To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for ...most adults with type 1 diabetes).
Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70-180 mg/dL) during the final 3 weeks.
Participants were randomized to HCL (
= 61) or control (
= 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA
was 7.4% (0.9%) (57 10 mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% 95% CI 11, 19;
< 0.0001). For HCL, HbA
was lower (median 95% CI difference -0.4% -0.6, -0.2; -4 mmol/mol -7, -2;
< 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 95% CI 0.4, 1.9;
< 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively.
In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA
, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.
To determine feasibility and compare acceptance of an investigational Medtronic enhanced advanced hybrid closed-loop (e-AHCL) system in adults with type 1 diabetes with earlier iterations.
This ...nonrandomized three-stage (12 weeks each) exploratory study compared e-AHCL (Bluetooth-enabled MiniMed 780G insulin pump with automatic data upload 780G incorporating an updated algorithm; calibration-free all-in-one disposable sensor; 7-day infusion set) preceded by a run-in (non-Bluetooth 780G 670G V4.0 insulin pump requiring manual data upload; Guardian Sensor 3 GS3 requiring calibration; 3-day infusion set), stage 1 (780G; GS3; 3-day infusion set), and stage 2 (780G; calibration-free Guardian Sensor 4; 3-day infusion set). Treatment satisfaction was assessed by Diabetes Technology Questionnaire (DTQ)-current (primary outcome) and other validated treatment satisfaction tools with glucose outcomes by continuous glucose monitoring metrics.
Twenty-one of 22 (11 women) participants (baseline HbA1c 6.7%/50 mmol/mol) completed the study. DTQ-current scores favored e-AHCL (123.1 17.8) versus run-in (101.6 24.2) and versus stage 1 (110.6 20.8) (both P < 0.001) but did not differ from stage 2 (119.4 16.0; P = 0.271). Diabetes Medication System Rating Questionnaire short-form scores for "Convenience and Efficacy" favored e-AHCL over run-in and all stages. Percent time in range 70-180 mg/dL was greater with e-AHCL versus run-in and stage 2 (+2.9% and +3.6%, respectively; both P < 0.001). Percent times of <70 mg/dL for e-AHCL were significantly lower than run-in, stage 1, and stage 2 (-0.9%, -0.6%, and -0.5%, respectively; all P < 0.01).
e-AHCL was feasible. User satisfaction increased compared with earlier Medtronic HCL iterations without compromising glucose control.
Background: Hybrid closed loop (HCL) systems are evolving. We aimed to assess treatment satisfaction and glucose control with an investigational eAHCL system.
Methods: Adults with type 1 diabetes ...(T1D) received sequentially the MiniMed™ 780G /Guardian™ Sensor 3 AHCL system, and a Medtronic investigational eAHCL system each for 12 weeks. The eAHCL system incorporates updated software, a new simple to use, no calibration, all-in-one sensor, and 7 day extended wear infusion set. The primary outcome was difference in treatment satisfaction measured using “current” and “change” versions of the Diabetes Technology Questionnaire (DTQ) following each 12 week period. Secondary outcomes included time spent changing infusion sets and sensors recorded on a phone app and CGM metrics.
Results: Twenty-one adults (11 men, mean SD age 48 12.4 years) completed the trial. DTQ “current” score improved on eAHCL, and 86% of participants reported less “Effort to keep low blood sugar from happening” on DTQ “change”. There was less fear of hypoglycemia; more time in Auto Mode; fewer alarms; less time spent changing infusion sets and sensors; reduced CGM hypoglycemia and glycemic variability (Table 1).
Conclusions: Transition to eAHCL in T1D adults resulted in a better user experience and reduced fear of and time in hypoglycemia while maintaining safety and >80% TIR.
Disclosure
C.Yuan: None. R.Macisaac: None. E.Netzer: None. B.Paldus: None. L.Robinson: None. A.Roy: Employee; Medtronic. C.M.Sims: Stock/Shareholder; Medtronic. S.Trawley: Research Support; Insulet Corporation, Juvenile Diabetes Research Foundation (JDRF). S.Vogrin: None. D.N.O'neal: None. Y.W.Kong: None. T.Amoore: None. K.Brown: None. B.Grosman: Employee; Medtronic. A.Jenkins: Advisory Panel; Insulet Corporation, Board Member; Insulin for Life, Research Support; Abbott Diabetes, Medtronic, Hemsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), National Institutes of Health. H.Jones: None. N.Kurtz: Employee; Medtronic. M.H.Lee: Speaker's Bureau; Medtronic.
Aim: To compare device tolerance & participant’s subjective experience wearing a surgically implanted long term glucose sensor versus conventional CGM in adults with Type 1 Diabetes.
Method: A ...prototype CGM (Eclipse 3 sensor, GlySens, San Diego, CA) with masked glucose data transmitted to a study iPhone was surgically inserted superficial to the rectus sheath in 8 Adults with Type 1 Diabetes (4 Female; Mean SD Age 56 7Y; BMI 253). One daily fingerstick glucose calibration was required. Participants simultaneously wore a conventional TGA approved multi-Day sensor that also transmitted unblinded glucose information to the Study iPhone. The two systems were compared using a standardized 5-point Leichardt scale questionnaire completed by participants at day 1, 7 and 14 post-implantation and monthly thereafter for the duration of study participation.
