Real-world lived experience of older adults with type 1 diabetes after an automated insulin delivery trial.

AIMS: First-generation closed-loop automated insulin delivery improves glycaemia and psychosocial outcomes among older adults with type 1 diabetes in clinical trials. However, no study has previously assessed real-world lived experience of older adults using closed-loop therapy outside a trial environment. METHODS: Semi-structured interviews were conducted with older adults who were pre-existing insulin pump users and previously completed the OldeR Adult Closed-Loop (ORACL) randomised trial. Interviews focused on perceptions of diabetes technology use, and factors influencing decisions regarding continuation. RESULTS: Twenty-eight participants, mean age 70 years (SD 5), were interviewed at median 650 days (IQR 608-694) after their final ORACL trial visit. At interview, 23 participants (82%) were still using a commercial closed-loop system (requiring manual input for prandial insulin bolus doses). Themes discussed in interviews relating to closed-loop system use included sustained psychosocial benefits, cost and retirement considerations and usability frustrations relating to sensor accuracy and system alarms. Of the five participants who had discontinued, reasons included cost, continuous glucose monitoring-associated difficulties and usability frustrations. Cost was the largest consideration regarding continued use; most participants considered the increased ease of diabetes management to be worth the associated costs, though cost was prohibitive for some. CONCLUSIONS: Almost 2 years after completing a closed-loop clinical trial, closed-loop automated insulin delivery remains the preferred type 1 diabetes therapy for the majority of older adult participants. Chronological age is not a barrier to real-world successful use of diabetes technology. Identifying age-related barriers, and solutions, to diabetes technology use among older adults is warranted.

Lived experience of older adults with type 1 diabetes using closed-loop automated insulin delivery in a randomised trial.

AIM: To explore the lived experience of older adults with type 1 diabetes using closed-loop automated insulin delivery, an area previously receiving minimal attention. METHODS: Semi-structured interviews were conducted with adults aged 60 years or older with long-duration type 1 diabetes who participated in a randomised, open-label, two-stage crossover trial comparing first-generation closed-loop therapy (MiniMed 670G) versus sensor-augmented pump therapy. Interview recordings were transcribed, thematically analysed and assessed. RESULTS: Twenty-one older adults participated in interviews after using closed-loop therapy. Twenty were functionally independent, without frailty or major cognitive impairment; one was dependent on caregiver assistance, including for diabetes management. Quality of life benefits were identified, including improved sleep and reduced diabetes-related psychological burden, in the context of experiencing improved glucose levels. Gaps between expectations and reality of closed-loop therapy were also experienced, encountering disappointment amongst some participants. The cost was perceived as a barrier to continued closed-loop access post-trial. Usability issues were identified, such as disruptive overnight alarms and sensor inaccuracy. CONCLUSIONS: The lived experience of older adults without frailty or major cognitive impairment using first-generation closed-loop therapy was mainly positive and concordant with glycaemic benefits found in the trial. Older adults' lived experience using automated insulin delivery beyond trial environments requires exploration; moreover, the usability needs of older adults should be considered during future device development.

Insulin antibodies are prevalent in adults with type 1 diabetes referred for islet cell transplantation and are modified by islet transplantation and immunosuppression: an Australian experience.

We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody-negative post islet cell transplantation.

Lipid-lowering therapy use and achievement of cholesterol targets in an Australian diabetes clinic.

We documented temporal changes in the use of lipid-lowering medications and achievement of cholesterol targets in an Australian diabetes clinic. The number of patients using lipid-lowering therapy for primary or secondary cardiovascular prevention increased from 6 to 69% between 1993-1995 and 2014-2016, which corresponded to a decrease in low-density lipoprotein cholesterol levels from 3.7 to 2.4 mmol/L (P < 0.01).

Suboptimal behaviour and knowledge regarding overnight glycaemia in adults with type 1 diabetes is common.

