Protocol for the Diabetes Technology Network UK and Association of British Clinical Diabetologists' closed-loop insulin delivery audit programme

Background: The Association of British Clinical Diabetologists (ABCD) closed-loop audit aims to capture real-world out- comes from all who use hybrid closed-loop (HCL) insulin delivery systems in routine clinical care. In addition, NHS England has announced a pilot programme this year to expand access to HCL insulin delivery systems to people with type 1 diabetes (T1D) who are already using pump therapy and FreeStyle Libre with a HbA1c ≥ 69mmol/mol (≥ 8.5%). This group is often underrepresented in current randomised control trial evidence and, vitally, the planned audit will capture their data. Methods: The ABCD nationwide audit programme has Caldicott guardian approval and has also been approved by Confidentiality Advisory Group (CAG). Clinical teams collect anonymised user data using a secure online tool. Baseline characteristics and routinely collected outcome data at follow-up will include: assessment of glycaemic outcomes ( HbA1c, time in range, time below range); patient-reported outcome measures (Gold score and diabetes-related distress); and frequency of resource utilisation (hospital admissions, paramedic callouts, diabetic ketoacidosis [DKA] and severe hypoglycaemia). Discussion: The ABCD closed-loop audit will produce an inde- pendent real-world dataset of outcomes in closed-loop users across multiple systems. These data will provide insight into the real-world benefits and challenges of HCL systems used within the NHS in England.</p

Association of British Clinical Diabetologists, Diabetes Technology Network UK and Association of Children's Diabetes Clinicians Survey of UK Healthcare Professional Attitudes Towards Open-Source Automated Insulin Delivery Systems

Introduction: Automated insulin delivery (AID) systems can enable improved glycaemic outcomes with reduced mental burden. Open-source AID (OS-AID) systems overcome some of the developmental and access barriers enabling a wider use of these systems. Limited data are available on healthcare professional (HCP) opinions and current practice regarding these systems. The aim of this survey was to gain insight into HCP perceptions and practices around OS-AID. Methods: This survey was developed collaboratively with OS-AID users and distributed to adult and children’s teams, using an online survey tool. Results were received between February and April 2019. Responses were assessed using simple descriptive statistics with analyses stratified by respondent characteristics. Results: 317 responses were obtained from a range of HCPs in both adult and paediatric services. Key results include: HCP perception of OS-AID as “risky in the wrong hands” (43%); 91% felt uncomfortable initiating discussions around OS-AID because of lack of regulation (67%) and/or their own lack of knowledge (63%). Half of HCPs (47%) reported that they would choose OS-AID if they themselves had type 1 diabetes. Conclusions: HCPs are generally supportive of OS-AID users but many feel uncomfortable with the technicalities of the systems given the lack of approval. Knowledge around the use of these systems was limited. Re-assessment of HCP perceptions should be performed in the future given the evolving landscape of diabetes technology, recent consensus statements and emerging ethical and legal perspectives

Real-world outcomes of Omnipod DASH system use in people with type 1 diabetes: Evidence from the Association of British Clinical Diabetologists (ABCD) study

AimsTo evaluate real-world outcomes in people with Type 1 Diabetes (PwT1D) initiated on Omnipod DASH® Insulin Management System.MethodsAnonymized clinical data were submitted to a secure web-based tool within the National Health Service network. Hemoglobin A1c (HbA1c), sensor-derived glucometrics, total daily dose of insulin (TDD), and patient-reported outcome changes between baseline and follow-up were assessed. Individuals were classified to "new-to-pump" (switched from multiple daily injections) and "established-on-pump" (switched from a tethered insulin pump) groups.Results276 individuals from 11 centers [66.7 % female; 92 % White British; median age 41 years (IQR 20-50); diabetes duration 20 years (IQR 11-31); 49.3 % within "new-to-pump" group] were included. Baseline HbA1c was 8.0 ± 1.3 % (64 ± 14 mmol/mol). At follow-up [3 years (IQR 1.5-3.2)], HbA1c reduced by 0.3 % [(3 mmol/mol); p = 0.002] across the total population, 0.4 % [(5 mmol/mol); p = 0.001] in those "new-to-pump" and remained unchanged in those "established-on-pump". TDD decreased in the "new-to-pump" cohort (baseline:44.9 ± 21.0units vs follow-up:38.1 ± 15.4units, p = 0.002). Of those asked, 141/143 (98.6 %) stated Omnipod DASH had a positive impact on quality of life.ConclusionsOmnipod DASH was associated with improvements in HbA1c in PwT1D "new-to-pump" and maintained previous HbA1c levels in those "established-on-pump". User satisfaction in all groups and TDD reduction in those "new-to-pump" were reported

Study population.

