Metabolic effect of adrenaline infusion in people with type 1 diabetes and healthy individuals.

AIMS/HYPOTHESIS: As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia. METHODS: Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic-euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure. RESULTS: While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant. CONCLUSIONS/INTERPRETATION: In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05095259.

Peer support for adults with type 2 diabetes starting continuous glucose monitoring-An exploratory randomised controlled trial.

AIMS: To explore the feasibility and potential benefits of a peer support programme for adults with insulin-treated type 2 diabetes (T2D) starting continuous glucose monitoring (CGM). METHODS: This part of the Steno2tech study is an exploratory, single-centre, open-labelled, prospective, randomised controlled trial (RCT). A total of 60 participants were randomised 2:1 to 12 months of CGM with or without peer support. All participants received a 3-h diabetes self-management education course including a CGM part on how to use the CGM and interpret the CGM-derived data. Peer support consisted of three 3-h peer support meetings over the first 6 months of the study period with groups of three to six people. The exploratory outcomes included the acceptability and feasibility of the peer support intervention, and the between-group difference in change in several glycaemic, metabolic and participant-reported outcomes measured at baseline, 6 and 12 months. RESULTS: The peer support intervention was found acceptable and feasible. Participants shared their experiences of using and interpreting CGM data and its association with health behaviour. While both groups had improvements in glycaemic, metabolic and participant-reported outcomes, there were no significant between-group differences. CONCLUSIONS: Although feasible, we found no measured additional benefits when adding a peer support programme after starting CGM in this exploratory RCT including adults with insulin-treated T2D. Understanding the perceived effect of and preferences for a peer support intervention from the participants' points of view, including why individuals declined to participate, would be of value for future research.

The impact of upper extremity impairments on work and everyday life of people with type 1 diabetes-A nationwide controlled study.

AIMS: The study objective was to explore how upper extremity impairments (UEIs) affect the everyday life and work-life of people with type 1 diabetes (T1D) and to compare them to a control group without T1D to determine if there are diabetes-specific consequences of UEIs. METHODS: In a controlled cross-sectional study, a survey was distributed across all regions of Denmark. A total of 2174 people with T1D and 827 controls were included in the study population. The survey addressed UEI symptoms, employment status, functional disability, mental well-being and diabetes distress. Data were analysed using multivariable logistic and linear regression. RESULTS: Upper extremity impairments were associated with a higher rate of work absence and modification, but no more so for people with T1D than for the control group. Among people with T1D, UEIs were significantly associated with worse mental well-being and diabetes distress, and across all outcomes including functional disability, additive effects were found with an increasing number of coexisting impairments. The impact of UEIs on functional disability was more severe for the T1D group than the control group, but this was primarily due to differences in the number of coexisting impairments. CONCLUSIONS: Upper extremity impairments have significant negative implications for the work-life and everyday life of people with T1D, and interventions to reduce UEIs and their impact among this group are highly relevant.

Pen-administered low-dose dasiglucagon vs usual care for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions: a Phase II, randomised, open-label, two-period crossover trial.

AIMS/HYPOTHESIS: Consumption of excess carbohydrates to manage hypoglycaemia can lead to rebound hyperglycaemia and promote weight gain. The objective of this trial was to evaluate the efficacy, safety and feasibility of pen-administered low-dose dasiglucagon for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions. METHODS: Twenty-four adults with insulin pump-treated type 1 diabetes (HbA1c ≤70 mmol/mol [8.5%]) completed a randomised, open-label, two-period crossover study with 2 week periods. During the usual care and dasiglucagon intervention (DASI) periods, participants managed impending and manifested episodes of hypoglycaemia with regular carbohydrate consumption or pen-administered low-dose (80 µg) s.c. dasiglucagon, respectively. Glycaemic control was evaluated using continuous glucose monitoring (Dexcom G6) and event registration of prevention and treatment episodes. RESULTS: Compared with usual care, the mean difference (95% CI) in the DASI period for time in (3.9-10.0 mmol/l) and below (<3.9 mmol/l) range was 2.4 %-points (-0.7, 5.5) and -0.5 %-points (-1.2, 0.2), respectively. In the DASI period, recovery rate (time from hypoglycaemia treatment to euglycaemia) was 44% (11, 87) faster while total daily carbohydrate intake was reduced by 11% (-18, -3). Dasiglucagon use was safe and well tolerated with mild nausea being the most frequent adverse effect. Among the participants, 96% (p<0.0001) were likely to include dasiglucagon in their future routine management of hypoglycaemia. CONCLUSIONS/INTERPRETATION: Use of low-dose dasiglucagon to prevent and treat non-severe hypoglycaemia during free-living conditions was safe, fast and efficacious while significantly reducing the total daily carbohydrate intake and yielding high treatment satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov NCT04764968 FUNDING: The study was an investigator-initiated trial. Zealand Pharma supplied the investigational drug and device and provided financial support for the conduct of the trial.