BACKGROUND: In people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH) can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts clinical outcomes and may be changed by education. AIM: To develop and utilise a survey to evaluate patient self-management of overnight glycaemia in adults with T1D. METHODS: Adults with T1D attending two Australian tertiary referral diabetes clinics completed a survey about their diabetes self-management and glycaemic control, including responses to hypothetical pre-bed blood glucose (BG) levels (4-20 mmol/L). Statistical analyses included t-tests, Chi square tests and ANOVA with significance considered at P < 0.05. RESULTS: There were 205 participants (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16) years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime (6.9(1.0); P < 0.0001 and P = 0.002 respectively). Only 36% of participants reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG scenarios, with higher rates for CSII users, P = 0.0005. Further education was desired by 32% of respondents, with higher rates in those with (44%) versus without IHA (25%), P = 0.006. CONCLUSIONS: Many adults with T1D have suboptimal knowledge and behaviour regarding overnight BG self-management. A survey, piloted herein, may facilitate the identification of patients who could benefit from further education.

Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of exercise, vs rest, on circulating insulin and glucose, following pre-exercise insulin pump basal rate reduction. METHODS: This was an open-label, two-stage randomised crossover study of 14 adults (seven women, seven men) with type 1 diabetes established on insulin pump therapy. In each stage, participants fasted and insulin delivery was halved following a single insulin basal rate overnight. Exercise (30 min moderate-intensity stationary bicycle exercise, starting 60 min post-basal reduction) and rest stages were undertaken in random order at a university hospital. Randomisation was computer-generated, and allocation concealed via sequentially numbered sealed opaque envelopes. Venous blood was collected at 15 min intervals from 60 min pre- until 210 min post-basal rate reduction. Changes in plasma free insulin (the primary outcome), and changes in plasma glucose, with exercise were compared with changes when resting. Outcomes were assessed blinded to group assignment. RESULTS: Following basal rate reduction when rested, mean (± SE) free insulin decreased by 4.9 ± 2.9%, 16.2 ± 2.6% and 18.6 ± 3.2% at 1, 2 and 3 h, respectively (p < 0.05 after 75 min). With exercise, relative to rest, mean free insulin increased by 6 ± 2 pmol/l after 15 min and 5 ± 2 pmol/l after 30 min (p < 0.001), then declined post-exercise (p < 0.001). Three participants (mean baseline glucose 5.0 ± 0.1 mmol/l) required glucose supplementation to prevent or treat exercise-related hypoglycaemia. In the other 11 participants (mean baseline glucose 8.4 ± 0.5 mmol/l), glucose increased by 0.8 ± 0.3 mmol/l with exercise (p = 0.028). CONCLUSIONS/INTERPRETATION: Halving the basal insulin rate 1 h prior to exercise did not significantly reduce circulating free insulin by exercise commencement. Exercise itself transiently increased insulin levels. In participants with low-normal glucose pre-exercise, hypoglycaemia was not prevented by insulin basal rate reduction alone. Greater insulin basal rate reduction and supplemental carbohydrate may be required to prevent exercise-induced hypoglycaemia. TRIAL REGISTRATION: ANZCTR.org.au ACTRN12613000581763 FUNDING: Australian Diabetes Society, Hugh DT Williamson Foundation, Lynne Quayle Charitable Trust Fund.

Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation.

BACKGROUND: This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. METHODS: Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing. RESULTS: Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation. CONCLUSIONS: The long-term maintenance of hypoglycaemia awareness that returns after islet cell/pancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure.

The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation does not improve the underestimation of Glomerular Filtration Rate (GFR) in people with diabetes and preserved renal function.