<p>Study population.</p

DSM illustrates unique facial phenotypes resulting from stage-specific ethanol exposure.

<p>(Left) Mean surface shape of the GD7 and GD8.5 exposure groups relative to the control group is shown in the first and second columns respectively, while the GD7 group is directly compared to the GD8.5 ethanol-exposed group in the third column. (A–C) Color-map comparisons reflecting the displacement of mean surface shape for the indicated groups, where red indicates regions most distant and internal, while blue indicates regions most distant and external. Other colors shown in the scales identify intermediate positions. (D–L) Color-map comparisons reflecting the displacement of the indicated mean surface shapes parallel to the three orthogonal axes. Red and blue color intensities reflect displacement in the direction indicated by the corresponding color-coded arrow. Changes are shown at a scale of 1.2 standard deviations. (Right) Snout width (SW) was measured between the most lateral 3^rd row of vibrissae; Median upper lip length (ULL) was measured from the lower edge of the nostrils to the bottom of the upper lip; Facial depth (FD) was measured from the middle of the ear to the top of the philtrum. Values represent the means + the S.E.M. ^*p<0.05 compared to control group.^∧p<0.05 compared to counterpart ethanol exposure group.</p

Scanning electron microscopy illustrates unique brain malformations in GD12 embryos exposed to ethanol at GD7 or GD8.5.

<p>(A–F) Images of specimens hemisected in the coronal (frontal) plane illustrate posterior and anterior aspects of the embryonic brain in control and ethanol-affected groups. (G–I) Additional GD12 embryos were cut to provide a sagittal view of the brain. Notable abnormalities include differences in width of the third ventricle (dashed calipers), and the area from which the septal region will develop (dashed outline in the anterior view and solid calipers in sagittal view). Ganglionic eminences (*).</p

Stage-specific ethanol exposure causes correlative face and brain abnormalities.

<p>Regression lines were plotted for the control group (solid line) and for the ethanol exposure groups (dashed line). In the exposed groups, a significant negative correlation between philtrum length and septal region volume, along with a significant positive correlation between snout width and olfactory bulb volume, was found. Correlations in the control group were not significant (p = 0.55, p = 0.30, respectively).</p

Unique facial dysmorphology induced by stage-specific ethanol exposure in the mouse corresponds to distinct clinical phenotypes.

<p>Along with a control animal (A), representative examples of fetuses severely affected by ethanol exposure on GD7 (B) and GD8.5 (C) are shown. The elongated upper lip with deficient philtrum of the GD7 exposed mouse mimics that seen in children with full-blown FAS <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043067#pone.0043067-Sulik3" target="_blank">[50]</a>. The “fish-shaped” upper lip and bulbous nasal tip of the mouse exposed at GD8.5 resembles that of children with DiGeorge syndrome <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043067#pone.0043067-Kretschmer1" target="_blank">[37]</a>. For the animals shown, the face and brain can be visualized concurrently in 3D in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043067#pone.0043067.s008" target="_blank">Movie S1</a>.</p

MRM enables concurrent 3D analyses of the brain and face of GD17 mouse fetuses.

<p>Forebrain and pituitary regions were manually segmented from transverse 39 µm MRM sections (A). 3D brain reconstructions were generated by overlaying manually segmented regions with whole-brain masks (B). From the same MRM scans, 3D head reconstructions were created featuring detailed facial surfaces (C). The brain and face can be visualized concurrently <i>in situ</i> by reducing head surface opacity (D). The size of a GD17 mouse fetus can be appreciated when shown in scale with a U.S. quarter dollar coin (E).</p

Volumetric brain measurements demonstrate unique brain abnormalities resulting from stage-specific ethanol exposure.

<p>(Right) Total brain volumes were derived from automated skull stripping. Values represent the mean + S.E.M. Letters above each bar indicate group classes; the same letter above a subset of bars denotes lack of statistical difference, whereas different letters represent statistically different classes (p<0.05). (Right) For determination of disproportionate differences, the volume of each manually segmented forebrain region was calculated as a percentage of total brain volume for each animal. Remaining volume includes mid- and hindbrain regions. To illustrate relative changes on the same scale, percent volumes are normalized to mean control values. Values represent the mean ± the S.E.M. ^*p<0.05 compared to control group. ^∧p<0.05 compared to counterpart ethanol exposure group.</p