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.

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.

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.

A collaborative comparison of international pediatric diabetes registries.

BACKGROUND: An estimated 1.1 million children and adolescents aged under 20 years have type 1 diabetes worldwide. Principal investigators from seven well-established longitudinal pediatric diabetes registries and the SWEET initiative have come together to provide an international collaborative perspective and comparison of the registries. WORK FLOW: Information and data including registry characteristics, pediatric participant clinical characteristics, data availability and data completeness from the Australasian Diabetes Data Network (ADDN), Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids), Diabetes prospective follow-up registry (DPV), Norwegian Childhood Diabetes Registry (NCDR), National Paediatric Diabetes Audit (NPDA), Swedish Childhood Diabetes Registry (Swediabkids), T1D Exchange Quality Improvement Collaborative (T1DX-QI), and the SWEET initiative was extracted up until 31 December 2020. REGISTRY OBJECTIVES AND OUTCOMES: The seven diabetes registries and the SWEET initiative collectively show data of more than 900 centers and around 100,000 pediatric patients, the majority with type 1 diabetes. All share the common objectives of monitoring treatment and longitudinal outcomes, promoting quality improvement and equality in diabetes care and enabling clinical research. All generate regular benchmark reports. Main differences were observed in the definition of the pediatric population, the inclusion of adults, documentation of CGM metrics and collection of raw data files as well as linkage to other data sources. The open benchmarking and access to regularly updated data may prove to be the most important contribution from registries. This study describes aspects of the registries to enable future collaborations and to encourage the development of new registries where they do not exist.

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.

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.

Preserved glucose response to low-dose glucagon after exercise in insulin-pump-treated individuals with type 1 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS: This study aimed to compare the increase in plasma glucose after a subcutaneous injection of 200 µg glucagon given after 45 min of cycling with resting (study 1) and to investigate the effects of glucagon when injected before compared with after 45 min of cycling (study 2). We hypothesised that: (1) the glucose response to glucagon would be similar after cycling and resting; and (2) giving glucagon before the activity would prevent the exercise-induced fall in blood glucose during exercise and for 2 h afterwards. METHODS: Fourteen insulin-pump-treated individuals with type 1 diabetes completed three visits in a randomised, placebo-controlled, participant-blinded crossover study. They were allocated by sealed envelopes. Baseline values were (mean and range): HbA1c 54 mmol/mol (43-65 mmol/mol) or 7.1% (6.1-8.1%); age 45 years (23-66 years); BMI 26 kg/m2 (21-30 kg/m2); and diabetes duration 26 years (8-51 years). At each visit, participants consumed a standardised breakfast 2 h prior to 45 min of cycling or resting. A subcutaneous injection of 200 µg glucagon was given before or after cycling or after resting. The glucose response to glucagon was compared after cycling vs resting (study 1) and before vs after cycling (study 2). RESULTS: The glucose response to glucagon was higher after cycling compared with after resting (mean ± SD incremental peak: 2.6 ± 1.7 vs 1.8 ± 2.0 mmol/l, p = 0.02). As expected, plasma glucose decreased during cycling (-3.1 ± 2.8 mmol/l) but less so when glucagon was given before cycling (-0.9 ± 2.8 mmol/l, p = 0.002). The number of individuals reaching glucose values ≤3.9 mmol/l was the same on the 3 days. CONCLUSIONS/INTERPRETATION: Moderate cycling for 45 min did not impair the glucose response to glucagon compared with the glucose response after resting. The glucose fall during cycling was diminished by a pre-exercise injection of 200 µg glucagon; however, no significant difference was seen in the number of events of hypoglycaemia. TRIAL REGISTRATION: Clinicaltrials.gov NCT02882737 FUNDING: The study was funded by the Danish Diabetes Academy founded by Novo Nordisk foundation and by an unrestricted grant from Zealand Pharma.

Low versus high carbohydrate diet in type 1 diabetes: A 12-week randomized open-label crossover study.