BACKGROUND: Our hypothesis was that both the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations would underestimate directly measured GFR (mGFR) to a similar extent in people with diabetes and preserved renal function. METHODS: In a cross-sectional study, bias (eGFR - mGFR) was compared for the CKD-EPI and MDRD equations, after stratification for mGFR levels. We also examined the ability of the CKD-EPI compared with the MDRD equation to correctly classify subjects to various CKD stages. In a longitudinal study of subjects with an early decline in GFR i.e., initial mGFR > 60 ml/min/1.73 m(2) and rate of decline in GFR (ΔmGFR) > 3.3 ml/min/1.73 m(2) per year, ΔmGFR (based on initial and final values) was compared with ΔeGFR by the CKD-EPI and MDRD equations over a mean of 9 years. RESULTS: In the cross-sectional study, mGFR for the whole group was 80 ± 2.2 ml/min/1.73 m(2) (n = 199, 75 % type 2 diabetes). For subjects with mGFR >90 ml/min/1.73 m(2) (mGFR: 112 ± 2.0, n = 76), both equations significantly underestimated mGFR to a similar extent: bias for CKD-EPI: -12 ± 1.4 ml/min/1.73 m(2) (p < 0.001) and for MDRD: -11 ± 2.1 ml/min/1.73 m(2) (p < 0.001). Using the CKD-EPI compared with the MDRD equation did not improve the number of subjects that were correctly classified to a CKD-stage. No biochemical or clinical patient characteristics were identified to account for the under estimation of mGFR values in the normal to high range by the CKD-EPI equation. In the longitudinal study (n = 30, 66 % type 1 diabetes), initial and final mGFR values were 102.8 ± 6 and 54.6 ± 6.0 ml/min/1.73 m(2), respectively. Mean ΔGFR (ml/min/1.73 m(2) per year) was 6.0 by mGFR compared with only 3.0 by MDRD and 3.2 by CKD-EPI (both p < 0.05 vs mGFR) CONCLUSIONS: Both the CKD-EPI and MDRD equations underestimate reference GFR values > 90 ml/min/1.73 m(2) as well as an early decline in GFR to a similar extent in people with diabetes. There is scope to improve methods for estimating an early decline in GFR.

The high burden of inpatient diabetes mellitus: the Melbourne Public Hospitals Diabetes Inpatient Audit.

OBJECTIVE: To determine the prevalence of diabetes in inpatients in Melbourne hospitals. DESIGN: Point prevalence survey of all inpatients in each hospital on a single day between 30 November 2010 and 22 November 2012. SETTING: 11 hospitals in metropolitan Melbourne including community, secondary and tertiary hospitals and one aged care and rehabilitation centre. PARTICIPANTS: 2308 adult inpatients in all wards apart from intensive care, emergency, obstetrics and psychiatry. MAIN OUTCOME MEASURES: Point prevalence of self-reported diabetes, details of current medication, self-reported frequency of complications. RESULTS: Diabetes status was obtained in 2273 of 2308 inpatients (98.5%). Of these, 562 (24.7%) had diabetes (95% CI, 22.9%-26.5%). Diabetes prevalence ranged from 15.7% to 35.1% in different hospitals (P < 0.001). Patients with diabetes were older, heavier and more likely to be taking lipid-lowering, antihypertensive and blood-thinning medications. Of 388 patients with complete medication information, 270 (69.6%) were taking oral hypoglycaemic agents alone or in combination with insulin, 158 (40.7%) were treated with insulin (67 [17.3%] with insulin alone) and 51 (13.1%) were not taking medication for diabetes. The frequency of diabetes complications was very high: 207/290 (71.4%) for any microvascular complication, 275/527 (52.2%) for any macrovascular complication and 227/276 (82.2%) for any complication. CONCLUSION: The high burden of diabetes in Melbourne hospital inpatients has major implications for patient health and health care expenditure. Optimising care of these high-risk patients has the potential to decrease inpatient morbidity and length of stay as well as preventing or delaying future complications. A formal Australian national audit of inpatient diabetes would determine its true prevalence and consequences, allowing rational planning to deal with shortcomings in its management.

New treatments for type 2 diabetes: cardiovascular protection beyond glucose lowering?

The health burden of type 2 diabetes mellitus (T2DM) is increasing worldwide, with a substantial portion of this burden being due to the development of cardiovascular (CV) disease. Multiple individual randomised clinical trials of intensive versus conventional glucose control, based on the use of traditional oral hypoglycaemic agents, have failed to convincingly show that intensive glucose control significantly reduces CV disease outcomes. In recent times, two new approaches to lowering glucose levels have become available. One targets the "incretin effect" which involves the modulation of peptide hormones that normally regulate glucose levels when nutrients are given orally. The other approach is based on inhibiting the sodium-glucose co-transporter 2 (SGLT-2) in the tubules of the kidney to promote glycosuria. Incretin-based therapies, especially glucagon-like peptide-1 receptor analogues, reduce glucose levels, with a low risk of hypoglycaemia, by increasing insulin secretion, inhibiting glucagon release and increasing satiety. Clinical and experimental studies have also shown favourable effects on CV disease risk factors such as dyslipidaemia, blood pressure, and improvements in endothelial function and cardiac contractility. Similarly, SGLT-2 inhibitors reduce glucose levels with a low risk for hypoglycaemia and have positive effects on multiple CV disease risk factors. Whether the beneficial effects of these new glucose lowering approaches on surrogate markers of CV disease risk translates to an improvement in CV events remains unknown. Several CV outcome trials are currently being performed to show that at a minimum, these novel glucose lowering agents are safe, but also have positive CV benefits.