Continuous Glucose Monitoring Reveals Perioperative Hypoglycemia in Most Patients With Diabetes Undergoing Major Surgery: A Prospective Cohort Study.

OBJECTIVE: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols. SUMMARY BACKGROUND DATA: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions. METHODS: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001. RESULTS: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses. CONCLUSIONS: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management.

Associations between insulin pump self-management and HbA1c in type 1 diabetes.

AIMS: Insulin pump self-management is important for glycaemic outcomes. We aimed to investigate associations between self-management factors and HbA1c. METHODS: Adult insulin pump users with type 1 diabetes (n = 770) completed an online questionnaire. The latest HbA1c and demographics were extracted from national registries. Associations between HbA1c and self-management (use of advanced features, timing of infusion set change, timing of meal bolus, data-upload and pump settings adjustments) were investigated using backward selected linear regression models. RESULTS: Of the 699 responders eligible for this study, 60% were women; the median age and diabetes duration were 49 and 25 years, respectively. Significant associations with HbA1c were found for changing infusion set every 0-4 days relative to 5-10 days (-5 mmol/mol (-0.4%), p = 0.003), and for never/rarely missing a bolus (-6 mmol/mol (-0.5%), p < 0.001) relative to often missing a bolus. Timing insulin 10-15 min before meal relative to after meal start was also associated with lower HbA1c (-3 mmol/mol (-0.3%), p = 0.023). Self-adjusting pump settings showed the strongest association with lower HbA1c (-6 mmol/mol (-0.6%), p < 0.001) relative to health care professionals doing all adjustments. CONCLUSION: Self-adjusting insulin pump settings, optimal timing and few omissions of meal boluses, and timely change of infusion set are associated with lower HbA1c.

Metabolic and physiological responses to graded exercise testing in individuals with type 1 diabetes using insulin pump therapy.

AIMS: To profile acute glycaemic dynamics during graded exercise testing (GXT) and explore the influence of glycaemic indicators on the physiological responses to GXT in adults with type 1 diabetes using insulin pump therapy. METHODS: This was a retrospective analysis of pooled data from four clinical trials with identical GXT protocols. Data were obtained from 45 adults with type 1 diabetes using insulin pumps [(30 females); haemoglobin A1c 59.5 ± 0.5 mmol/mol (7.6 ± 1.0%); age 49.7 ± 13.0 years; diabetes duration 31.2 ± 13.5 years; V̇O2peak 29.5 ± 8.0 ml/min/kg]. Integrated cardiopulmonary variables were collected continuously via spiroergometry. Plasma glucose was obtained every 3 min during GXT as well as the point of volitional exhaustion. Data were assessed via general linear modelling techniques with age and gender adjustment. Significance was accepted at p ≤ .05. RESULTS: Despite increasing duration and intensity, plasma glucose concentrations remained similar to rest values (8.8 ± 2.3 mmol/L) throughout exercise (p = .419) with an overall change of +0.3 ± 1.1 mmol/L. Starting glycaemia bore no influence on subsequent GXT responses. Per 1% increment in haemoglobin A1c there was an associated decrease in V̇O2peak of 3.8 ml/min/kg (p < .001) and powerpeak of 0.33 W/kg (p < .001) concomitant with attenuations in indices of peripheral oxygen extraction [(O2 pulse) -1.2 ml/beat, p = .023]. CONCLUSION: In adults with long-standing type 1 diabetes using insulin pump therapy, circulating glucose remains stable during a graded incremental cycle test to volitional exhaustion. Glycaemic indicators are inversely associated with aerobic rate, oxygen economy and mechanical output across the exercise intensity spectrum. An appreciation of these nexuses may help guide appropriate decision making for optimal exercise management strategies.

