Closed-loop Insulin Delivery In Adults Research Articles

Hypoglycemia and Hyperglycemia According to Type of Diabetes: Observations During Fully Closed-Loop Insulin Delivery in Adults With Type 1 and Type 2 Diabetes.

CamAPS HX fully closed-loop (FCL) system, with no user input required at mealtimes, has been shown to be safe and effective in adults with type 1 and type 2 diabetes. We assessed whether time spent in hypoglycemia and hyperglycemia during FCL insulin delivery in adults varied by type of diabetes over the 24-hour period. We retrospectively analyzed eight weeks of data from 52 participants (adults with type 1 diabetes and adults with insulin-treated type 2 diabetes) recruited to two single-center randomized controlled studies using FCL insulin delivery during unrestricted-living conditions. Key outcomes were time spent in hypoglycemia <70 mg/dL and marked hyperglycemia >300 mg/dL by type of diabetes. The median percentage of time spent in hypoglycemia <70 mg/dL over the 24-hour period was lower for those with type 2 diabetes than for those with type 1 diabetes (median [interquartile range (IQR)] 0.43% [0.20-0.77] vs 0.86%, [0.54-1.46]; mean difference 0.46 percentage points [95% CI 0.23-0.70]; P < .001). Median percentage time in marked hyperglycemia >300 mg/dL was lower for those with type 2 diabetes than for those with type 1 diabetes (median [IQR] 1.8% [0.6-3.5] vs 9.3% [6.9-11.8]; mean difference 7.8 percentage points [95% CI 5.5-10.0]; P < .001). Using the FCL system, hypoglycemia and marked hyperglycemia exposure were lower in type 2 diabetes than in type 1 diabetes.

Fully automated closed-loop insulin delivery in adults with type 2 diabetes: an open-label, single-center, randomized crossover trial

In adults with type 2 diabetes, the benefits of fully closed-loop insulin delivery, which does not require meal bolusing, are unclear. In an open-label, single-center, randomized crossover study, 26 adults with type 2 diabetes (7 women and 19 men; (mean ± s.d.) age, 59 ± 11 years; baseline glycated hemoglobin (HbA1c), 75 ± 15 mmol mol−1 (9.0% ± 1.4%)) underwent two 8-week periods to compare the CamAPS HX fully closed-loop app with standard insulin therapy and a masked glucose sensor (control) in random order, with a 2-week to 4-week washout between periods. The primary endpoint was proportion of time in target glucose range (3.9–10.0 mmol l−1). Analysis was by intention to treat. Thirty participants were recruited between 16 December 2020 and 24 November 2021, of whom 28 were randomized to two groups (14 to closed-loop therapy first and 14 to control therapy first). Proportion of time in target glucose range (mean ± s.d.) was 66.3% ± 14.9% with closed-loop therapy versus 32.3% ± 24.7% with control therapy (mean difference, 35.3 percentage points; 95% confidence interval (CI), 28.0–42.6 percentage points; P < 0.001). Time > 10.0 mmol l−1 was 33.2% ± 14.8% with closed-loop therapy versus 67.0% ± 25.2% with control therapy (mean difference, −35.2 percentage points; 95% CI, −42.8 to −27.5 percentage points; P < 0.001). Mean glucose was lower during the closed-loop therapy period than during the control therapy period (9.2 ± 1.2 mmol l−1 versus 12.6 ± 3.0 mmol l−1, respectively; mean difference, −3.6 mmol l−1; 95% CI, −4.6 to −2.5 mmol l−1; P < 0.001). HbA1c was lower following closed-loop therapy (57 ± 9 mmol mol−1 (7.3% ± 0.8%)) than following control therapy (72 ± 13 mmol mol−1 (8.7% ± 1.2%); mean difference, −15 mmol mol−1; 95% CI, −11 to −20 mmol l−1 (mean difference, −1.4%; 95% CI, −1.0 to −1.8%); P < 0.001). Time < 3.9 mmol l−1 was similar between treatments (a median of 0.44% (interquartile range, 0.19–0.81%) during the closed-loop therapy period versus a median of 0.08% (interquartile range, 0.00–1.05%) during the control therapy period; P = 0.43). No severe hypoglycemia events occurred in either period. One treatment-related serious adverse event occurred during the closed-loop therapy period. Fully closed-loop insulin delivery improved glucose control without increasing hypoglycemia compared with standard insulin therapy and may represent a safe and efficacious method to improve outcomes in adults with type 2 diabetes. This study is registered with ClinicalTrials.gov (NCT04701424).

