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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Using the FCL system, hypoglycemia and marked hyperglycemia exposure were lower in type 2 diabetes than in type 1 diabetes.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Glycemic Outcomes with Closed-Loop Insulin Delivery.

The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9-10.0 mmol/L (70-180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis.

Lived Experience of Fully Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes.

Introduction: The Closing the Loop in Adults With Type 1 Diabetes (CLEAR) randomized crossover study compared a novel fully closed-loop insulin delivery system with no carbohydrate entry or mealtime bolusing (CamAPS HX), with standard insulin pump therapy and glucose sensor in adults with type 1 diabetes and suboptimal glycemic outcomes. This qualitative substudy aimed to understand the psychosocial impact of using the fully automated system. Materials and Methods: Adults participating in the CLEAR study were invited to take part in a virtual semistructured interview after they had completed 8 weeks using the fully closed-loop system. Recruitment continued until there was adequate representation and data saturation occurred. Interviews were anonymized and transcribed for in-depth thematic analysis using an inductive-deductive approach. Study participants were also asked to complete questionnaires assessing diabetes distress, hypoglycemia confidence, and closed-loop treatment satisfaction. Results: Eleven participants (eight male and three female; age range 26-66 years) were interviewed. After an initial adjustment period, interviewees reported enjoying a reduction in diabetes burden, freed-up mental capacity, and improved mood. All were happy with overnight glycemic outcomes, with the majority reporting benefits on sleep. Although experiences of postprandial glucose outcomes varied, all found mealtimes easier and less stressful, particularly when eating out. Negatives raised by participants predominantly related to the insulin pump hardware, but some also reported increased snacking and challenges around resuming carbohydrate counting at trial closeout. Conclusions: In adults with type 1 diabetes, use of a fully closed-loop insulin delivery system had significant quality-of-life benefits and provided a welcome break from the day-to-day demands of living with diabetes. Clinical Trial Registration: NCT04977908.

Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogs in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes.

Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.

CamAPS FX Hybrid Closed-Loop with Ultra-Rapid Lispro Compared with Standard Lispro in Adults with Type 1 Diabetes: A Double-Blind, Randomized, Crossover Study.

Introduction: To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) compared with hybrid closed-loop with standard insulin lispro in adults with type 1 diabetes. Materials and Methods: In a single-center, double-blind, randomized, crossover study, 28 adults with type 1 diabetes (mean ± standard deviation [SD]: age 44.5 ± 10.7 years, glycated hemoglobin (HbA1c) 7.1 ± 0.9% [54 ± 10 mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with ultra-rapid insulin lispro and hybrid closed-loop with standard insulin lispro in random order. The same CamAPS FX closed-loop algorithm was used in both periods. Results: In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9-10 mmol/L [70-180 mg/dL]; primary endpoint) was greater with ultra-rapid lispro compared with standard insulin lispro (mean ± SD: 78.7 ± 9.8% vs. 76.2 ± 9.6%; mean difference 2.5 percentage points [95% confidence interval 0.8 to 4.2]; P = 0.005). Mean sensor glucose was lower with ultra-rapid lispro compared with standard insulin lispro (7.9 ± 0.8 mmol/L [142 ± 14 mg/dL] vs. 8.1 ± 0.9 mmol/L [146 ± 16 mg/dL]; P = 0.048). The proportion of time with sensor glucose <3.9 mmol/L [70 mg/dL] was similar between interventions (median [interquartile range] ultra-rapid lispro 2.3% [1.3%-2.7%] vs. standard insulin lispro 2.1% [1.4%-3.3%]; P = 0.33). No severe hypoglycemia or ketoacidosis occurred. Conclusions: The use of ultra-rapid lispro with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with type 1 diabetes. ClinicalTrials.gov: Trial registration number NCT05257460.

Fully Closed-Loop Glucose Control Compared With Insulin Pump Therapy With Continuous Glucose Monitoring in Adults With Type 1 Diabetes and Suboptimal Glycemic Control: A Single-Center, Randomized, Crossover Study.

OBJECTIVE: We evaluated the safety and efficacy of fully closed-loop with ultrarapid insulin lispro in adults with type 1 diabetes and suboptimal glycemic control compared with insulin pump therapy with continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS: This single-center, randomized, crossover study enrolled 26 adults with type 1 diabetes using insulin pump therapy with suboptimal glycemic control (mean ± SD, age 41 ± 12 years, HbA1c 9.2 ± 1.1% [77 ± 12 mmol/mol]). Participants underwent two 8-week periods of unrestricted living to compare fully closed-loop with ultrarapid insulin lispro (CamAPS HX system) with insulin pump therapy with CGM in random order. RESULTS: In an intention-to-treat analysis, the proportion of time glucose was in range (primary end point 3.9-10.0 mmol/L) was higher during closed-loop than during pump with CGM (mean ± SD 50.0 ± 9.6% vs. 36.2 ± 12.2%, mean difference 13.2 percentage points [95% CI 9.5, 16.9], P < 0.001). Time with glucose >10.0 mmol/L and mean glucose were lower during closed-loop than during pump with CGM (mean ± SD time >10.0 mmol/L: 49.0 ± 9.9 vs. 62.9 ± 12.6%, mean difference -13.3 percentage points [95% CI -17.2, -9.5], P < 0.001; mean ± SD glucose 10.7 ± 1.1 vs. 12.0 ± 1.6 mmol/L, mean difference -1.2 mmol/L [95% CI -1.8, -0.7], P < 0.001). The proportion of time with glucose <3.9 mmol/L was similar between periods (median [interquartile range (IQR)] closed-loop 0.88% [0.51-1.55] vs. pump with CGM 0.64% [0.28-1.10], P = 0.102). Total daily insulin requirements did not differ (median [IQR] closed-loop 51.9 units/day [35.7-91.2] vs. pump with CGM 50.7 units/day [34.0-70.0], P = 0.704). No severe hypoglycemia or ketoacidosis occurred. CONCLUSIONS: Fully closed-loop insulin delivery with CamAPS HX improved glucose control compared with insulin pump therapy with CGM in adults with type 1 diabetes and suboptimal glycemic control.

The changing landscape of automated insulin delivery in the management of type 1 diabetes.

Automated insulin delivery systems, also known as closed-loop or 'artificial pancreas' systems, are transforming the management of type 1 diabetes. These systems consist of an algorithm which responds to real-time glucose sensor levels by automatically modulating insulin delivery through an insulin pump. We review the rapidly changing landscape of automated insulin-delivery systems over recent decades, from initial prototypes to the different hybrid closed-loop systems commercially available today. We discuss the growing body of clinical trials and real-world evidence demonstrating their glycaemic and psychosocial benefits. We also address future directions in automated insulin delivery such as dual-hormone systems and adjunct therapy as well as the challenges around ensuring equitable access to closed-loop technology.

Time Spent in Hypoglycemia According to Age and Time of Day: Observations During Closed-Loop Insulin Delivery.

Objective: We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age group and time of day. Methods: We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9 mmol/L (<70 mg/dL). Eight weeks of data for 88 participants were analyzed. Results: Median time spent in hypoglycemia over the 24-h period was highest in children and adolescents (4.4% [interquartile range 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); P < 0.001 for difference between age groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age groups. Conclusion: Time in hypoglycemia was highest in the pediatric age group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age groups.

Noninvasive Biomarkers for Cardiovascular Dysfunction Programmed in Male Offspring of Adverse Pregnancy.

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