Effect of insulin degludec versus insulin glargine U100 on nocturnal glycaemia assessed by plasma glucose profiles in people with type 1 diabetes prone to nocturnal severe hypoglycaemia.

AIM: To compare nocturnal glucose profiles according to hourly plasma glucose measurements during treatment with insulin degludec and insulin glargine U100 in a cohort of people with type 1 diabetes prone to nocturnal severe hypoglycaemia. MATERIALS AND METHODS: The HypoDeg trial is a 2-year investigator-initiated, randomized, controlled crossover trial in 149 participants randomized to treatment with insulin degludec and insulin glargine U100 for 12 months each. The 51 participants in this predefined substudy stayed at least one night in hospital during each treatment arm for plasma glucose samples to be taken. Endpoints were glucose profiles, including mean plasma glucose, glycaemic variability and risk of hypoglycaemia. RESULTS: There were no differences between treatments regarding mean plasma glucose. We saw a flatter glucose profile during insulin degludec compared with insulin glargine U100 treatment, which had a nadir at 4:00 AM, with a subsequent rise. During treatment with insulin degludec, the participants had lower glycaemic variability, with an estimated treatment difference of -4.3% (95% confidence interval [CI] -8.1 to -0.5; P < 0.05). Participants treated with insulin degludec were less likely to experience nocturnal hypoglycaemia below 3.0 mmol/L (hazard ratio 0.36 [95% CI 0.17-0.73; P < 0.05]). CONCLUSION: Based on nocturnal plasma glucose measurements, treatment with insulin degludec compared with insulin glargine U100 administered in the evening results in lower glycaemic variability and lower risk of nocturnal hypoglycaemia without differences in mean plasma glucose.

Factory-Calibrated Continuous Glucose Monitoring Systems in Type 1 Diabetes: Accuracy during In-Clinic Exercise and Home Use.

Continuous glucose monitors (CGMs) are valuable tools for improving glycemic control, yet their accuracy might be influenced by physical activity. This study sought to assess the accuracy of the three latest factory-calibrated CGM systems available in Europe at the time the study was conducted, both during aerobic exercise and in typical daily scenarios. The accuracy evaluation, based on metrics such as the median absolute relative difference (MARD) and point and rate error-grid analyses (PEGA and REGA), involved 13 adults with type 1 diabetes. Participants wore all sensors during a 1 h in-clinic exercise session followed by a subsequent 3-day home period, with blood glucose measurements serving as reference values in both contexts. During exercise, no statistically significant differences in MARD were observed (Dexcom G6: 12.6%, Guardian 4: 10.7%, and Freestyle Libre 2: 17.2%; p = 0.31), and similarly, no significant differences emerged in PEGA-zone-AB (100%, 100%, 96.8%; p = 0.37). Nevertheless, Freestyle Libre 2 showed comparatively diminished accuracy in estimating glucose trends during exercise (REGA-zone-AB: 100%, 93.0%, 73.3%; p = 0.0003). In the home environment, Freestyle Libre 2 exhibited a significantly higher MARD when compared to the other systems (10.2%, 11.9%, 16.7%, p = 0.02). Overall, Dexcom G6 and Guardian 4 demonstrated superior accuracy in both exercise and daily life scenarios compared to Freestyle Libre 2.

Flexible inclusion of dialogue about psychosocial aspects of life with type 1 diabetes in routine consultations: A study of a questionnaire-based dialogue tool to promote person-centred support.

