Basal insulin delivery reduction for exercise in type 1 diabetes: finding the sweet spot

Exercise poses significant challenges to glucose management in type 1 diabetes. In spite of careful planning and manipulation of subcutaneous insulin administration, increased risk of hypoglycaemia and glycaemic variability during and after exercise may occur as a result of inherent delays in insulin action and impaired counter-regulatory hormone responses. Various strategies to mitigate this issue have been advocated in clinical practice, including ingestion of supplementary carbohydrate prior to exercise, reducing background and pre-meal insulin bolus and performing bouts of resistance/high intensity exercise before aerobic exercise. Insulin pump therapy, considered the most physiological form of insulin replacement for type 1 diabetes allows modulation of basal insulin delivery before, during and after exercise. However uncertainty remains regarding the optimal strategy to reduce basal insulin delivery and its efficacy. In this issue of Diabetologia, McAuley and colleagues (DOI: 10.1007/s00125-016-3981-9) report on the impact of a 50% reduction of basal insulin delivery before, during and after moderate-intensity aerobic exercise. Results from this study may contribute to a better understanding of the effects of basal insulin delivery manipulation and may aid in devising therapeutic approaches for glucose management during exercise

Use of Factory-Calibrated Real-time Continuous Glucose Monitoring Improves Time in Target and HbA1c in a Multiethnic Cohort of Adolescents and Young Adults With Type 1 Diabetes:The MILLENNIALS Study

OBJECTIVEInternational type 1 diabetes registries have shown that HbA1c levels are highest in young people with type 1 diabetes; however, improving their glycemic control remains a challenge. We propose that use of the factory-calibrated Dexcom G6 CGM system would improve glycemic control in this cohort.RESEARCH DESIGN AND METHODSWe conducted a randomized crossover trial in young people with type 1 diabetes (16–24 years old) comparing the Dexcom G6 CGM system and self-monitoring of blood glucose (SMBG). Participants were assigned to the interventions in random order during two 8-week study periods. During SMBG, blinded continuous glucose monitoring (CGM) was worn by each participant for 10 days at the start, week 4, and week 7 of the control period. HbA1c measurements were drawn after enrollment and before and after each treatment period. The primary outcome was time in range 70–180 mg/dL.RESULTSTime in range was significantly higher during CGM compared with control (35.7 ± 13.5% vs. 24.6 ± 9.3%; mean difference 11.1% [95% CI 7.0–15.2]; P < 0.001). CGM use reduced mean sensor glucose (219.7 ± 37.6 mg/dL vs. 251.9 ± 36.3 mg/dL; mean difference −32.2 mg/dL [95% CI −44.5 to −20.0]; P < 0.001) and time above range (61.7 ± 15.1% vs. 73.6 ± 10.4%; mean difference 11.9% [95% CI −16.4 to −7.4]; P < 0.001). HbA1c level was reduced by 0.76% (95% CI −1.1 to −0.4) (−8.5 mmol/mol [95% CI −12.4 to −4.6]; P < 0.001). Times spent below range (<70 mg/dL and <54 mg/dL) were low and comparable during both study periods. Sensor wear was 84% during the CGM period.CONCLUSIONSCGM use in young people with type 1 diabetes improves time in target and HbA1c levels compared with SMBG

Closing the loop overnight at home setting: psychosocial impact for adolescents with type 1 diabetes and their parents.

OBJECTIVE: To explore the experiences of adolescents with type 1 diabetes mellitus (T1DM) and their parents taking part in an overnight closed loop study at home, using qualitative and quantitative research methods. RESEARCH DESIGN AND METHODS: Adolescents aged 12-18 years on insulin pump therapy were recruited to a pilot closed loop study in the home setting. Following training on the use of a study insulin pump and continuous glucose monitoring (CGM), participants were randomized to receive either real-time CGM combined with overnight closed loop or real-time CGM alone followed by the alternative treatment for an additional 21 days with a 2-3-week washout period in between study arms. Semistructured interviews were performed to explore participants' perceptions of the impact of the closed loop technology. At study entry and again at the end of each 21-day crossover arm of the trial, participants completed the Diabetes Technology Questionnaire (DTQ) and Hypoglycemia Fear Survey (HFS; also completed by parents). RESULTS: 15 adolescents and 13 parents were interviewed. Key positive themes included reassurance/peace of mind, confidence, 'time off' from diabetes demands, safety, and improved diabetes control. Key negative themes included difficulties with calibration, alarms, and size of the devices. DTQ results reflected these findings. HFS scores were mixed. CONCLUSIONS: Closed loop insulin delivery represents cutting-edge technology in the treatment of T1DM. Results indicate that the psychological and physical benefits of the closed loop system outweighed the practical challenges reported. Further research from longitudinal studies is required to determine the long-term psychosocial benefit of the closed loop technology

Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial.