Interactive calculator to estimate insulin sensitivity in type 1 diabetes.

The gold standard for measuring insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp, a time, costly, and labor-intensive research tool. A low insulin sensitivity is associated with a complication-risk in type 1 diabetes. Various formulae using clinical data have been developed and correlated with measured IS in type 1 diabetes. We consolidated multiple formulae into an online calculator (bit.ly/estimated-GDR), enabling comparison of IS and its probability of IS <4.45 mg/kg/min (low) or >6.50 mg/kg/min (high), as measured in a validation set of clamps in 104 adults with type 1 diabetes. Insulin sensitivity calculations using different formulae varied significantly, with correlations (R2) ranging 0.005-0.87 with agreement in detecting low and high glucose disposal rates in the range 49-93% and 89-100%, respectively. We demonstrate that although the calculated IS varies between formulae, their interpretation remains consistent. Our free online calculator offers a user-friendly tool for individual IS calculations and also offers efficient batch processing of data for research.

Hybrid Closed Loop in Adults With Type 1 Diabetes and Severely Impaired Hypoglycemia Awareness.

BACKGROUND: Benefits of hybrid closed-loop (HCL) systems in a high-risk group with type 1 diabetes and impaired awareness of hypoglycemia (IAH) have not been well-explored. METHODS: Adults with Edmonton HYPO scores ≥1047 were randomized to 26-weeks HCL (MiniMed™ 670G) vs standard therapy (multiple daily injections or insulin pump) without continuous glucose monitoring (CGM) (control). Primary outcome was percentage CGM time-in-range (TIR; 70-180 mg/dL) at 23 to 26 weeks post-randomization. Major secondary endpoints included magnitude of change in counter-regulatory hormones and autonomic symptom responses to hypoglycemia at 26-weeks post-randomization. A post hoc analysis evaluated glycemia risk index (GRI) comparing HCL with control groups at 26 weeks post-randomization. RESULTS: Nine participants (median [interquartile range (IQR)] age 51 [41, 59] years; 44% male; enrolment HYPO score 1183 [1058, 1308]; Clarke score 6 [6, 6]; n = 5 [HCL]; n = 4 [control]) completed the study. Time-in-range was higher using HCL vs control (70% [68, 74%] vs 48% [44, 50%], P = .014). Time <70 mg/dL did not differ (HCL 3.8% [2.7, 3.9] vs control 6.5% [4.3, 8.6], P = .14) although hypoglycemia episode duration was shorter (30 vs 50 minutes, P < .001) with HCL. Glycemia risk index was lower with HCL vs control (38.1 [30.0, 39.2] vs 70.8 [58.5, 72.4], P = .014). Following 6 months of HCL use, greater dopamine (24.0 [12.3, 27.6] vs -18.5 [-36.5, -4.8], P = .014), and growth hormone (6.3 [4.6, 16.8] vs 0.5 [-0.8, 3.0], P = .050) responses to hypoglycemia were observed. CONCLUSIONS: Six months of HCL use in high-risk adults with severe IAH increased glucose TIR and improved GRI without increased hypoglycemia, and partially restored counter-regulatory responses. CLINICAL TRIAL REGISTRATION: ACTRN12617000520336.

Driving-Related Glucose Patterns Among Older Adults with Type 1 Diabetes.