AIMS: To compare the effects of a low carbohydrate diet (LCD < 100 g carbohydrate/d) and a high carbohydrate diet (HCD > 250 g carbohydrate/d) on glycaemic control and cardiovascular risk factors in adults with type 1 diabetes. MATERIALS AND METHODS: In a randomized crossover study with two 12-week intervention arms separated by a 12-week washout, 14 participants using sensor-augmented insulin pumps were included. Individual meal plans meeting the carbohydrate criteria were made for each study participant. Actual carbohydrate intake was entered into the insulin pumps throughout the study. RESULTS: Ten participants completed the study. Daily carbohydrate intake during the two intervention periods was (mean ± standard deviation) 98 ± 11 g and 246 ± 34 g, respectively. Time spent in the range 3.9-10.0 mmol/L (primary outcome) did not differ between groups (LCD 68.6 ± 8.9% vs. HCD 65.3 ± 6.5%, P = 0.316). However, time spent <3.9 mmol/L was less (1.9 vs. 3.6%, P < 0.001) and glycaemic variability (assessed by coefficient of variation) was lower (32.7 vs. 37.5%, P = 0.013) during LCD. No events of severe hypoglycaemia were reported. Participants lost 2.0 ± 2.1 kg during LCD and gained 2.6 ± 1.8 kg during HCD (P = 0.001). No other cardiovascular risk factors, including fasting levels of lipids and inflammatory markers, were significantly affected. CONCLUSIONS: Compared with an intake of 250 g of carbohydrate per day, restriction of carbohydrate intake to 100 g per day in adults with type 1 diabetes reduced time spent in hypoglycaemia, glycaemic variability and weight with no effect on cardiovascular risk factors.

Myeloproliferative Neoplasms in Danish Twins.

OBJECTIVE: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases characterized by clonal hyperproliferation of immature and mature cells of the myeloid lineage. Genetic differences have been proposed to play a role in the development of MPNs. Monozygotic twin pairs with MPNs have been reported in a few case reports, but the MPN concordance pattern in twins remains unknown. METHOD: All twin pairs born in the period 1900-2010 were identified in the nationwide Danish Twin Registry. Only pairs with both twins alive on January 1, 1977, and those born thereafter were included to allow identification in the Danish National Patient Registry. RESULTS: A total of 158 twin pairs were registered with an MPN diagnosis: 36 monozygotic, 104 dizygotic, and 18 pairs with unknown zygosity. MPNs were diagnosed in both twins in 4 pairs. The probandwise concordance rates for monozygotic twin pairs were higher than for dizygotic twin pairs (15 vs. 0%; p = 0.016). CONCLUSION: An estimated concordance rate of 15% (95% CI 0.059-0.31) is modest, but given the rarity of MPNs this finding is clinically relevant and provides further support for the role of genetic predisposition in the development of MPNs.

Short-term effects of a low carbohydrate diet on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes: A randomized open-label crossover trial.

The aim of the present study was to assess the effects of a high carbohydrate diet (HCD) vs a low carbohydrate diet (LCD) on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes. Ten patients (4 women, insulin pump-treated, median ± standard deviation [s.d.] age 48 ± 10 years, glycated haemoglobin [HbA1c] 53 ± 6 mmol/mol [7.0% ± 0.6%]) followed an isocaloric HCD (≥250 g/d) for 1 week and an isocaloric LCD (≤50 g/d) for 1 week in random order. After each week, we downloaded pump and sensor data and collected fasting blood and urine samples. Diet adherence was high (225 ± 30 vs 47 ± 10 g carbohydrates/d; P < .0001). Mean sensor glucose levels were similar in the two diets (7.3 ± 1.1 vs 7.4 ± 0.6 mmol/L; P = .99). The LCD resulted in more time with glucose values in the range of 3.9 to 10.0 mmol/L (83% ± 9% vs 72% ± 11%; P = .02), less time with values ≤3.9 mmol/L (3.3% ± 2.8% vs 8.0% ± 6.3%; P = .03), and less glucose variability (s.d. 1.9 ± 0.4 vs 2.6 ± 0.4 mmol/L; P = .02) than the HCD. Cardiovascular markers were unaffected, while fasting glucagon, ketone and free fatty acid levels were higher at end of the LCD week than the HCD week. In conclusion, the LCD resulted in more time in euglycaemia, less time in hypoglycaemia and less glucose variability than the HCD, without altering mean glucose levels.

Sensor-Based Glucose Metrics during Different Diet Compositions in Type 1 Diabetes-A Randomized One-Week Crossover Trial.

