Two subsets of conventional dendritic cells (cDCs) with distinct cell surface markers and functions exist in mouse and human. The two subsets of cDCs are specialized antigen-presenting cells that ...initiate T cell immunity and tolerance. In the mouse, a migratory cDC precursor (pre-CDC) originates from defined progenitors in the bone marrow (BM). Small numbers of short-lived pre-CDCs travel through the blood and replace cDCs in the peripheral organs, maintaining homeostasis of the highly dynamic cDC pool. However, the identity and distribution of the immediate precursor to human cDCs has not been defined. Using a tissue culture system that supports the development of human DCs, we identify a migratory precursor (hpre-CDC) that exists in human cord blood, BM, blood, and peripheral lymphoid organs. hpre-CDCs differ from premonocytes that are restricted to the BM. In contrast to earlier progenitors with greater developmental potential, the hpre-CDC is restricted to producing CD1c(+) and CD141(+) Clec9a(+) cDCs. Studies in human volunteers demonstrate that hpre-CDCs are a dynamic population that increases in response to levels of circulating Flt3L.
In mice, two restricted dendritic cell (DC) progenitors, macrophage/dendritic progenitors (MDPs) and common dendritic progenitors (CDPs), demonstrate increasing commitment to the DC lineage, as they ...sequentially lose granulocyte and monocyte potential, respectively. Identifying these progenitors has enabled us to understand the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34(+) hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, and NK and B cells. Using this culture system, we defined the pathway for human DC development and revealed the sequential origin of human DCs from increasingly restricted progenitors: a human granulocyte-monocyte-DC progenitor (hGMDP) that develops into a human monocyte-dendritic progenitor (hMDP), which in turn develops into monocytes, and a human CDP (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte-macrophage progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues.
Background:
The perceived value and consistent use of continuous glucose monitoring (CGM) systems depends in part on their accuracy. We assessed the performance of a sixth-generation CGM system ...(Dexcom G6) in children and adolescents.
Methods:
Forty-nine participants (6-17 years of age, mean ± SD of 13.5 ± 3.3 years), all with type 1 diabetes, enrolled and data were available from 37. Each participant wore 1 sensor for up to 10 days and was asked to undergo an in-clinic visit lasting 6-12 hours for frequent blood glucose (BG) sample testing on one of the sensor wear days. Estimated glucose values (EGVs) from the G6 system were compared with venous BG values measured with a laboratory reference instrument (YSI).
Results:
The overall mean absolute relative difference (MARD) for 1387 EGV-YSI pairs was 7.7%, and the overall percentage of EGVs within 20% or 20 mg/dL of the YSI reference value (for YSI > or ⩽100 mg/dL, respectively, the “%20/20”) was 96.2%. The %20/20 was 92.1% on Day 1 and 91.0% on Day 10 of sensor wear. For EGVs <70 mg/dL, 92.6% of the YSI values were within 20 mg/dL and for EGVs >250 mg/dL, 100% of the YSI values were within 20%. Differences between EGVs and YSI values in over 99.9% of the pairs posed no or only slight clinical risk as evaluated by surveillance error grid analysis.
Conclusions:
The accuracy of the G6 CGM system in pediatrics may encourage consistent use of the system and contribute to improved glycemic outcomes in this population.
Introduction
Few studies have evaluated glycaemic control using continuous glucose monitoring (CGM) in individuals before and after attendance at a diabetes camp or by comparing control groups at ...home to control groups at camp.
Methods
Youth (6–17 years) with T1D and receiving insulin therapy were enrolled at a week‐long diabetes camp. They participated in three clinic visits: at the start of a week at home, by initiating a Dexcom G6 CGM system; at the start of a week at camp, where the home week G6 was removed and a camp week G6 was inserted; and after camp, where the camp week G6 was removed. We administered Problem Areas in Diabetes (PAID) surveys at the second and third visits. Participants with <80% CGM data coverage or who did not complete all PAID surveys were excluded from analysis. We compared glycaemic control and PAID scores between the week at home and week at camp.
