In two studies, a wearable, automated, bihormonal, “bionic” pancreas used in adults and adolescents with type 1 diabetes mellitus in unrestricted outpatient settings improved mean glycemic control, ...with fewer hypoglycemic episodes, as compared with usual care.
Maintaining glycemic values as close to the nondiabetic range as possible is effective in preventing or delaying long-term complications of type 1 diabetes mellitus,
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but achieving near normoglycemia is challenging. Most patients are unable to meet glycemic targets
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and have frequent episodes of hypoglycemia, which can be life-threatening.
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The availability of accurate continuous glucose monitoring has made feasible the development of bionic endocrine pancreatic systems that are designed to improve glycemic control and reduce the burden on patients. Tests of glycemic regulation lasting 1 day or more with the use of such systems have been limited to . . .
The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the ...safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting.
In this randomised, open-label, crossover study, we enrolled preadolescent children (aged 6-11 years) with type 1 diabetes (diagnosed for ≥1 year) who were on insulin pump therapy, from two diabetes camps in the USA. With the use of sealed envelopes, participants were randomly assigned in blocks of two to either 5 days with the bionic pancreas or conventional insulin pump therapy (control) as the first intervention, followed by a 3 day washout period and then 5 days with the other intervention. Study allocation was not masked. The autonomously adaptive algorithm of the bionic pancreas received data from a continuous glucose monitoring (CGM) device to control subcutaneous delivery of insulin and glucagon. Conventional insulin pump therapy was administered by the camp physicians and other clinical staff in accordance with their established protocols; participants also wore a CGM device during the control period. The coprimary outcomes, analysed by intention to treat, were mean CGM-measured glucose concentration and the proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L, on days 2-5. This study is registered with ClinicalTrials.gov, number NCT02105324.
Between July 20, and Aug 19, 2014, 19 children with a mean age of 9·8 years (SD 1·6) participated in and completed the study. The bionic pancreas period was associated with a lower mean CGM-measured glucose concentration on days 2-5 than was the control period (7·6 mmol/L SD 0·6 vs 9·3 mmol/L 1·7; p=0·00037) and a lower proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L on days 2-5 (1·2% SD 1·1 vs 2·8% 1·2; p<0·0001). The median number of carbohydrate interventions given per participant for hypoglycaemia on days 1-5 (ie, glucose <3·9 mmol/L) was lower during the bionic pancreas period than during the control period (three range 0-8 vs five 0-14; p=0·037). No episodes of severe hypoglycaemia were recorded. Medium-to-large concentrations of ketones (range 0·6-3·6 mmol/dL) were reported on seven occasions in five participants during the control period and on no occasion during the bionic pancreas period (p=0·063).
The improved mean glycaemia and reduced hypoglycaemia with the bionic pancreas relative to insulin pump therapy in preadolescent children with type 1 diabetes in a diabetes camp setting is a promising finding. Studies of a longer duration during which children use the bionic pancreas during their normal routines at home and school should be done to investigate the potential for use of the bionic pancreas in real-world settings.
The Leona M and Harry B Helmsley Charitable Trust and the US National Institute of Diabetes and Digestive and Kidney Diseases.
Summary Background The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We ...aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. Methods We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2–11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov , number NCT02092220. Findings We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7–1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 SD 0·83) than in the comparator period (0·05 0·17; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Interpretation Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. Funding National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.
Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and adds significant morbidity and treatment burden. We evaluated the safety and efficacy of automated insulin ...delivery with the iLet bionic pancreas (BP) in adults with CFRD in a single-center, open-label, random-order, crossover trial.
Twenty participants with CFRD were assigned in random order to 14 days each on the BP or their usual care (UC). No restrictions were placed on diet or activity. The primary outcome was the percent time sensor-measured glucose was in target range 70-180 mg/dL (time in range TIR) on days 3-14 of each arm, and key secondary outcomes included mean continuous glucose monitoring (CGM) glucose and the percent time sensor-measured glucose was in hypoglycemic range <54 mg/dL.
TIR was significantly higher in the BP arm than the UC arm (75 ± 11% vs. 62 ± 22%, P = 0.001). Mean CGM glucose was lower in the BP arm than in the UC arm (150 ± 19 vs. 171 ± 45 mg/dL, P = 0.007). There was no significant difference in percent time with sensor-measured glucose <54 mg/dL (0.27% vs. 0.36%, P = 1.0), although self-reported symptomatic hypoglycemia episodes were higher during the BP arm than the UC arm (0.7 vs. 0.4 median episodes per day, P = 0.01). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either arm.
Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared with their UC, suggesting that this may be an important therapeutic option for this patient population.
Tight glycemic control of hospitalized patients is difficult and labor intensive to achieve. We evaluated the feasibility of fully automated glycemic control with a version of the bionic pancreas ...(BP) designed for use in the critical-care setting. The fully automated BP controlled the intravenous delivery of insulin and 20% dextrose based on glucose values from the Abbott FreeStyle Navigator CGM. The same algorithm, initialized only with body mass, was used in all subjects. Adult subjects with type 1 (n=6) or type 2 (n=6) diabetes with a total daily dose (TDD) of insulin under usual care of 0.5-2.9 u/kg/day were under automated glucose control for an 8-hour period. Subjects started the study period fasted, later consumed an unrestricted meal of their choice, and still later took liquid nutrition nearly continuously for 2 hours before abruptly stopping, in order to simulate continuous enteral feeding and its interruption. Food intake was not announced to the BP. The primary outcome, mean plasma glucose (measured every 15 minutes), was 116±20 mg/dL. The % time within 70-180 mg/dL was 95±8% and the median (IQR) % of time <70 mg/dL was 0 (0, 2.3) and <54 mg/dl was 0 (0, 0). We concluded that the BP can achieve excellent glycemic control in volunteers with a wide range of insulin needs and in the face of realistic glycemic challenges. These results support feasibility testing of the critical care BP in the critical-care setting.
Disclosure
J. Sherwood: None. M.A. Hillard: None. K.B. Grennan: None. F. El-Khatib: Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. E. Damiano: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Beta Bionics. Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. Stock/Shareholder; Spouse/Partner; Beta Bionics. Other Relationship; Self; Ascensia Diabetes Care, Senseonics. S.J. Russell: Advisory Panel; Self; Companion Medical, Unomedical a/s. Consultant; Self; Flexion Therapeutics. Research Support; Self; Beta Bionics, MITRE Corporation, Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Self; ADOCIA, Ascensia Diabetes Care, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, Senseonics.
Funding
Wallace H. Coulter Foundation
Background: Approximately 25 million people around the world identify as transgender, and the numbers are growing. While visibility of transgender communities has increased, significant healthcare ...disparities remain. Transgender individuals report being less inclined to share their sex assigned at birth due to fear of stigmatization and mistrust of the medical community. The mistrust and inequity experienced by transgender individuals are not limited to clinical care and may extend to clinical research as well.
Aim and method: The aim of this paper is to start a conversation about barriers to participating in research and the role of research staff, specifically the Clinical Research Nurse, in promoting engagement of transgender individuals in clinical research trials.
Discussion and conclusions: A discussion of safety considerations, data integrity, and implications for data management is included. Because disparities may result in large part from lack of education and knowledge on best practices for providing care for this population, recommendations for fostering a culture of competence and gender-affirming care among research professionals featuring the role of the research nurse will be discussed.
In a 13-week, randomized trial involving persons 6 to 79 years of age with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction in the glycated hemoglobin level than ...standard care.