By reducing carbohydrate intake, people with type 1 diabetes may reduce fluctuations in blood glucose, but the evidence in this area is sparse. The aim of this study was to investigate glucose metrics during a one-week low-carbohydrate-high-fat (HF) and a low-carbohydrate-high-protein (HP) diet compared with an isocaloric high-carbohydrate (HC) diet. In a randomized, three-period cross-over study, twelve adults with insulin-pump-treated type 1 diabetes followed an HC (energy provided by carbohydrate: 48%, fat: 33%, protein: 19%), HF (19%, 62%, 19%), and an HP (19%, 57%, 24%) diet for one week. Glucose values were obtained during intervention periods using a Dexcom G6 continuous glucose monitoring system. Participant characteristics were: 33% females, median (range) age 50 (22-70) years, diabetes duration 25 (11-52) years, HbA1c 7.3 (5.5-8.3)% (57 (37-67) mmol/mol), and BMI 27.3 (21.3-35.9) kg/m2. Glycemic variability was lower with HF (30.5 ± 6.2%) and HP (30.0 ± 5.5%) compared with HC (34.5 ± 4.1%) (PHF-HC = 0.009, PHP-HC = 0.003). There was no difference between groups in mean glucose (HF: 8.7 ± 1.1, HP: 8.2 ± 1.0, HC: 8.7 ± 1.0 mmol/L, POverall = 0.08). Time > 10.0 mmol/L was lower with HP (22.3 ± 11.8%) compared with HF (29.4 ± 12.1%) and HC (29.5 ± 13.4%) (PHF-HP = 0.037, PHC-HP = 0.037). In conclusion, a one-week HF and, specifically, an HP diet improved glucose metrics compared with an isocaloric HC diet.

Automated Insulin Delivery in Adults With Type 1 Diabetes and Suboptimal HbA1c During Prior Use of Insulin Pump and Continuous Glucose Monitoring: A Randomized Controlled Trial.

BACKGROUND: Automated insulin delivery (AID) systems offer promise in improving glycemic outcomes for individuals with type 1 diabetes. However, data on those who struggle with suboptimal glycemic levels despite insulin pump and continuous glucose monitoring (CGM) are limited. We conducted a randomized controlled trial to assess the effects of an AID system in this population. METHODS: Participants with hemoglobin A1c (HbA1c) ≥ 58 mmol/mol (7.5%) were allocated 1:1 to 14 weeks of treatment with the MiniMed 780G system (AID) or continuation of usual care (UC). The primary endpoint was change in time in range (TIR: 3·9-10·0 mmol/L) from baseline to week 14. After this trial period, the UC group switched to AID treatment while the AID group continued using the system. Both groups were monitored for a total of 28 weeks. RESULTS: Forty adults (mean ± SD: age 52 ± 11 years, HbA1c 67 ± 7 mmol/mol [8.3% ± 0.6%], diabetes duration 29 ±13 years) were included. After 14 weeks, TIR increased by 18.7% (95% confidence interval [CI] = 14.5, 22.9%) in the AID group and remained unchanged in the UC group (P < .0001). Hemoglobin A1c decreased by 10.0 mmol/mol (95% CI = 7.0, 13.0 mmol/mol) (0.9% [95% CI = 0.6%, 1.2%]) in the AID group but remained unchanged in the UC group (P < .0001). The glycemic benefits of AID treatment were reproduced after the 14-week extension phase. There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the study. CONCLUSIONS: For adults with type 1 diabetes not meeting glycemic targets despite use of insulin pump and CGM, transitioning to an AID system confers considerable glycemic benefits.

Impact of Missed and Late Meal Boluses on Glycemic Outcomes in Automated Insulin Delivery-Treated Children and Adolescents with Type 1 Diabetes: A Two-Center, Population-Based Cohort Study.