Results
Of 76 enrolled campers, 69 completed the study and 52 had results that qualified for analysis. The mean participant age was 12.5 ± 2.2 years. Camp was associated with significantly improved treatment satisfaction, time in desired glucose range and insulin sensitivity. Time in hyperglycaemia and basal insulin requirements decreased significantly.
Conclusions
Diabetes camp is associated with significant improvements in diabetes treatment satisfaction and glycaemic control compared to home care.
Children with Type I Diabetes enjoying fun and safe activities at Barton Diabetes Camp. Glycemic control and satisfaction with diabetes improved during camp weeks.
Real-time continuous glucose monitoring (CGM) systems with threshold alerts can disencumber users by automatically warning of out-of-range glucose values. We examined correlations between time in ...range (TIR; 70-180 mg/dL), hyperglycemia alert use, and screen view frequency in a large real-world cohort. Anonymized data uploaded in 2020 by 19,367 US-based users of the G6 CGM System (Dexcom, Inc., San Diego, CA) were assessed. Data from users with >70% device utilization and validated alert settings were included. Users were stratified by screen view frequency and hyperglycemia alert use. Panel A shows TIR vs. screen view frequency for 3 cohorts defined as having the hyperglycemia alert always, sometimes, or never on. Compared to non-use, consistent use of the hyperglycemia alert corresponded to a ~5.5% higher TIR. By contrast, screen view frequency was weakly associated with increased TIR, likely because the trend screen must be accessed to silence the alert. Panel B shows the moderate inverse correlation between TIR and hyperglycemia alert setting. Automated hyperglycemia alerts may motivate appropriate treatment decisions without requiring constant scrutiny of the CGM trend screen. Lowering the hyperglycemia alert threshold may be an appropriate strategy for patients wishing to improve their TIR.
Accuracy and feature sets of continuous glucose monitoring (CGM) systems may influence device utilization and outcomes. We compared clinical trial accuracy and real-world utilization and ...effectiveness of two different CGM systems.
Separately conducted accuracy studies of a fifth-generation and a sixth-generation CGM system involved 50 and 159 adults, respectively. For between-system performance comparisons, propensity score methods were utilized to balance cohort characteristics. Real-world outcomes were assessed in 10,000 anonymized patients who had switched from the fifth-generation to the sixth-generation system and had used connected mobile devices to upload data from both systems, allowing pairwise comparisons of device utilization and glucose concentration distributions.
Propensity score-adjusted mean absolute relative differences for the fifth- and sixth-generation systems were 9.0% and 9.9%, and the percentages of values within ±20%/20 mg/dL were 93.1% and 92.5%, respectively. The sixth-generation system, but not the fifth-generation system, met accuracy criteria for interoperable CGM systems. Both systems had high real-world utilization rates (93.8% and 95.3% in the fifth- and sixth-generation systems, respectively). Use of the sixth-generation system was associated with fewer glucose values <55 mg/dL (<3.1 mmol/L) (0.7% vs. 1.1%, P < 0.001) and more values 70-180 mg/dL (3.9-10.0 mmol/L) (57.3% vs. 56.0%, P < 0.001) than the fifth-generation system.
CGM performance outcomes can be compared through the propensity score analysis of clinical trial data and pairwise comparisons of real-world data. The systems compared here had nearly equivalent accuracy and utilization rates. Longer term biochemical and psychosocial benefits observed with the fifth-generation system are also expected with the sixth-generation system.
Programmable and fixed auditory and/or vibratory threshold alerts are essential features of real-time continuous glucose monitoring (rtCGM) systems that provide users time to intervene before the ...onset of clinical hypoglycemia or hyperglycemia. A sixth-generation rtCGM system from Dexcom, Inc. (G6) includes a new alert that is triggered when an algorithm predicts that an estimated glucose value ≤55 mg/dL will occur within 20 min, allowing users more time to act to avoid hypoglycemia. We examined whether this predictive low glucose alert provided added benefit to traditional low threshold alerts.