Results: The investigation and comparator sensors were worn 100% and 98% percent of the time respectively over the study duration. Figure 1 summarizes the participant experience.
Conclusions: Over time there was a general trend by all participants to favour the GlySens sensor and experience over the comparator CGM.
.
Figure 1: Participant experience over 10 months of sensor implantation.
Disclosure
L.Robinson: None. J.Tan: None. S.L.Martha: Employee; GlySens Incorporated. D.N.O'neal: None. V.R.Obeyesekere: None. H.Jones: None. Y.W.Kong: None. C.Yuan: None. K.Bertsch: Employee; GlySens. T.L.Routh: Employee; GlySens Incorporated. C.M.Sims: Stock/Shareholder; Medtronic. A.Butler: Employee; GlySens Incorporated.
Background: In our published trial in 120 adults with type 1 diabetes (T1D), allocation to hybrid closed loop (HCL) increased Continuous Glucose Monitoring (CGM) Time in Range ((TIR), 70-180mg/dL) by ...15 percentage points vs. user-determined insulin dosing. Recommended TIR is >70%. Objective: To examine associations of pre-randomization factors with trial-end 3-weeks masked CGM TIR in adults with T1D treated with 6-months HCL. Methods: MDI and non-HCL pump users (no CGM) were randomized 1:1 to 26-weeks HCL (Medtronic 670G) or ongoing standard care. Analyses are on HCL group (n=55): Pre-randomization factors are related to trial-end masked CGM TIR >70 vs. ≤70% and to TIR as a continuous variable. Continuous variables are compared by t-test and binary variables by chi-square with significance at P<0.05. Results: Table: Pre-randomization characteristics by trial-end TIR > vs. ≤70%. Significant univariate correlations between trial-end TIR as a continuous variable existed for pre-randomization factors: HbA1c (at enrolment and randomization), 1,5-anhydroglucitol, CGM metrics: %TIR (70-180mg/dl), %TIR (70-140mg/dl), mean glucose, SD glucose. Conclusions: The main factor associated with HCL users achieving higher TIR was pre-randomization glycemia. TIR was not associated with age, sex, prior pump use and socioeconomic status.
Background: Faster-acting insulin aspart (FiAsp) may improve responsiveness of closed-loop (CL) systems and provide better postprandial glucose (PPG) management due to its more rapid onset and offset ...compared to insulin aspart (Asp). The Medtronic Advanced Hybrid Closed Loop (AHCL) System features auto-basal and auto-bolus functions.
Aim: To compare PPG control using FiAsp vs. Asp delivered using AHCL.
Methods: Twelve adults with T1D (median HbA1c 7.1% IQR 6.8, 7.2; 54mmol/mol 51, 55) were assigned to FiAsp or Asp (unblinded) in random-order over two-stages (6-weeks duration each) using AHCL. Postprandial periods were defined using set time-blocks for breakfast (06:00-10:00); lunch (11:00-15:00); and dinner (17:00-21:00), based on conventional meal-times and meal distribution. CGM data was analyzed using signed-rank test.
Results: With all postprandial time-block data aggregated, FiAsp demonstrated greater overall time-in-range (TIR) (70-180mg/dL) (p=0.028) and less hyperglycaemia (p=0.041) compared with Asp (Table). TIR was greater during lunch (p=0.034) for FiAsp vs. Asp, with no difference during breakfast or dinner. Over the 6-week duration, FiAsp use trended towards greater TIR vs. Asp (82.7% vs. 80.4%, p=0.07).
Conclusions: FiAsp appears to confer an advantage compared with Asp for PPG control whilst using AHCL even in subjects with high overall TIR.
Disclosure
M.H. Lee: Research Support; Self; Medtronic. Speaker’s Bureau; Self; AstraZeneca, Medtronic. S. Vogrin: None. B. Paldus: Research Support; Self; JDRF. Speaker’s Bureau; Self; Australian Diabetes Society, Medtronic. D. Morrison: None. D. Zaharieva: Speaker’s Bureau; Self; Ascensia Diabetes Care, Insulet Corporation, Medtronic. J. Lu: None. H. Jones: None. S.A. Wyatt: Other Relationship; Self; Medtronic, Ypsomed AG. E. Netzer: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. R. MacIsaac: None. B. Grosman: Employee; Self; Medtronic. A. Roy: Employee; Self; Medtronic. N. Kurtz: Employee; Self; Medtronic. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. D.N. ONeal: None.
Background: A missed or late meal insulin bolus can impact glycemia in type 1 diabetes (T1D).
Aim: To study glucose control after missed and late meal boluses in T1D adults using a prototype enhanced ...hybrid closed-loop (E-HCL) system (Medtronic) providing automated basal insulin and correction boluses.
