinsulinaemic-hypoglycaemic clamps have been performed and elucidates potential important differences. METHODS: A literature search in PubMed and EMBASE was conducted. Articles in English published between 1980 and 2018, involving adults with or without diabetes, were included. RESULTS: A total of 383 articles were included. There was considerable variation in essential methodology of the hypoglycaemic clamp procedures, including the insulin dose used (49-fold difference between the lowest and the highest rate), the number of hypoglycaemic steps (range 1-6), the hypoglycaemic nadirs (range 2.0-4.3 mmol/l) and the duration (ranging from 5 to 660 min). Twenty-seven per cent of the articles reported whole blood glucose levels, most venous levels. In 70.8% of the studies, a dorsal hand vein was used for blood sampling, with some form of hand warming to arterialise venous blood in 78.8% of these. Key information was missing in 61.9% of the articles. CONCLUSIONS/INTERPRETATION: Although the hyperinsulinaemic-hypoglycaemic clamp procedure is considered the gold standard to study experimental hypoglycaemia, a uniform standard with key elements on how to perform these experiments is lacking. Methodological differences should be considered when comparing results between hypoglycaemic clamp studies. PROSPERO REGISTRATION: This systematic review is registered in PROSPERO (CRD42019120083).

Item does not contain fulltext, 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.

Radboud University, 08 oktober 2021, Promotores : Galan, B.E. de, Tack, C.J.J., Contains fulltext : 236685.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 218710.pdf (Publisher’s version ) (Closed access), The aim of this review was to provide an overview of developments, clinical implications and gaps in knowledge regarding the relationship between diabetes and sleep over the past 25 years, with special focus on contributions from the behavioural sciences. Multiple prospective observational and experimental studies have shown a link between suboptimal sleep and impaired glucose tolerance, decreased insulin sensitivity and the development of type 2 diabetes. While prevalence rates of suboptimal sleep vary widely according to definition, assessment and sample, suboptimal subjective sleep quality appears to be a common reality for one-third of people with type 1 diabetes and over half of people with type 2 diabetes. Both physiological and psychosocial factors may impair sleep in these groups. In turn, suboptimal sleep can negatively affect glycaemic outcomes directly or indirectly via suboptimal daytime functioning (energy, mood, cognition) and self-care behaviours. Technological devices supporting diabetes self-care may have both negative and positive effects. Diabetes and its treatment also affect the sleep of significant others. Research on the merits of interventions aimed at improving sleep for people with diabetes is in its infancy. Diabetes and sleep appear to be reciprocally related. Discussion of sleep deserves a central place in regular diabetes care. Multi-day, multi-method studies may shed more light on the complex relationship between sleep and diabetes at an individual level. Intervention studies are warranted to examine the potential of sleep interventions in improving outcomes for people with diabetes.

Contains fulltext : 220541.pdf (Publisher’s version ) (Open Access), 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.

Contains fulltext : 218277.pdf (publisher's version ) (Open Access), 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.

Contains fulltext : 220542.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND Checkpoint inhibitors are relatively new anti-cancer medicines that activate tumour cell immunity. CASE DESCRIPTION We describe two patients who presented to the emergency department due to severe ketoacidosis, this being the first symptom of diabetes in said patients. A few weeks prior to this, they each commenced treatment with the checkpoint inhibitor pembrolizumab. HbA1c level, assessed in one of the patients, was not elevated upon presentation. CONCLUSION Type 1 diabetes mellitus is a rare, but potentially life-threatening, complication of treatment with checkpoint inhibitors. However, routine measurement of glucose or HbA1c levels is not useful in patients who are treated with checkpoint inhibitors. Both patients and healthcare professionals should be (made) aware of the symptoms of hyperglycaemia, thereby ensuring immediate treatment with insulin in order to prevent severe ketoacidosis.