We analyzed glucose values from an anonymized sample of 1424 patients who transitioned to G6 from the preceding fifth-generation system (G5) with no predictive alert. Users with the low threshold alert setting of 70 or 80 mg/dL were evaluated separately. Receiver users, those who disabled the predictive low glucose alert, or those with <30 days of data immediately before or after the transition to G6 were excluded.
Percent time <54, ≤55, <70, and >250 mg/dL fell significantly after the transition to G6, independent of low threshold alert setting. Time in range improved for G6 users with a low threshold alert setting of 70 mg/dL.
Advance warning provided by predictive low glucose alerts may further reduce hypoglycemia among rtCGM-experienced users.
Background: Children and adolescents with diabetes may use data from continuous glucose monitoring (CGM) in management decisions and may share it in real time with others involved in their care. CGM ...systems from Dexcom (San Diego, CA) allow real-time sharing with up to 5 remote “Followers.” We explored associations between the presence of Follower(s), device utilization, and glycemic parameters.
Methods: We used estimated glucose values (EGVs) from a convenience sample of 25,000 CGM users of Dexcom's G5 or G6 system ages 2-24 that were uploaded between 5/1/2018 and 9/30/2018 by an app that allows for sharing. The number of Follower(s) was established on 8/10/2018. Each day with ≥1 valid EGV was counted as a day of device usage. Comparisons were made with two-sided Welch’s t-tests.
Results: Overall, 90.0% of the population used the sharing feature and had ≥1 Follower; the mean numbers of Followers for patients ages <8, 8-14, and 15-24 years were 2.73, 2.69, and 1.83, respectively. In all 3 age groups, having a Follower was associated with lower mean EGVs, more EGVs in the 70-180 mg/dL range, fewer EGVs in hypo- or hyperglycemia, and more device utilization (Table).
Conclusions: Real-time sharing and following of CGM data may encourage consistent device usage and facilitate timely interventions by parents of young children with diabetes or improve self-care behaviors among adolescents and young adults with diabetes.
Disclosure
A. Parker: Employee; Self; Dexcom, Inc. M. Derdzinski: Employee; Self; Dexcom, Inc. S. Puhr: None. J. Welsh: Employee; Self; Dexcom, Inc. T.C. Walker: Employee; Self; Dexcom, Inc. A. Jimenez: Employee; Self; Dexcom, Inc.
Background: The Dexcom G6 continuous glucose monitoring (CGM) system differs from Dexcom’s earlier G5 system in that G6 includes a predictive “Urgent Low Soon” (ULS) alert that notifies users when an ...estimated glucose value (EGV) ≤55 mg/dL is predicted in the next 20 minutes. The effect of the ULS alert on the distribution of EGVs was evaluated in the context of traditional threshold alerts.
Methods: We identified individuals who had used G5 and transitioned to G6 between 5/1/2018 and 10/31/2018. Evaluable data were from a subset of 4083 users who had maintained low threshold alerts at either 70 or 80 mg/dL, who used a smartphone to view and upload ≥30 days of data from each system, and who maintained the G6 ULS alert in its default (enabled) state.
Results: Use of the 80 mg/dL low threshold alert was associated with higher mean EGVs, less hypoglycemia, and more hyperglycemia than use of the 70 mg/dL low threshold alert (Table). Over 97% of the G6 systems were used with the ULS feature enabled, and the ULS alert was activated less than once daily. At either low threshold setting, the transition to G6 was associated with reductions in hypoglycemia (<55 and <70 mg/dL) and severe hyperglycemia (>250 mg/dL).
Conclusions: When used in the context of traditional low threshold alerts, the predictive ULS alert may enable timely and appropriate interventions that contribute to further reductions in hypoglycemia among CGM-experienced users.
Disclosure
M. Derdzinski: Employee; Self; Dexcom, Inc. J. Welsh: Employee; Self; Dexcom, Inc. S. Puhr: None. T.C. Walker: Employee; Self; Dexcom, Inc. A. Parker: Employee; Self; Dexcom, Inc. A. Jimenez: Employee; Self; Dexcom, Inc.
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