AIMS: To explore (1) experiences among people with type 1 diabetes and diabetologists of using a questionnaire-based dialogue tool in routine consultations to identify and address psychosocial challenges and (2) experiences of person-centredness in this group compared with a group who did not use the tool. METHODS: In all, 42 people with type 1 diabetes (mean age 54 years, mean diabetes duration 31 years and 60% women) were interviewed and completed an evaluation questionnaire following a routine consultation with the use of a dialogue tool including PAID-5, WHO-5 and open-ended questions. A comparison group of 42 people with type 1 diabetes attending routine consultations without the use of dialogue tools completed evaluation questionnaires. All consultations were audio recorded. Diabetologists were interviewed after completing all test consultations. Interviews were analysed using thematic text condensation. Evaluation questionnaires were analysed using descriptive statistics, chi square tests and Student's two-sided t-tests. RESULTS: Most participants found questions in the dialogue tool relevant to discuss with the diabetologist, and two-thirds were satisfied with the time spent on that. Experiences of people with type 1 diabetes and diabetologists were related to three pathways: (1) the tool supported valuable conversations with the diabetologist, (2) conversations with the diabetologist were unchanged and (3) the tool derailed conversations. All participants reported high levels of person centredness; however, significantly more in the comparison group reported that the diabetologist made them feel at ease (80 vs. 55%) and discussed and planned specific changes with them (93 vs. 67%). CONCLUSION: A questionnaire-based dialogue tool in consultations can support the discussion of psychosocial issues of people with type 1 diabetes. However, flexible and tailored use of the dialogue tool is crucial as consultations may otherwise be derailed.

Liraglutide changes body composition and lowers added sugar intake in overweight persons with insulin pump-treated type 1 diabetes.

AIMS: To present secondary outcome analyses of liraglutide treatment in overweight adults with insulin pump-treated type 1 diabetes (T1D), focusing on changes in body composition and dimensions, and to evaluate changes in food intake to identify potential dietary drivers of liraglutide-associated weight loss. MATERIALS AND METHODS: A 26-week randomized placebo-controlled study was conducted to investigate the efficacy and safety of liraglutide 1.8 mg daily in 44 overweight adults with insulin pump-treated T1D and glucose levels above target, and demonstrated significant glycated haemoglobin (HbA1c)- and body weight-reducing effects. For secondary outcome analysis, dual X-ray absorptiometry scans were completed at Weeks 0 and 26, and questionnaire-based food frequency recordings were obtained at Weeks 0, 13 and 26 to characterize liraglutide-induced changes in body composition and food intake. RESULTS: Total fat and lean body mass decreased in liraglutide-treated participants (fat mass -4.6 kg [95% confidence interval {CI} -5.7; -3.5], P < 0.001; lean mass -2.5 kg [95% CI -3.2;-1.7], P < 0.001), but remained stable in placebo-treated participants (fat mass -0.3 kg [95% CI -1.3;0.8], P = 0.604; lean mass 0.0 kg [95% CI -0.7;0.7]; P = 0.965 [between-group P values <0.001]). Participants reduced their energy intake numerically more in the liraglutide arm (-1.1 MJ [95% CI -2.0;-0.02], P = 0.02) than in the placebo arm (-0.9 MJ [95% CI -2.0;0.1], P = 0.22), but the between-group difference was statistically insignificant (P = 0.42). However, energy derived from added sugars decreased by 27% in the liraglutide arm compared with an increase of 14% in the placebo arm (P = 0.004). CONCLUSIONS: Liraglutide lowered fat and lean body mass compared with placebo. Further, liraglutide reduced intake of added sugars. However, no significant difference in total daily energy intake was detected between liraglutide- and placebo-treated participants.

Comparison of treatment with insulin degludec and glargine U100 in patients with type 1 diabetes prone to nocturnal severe hypoglycaemia: The HypoDeg randomized, controlled, open-label, crossover trial.

AIM: To investigate whether the long-acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D). METHODS: Adults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2-year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal-bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run-in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention-to-treat. RESULTS: Treatment with insulin degludec resulted in a 28% (95% CI: 9%-43%; P = .02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%-53%; P = .002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%-58%; P = .04) RRR in all-day severe hypoglycaemia compared with insulin glargine U100. CONCLUSIONS: Patients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all-day severe hypoglycaemia with insulin degludec compared with insulin glargine U100.

Flash glucose monitoring and automated bolus calculation in type 1 diabetes treated with multiple daily insulin injections: a 26 week randomised, controlled, multicentre trial.