Older adults with type 1 diabetes may face challenges driving safely. Glucose "above-5-to-drive" is often recommended for insulin-treated diabetes to minimize hypoglycemia while driving. However, the effectiveness of this recommendation among older adults has not been evaluated. Older drivers with type 1 diabetes were assessed while using sensor-augmented insulin pumps during a 2-week clinical trial run-in. Twenty-three drivers (median age 69 years [interquartile range; IQR 65-72]; diabetes duration 37 years [20-45]) undertook 618 trips (duration 10 min [5-21]). Most trips (n = 535; 87%) were <30 min duration; 9 trips (1.5%) exceeded 90 min and 3 trips (0.5%) exceeded 120 min. Pre-trip continuous glucose monitoring (CGM) was >5.0 mmol/L for 577 trips (93%) and none of these had CGM <3.9 mmol/L during driving (including 8 trips >90 min and 3 trips >120 min). During 41 trips with pre-trip CGM ≤5.0 mmol/L, 11 trips had CGM <3.9 mmol/L. Seventy-one CGM alerts occurred during 60 trips (10%), of which 54 of 71 alerts (76%) were unrelated to hypoglycemia. Our findings support a glucose "above-5-to-drive" recommendation to avoid CGM-detected hypoglycemia among older drivers, including for prolonged drives, and highlight the importance of active CGM low-glucose alerts to prevent hypoglycemia during driving. Driving-related CGM usability and alert functionality warrant investigation. Clinical trial ACTRN1261900515190.

Stimulation parameters for directional vagus nerve stimulation.

BACKGROUND: Autonomic nerve stimulation is used as a treatment for a growing number of diseases. We have previously demonstrated that application of efferent vagus nerve stimulation (eVNS) has promising glucose lowering effects in a rat model of type 2 diabetes. This paradigm combines high frequency pulsatile stimulation to block nerve activation in the afferent direction with low frequency stimulation to activate the efferent nerve section. In this study we explored the effects of the parameters for nerve blocking on the ability to inhibit nerve activation in the afferent direction. The overarching aim is to establish a blocking stimulation strategy that could be applied using commercially available implantable pulse generators used in the clinic. METHODS: Male rats (n = 20) had the anterior abdominal vagus nerve implanted with a multi-electrode cuff. Evoked compound action potentials (ECAP) were recorded at the proximal end of the electrode cuff. The efficacy of high frequency stimulation to block the afferent ECAP was assessed by changes in the threshold and saturation level of the response. Blocking frequency and duty cycle of the blocking pulses were varied while maintaining a constant 4 mA current amplitude. RESULTS: During application of blocking at lower frequencies (≤ 4 kHz), the ECAP threshold increased (ANOVA, p < 0.001) and saturation level decreased (p < 0.001). Application of higher duty cycles (> 70%) led to an increase in evoked neural response threshold (p < 0.001) and a decrease in saturation level (p < 0.001). During the application of a constant pulse width and frequency (1 or 1.6 kHz, > 70% duty cycle), the charge delivered per pulse had a significant influence on the magnitude of the block (ANOVA, p = 0.003), and was focal (< 2 mm range). CONCLUSIONS: This study has determined the range of frequencies, duty cycles and currents of high frequency stimulation that generate an efficacious, focal axonal block of a predominantly C-fiber tract. These findings could have potential application for the treatment of type 2 diabetes.

Continuous Glucose Monitoring-Based Composite Metrics: A Review and Assessment of Performance in Recent-Onset and Long-Duration Type 1 Diabetes.

This study examined correlations between continuous glucose monitoring (CGM)-based composite metrics and standard glucose metrics within CGM data sets from individuals with recent-onset and long-duration type 1 diabetes. First, a literature review and critique of published CGM-based composite metrics was undertaken. Second, composite metric results were calculated for the two CGM data sets and correlations with six standard glucose metrics were examined. Fourteen composite metrics met selection criteria; these metrics focused on overall glycemia (n = 8), glycemic variability (n = 4), and hypoglycemia (n = 2), respectively. Results for the two diabetes cohorts were similar. All eight metrics focusing on overall glycemia strongly correlated with glucose time in range; none strongly correlated with time below range. The eight overall glycemia-focused and two hypoglycemia-focused composite metrics were all sensitive to automated insulin delivery therapeutic intervention. Until a composite metric can adequately capture both achieved target glycemia and hypoglycemia burden, the current two-dimensional CGM assessment approach may offer greatest clinical utility.

Independent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes.