A single-blind, randomised, crossover study to reduce hypoglycaemia risk during postprandial exercise with closed-loop insulin delivery in adults with type 1 diabetes: announced (with or without bolus reduction) vs unannounced exercise strategies.

For individuals living with type 1 diabetes, closed-loop insulin delivery improves glycaemic control. Nonetheless, maintenance of glycaemic control during exercise while a prandial insulin bolus remains active is a challenge even to closed-loop systems. We investigated the effect of exercise announcement on the efficacy of a closed-loop system, to reduce hypoglycaemia during postprandial exercise. A single-blind randomised, crossover open-label trial was carried out to compare three strategies applied to a closed-loop system at mealtime in preparation for exercise taken 90min after eating at a research testing centre: (1) announced exercise to the closed-loop system (increases target glucose levels) in addition to a 33% reduction in meal bolus (A-RB); (2) announced exercise to the closed-loop system and a full meal bolus (A-FB); (3) unannounced exercise and a full meal bolus (U-FB). Participants performed 60min of exercise at 60% [Formula: see text] 90min after eating breakfast. The investigators were not blinded to the interventions. However, the participants were blinded to the sensor glucose readings and to the insulin infusion rates throughout the intervention visits. The trial was completed by 37 adults with type 1 diabetes, all using insulin pumps: mean±SD, 40.0 ± 15.0years of age, HbA1c 57.1 ± 10.8mmol/mol (7.3 ± 1.0%). Reported results were based on plasma glucose values. During exercise and the following 1h recovery period, time spent in hypoglycaemia (<3.9mmol/l; primary outcome) was reduced with A-RB (mean ± SD; 2.0 ± 6.2%) and A-FB (7.0 ± 12.6%) vs U-FB (13.0 ± 19.0%; p < 0.0001 and p = 0.005, respectively). During exercise, A-RB had the least drop in plasma glucose levels: A-RB -0.3 ± 2.8mmol/l, A-FB -2.6 ± 2.9mmol/l vs U-FB -2.4 ± 2.7mmol/l (p < 0.0001 and p = 0.5, respectively). Comparison of A-RB vs U-FB revealed a decrease in the time spent in target (3.9-10mmol/l) by 12.7% (p = 0.05) and an increase in the time spent in hyperglycaemia (>10mmol/l) by 21% (p = 0.001). No side effects were reported during the applied strategies. Combining postprandial exercise announcement, which increases closed-loop system glucose target levels, with a 33% meal bolus reduction significantly reduced time spent in hypoglycaemia compared with the other two strategies, yet at the expense of more time spent in hyperglycaemia. ClinicalTrials.gov NCT0285530 FUNDING: JDRF (2-SRA-2016-210-A-N), the Canadian Institutes of Health Research (354024) and the Fondation J.-A. DeSève chair held by RR-L.

Pharmacokinetics of Faster and Standard Insulin Aspart During Fully Closed-Loop Insulin Delivery in Type 2 Diabetes.

Background: Faster insulin aspart is a novel formulation of insulin aspart aiming to accelerate its subcutaneous absorption. The aim of this study was to compare pharmacokinetics of faster insulin aspart versus standard insulin aspart in adults with type 2 diabetes during closed-loop insulin delivery. Methods: We assessed the pharmacokinetics of faster and standard insulin aspart from data obtained in a randomized double-blind crossover study evaluating fully closed-loop insulin delivery in adults with type 2 diabetes (n = 13, age 59 ± 10 years, BMI 34.5 ± 9.1 kg/m2, HbA1c 7.7% ± 1.2% [60 ± 13 mmol/mol]). Blood samples were collected every 15-30 min for 10 h to determine plasma insulin aspart concentration using liquid chromatography mass spectrometry. Time to peak plasma concentration (Tmax) was calculated using a two-compartment model. Results:Tmax was 68.7 ± 21.6 min for faster aspart and 89.7 ± 31.8 min for aspart (mean paired difference faster aspart minus aspart -15.5 min, 95% CI [-31.6 to 0.6 min], P = 0.06). Metabolic clearance rate did not differ between the two insulins (P = 0.61). Insulin amount delivered during closed-loop with faster aspart positively correlated with Tmax (rS = 0.73, P = 0.01), whereas no statistically significant correlation was found with body mass index (BMI), weight or HbA1C (all P > 0.18). Conclusion: In conclusion, Tmax tended to be shorter for faster aspart versus aspart during fully automated closed-loop insulin delivery and positively correlated with the amount of insulin delivered.