INTRODUCTION: Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol. METHODS: Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM. RESULTS: The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without hypoglycemia (<4 mM) during either therapy. CONCLUSIONS: Fully automated closed-loop control based on subcutaneous glucose measurements is feasible and may provide efficacious and hypoglycemia-free glucose control in critically ill adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01440842

Pharmacokinetics of insulin aspart in pump-treated subjects with type 1 diabetes: reproducibility and effect of age, weight, and duration of diabetes.

Insulin aspart, lispro, or glulisine are recommended in pump-treated type 1 diabetes (T1D). Aspart pharmacokinetics has been studied (1), but little is known about its reproducibility and associations with anthropometric and clinical factors. We analyzed retrospectively data collected in 70 pump-treated subjects with T1D, comprising 39 females, 46 young, with mean (SD) BMI 22.7 (4.2) kg/m2, A1C 8.1% (1.3) (65.3 [14.4] mmol/mol), and total daily insulin 0.8 (0.3) units/kg/day, who were undergoing investigations, with ethical approval, of closed-loop insulin delivery. Participants/guardians signed consent/assent as appropriate. Participants were admitted twice to the research facility, 1–6 weeks apart, for 15–37 h, and consumed 1–4 meals accompanied by prandial insulin aspart. Basal aspart was delivered using closed-loop insulin delivery or conventional pump therapy. Venous blood samples were collected every 30–60 min to measure plasma insulin (Invitron, Monmouth, U.K.). From 5,804 plasma insulin measurements, we estimated, using a two-compartment model, the time-to-peak plasma insulin concentration (tmax [min]), the metabolic clearance rate of insulin (MCR in mL/kg/min), and the background residual plasma insulin concentration (mU/L). Results are presented in Table 1. Sex differences in aspart kinetics were not observed. Aspart pharmacokinetics was weakly influenced by common clinical and anthropometric factors, because less than 20% of intersubject variability was explained by sex, BMI, total daily dose, A1C, and diabetes duration

Evaluating Glucose Control With a Novel Composite Continuous Glucose Monitoring Index.

OBJECTIVE: The objective was to describe a novel composite continuous glucose monitoring index (COGI) and to evaluate its utility, in adults with type 1 diabetes, during hybrid closed-loop (HCL) therapy and multiple daily injections (MDI) therapy combined with real-time continuous glucose monitoring (CGM). METHODS: COGI consists of three key components of glucose control as assessed by CGM: Time in range (TIR), time below range (TBR), and glucose variability (GV) (weighted by 50%, 35% and 15%). COGI ranges from 0 to 100, where 1% increase of time 7.5-10%, had significantly higher COGI during 12 weeks of HCL compared to sensor-augmented pump therapy, mean (SD), 60.3 (8.6) versus 69.5 (6.9), P 7.5% to 9.9%, use of real-time CGM led to improved COGI, 49.8 (14.2) versus 58.2 (9.1), P < .0001. In MDI users with impaired awareness of hypoglycemia, use of real-time CGM led to improved COGI, 53.4 (12.2) versus 66.7 (11.1), P < .001. CONCLUSIONS: COGI summarizes three key aspects of CGM data into a concise metric that could be utilized to evaluate the quality of glucose control and to demonstrate the incremental benefit of a wide range of treatment modalities

Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial.