Objective: To evaluate the impact of missed or late meal boluses (MLBs) on glycemic outcomes in children and adolescents with type 1 diabetes using automated insulin delivery (AID) systems. Research Design and Methods: AID-treated (Tandem Control-IQ or Medtronic MiniMed 780G) children and adolescents (aged 6-21 years) from Stanford Medical Center and Steno Diabetes Center Copenhagen with ≥10 days of data were included in this two-center, binational, population-based, retrospective, 1-month cohort study. The primary outcome was the association between the number of algorithm-detected MLBs and time in target glucose range (TIR; 70-180 mg/dL). Results: The study included 189 children and adolescents (48% females with a mean ± standard deviation age of 13 ± 4 years). Overall, the mean number of MLBs per day in the cohort was 2.2 ± 0.9. For each additional MLB per day, TIR decreased by 9.7% points (95% confidence interval [CI] 11.3; 8.1), and compared with the quartile with fewest MLBs (Q1), the quartile with most (Q4) had 22.9% less TIR (95% CI: 27.2; 18.6). The age-, sex-, and treatment modality-adjusted probability of achieving a TIR of >70% in Q4 was 1.4% compared with 74.8% in Q1 (P < 0.001). Conclusions: MLBs significantly impacted glycemic outcomes in AID-treated children and adolescents. The results emphasize the importance of maintaining a focus on bolus behavior to achieve a higher TIR and support the need for further research in technological or behavioral support tools to handle MLBs.

Performance of a dual-hormone closed-loop system versus insulin-only closed-loop system in adolescents with type 1 diabetes. A single-blind, randomized, controlled, crossover trial.

Objective: To assess the efficacy and safety of a dual-hormone (DH [insulin and glucagon]) closed-loop system compared to a single-hormone (SH [insulin only]) closed-loop system in adolescents with type 1 diabetes. Methods: This was a 26-hour, two-period, randomized, crossover, inpatient study involving 11 adolescents with type 1 diabetes (nine males [82%], mean ± SD age 14.8 ± 1.4 years, diabetes duration 5.7 ± 2.3 years). Except for the treatment configuration of the DiaCon Artificial Pancreas: DH or SH, experimental visits were identical consisting of: an overnight stay (10:00 pm until 7:30 am), several meals/snacks, and a 45-minute bout of moderate intensity continuous exercise. The primary endpoint was percentage of time spent with sensor glucose values below range (TBR [<3.9 mmol/L]) during closed-loop control over the 26-h period (5:00 pm, day 1 to 7:00 pm, day 2). Results: Overall, there were no differences between DH and SH for the following glycemic outcomes (median [IQR]): TBR 1.6 [0.0, 2.4] vs. 1.28 [0.16, 3.19]%, p=1.00; time in range (TIR [3.9-10.0 mmol/L]) 68.4 [48.7, 76.8] vs. 75.7 [69.8, 87.1]%, p=0.08; and time above range (TAR [>10.0 mmol/L]) 28.1 [18.1, 49.8] vs. 23.3 [12.3, 27.2]%, p=0.10. Mean ( ± SD) glucose was higher during DH than SH (8.7 ( ± 3.2) vs. 8.1 ( ± 3.0) mmol/L, p<0.001) but coefficient of variation was similar (34.8 ( ± 6.8) vs. 37.3 ( ± 8.6)%, p=0.20). The average amount of rescue carbohydrates was similar between DH and SH (6.8 ( ± 12.3) vs. 9.5 ( ± 15.4) grams/participant/visit, p=0.78). Overnight, TIR was higher, TAR was lower during the SH visit compared to DH. During and after exercise (4:30 pm until 7 pm) the SH configuration produced higher TIR, but similar TAR and TBR compared to the DH configuration. Conclusions: DH and SH performed similarly in adolescents with type 1 diabetes during a 26-hour inpatient monitoring period involving several metabolic challenges including feeding and exercise. However, during the night and around exercise, the SH configuration outperformed DH.

Glucose Monitoring Metrics in Individuals With Type 1 Diabetes Using Different Treatment Modalities: A Real-World Observational Study.

