Patient-reported outcomes in studies of diabetes technology: What matters.

In recent years, diabetes technologies have revolutionized the care of people with type 1 diabetes (T1D). Emerging evidence suggests that people with type 2 diabetes (T2D) can experience similar benefits from these advances in technology. While glycaemic outcomes are often a primary focus, the lived experience of the person with diabetes is equally important. In this review, we describe the impact of diabetes technologies on patient-reported outcome measures (PROMs). We highlight that most of the published studies investigated PROMs as secondary outcomes. Continuous glucose monitoring systems may have an important role in improving PROMs in individuals with T1D, which may be driven by the prevention or proactive management of hypoglycaemia. In people with T2D, continuous glucose monitoring may also have an important role in improving PROMs, particularly in those treated with insulin therapy. The impact of insulin pumps on PROMs seems positive in T1D, while there is limited evidence in T2D. Studies of hybrid closed-loop therapies suggest increased treatment satisfaction, improved quality of life and decreased diabetes-related distress in T1D, but it is unclear whether these benefits are because of a 'class-effect' or individual systems. We conclude that PROMs deserve a more central role in trials and clinical practice, and we discuss directions for future research.

UK's Association of British Clinical Diabetologist's Diabetes Technology Network (ABCD-DTN): Best practice guide for hybrid closed-loop therapy.

This best practice guide is written with the aim of providing an overview of current hybrid closed-loop (HCL) systems in use within the United Kingdom's (UK) National Health Service (NHS) and to provide education and advice for their management on both an individual and clinical service level. The environment of diabetes technology, and particularly HCL systems, is rapidly evolving. The past decade has seen unprecedented advances in the development of HCL systems. These systems improve glycaemic outcomes and reduce the burden of treatment for people with type 1 diabetes (pwT1D). It is anticipated that access to these systems will increase in England as a result of updates in National Institute of Health and Care Excellence (NICE) guidance providing broader support for the use of real-time continuous glucose monitoring (CGM) for pwT1D. NICE is currently undertaking multiple-technology appraisal into HCL systems. Based on experience from centres involved in supporting advanced technologies as well as from the recent NHS England HCL pilot, this guide is intended to provide healthcare professionals with UK expert consensus on the best practice for initiation, optimisation and ongoing management of HCL therapy.

Impact of glycaemic technologies on quality of life and related outcomes in adults with type 1 diabetes: A narrative review.

AIMS: To explore the association between the use of glycaemic technologies and person-reported outcomes (PROs) in adults with type 1 diabetes (T1D). METHODS: We included T1D and technology publications reporting on PROs since 2014. Only randomised controlled trials and cohort studies that used validated PRO measures (PROMs) were considered. RESULTS: T1D studies reported on a broad range of validated PROMs, mainly as secondary outcome measures. Most studies examined continuous glucose monitoring (CGM), intermittently scanned CGM (isCGM), and the role of continuous subcutaneous insulin infusion (CSII), including sensor-augmented CSII and closed loop systems. Generally, studies demonstrated a positive impact of technology on hypoglycaemia-specific and diabetes-specific PROs, including reduced fear of hypoglycaemia and diabetes distress, and greater satisfaction with diabetes treatment. In contrast, generic PROMs (including measures of health/functional status, emotional well-being, depressive symptoms, and sleep quality) were less likely to demonstrate improvements associated with the use of glycaemic technologies. Several studies showed contradictory findings, which may relate to study design, population and length of follow-up. Differences in PRO findings were apparent between randomised controlled trials and cohort studies, which may be due to different populations studied and/or disparity between trial and real-world conditions. CONCLUSIONS: PROs are usually assessed as secondary outcomes in glycaemic technology studies. Hypoglycaemia-specific and diabetes-specific, but not generic, PROs show the benefits of glycaemic technologies, and deserve a more central role in future studies as well as routine clinical care.

Safety and effectiveness of do-it-yourself artificial pancreas system compared with continuous subcutaneous insulin infusions in combination with free style libre in people with type 1 diabetes.