Introduction & Objective: While about half of US adults with T1D are managed by primary care (PC), automated insulin delivery (AID) use is rare in PC compared to endocrinology (EN). The iLet Bionic ...Pancreas (BP) has a unique initiation process of simply entering the user’s weight, followed by perpetual autonomous adaptation to meet each user’s changing insulin needs; the BP may thus be more feasible for PC and/or telehealth (TH) deployment than AID systems with more intensive startup and follow-on care. This random order crossover trial (NCT05168657) evaluated feasibility of BP startup and management by PC versus EN and training via TH versus in person (IP). Methods: Forty adults with T1D (20 at a PC site, 20 at an EN site) were assigned to complete two study arms (14 days of BP use, 14 days of their usual diabetes care UC) in random order. PC participants’ UC was required to be multiple daily injections with or without CGM; EN participants’ UC was CGM sensor augmented pump. Half of each group were trained and managed by IP visits and half by TH. Primary outcome: % of each group achieving average glucose (AG) <183 mg/dL during BP use. Results: Both arms were completed by 39 participants. With BP use, 38 (97.4%) achieved AG <183 mg/dL, with no differences between PC and EN groups or the respective IP and TH subgroups (all p>0.05). Decreased AG was seen with BP use compared to UC in all four groups (all p<0.05). With BP use, PC and EN groups achieved similar results in AG, time <70, time between 70 and 180, time >180, and time >250 mg/dL. The PC group had slightly lower CV and time <54 mg/dL than EN with BP use (both p=0.03). There were no severe adverse events during BP or UC use. Conclusion: Training and initiation of the BP by PC and EN subspecialists, and through IP versus TH visits, resulted in similar CGM outcomes with the BP, which were improved relative to UC. These findings suggest that the BP, with its uniquely simple initiation, use, and follow-on care, may expand AID access for people limited by geographic and/or subspecialty access. Disclosure S. Oser: Other Relationship; American Diabetes Association, Association of Diabetes Care & Education Specialists. Research Support; Abbott. Advisory Panel; Dexcom, Inc., Jaeb Center for Health Research. M.S. Putman: Research Support; Dexcom, Inc. Other Relationship; Vertex Pharmaceuticals Incorporated. Research Support; Vertex Pharmaceuticals Incorporated. Advisory Panel; Anagram Therapeutics. E. Westfeldt: None. K.B. Huss: None. B. Prince: None. D.L. Buss: None. J.K. Oser: None. C.M. Lyon: None. M. O'Connor: None. A. Sabean: None. A. Ashley: None. E. Greaux: None. R. Bartholomew: None. S. Gaston: None. N. Anandakugan: None. C. Balliro: Employee; Beta Bionics, Inc. M.A. Hillard: Employee; Beta Bionics, Inc. S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. Other Relationship; Beta Bionics, Inc. Consultant; Beta Bionics, Inc. Research Support; Beta Bionics, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk. E. Damiano: Board Member; Beta Bionics, Inc. Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. T. Oser: Research Support; Abbott. Advisory Panel; Medscape. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2107-04767)
There are no published studies directly comparing the accuracy of continuous glucose monitoring (CGM) devices in the outpatient setting. We tested the performance of the Dexcom G5, Abbot Freestyle ...Libre Pro, and Senseonics Eversense (an implantable CGM approved in Europe) during a 6-week, free-living, outpatient bionic pancreas study involving 23 subjects with type 1 diabetes who wore all 3 devices concomitantly. The primary outcome was the mean absolute relative difference (MARD) vs. plasma glucose (PG) values measured with the Nova Biomedical StatStrip Xpress meter that was also used for calibrations according to the manufacturer's instruction (except for Libre Pro that is not calibrated). We compared PG values with CGM readings when they were available from all 3 CGMS in the 5 minutes preceding the PG values (n=829 sets). Since the Libre Pro records readings every 15 minutes, we also did a two-way comparison between the G5 and the Eversense that allowed a higher number of comparisons (n=2277 sets). Statistical significance was determined using a repeated measurements model fitted with the generalized estimating equation method. All 3 CGM systems produced higher average MARDs than during in-clinic studies. However, since all three CGM systems were worn by the same individuals and used the same meter for calibration and as comparator, we were able to directly compare their performance under real-world conditions. In the 3-way comparison Eversense achieved the lowest nominal MARD (14.8%) followed by Dexcom G5 (16.3%) and Libre Pro (18.0%) (Eversense vs. Libre Pro p=0.004, other comparisons p=NS). In the 2-way comparison the MARD difference between Eversense (15.1%) and G5 (16.9%) was statistically significant (p=0.008). We found that the point accuracy of the Eversense was significantly better than two other CGM systems. The Eversense CGM system may be useful to provide glucose values to artificial pancreas devices.
Disclosure
R.Z. Jafri: None. C.A. Balliro: None. F. El-Khatib: Stock/Shareholder; Self; Beta Bionics. Employee; Self; Beta Bionics. M. Maheno: None. M.A. Hillard: None. A.J. O'Donovan: None. R. Selagamsetty: None. H. Zheng: None. E. Damiano: Other Relationship; Self; Beta Bionics. S.J. Russell: Other Relationship; Self; Beta Bionics, Novo Nordisk Inc.. Advisory Panel; Self; Companion Medical, Tandem Diabetes Care, Inc., Unomedical a/s. Research Support; Self; Beta Bionics, Zealand Pharma A/S, MITRE Corporation.
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