OBJECTIVE: This study aimed to investigate the association between continuous glucose monitoring (CGM)-derived glycemic metrics and different insulin treatment modalities using real-world data. RESEARCH DESIGN AND METHODS: A cross-sectional study at Steno Diabetes Center Copenhagen, Denmark, included individuals with type 1 diabetes using CGM. Data from September 2021 to August 2022 were analyzed if CGM was used for at least 20% of a 4-week period. Individuals were divided into four groups: multiple daily injection (MDI) therapy, insulin pumps with unintegrated CGM (SUP), sensor-augmented pumps with low glucose management (SAP), and automated insulin delivery (AID). The MDI and SUP groups were further subdivided based on CGM alarm features. The primary outcome was percentage of time in range (TIR: 3.9-10.0 mmol/L) for each treatment group. Secondary outcomes included other glucose metrics and HbA1c. RESULTS: Out of 6,314 attendees, 3,184 CGM users were included in the analysis. Among them, 1,622 used MDI, 504 used SUP, 354 used SAP, and 561 used AID. Median TIR was 54.0% for MDI, 54.9% for SUP, 62,9% for SAP, and 72,1% for AID users. The proportion of individuals achieving all recommended glycemic targets (TIR >70%, time above range <25%, and time below range <4%) was significantly higher in SAP (odds ratio [OR] 2.4 [95% CI 1.6-3.5]) and AID (OR 9.4 [95% CI 6.7-13.0]) compared with MDI without alarm features. CONCLUSIONS: AID appears superior to other insulin treatment modalities with CGM. Although bias may be present because of indications, AID should be considered the preferred choice for insulin pump therapy.

Effects of a Low-Carbohydrate-High-Protein Pre-Exercise Meal in Type 1 Diabetes-a Randomized Crossover Trial.

CONTEXT: Current guidelines for exercise-related glucose management focus on reducing bolus and/or basal insulin doses and considering carbohydrate intake. Yet far less attention has been paid to the potential role of other macronutrients alongside carbohydrates on glucose dynamics around exercise. OBJECTIVE: To investigate the effects of a low-carbohydrate-high-protein (LCHP) compared with a high-carbohydrate-low-protein (HCLP) pre-exercise meal on the metabolic, hormonal, and physiological responses to exercise in adults with insulin pump-treated type 1 diabetes. METHODS: Fourteen adults (11 women, 3 men) with insulin pump-treated type 1 diabetes (median [range] HbA1c of 50 [43-59] mmol/mol (6.7% [6.1%-7.5%]), age of 49 [25-65] years, and body mass index of 24.0 [19.3-27.1] kg/m2) completed an unblinded, 2-arm, randomized, crossover study. Participants ingested isocaloric meals that were either LCHP (carbohydrate 21%, protein 52%, fat 27%) or HCLP (carbohydrate 52%, protein 21%, fat 27%) 90 minutes prior to undertaking 45 minutes of cycling at moderate intensity. Meal insulin bolus was dosed according to meal carbohydrate content but reduced by 25%. Basal insulin rates were reduced by 35% from meal ingestion to end of exercise. RESULTS: Around exercise the coefficient of variability was lower during LCHP (LCHP: 14.5 ± 5.3 vs HCLP: 24.9 ± 7.7%, P = .001). Over exercise, LCHP was associated with a lesser drop (LCHP: Δ-1.49 ± 1.89 vs HCLP: Δ-3.78 ± 1.95 mmol/L, P = .001). Mean insulin concentration was 30% lower during exercise for LCHP compared with HCLP (LCHP: 25.5 ± 11.0 vs HCLP: 36.5 ± 15.9 mU/L, P < .001). CONCLUSION: Ingesting a LCHP pre-exercise meal lowered plasma glucose variability around exercise and diminished the drop in plasma glucose over exercise.

Glycemia Around Exercise in Adults with Type 1 Diabetes Using Automated and Nonautomated Insulin Delivery Pumps: A Switch Pilot Trial.

In an in-patient switch study, 10 adults with type 1 diabetes (T1D) performed 45 min of moderate-intensity exercise on 2 occasions: (1) when using their usual insulin pump (UP) and (2) after transitioning to automated insulin delivery (AID) treatment (MiniMed™ 780G). Consensus glucose management guidelines for performing exercise were applied. Plasma glucose concentrations measured over a 3-h monitoring period were stratified into time below range (TBR, <3.9 mmol/L), time in range (TIR, 3.9-10.0 mmol/L), and time above range (TAR, >10.0 mmol/L). Overall, TBR (UP: 11 ± 21 vs. AID: 3% ± 10%, P = 0.413), TIR (UP: 53 ± 27 vs. AID: 66% ± 39%, P = 0.320), and TAR (UP: 37 ± 34 vs. AID: 31% ± 41%, P = 0.604) were similar between arms. A proportionately low number of people experienced exercise-induced hypoglycemia (UP: n = 2 vs. AID: n = 1, P = 1.00). In conclusion, switching to AID therapy did not alter patterns of glycemia around sustained moderate-intensity exercise in adults with T1D. Clinical Trial Registration number: NCT05133765.