AIMS: The use of do-it-yourself artificial pancreas systems (DIYAPS) among people with type 1 diabetes is increasing. At present, it is unclear how DIYAPS compares with other technologies such as FreeStyle Libre (FSL) and continuous subcutaneous insulin infusion (CSII). The aim of this analysis is to compare safety, effectiveness and quality-of-life outcomes of DIYAPS use with the addition of FSL to CSII. METHOD: Data from two large UK hospitals were extracted from the Association of British Clinical Diabetologists (ABCD) DIYAPS and FSL audits. Outcomes included HbA1c , glucose TBR (time-below-range), TIR (time-in-range), Diabetes Distress Score (DDS), and Gold hypoglycaemia score. Any adverse events were noted. Changes at follow-up were assessed using paired t-tests and ANOVA in Stata; TIR/TBR at follow-up assessed using unpaired t-tests; chi-square tests assessed the change in frequency of health utilisation (e.g. hospital admissions). RESULTS: DIYAPS (n = 35) and FSL+CSII (n = 149) users, with median follow-up duration of 1.4 (IQR 0.8-2.1) and 1.3 (IQR 0.7-1.8) years, respectively, were included. HbA1c with DIYAPS use changed by -10 mmol/mol [0.9%] (p < 0.001, 95% CI 5, 14 [0.5, 1.3%]) significantly lower (p < 0.001) than in the FSL+CSII group -3 mmol/mol [0.25%] (p < 0.001, 95% CI 1, 4 [0.1, 0.4%]). TIR was higher and TBR was lower in the DIYAPS group. Adverse events were rare in both groups and no significant differences were observed in the frequency of healthcare utilisation. CONCLUSION: DIYAPS use was associated with a lower HbA1c levels, higher TIR and lower TBR compared with FSL+CSII. There was no significant increase in adverse events, although this should be interpreted cautiously given the low numbers of users. Full results from the ABCD DIYAPS audit are awaited.

Injectable semaglutide and reductions in HbA1c and weight in the real world in people switched from alternative glucagon-like peptide-1 receptor agonists.

The ABCD semaglutide audit was designed to capture the routine clinical outcomes of people commenced on semaglutide in the UK. Previous work showed differential reductions in HbA1c and weight dependent on previous glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure. The analysis, in this research letter, shows that decreases in HbA1c and weight associated with semaglutide occur irrespective of previous GLP-1RA use. However, HbA1c reductions were less if switched from dulaglutide or liraglutide and weight changes were attenuated if switched from dulaglutide or exenatide, potentially suggesting differing potencies between GLP-1RAs. Dedicated studies with head-to-head comparisons are needed to confirm these findings.

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

AIMS: To evaluate real-world outcomes in people with Type 1 Diabetes (PwT1D) initiated on Omnipod DASH® Insulin Management System. METHODS: Anonymized 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. RESULTS: 276 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. CONCLUSIONS: Omnipod 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.

Efficacy and safety of intensive versus conventional glucose targets in people with type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVE: The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D. METHODS: We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbA1clevels. Subgroup analysis was also performed to account for the inclusion of glucose only versus multi-factorial intervention trials. Results are reported as risk ratio (RR) and 95% confidence interval (CI). RESULTS: Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5--0.87), microalbuminuria (0.67, 0.52-0.85), major amputation (0.6, 0.38-0.96), retinopathy (0.75 ,0.63-0.9), and nephropathy (0.78, 0.63-0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34-3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57-0.95). CONCLUSION: Targeting HbA1c levels should be individualized based on the clinical status, balancing risks and benefits and potential risk for developing these complications among people with T2D.

Hybrid Closed-Loop Therapy in Adults With Type 1 Diabetes and Above-Target HbA1c: A Real-world Observational Study.

OBJECTIVE: We explored longitudinal changes associated with switching to hybrid closed-loop (HCL) insulin delivery systems in adults with type 1 diabetes and elevated HbA1c levels despite the use of intermittently scanned continuous glucose monitoring (isCGM) and insulin pump therapy. RESEARCH DESIGN AND METHODS: We undertook a pragmatic, preplanned observational study of participants included in the National Health Service England closed-loop pilot. Adults using isCGM and insulin pump across 31 diabetes centers in England with an HbA1c ≥8.5% who were willing to commence HCL therapy were included. Outcomes included change in HbA1c, sensor glucometrics, diabetes distress score, Gold score (hypoglycemia awareness), acute event rates, and user opinion of HCL. RESULTS: In total, 570 HCL users were included (median age 40 [IQR 29-50] years, 67% female, and 85% White). Mean baseline HbA1c was 9.4 ± 0.9% (78.9 ± 9.1 mmol/mol) with a median follow-up of 5.1 (IQR 3.9-6.6) months. Of 520 users continuing HCL at follow-up, mean adjusted HbA1c reduced by 1.7% (95% CI 1.5, 1.8; P < 0.0001) (18.1 mmol/mol [95% CI 16.6, 19.6]; P < 0.0001). Time in range (70-180 mg/dL) increased from 34.2 to 61.9% (P < 0.001). Individuals with HbA1c of ≤58 mmol/mol rose from 0 to 39.4% (P < 0.0001), and those achieving ≥70% glucose time in range and <4% time below range increased from 0.8 to 28.2% (P < 0.0001). Almost all participants rated HCL therapy as having a positive impact on quality of life (94.7% [540 of 570]). CONCLUSIONS: Use of HCL is associated with improvements in HbA1c, time in range, hypoglycemia, and diabetes-related distress and quality of life in people with type 1 diabetes in the real world.