Methods: Twelve T1D adults (median HbA1c 6.8% IQR 6.2-7.2 | 51mmol/mol 44-55 participated. After 1-week run-in at home in Open Loop, E-HCL was activated during 1-week supervised hotel phase followed by 3 weeks free-living at-home. Participants consumed a standardized 40g carbohydrate dinner in the supervised phase. Four hours of post-prandial glucose data following a standard bolus pre-meal in E-HCL at home were compared in a pairwise manner to 1) Pre-meal bolus in Open Loop Run-In; 2) 20minute Late bolus in E-HCL supervised; 3) Missed bolus in E-HCL supervised using Wilcoxon Signed-Rank Test.
Results: Late bolus was associated with mild hypoglycemia and higher glucose variability; missed bolus was associated with hyperglycemia (Table). Overall time in CL was 99.98%. E-HCL at home vs. Open Loop (run-in) had greater time-in-70-180mg/dL range (85.3 vs. 75.0%, p=0.003). There was no severe hypoglycemia or ketoacidosis.
Conclusions: While glucose excursions were modest, the administration and timing of meal boluses influenced post-meal glycemia in well-controlled T1D adults using E-HCL.
Disclosure
M.H. Lee: Research Support; Self; Medtronic. Speaker's Bureau; Self; AstraZeneca. S. Vogrin: None. B. Paldus: Other Relationship; Self; Australian Diabetes Society, JDRF, Medtronic. H. Jones: None. V.R. Obeyesekere: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. S.A. Wyatt: Other Relationship; Self; Animas Corporation, Medtronic. G.M. Ward: None. S.A. McAuley: Research Support; Self; JDRF, Medtronic. Speaker's Bureau; Self; Australian Diabetes Society, Eli Lilly and Company. R. MacIsaac: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. Other Relationship; Self; AstraZeneca, Novo Nordisk Inc. B. Krishnamurthy: None. V. Sundararajan: None. A. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. D.N. O'Neal: None.
Background: Few long-term RCTs compare Hybrid Closed Loop (HCL) insulin delivery to manual (non-HCL) insulin dosing in type 1 diabetes (T1D).
Objective: To examine glycemic and psychosocial outcomes ...in adults with T1D using HCL vs. manual insulin dosing with self-monitoring of blood glucose (SMBG) for 6 months.
Methods: Adults using multiple daily injections or pumps with SMBG were randomized 1:1 after insulin dose optimization to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was time in target range (70-180mg/dL) with masked CGM during the final 3 weeks. Secondary outcomes included other CGM metrics, HbA1c, treatment satisfaction (DTSQs) and diabetes distress (PAID). Intention to treat analysis was performed with ANCOVA or rank sum test.
Results: HCL and control groups were well balanced at baseline (Table). At 26 weeks, mean (95% CI) CGM time in range with HCL was greater by 14.8% (11.1, 18.5), with reduced high and low glucose time, and lower HbA1c. There were no between-group differences in treatment satisfaction or diabetes distress (Table).
Conclusions: HCL provided a significant and sustained glycemic benefit compared with standard therapy. Results will inform potential users and health professionals and a cost-benefit analysis may facilitate HCL access.
Disclosure
S.A. McAuley: Advisory Panel; Self; Medtronic. Research Support; Self; Medtronic, Roche Diabetes Care. Speaker’s Bureau; Self; Lilly Diabetes, Roche Diabetes Care. M.H. Lee: Research Support; Self; Medtronic. Speaker’s Bureau; Self; AstraZeneca, Medtronic. B. Paldus: Research Support; Self; JDRF. Speaker’s Bureau; Self; Australian Diabetes Society, Medtronic. S. Vogrin: None. M.B. Abraham: Speaker’s Bureau; Self; Lilly Diabetes. L. Bach: None. M. Burt: None. N. Cohen: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes. Research Support; Self; Ypsomed AG. Speaker’s Bureau; Self; Novo Nordisk A/S. P.G. Colman: None. E.A. Davis: None. C. Hendrieckx: None. M. de Bock: None. J. Holmes-Walker: None. J. Kaye: Advisory Panel; Self; Abbott. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. K. Kumareswaran: None. R. MacIsaac: None. R.W. McCallum: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. J. Speight: Research Support; Self; Abbott, AstraZeneca, Medtronic, Sanofi-Aventis. Speaker’s Bureau; Self; American Diabetes Association, Australian Diabetes Society, Roche Diabetes Care. S. Stranks: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Sanofi-Aventis. S. Trawley: None. V. Sundararajan: None. G. Ward: None. A.C. Keech: Advisory Panel; Self; Amgen, Kowa Research Institute, Inc. Consultant; Self; Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Amgen. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. T. Jones: Other Relationship; Self; Medtronic. D.N. ONeal: None.
This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin ...pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG).
Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16
Adults using MDIs (
= 61) versus pump (
= 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA
at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump (
= 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively (
= 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio 95% confidence interval 2.48 1.51, 4.06;
< 0.001).
Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps.
There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were ...monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median IQR age 40 35, 51 years; 11 men) undertook 475 trips (duration 15 13, 21 min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%;
= 436). Thirteen drivers recorded at least one trip (total
= 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.