AIMS/HYPOTHESIS: We aimed to compare the effects of intermittently scanned continuous glucose monitoring (isCGM) and carbohydrate counting with automated bolus calculation (ABC) with usual care. METHODS: In a randomised, controlled, open-label trial carried out at five diabetes clinics in the Capital Region of Denmark, 170 adults with type 1 diabetes for ≥1 year, multiple daily insulin injections and HbA1c > 53 mmol/mol (7.0%) were randomly assigned 1:1:1:1 with centrally prepared envelopes to usual care (n = 42), ABC (n = 41), isCGM (n = 48) or ABC+isCGM (n = 39). Blinded continuous glucose monitoring data, HbA1c and patient-reported outcomes were recorded at baseline and after 26 weeks. The primary outcome was change in time in range using isCGM vs usual care. RESULTS: Baseline characteristics were comparable across arms: mean age 47 (SD 13.7) years, median (IQR) diabetes duration 18 (10-28) years and HbA1c 65 (61-72) mmol/mol (8.1% [7.7-8.7%]). Change in time in range using isCGM was comparable to usual care (% difference of 3.9 [-12-23], p = 0.660). The same was true for the ABC and ABC+isCGM arms and for hypo- and hyperglycaemia. Also compared with usual care, using ABC+isCGM reduced HbA1c (4 [95% CI 1, 8] mmol/mol) (0.4 [0.1, 0.7] %-point) and glucose CV (11% [4%, 17%]) and improved treatment satisfaction, psychosocial self-efficacy and present life quality. Treatment satisfaction also improved by using isCGM alone vs usual care. Statistical significance was maintained after multiple testing adjustment concerning glucose CV and treatment satisfaction with ABC+isCGM, and treatment satisfaction with isCGM. Discontinuation was most common among ABC only users, and among completers the ABC was used 4 (2-5) times/day and the number of daily isCGM scans was 5 (1-7) at study end. CONCLUSIONS/INTERPRETATION: isCGM alone did not improve time in range, but treatment satisfaction increased in technology-naive people with type 1 diabetes and suboptimal HbA1c. The combination of ABC+isCGM appears advantageous regarding glycaemic variables and patient-reported outcomes, but many showed resistance towards ABC. TRIAL REGISTRATION: ClinicalTrials.gov NCT03682237. FUNDING: The study is investigator initiated and financed by the Capital Region of Denmark.

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors. Graphical abstract.

Education programmes for persons with type 1 diabetes using an insulin pump: A systematic review.

Education is essential in insulin pump therapy, but literature in the field is limited. We systematically reviewed insulin pump education programmes and their effects in two situations as follows: (1) basic education at the start of insulin pump therapy, providing the study design enabled us to separate the effects of insulin pump therapy itself from the effects of education and (2) re-education of experienced pump users. Population: individuals ≥16 years with type 1 diabetes using insulin pumps with or without continuous glucose monitoring. Systematic searches were run in MEDLINE, Embase, CINAHL and ERIC. Original studies reporting an effect of insulin pump education programmes were included if published in English between January 1999 and May 2019. Of 988 potentially relevant studies, 48 were assessed in full text. Nine studies fulfilled the inclusion criteria, including one randomised controlled trial. Educational approaches and settings were sparsely described in all studies, and the content was usually reported as teaching points. Two studies considered basic education, reporting evaluations of knowledge and application skills, and programme satisfaction. The remaining seven studies referred to re-education. Two studies measured severe hypoglycaemic events before and after a re-education intervention, both reporting a significant event reduction. HbA1c decreased significantly in three of four studies. Two studies reported increased knowledge and improved application skills. In conclusion, this review indicates benefits from basic education and from re-education. The strength of the conclusions is limited by the low number of studies and study designs. High-quality studies are needed comparing different approaches for insulin pump education.

The effect of preceding glucose decline rate on low-dose glucagon efficacy in individuals with type 1 diabetes: A randomized crossover trial.