Intensive glycemic control and macrovascular, microvascular, hypoglycemia complications and mortality in older (age ≥60years) or frail adults with type 2 diabetes: a systematic review and meta-analysis from randomized controlled trial and observation studies.

INTRODUCTION: Guidelines for type 2 diabetes (T2D) recommend individualized HbA1c targets to take into account patient age or frailty. We synthesized evidence from randomized controlled trials and observational studies for intensive glycemic control (HbA1c target ≤58 mmol/mol) versus standard care, in elderly (age ≥60 years) or frail adults with T2D. METHODS: Searches were performed utilizing recognized terms for T2D, frailty, older age, and HbA1c control and outcomes of interest. Meta-analysis was performed where possible. Primary outcomes included all-cause mortality, severe hypoglycemia, and hospital admission rates. Vascular complications, cognitive decline, and falls/fractures were secondary outcomes. RESULTS: 7,528 studies were identified of which 15 different clinical studies were selected. No difference was noted in all-cause mortality with intensive control (pooled hazard ratio 0.96, 95% confidence interval 0.90-1.03), but risk of severe hypoglycemia increased (2.45, 2.22-2.72). Intensive control was associated reductions in microvascular (0.73, 0.68-0.79) and macrovascular complications (0.84, 0.79-0.89). Outcome data for risk of hospitalization, cognition, and falls/fractures were limited. CONCLUSION: Intensive glycemic control was associated with reduced rates of complications but increased severe hypoglycemia. Significant heterogeneity exists and the impact of different drug regimens is unclear. Caution is needed when setting glycemic targets in elderly or frail individuals.

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.

Open-source automated insulin delivery systems are an increasingly encountered diabetes technology. These involve a small glucose sensor and an insulin delivery device called an insulin pump. These two devices interact to allow adjustment of insulin delivery to maintain glucose levels in a desirable range. The computer codes which drive these systems are developed by people with diabetes or their families rather than by device companies; as such, they have not been through formal approval processes and therefore there is limited formal evidence concerning whether they are safe or beneficial to use. Users report high satisfaction with these devices and improvements in their diabetes management. This survey was performed to assess the opinions of UK healthcare professionals and their usual practice. Key results include: UK healthcare professionals would not routinely recommend the use of these devices and there was concern about the medicolegal implications of use. However, UK healthcare professionals were generally supportive of those who chose to use the devices. Interestingly, almost half of the healthcare professionals would use the systems if they had diabetes.

The metabolic and liver-related outcomes of bariatric surgery in adult patients with insulin-treated type 2 diabetes and nonalcoholic fatty liver disease at high risk of liver fibrosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease, with a prevalence estimated to between 20% and 30% of the general population and approximately 70% of stage 2 obese people with type 2 diabetes (T2D) with normal liver enzymes. OBJECTIVES: To investigate the metabolic and liver-related outcomes of bariatric surgery among patients with insulin-treated T2D and NAFLD who are at high risk of liver fibrosis. SETTING: More than 600 locations within the United Kingdom. METHODS: The study comprises a retrospective cohort comparison of patients with NAFLD and a fibrosis 4 (Fib-4) score > 1.45 who received a bariatric intervention versus comparable patients who received no bariatric intervention. Metabolic outcomes (glycated hemoglobin [HbA1C] level, weight, body mass index [BMI], and Fib-4 score) and composite liver-related outcomes (cirrhosis, portal hypertension, liver failure, and hepatoma) were compared between groups over a period of 5 years. The outcomes were adjusted for baseline and time-varying covariates. RESULTS: The study sample included 4108 patients, 45 of whom underwent bariatric surgery. The mean age at baseline was 62.4 ± 12.4 years; 43.8% of patients were female; the mean weight was 89.5 ± 20.8 kg; the mean BMI was 31.7 ± 7.6 kg/m2; and the mean HbA1C level was 68.4 ± 16.7 mmol/mol. In addition, the median Fib-4 score was 2.3 (interquartile range, 1.7-4.2). During the 5 years during which follow-up outcomes were recorded, the weight and BMI reductions were significantly lowered compared with baseline in the bariatric surgery group. Similarly, the HbA1C levels were lower in the bariatric surgery group, with statistically significant differences observed in the first and second postintervention years (bariatric surgery versus non-bariatric surgery patient levels at 1 year, 63.1 mmol/mol versus 68.1 mmol/mol, respectively [P = .042], and at 2 years, 62.7 mmol/mol versus 68.1 mmol/mol, respectively [P = .028]). No significant difference was observed between groups in the proportion of patients with liver fibrosis or the likelihood of developing composite liver disease during the follow-up period (bariatric surgery group, 8.9%; non-bariatric surgery group, 4.7%; X2 = 1.75; P = .18). CONCLUSION: Bariatric surgery amongst patients with insulin-treated T2D with NAFLD who were at high risk of liver fibrosis was associated with significant improvements in metabolic outcomes. No significant adverse effects were observed with regards to liver-related outcomes.