725-P: Reducing Hypoglycemic Risk during Postprandial Exercise with Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes: Announced and Unannounced Exercise

Background: Exercise-induced hypoglycemia is a major barrier for physical activity practice. Compared to conventional insulin therapy, closed-loop (CL) insulin delivery reduces hypoglycemic risk during post-absorptive exercise but has not been studied during postprandial exercise. Methods: Randomized crossover trial comparing 3 strategies for a postprandial (PP) exercise (90 min after breakfast) at 60% of VO2peak for 60min: 1) Unannounced exercise (Unann); 2) Announced exercise with reduced insulin bolus (Ann+RB): increased glucose target combined with a 33% meal bolus reduction); 3) Announced exercise with full bolus (Ann+FB): increased glucose target combined with usual meal bolus in 37 adults with type 1 diabetes. Results: Median percentage time spent in hypoglycemia (&amp;lt;70 mg/dl) was reduced with Ann+RB compared to Unann (Primary outcome; 0[0-0]% vs. 0[0-26]%; p&amp;lt;0.05). The drop in plasma glucose during exercise was smaller with Ann+RB (-5.5 ± 50.5 than with Ann+FB (-46.8 ± 52.2) and Unann (-43.2 ± 48.6) strategies (p &amp;lt;0.05). Accordingly, hypoglycemic events were reduced with Ann+RB (n=2) compared to Ann+FB (n=3) and Unann (n=9). However, Ann+BR strategy was associated with increased time in hyperglycemia (&amp;gt; 250mg/dl). Conclusion: Announcement of postprandial exercise to the closed-loop algorithm combined with meal bolus reduction reduced hypoglycemic risk, yet at the expense of mild increase in hyperglycemia. Disclosure S. Tagougui: None. N. Taleb: None. C. Suppere: None. I. Boukabous: None. V. Messier: Other Relationship; Self; Eli Lilly and Company. R. Rabasa-Lhoret: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S.

Closed-loop insulin delivery in adults with type 1 diabetes in real-life conditions: a 12-week multicentre, open-label randomised controlled crossover trial

Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy. In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA1c) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556. Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error. The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes. French Innovation Fund, Diabeloop.

Impact of macronutrient content of meals on postprandial glucose control in the context of closed-loop insulin delivery: A randomized cross-over study.

The aim of this randomized four-way cross-over study was to examine the effect of added protein and/or fat in standard meals with a fixed carbohydrate content on postprandial glucose control with closed-loop insulin delivery in adults with type 1 diabetes. Participants (n = 15) consumed breakfast meals with a fixed carbohydrate content (75 ± 1 g) and added protein and/or fat (35 ± 2 g): (1) carbohydrate-only (standard), (2) high protein (HP), (3) high fat (HF) and (4) high fat + protein (HFHP). The closed-loop insulin delivery algorithm generated insulin bolus and infusion rates. The addition of fat, protein or both did not impact 5-hour post-meal sensor glucose area under the curve (AUC) (main outcome), mean sensor glucose or glycaemic peak as compared with a standard meal (P > 0.05). However, time to glycaemic peak was delayed by 40 minutes (P = 0.03) and 5-hour post-meal basal insulin requirements were 39% higher (P = 0.04) with an HFHP meal compared with a standard meal. In conclusion, in the context of closed-loop insulin delivery, protein and/or fat meal content affects the timing of postprandial glycaemic peak, insulin requirements and late glycaemic excursion, without impacting overall 5-hour AUC.

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol

IntroductionManual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective...

Behavioral Patterns and Associations with Glucose Control During 12-Week Randomized Free-Living Clinical Trial of Day and Night Hybrid Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes.

Objectives: We evaluated patterns of meal intake, insulin bolus delivery, and fingerstick glucose measurements during hybrid closed-loop and sensor-augmented pump (SAP) therapy, including associations with glucose control.Methods: Data were retrospectively analyzed from pump-treated adults with type 1 diabetes who underwent, in random order, 12 weeks free-living closed-loop (n = 32) and 12 weeks SAP (n = 33) periods. We quantified daily patterns of main meals, snacks, prandial insulin boluses, correction boluses, and fingerstick glucose measurements by analyzing data recorded on the study glucometer and on study insulin pump.Results: We analyzed 1942 closed-loop days and 2530 SAP days. The total number of insulin boluses was reduced during closed-loop versus SAP periods by mean 1.0 per day (95% confidence interval 0.6–1.4, P < 0.001) mainly because of a reduced number of correction boluses by mean 0.7 per day (0.4–1.0, P < 0.001). Other behavioral patterns were unchanged. The carbohydrate content of snacks but not the number of snacks was positively correlated with (1) glycemic variability as measured by standard deviation of sensor glucose (closed-loop P < 0.05; SAP P < 0.01), (2) mean sensor glucose (P < 0.05), and (3) postintervention HbA1c (P < 0.05). Behavioral patterns explained 47% of between-subject variance in glucose variability during SAP period and 30%–33% of variance of means sensor glucose and postintervention HbA1c.Conclusion: Fewer correction boluses are delivered during closed-loop period. The size of snacks appears to worsen glucose control possibly because of carbohydrate-rich content of snacks. Modifiable behavioral patterns may be important determinants of glucose control.