Automated Insulin Delivery Around Exercise in Adults with Type 1 Diabetes: A Pilot Randomized Controlled Study.

Aim: To assess the effectiveness of an automated insulin delivery (AID) system around exercise in adults with type 1 diabetes (T1D). Methods: This was a three-period, randomized, crossover trial involving 10 adults with T1D (hemoglobin A1C; HbA1c: 8.3% ± 0.6% [67 ± 6 mmol/mol]) using an AID system (MiniMed 780G; Medtronic USA). Participants performed 45 min of moderate intensity continuous exercise 90 min after consuming a carbohydrate-based meal using three strategies: (1) a 100% dose of bolus insulin with exercise announcement immediately at exercise onset "spontaneous exercise" (SE) or a 25% reduced dose of bolus insulin with exercise announcement either (2) 90 min (AE90) or (3) 45 min (AE45) before exercise. Venous-derived plasma glucose (PG) taken in 5 and 15 min intervals over a 3 h collection period was stratified into the percentage of time spent below (TBR [<3.9 mmol/L]), time in range (TIR [3.9-10 mmol/L]), and time above range (TAR [ > 10 mmol/L]). In instances of hypoglycemia, PG data were carried forward for the remainder of the visit. Results: Overall, TBR was greatest during SE (SE: 22.9 ± 22.2, AE90: 1.1 ± 1.9, AE45: 7.8% ± 10.3%, P = 0.029). Hypoglycemia during exercise occurred in four participants in SE but one in both AE90 and AE45 (ꭓ2 [2] = 3.600, P = 0.165). In the 1 h postexercise period, AE90 was associated with higher TIR (SE: 43.8 ± 49.6, AE90: 97.9 ± 5.9, AE45: 66.7% ± 34.5%, P = 0.033), lower TBR (SE: 56.3 ± 49.6, AE90: 2.1 ± 5.9, AE45: 29.2% ± 36.5%, P = 0.041) with the greatest source of discrepancy observed relative to SE. Conclusion: In adults using an AID system and undertaking postprandial exercise, a strategy involving both bolus insulin dose reduction and exercise announcement 90 min before commencing the activity may be most effective in minimizing dysglycemia. The study was registered as a clinical trial (Clinical Trials Register; NCT05134025).

Modeling the effect of glucagon on endogenous glucose production in type 1 diabetes: On the role of glucagon receptor dynamics.

This paper validates a glucoregulatory model including glucagon receptors dynamics in the description of endogenous glucose production (EGP). A set of models from literature are selected for a head-to-head comparison in order to evaluate the role of glucagon receptors. Each EGP model is incorporated into an existing glucoregulatory model and validated using a set of clinical data, where both insulin and glucagon are administered. The parameters of each EGP model are identified in the same optimization problem, minimizing the root mean square error (RMSE) between the simulation and the clinical data. The results show that the RMSE for the proposed receptors-based EGP model was lower when compared to each of the considered models (Receptors approach: 7.13±1.71 mg/dl vs. 7.76±1.45 mg/dl (p=0.066), 8.45±1.38 mg/dl (p=0.011) and 8.99±1.62 mg/dl (p=0.007)). This raises the possibility of considering glucagon receptors dynamics in type 1 diabetes simulators.

Accurate Post-Calibration Predictions for Noninvasive Glucose Measurements in People Using Confocal Raman Spectroscopy.

In diabetes prevention and care, invasiveness of glucose measurement impedes efficient therapy and hampers the identification of people at risk. Lack of calibration stability in non-invasive technology has confined the field to short-term proof of principle. Addressing this challenge, we demonstrate the first practical use of a Raman-based and portable non-invasive glucose monitoring device used for at least 15 days following calibration. In a home-based clinical study involving 160 subjects with diabetes, the largest of its kind to our knowledge, we find that the measurement accuracy is insensitive to age, sex, and skin color. A subset of subjects with type 2 diabetes highlights promising real-life results with 99.8% of measurements within A + B zones in the consensus error grid and a mean absolute relative difference of 14.3%. By overcoming the problem of calibration stability, we remove the lingering uncertainty about the practical use of non-invasive glucose monitoring, boding a new, non-invasive era in diabetes monitoring.