Clinical cost evaluation and health benefits of post-bariatric intervention for patients with type 2 diabetes living in the UK.

To assess associated healthcare costs and risk of developing obesity-related comorbidities among patients with type 2 diabetes with severe obesity and receiving insulin treatment, following bariatric surgery (BS). A retrospective cohort study was conducted from a UK electronic primary care database. Propensity score matching (1:1) was performed for BS with non-BS cohort. Follow-up was over 5 years (694 person-years), comparing drug utilization with clinical cost differences, such as visits to General practitioners (GPs), hospitalization, and laboratory use. Cox proportional regression was used to compute differences in the risk of obesity-related comorbidities and chi-square analysis to explore differences in insulin independency and diabetes remission proportions during follow-up. Eighty patients who received BS were matched to 80 non-BS (N = 160). The baseline mean age was 48.3 years (SD: 12.9) (61% female), and body mass index was 39.3 kg/m2 (SD: 9.3). During follow-up, antidiabetic drug cost was significantly lower in the BS group than in the non-BS (median cost/person [£]: 527.77 [interquartile range (IQR): 1196.11] vs. 1564.13 [IQR: 1576.01]; p < 0.001). Overall, aggregate cost analysis showed a significant total healthcare cost reduction in the BS group (median cost/person [£]: 1597.96 [IQR: 2631.84] vs. 2440.12 [IQR: 2242.95]; p = 0.050). BS significantly protected against obesity-related comorbidities compared with the non-BS (adjusted hazard ratio: 0.56; 95% confidence interval: 0.32-0.96; p = 0.036) and increased insulin independency throughout all follow-up points: at year 5: 48.1% versus 28.9%; p = 0.044, respectively. While BS shows evidence of cost efficiency, cost saving was not identified. The efficiency is evident by the protective effect against crude obesity-related comorbidities associated with increased insulin independency.

Application of outcome measures in international humanitarian aid: comparing indices through retrospective analysis of corrective surgical care cases.

It is common for international organizations to provide surgical corrective care to vulnerable populations in developing countries. However, a current worsening of the overall surgical burden of disease in developing countries reflects an increasing lack of sufficient numbers of trained healthcare personnel, and renders outside volunteer assistance more desirable and crucial than ever. Unfortunately, program evaluation and monitoring, including outcome indices and measures of effectiveness, is not measured commonly. In 2005, Operation Smile International implemented an electronic medical record system that helps monitor a number of critical indices during surgical missions that are essential for quality assurance reviews. This record system also provided an opportunity to retrospectively evaluate cases from previous missions. Review of data sets from >8,000 cases in 2005 and 2006 has provided crucial information regarding the priority of surgery, perioperative and operative complications, and surgical program development. The most common procedure provided was unilateral cleft lip repair, followed closely by cleft palate. A majority of these interventions occurred for patients who were older than routinely provided for in the western world. The average child treated had an age:weight ratio at or below the [US] Centers for Disease Control and Prevention (CDC) 50th percentile, with a small percentage falling below the CDC 20th percentile. A majority of children had acceptable levels of hemoglobin, but the relative decreased age:weight ratio nonetheless can reflect mild malnutrition. Complications requiring medical intervention were seen in 1.2% of cases in 2005 and 1.0% in 2006. Thirty percent were reported as anesthesia complications, and 61% reported as surgical complications. One death was reported, but occurred after discharge outside the perioperative period. Complication rates are similar to rates reported in the US and UK and emphasizes the importance of standardization with uniform indices to compare quality performance and equity of care. This study offers an important example of the importance of collecting, analyzing, and reporting measures of effectiveness in all surgical settings.

Scope of wounds.

The scope of extremity wounds in the current conflict presents surgeons with new lessons to master. Unique to this conflict is a new type of patient, one with multiple and severely injured extremities who is otherwise free of serious injury. These injuries provide challenges to the medical system in terms of the volume and complexity of care, and to the patient and surgeon trying to achieve limb salvage and rehabilitation. These patients present with a combination of high-energy injury, massive evolving tissue destruction, and widespread contamination, resulting in an evolving zone of injury that respects no tissue planes, anatomic boundaries, or normal physiologic rules. We must ensure that our skills and techniques as surgeons evolve faster than do the injuries themselves.