Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes.

BACKGROUND: Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear. METHODS: In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes. RESULTS: A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).

Accuracy of Three Commercial Home-Use Hemoglobin A1c Tests.

Background: The COVID-19 pandemic and the rapid expansion of telemedicine have increased the need for accurate and reliable capillary hemoglobin A1c (HbA1c) testing. Nevertheless, validation studies of commercially available products suitable for home use have been in short supply. Methods: Three commercial home-use capillary blood sample HbA1c tests (Home Access, CoreMedica, and A1cNow+) were evaluated in 219 participants with type 1 or type 2 diabetes (4-80 years years of age, HbA1c 5.1%-13.4% [32-123 mmol/mol]) at four clinical sites. Comparisons were made between HbA1c measurements from the commercial tests and paired venous samples for which HbA1c was measured at two central reference laboratories. The primary outcome was percentage of commercial HbA1c values within 5% of the corresponding reference values. Results: HbA1c values were within 5% (relative difference) of paired reference values for 82% of Home Access samples, 29% of CoreMedica samples, and 46% of A1cNow+ samples. Absolute differences were within 0.3% of the reference value for 75% of Home Access samples, 28% of CoreMedica samples, and 44% of A1cNow+ samples and exceeded 0.5% for 8%, 55%, and 37%, respectively. Conclusions: None of the commercial home-use HbA1c tests produced the National Glycohemoglobin Standardization Program goal of ≥90% measurements within 5% of a DCCT venous reference. However, the Home Access product performed substantially better than the CoreMedica or A1cNow+ products. Telemedicine is likely to persist as a mainstay of diabetes care well after the COVID-19 era. As such, accurate home-based HbA1c assessment represents an urgent need for the diabetes community.

Outpatient Randomized Crossover Comparison of Zone Model Predictive Control Automated Insulin Delivery with Weekly Data Driven Adaptation Versus Sensor-Augmented Pump: Results from the International Diabetes Closed-Loop Trial 4.

Background: Automated insulin delivery (AID) systems have proven effective in increasing time-in-range during both clinical trials and real-world use. Further improvements in outcomes for single-hormone (insulin only) AID may be limited by suboptimal insulin delivery settings. Methods: Adults (≥18 years of age) with type 1 diabetes were randomized to either sensor-augmented pump (SAP) (inclusive of predictive low-glucose suspend) or adaptive zone model predictive control AID for 13 weeks, then crossed over to the other arm. Each week, the AID insulin delivery settings were sequentially and automatically updated by an adaptation system running on the study phone. Primary outcome was sensor glucose time-in-range 70-180 mg/dL, with noninferiority in percent time below 54 mg/dL as a hierarchical outcome. Results: Thirty-five participants completed the trial (mean age 39 ± 16 years, HbA1c at enrollment 6.9% ± 1.0%). Mean time-in-range 70-180 mg/dL was 66% with SAP versus 69% with AID (mean adjusted difference +2% [95% confidence interval: -1% to +6%], P = 0.22). Median time <70 mg/dL improved from 3.0% with SAP to 1.6% with AID (-1.5% [-2.4% to -0.5%], P = 0.002). The adaptation system decreased initial basal rates by a median of 4% (-8%, 16%) and increased initial carbohydrate ratios by a median of 45% (32%, 59%) after 13 weeks. Conclusions: Automated adaptation of insulin delivery settings with AID use did not significantly improve time-in-range in this very well-controlled population. Additional study and further refinement of the adaptation system are needed, especially in populations with differing degrees of baseline glycemic control, who may show larger benefits from adaptation.

The Inaccuracy of Commercial Home Hemoglobin A1c Tests

The COVID-19 pandemic and rapid expansion of telemedicine has increased the need for accurate and reliable capillary A1c testing. Nevertheless, validation studies of commercially available kits have been in short supply. As such, capillary and venous A1c samples were assessed using 3 commercial home kits (Home Access, CoreMedica, A1cNow) and 2 non-commercial kits from academic centers (U of MN Advanced Research and Diagnostic Lab [ARDL] and Children's Mercy Hospital [CMH]). Samples were collected either with study staff guidance (non-commercial) or hands-on assistance (commercial) and sent by USPS for processing except for the immediate response A1cNow+ kit. Differences in A1c between commercial kits and reference values were appreciable (Table). Notably, none of the commercially tested kits reached the National Glycohemoglobin Standardization Program target of more than 90% of values within 5% of DCCT venous reference values although the Home Access kit performed much better than the other two. In contrast, evaluation of kits from ARDL and CMH showed 97.4% of values within the 5% standard. Ease of use and discomfort with sample collection varied between kits. While the accuracy of the commercial kits analyzed was limited, participants' response was positive overall. Telemedicine is likely to persist as a mainstay of diabetes care well after the COVID-19 era. As such, accurate home A1c testing represents an urgent need for the diabetes community.

An Evaluation of Two Capillary Sample Collection Kits for Laboratory Measurement of HbA1c.

Background: The COVID-19 pandemic has impacted the conduct of clinic visits. We conducted a study to evaluate two academic laboratories' fingerstick capillary blood collection kits suitable for home use for laboratory measurement of HbA1c. Methods: Four clinical sites recruited 240 participants (aged 4-80 years, HbA1c 5.1%-13.5%). Capillary blood samples were obtained by the participant or parent using collection kits from two laboratories (University of Minnesota Advanced Research and Diagnostic Laboratory (ARDL) and Children's Mercy Hospital Laboratory (CMH)) and mailed under varying shipping conditions by United States Postal Service to the laboratories. Comparisons were made between HbA1c measurements from capillary samples and contemporaneously obtained venous samples. The primary outcome was percentage of capillary HbA1c values within 5% of the corresponding venous values. Results: HbA1c values were within 5% of venous values for 96% of ARDL kit specimens shipped with a cold pack and 98% without a cold pack and 99% and 99%, respectively, for the CMH kits. R2 values were 0.98, 0.99, 0.99, and 0.99, respectively. Results appeared similar across HbA1c levels and for pediatric and adult participants. Usability survey scores were high. Conclusions: Capillary blood collection kits, suitable for home use, from two academic laboratories, were demonstrated to be easy to use and provided results that are comparable with those obtained from venous specimens. Based on these results, there is strong evidence that HbA1c measurements from capillary specimens obtained with these specific kits can be used interchangeably with HbA1c measurements from venous specimens for clinical research and clinical care.