Variability of Insulin Requirements Over 12 Weeks of Closed-Loop Insulin Delivery in Adults With Type 1 Diabetes.

To quantify variability of insulin requirements during closed-loop insulin delivery. We retrospectively analyzed overnight, daytime, and total daily insulin amounts delivered during a multicenter closed-loop trial involving 32 adults with type 1 diabetes. Participants applied hybrid day-and-night closed-loop insulin delivery under free-living home conditions over 12 weeks. The coefficient of variation was adopted to measure variability of insulin requirements in individual subjects. Data were analyzed from 1,918 nights, 1,883 daytime periods and 1,564 total days characterized by closed-loop use over 85% of time. Variability of overnight insulin requirements (mean [SD] coefficient of variation 31% [4]) was nearly twice as high as variability of total daily requirements (17% [3], P < 0.001) and was also higher than variability of daytime insulin requirements (22% [4], P < 0.001). Overnight insulin requirements were significantly more variable than daytime and total daily amounts. This may explain why some people with type 1 diabetes report frustrating variability in morning glycemia.

Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol.

IntroductionDespite therapeutic advances, many people with type 1 diabetes are still unable to achieve optimal glycaemic control, limited by the occurrence of hypoglycaemia. The objective of the present study is to determine the effectiveness of day and night home closed-loop over the medium term compared with sensor-augmented pump therapy in adults with type 1 diabetes and suboptimal glycaemic control.Methods and analysisThe study will adopt an open label, three-centre, multinational, randomised, two-period crossover study design comparing automated closed-loop glucose control with sensor augmented insulin pump therapy. The study will aim for 30 completed participants. Eligible participants will be adults (≥18 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c) ≥7.5% (58 mmol/mmol) and ≤10% (86 mmol/mmol)). Following a 4-week optimisation period, participants will undergo a 3-month use of automated closed-loop insulin delivery and sensor-augmented pump therapy, with a 4–6 week washout period in between. The order of the interventions will be random. All analysis will be conducted on an intention to treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3 months free living phase. Secondary outcomes include HbA1c changes; mean glucose and time spent above and below target glucose levels. Further, participants will be invited at baseline, midpoint and study end to participate in semistructured interviews and complete questionnaires to explore usability and acceptance of the technology, impact on quality of life and fear of hypoglycaemia.Ethics and disseminationEthical approval has been obtained at all sites. Before screening, all participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.Trial registration numberNCT01961622 (ClinicalTrials.gov).

Day and Night Home Closed-Loop Insulin Delivery in Adults With Type 1 Diabetes: Three-Center Randomized Crossover Study

To evaluate the feasibility of day and night closed-loop insulin delivery in adults with type 1 diabetes under free-living conditions. Seventeen adults with type 1 diabetes on insulin pump therapy (means ± SD age 34 ± 9 years, HbA1c 7.6 ± 0.8%, and duration of diabetes 19 ± 9 years) participated in an open-label multinational three-center crossover study. In a random order, participants underwent two 8-day periods (first day at the clinical research facility followed by 7 days at home) of sensor-augmented insulin pump therapy (SAP) or automated closed-loop insulin delivery. The primary end point was the time when sensor glucose was in target range between 3.9 and 10.0 mmol/L during the 7-day home phase. During the home phase, the percentage of time when glucose was in target range was significantly higher during closed-loop compared with SAP (median 75% [interquartile range 61-79] vs. 62% [53-70], P = 0.005). Mean glucose (8.1 vs. 8.8 mmol/L, P = 0.027) and time spent above target (P = 0.013) were lower during closed loop, while time spent below target was comparable (P = 0.339). Increased time in target was observed during both daytime (P = 0.017) and nighttime (P = 0.013). Compared with SAP, 1 week of closed-loop insulin delivery at home reduces mean glucose and increases time in target without increasing the risk of hypoglycemia in adults with relatively well-controlled type 1 diabetes.

Closing the loop

Closing the loop

Automated Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes

Automated closed-loop insulin delivery systems control blood glucose by linking continuous subcutaneous glucose monitoring with subcutaneous insulin pump delivery. In two randomized crossover studies, investigators compared the safety and efficacy of overnight closed-loop insulin delivery with those of conventional insulin pump delivery in 24 …