BACKGROUND AND AIM: Low insulin sensitivity (IS) increases Type 1 diabetes (T1D) complication risk and can be estimated by simple formulae developed from complex euglycemic hyperinsulinaemic clamp studies. We aimed to validate these formulae using independent clamp data. METHODS: Clamps were performed in 104 T1D adults. Measured glucose disposal rate (GDR) was correlated with eGDR and eLog10 M/I calculated by five IS formulae. RESULTS: Correlations ranged between 0.23-0.40. Two IS formulae (by the authors), using age, sex, HDL-C, HbA1c, pulse pressure, BMI, and waist-hip-ratio had the highest correlation with measured GDR and the best performance in detecting low IS.

Closed-Loop Insulin Delivery Effects on Glycemia During Sleep and Sleep Quality in Older Adults with Type 1 Diabetes: Results from the ORACL Trial.

Sleep-related effects of closed-loop therapy among older adults with type 1 diabetes have not been well established. In the OldeR Adult Closed-Loop (ORACL) randomized, crossover trial of first-generation closed-loop therapy (MiniMed 670G), participants wore actigraphy and completed sleep diaries for 14-day periods at stage end. During objectively measured sleep (actigraphy) with closed-loop versus sensor-augmented pump therapy, glucose time-in-range 70-180 mg/dL (3.9-10.0 mmol/L) was greater (90.3% vs. 78.7%, respectively; difference 8.2 percentage points [95% confidence interval {CI} 1.5 to 13.0]; P = 0.008), and there were fewer sensor hypoglycemia episodes (18 vs. 43, respectively; incident rate ratio 0.40 [95% CI 0.20 to 0.55]; P = 0.007). Sleep quality recorded daily was worse with closed-loop therapy (P = 0.006); Pittsburgh Sleep Quality Index did not differ. There were 30% more system alarms during monitored sleep with closed-loop therapy (P < 0.001). First-generation closed-loop therapy has important glycemic benefits during sleep for older adults, with deterioration in some sleep quality measures. Sleep quality warrants prioritization and investigation during advancement of closed-loop technology.

Closed-Loop Insulin Delivery Versus Sensor-Augmented Pump Therapy in Older Adults With Type 1 Diabetes (ORACL): A Randomized, Crossover Trial.

OBJECTIVE: To assess the efficacy and safety of closed-loop insulin delivery compared with sensor-augmented pump therapy among older adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: This open-label, randomized (1:1), crossover trial compared 4 months of closed-loop versus sensor-augmented pump therapy. Eligible adults were aged ≥60 years, with type 1 diabetes (duration ≥10 years), using an insulin pump. The primary outcome was continuous glucose monitoring (CGM) time in range (TIR; 3.9-10.0 mmol/L). RESULTS: There were 30 participants (mean age 67 [SD 5] years), with median type 1 diabetes duration of 38 years (interquartile range [IQR] 20-47), randomized (n = 15 to each sequence); all completed the trial. The mean TIR was 75.2% (SD 6.3) during the closed-loop stage and 69.0% (9.1) during the sensor-augmented pump stage (difference of 6.2 percentage points [95% CI 4.4 to 8.0]; P < 0.0001). All prespecified CGM metrics favored closed loop over the sensor-augmented pump; benefits were greatest overnight. Closed loop reduced CGM time <3.9 mmol/L during 24 h/day by 0.5 percentage points (95% CI 0.3 to 1.1; P = 0.0005) and overnight by 0.8 percentage points (0.4 to 1.1; P < 0.0001) compared with sensor-augmented pump. There was no significant difference in HbA1c between closed-loop versus sensor-augmented pump stages (7.3% [IQR, 7.1-7.5] (56 mmol/mol [54-59]) vs. 7.5% [7.1-7.9] (59 mmol/mol [54-62]), respectively; P = 0.13). Three severe hypoglycemia events occurred during the closed-loop stage and two occurred during the sensor-augmented pump stage; no hypoglycemic events required hospitalization. One episode of diabetic ketoacidosis occurred during the sensor-augmented pump stage; no serious adverse events occurred during the closed-loop stage. CONCLUSIONS: Closed-loop therapy is an effective treatment option for older adults with long-duration type 1 diabetes, and no safety issues were identified. These older adults had higher TIR accompanied by less time below range during closed loop than during sensor-augmented pump therapy. Of particular clinical importance, closed loop reduced the time spent in hypoglycemic range overnight.