Identifying determinants of low-dose glucagon efficacy is important to optimise its utilization for prevention and treatment of hypoglycaemia in individuals with type 1 diabetes. The study objective was to investigate whether the preceding glucose decline rate affects glucose response to low-dose glucagon administration. Ten adults with insulin pump-treated type 1 diabetes were included in this randomized, single-blind, two-way crossover study. Using a hyperinsulinaemic clamp technique, plasma glucose levels were reduced with either a rapid or slow decline rate while maintaining fixed insulin levels. When the plasma glucose level reached 3.9 mmoL/L, insulin and glucose infusions were discontinued and 150 µg subcutaneous glucagon was administered, followed by 120 minutes of plasma glucose monitoring. The positive incremental area under the glucose curve after administration of low-dose glucagon did not differ between the rapid-decline and slow-decline visits (mean ± SEM: 220 ± 49 vs. 174 ± 31 mmoL/L x min; P = 0.21). Similarly, no differences in total area under the glucose curve, peak plasma glucose, incremental peak plasma glucose, time-to-peak plasma glucose or end plasma glucose were observed. Thus, preceding glucose decline rate did not significantly affect the glucose response to low-dose glucagon.

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (i.e. before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes. Graphical abstract.

Glucagon for hypoglycaemia treatment in type 1 diabetes.

To achieve strict glycaemic control and avoid chronic diabetes complications, individuals with type 1 diabetes (T1D) are recommended to follow an intensive insulin regimen. However, the risk and fear of hypoglycaemia often prevent individuals from achieving the treatment goals. Apart from early insulin suspension in insulin pump users, carbohydrate ingestion is the only option for preventing and treating non-severe hypoglycaemic events. These rescue treatments may give extra calories and cause overweight. As an alternative, the use of low-dose glucagon to counter hypoglycaemia has been proposed as a tool to raise glucose concentrations without adding extra calories. Previously, the commercially available glucagon formulations required reconstitution from powder to a solution before being injected subcutaneously or intramuscularly-making it practical only for treating severe hypoglycaemia. Several companies have developed more stable formulations that do not require the time-consuming reconstitution process before use. As well as treating severe hypoglycaemia, non-severe and impending hypoglycaemia can also be treated with lower doses of glucagon. Once available, low-dose glucagon can be either delivered manually, as an injection, or automatically, by an infusion pump. This review focuses on the role and perspectives of using glucagon to treat and prevent hypoglycaemia in T1D.

Liraglutide reduces hyperglycaemia and body weight in overweight, dysregulated insulin-pump-treated patients with type 1 diabetes: The Lira Pump trial-a randomized, double-blinded, placebo-controlled trial.

AIM: To investigate the efficacy of adding the glucagon-like peptide-1 receptor agonist liraglutide to continuous subcutaneous insulin infusion (CSII) in overweight or obese persons with type 1 diabetes and non-optimal glycaemic control. MATERIALS AND METHODS: A 26-week, randomized, double-blind, placebo-controlled trial including 44 overweight or obese adults with type 1 diabetes randomized 1:1 to liraglutide 1.8 mg once daily (QD) or placebo added to CSII treatment. The primary endpoint was change in haemoglobin A1c (HbA1c). Secondary endpoints included change in insulin dose, CSII settings, glycaemic variability, body weight and patient-reported outcome measures. Finally, adverse effects including hypoglycaemic events were registered. RESULTS: HbA1c was reduced by 5 mmol/mol (0.5%) from a baseline of 66 mmol/mol (8.2%) in patients treated with liraglutide compared with a non-significant change of +2.3 mmol/mol (0.2%) from a baseline of 66 mmol/mol (8.1%) in patients treated with placebo (between-group difference 7 mmol/mol [0.7%], P < 0.001). Liraglutide reduced total insulin dose by 8 units/day or 16% of total insulin dose (P = 0.008). Mean body weight was reduced by 6.3 kg (P < 0.001) compared with placebo. Concomitantly, time spent in glycaemic target range 4-10 mmol/L (71-180 mg/dL) increased while the risk of hypoglycaemia did not differ between groups at the end of treatment. CONCLUSION: Liraglutide treatment reduced HbA1c, total daily insulin dose and body weight without increasing the risk of hypoglycaemia in CSII-treated patients with type 1 diabetes and insufficient glycaemic control. Liraglutide may be considered a potential add-on therapy to insulin in this subgroup of patients.

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.