OBJECTIVE: To evaluate feasibility, safety, and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Overnight closed loop was evaluated at home by 16 pump-treated adolescents with type 1 diabetes aged 12-18 years. Over a 3-week period, overnight insulin delivery was directed by a closed-loop system, and on another 3-week period sensor-augmented therapy was applied. The order of interventions was random. The primary end point was time when adjusted sensor glucose was between 3.9 and 8.0 mmol/L from 2300 to 0700 h. RESULTS: Closed loop was constantly applied over at least 4 h on 269 nights (80%); sensor data were collected over at least 4 h on 282 control nights (84%). Closed loop increased time spent with glucose in target by a median 15% (interquartile range -9 to 43; P < 0.001). Mean overnight glucose was reduced by a mean 14 (SD 58) mg/dL (P < 0.001). Time when glucose was <70 mg/dL was low in both groups, but nights with glucose <63 mg/dL for at least 20 min were less frequent during closed loop (10 vs. 17%; P = 0.01). Despite lower total daily insulin doses by a median 2.3 (interquartile range -4.7 to 9.3) units (P = 0.009), overall 24-h glucose was reduced by a mean 9 (SD 41) mg/dL (P = 0.006) during closed loop. CONCLUSIONS: Unsupervised home use of overnight closed loop in adolescents with type 1 diabetes is safe and feasible. Glucose control was improved during the day and night with fewer episodes of nocturnal hypoglycemia.Supported by Juvenile Diabetes Research Foundation (#22-2006-1113, #22-2007-1801, #22-2009-801, #22-2009-802), Diabetes UK (BDA07/0003549), National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621), Medical Research Council Centre for Obesity and Related metabolic Diseases, and National Institute for Health Research Cambridge Biomedical Research Centre. Abbott Diabetes Care supplied continuous glucose delivery devices and sensors and modified devices to facilitate real-time connectivity.This is the final published version, also available from the American Diabetes Association at http://care.diabetesjournals.org/content/37/5/1204

Real-World Outcomes of Glucose Sensor Use in Type 1 Diabetes—Findings from a Large UK Centre

From MDPI via Jisc Publications RouterHistory: accepted 2021-11-10, pub-electronic 2021-11-15Publication status: PublishedFlash glucose monitoring (FGM) and real-time continuous glucose monitoring (RT-CGM) are increasingly used in clinical practice, with improvements in HbA1c and time in range (TIR) reported in clinical studies. We aimed to evaluate the impact of FGM and RT-CGM use on glycaemic outcomes in adults with type 1 diabetes (T1DM) under routine clinical care. We performed a retrospective data analysis from electronic outpatient records and proprietary web-based glucose monitoring platforms. We measured HbA1c (pre-sensor vs. on-sensor data) and sensor-based outcomes from the previous three months as per the international consensus on RT-CGM reporting guidelines. Amongst the 789 adults with T1DM, HbA1c level decreased from 61.0 (54.0, 71.0) mmol/mol to 57 (49, 65.8) mmol/mol in 561 people using FGM, and from 60.0 (50.0, 70.0) mmol/mol to 58.8 (50.3, 66.8) mmol/mol in 198 using RT-CGM (p 0.001 for both). We found that 23% of FGM users and 32% of RT-CGM users achieved a time-in-range (TIR) (3.9 to 10 mmol/L) of >70%. For time-below-range (TBR) 4 mmol/L, 70% of RT-CGM users and 58% of FGM users met international recommendations of 4%. Our data add to the growing body of evidence supporting the use of FGM and RT-CGM in T1DM

Closed-loop basal insulin delivery over 36 hours in adolescents with type 1 diabetes: randomized clinical trial.

OBJECTIVE: We evaluated the safety and efficacy of closed-loop basal insulin delivery during sleep and after regular meals and unannounced periods of exercise. RESEARCH DESIGN AND METHODS: Twelve adolescents with type 1 diabetes (five males; mean age 15.0 [SD 1.4] years; HbA1c 7.9 [0.7]%; BMI 21.4 [2.6] kg/m(2)) were studied at a clinical research facility on two occasions and received, in random order, either closed-loop basal insulin delivery or conventional pump therapy for 36 h. During closed-loop insulin delivery, pump basal rates were adjusted every 15 min according to a model predictive control algorithm informed by subcutaneous sensor glucose levels. During control visits, subjects' standard infusion rates were applied. Prandial insulin boluses were given before main meals (50-80 g carbohydrates) but not before snacks (15-30 g carbohydrates). Subjects undertook moderate-intensity exercise, not announced to the algorithm, on a stationary bicycle at a 140 bpm heart rate in the morning (40 min) and afternoon (20 min). Primary outcome was time when plasma glucose was in the target range (71-180 mg/dL). RESULTS: Closed-loop basal insulin delivery increased percentage time when glucose was in the target range (median 84% [interquartile range 78-88%] vs. 49% [26-79%], P = 0.02) and reduced mean plasma glucose levels (128 [19] vs. 165 [55] mg/dL, P = 0.02). Plasma glucose levels were in the target range 100% of the time on 17 of 24 nights during closed-loop insulin delivery. Hypoglycemia occurred on 10 occasions during control visits and 9 occasions during closed-loop delivery (5 episodes were exercise related, and 4 occurred within 2.5 h of prandial bolus). CONCLUSIONS: Day-and-night closed-loop basal insulin delivery can improve glucose control in adolescents. However, unannounced moderate-intensity exercise and excessive prandial boluses pose challenges to hypoglycemia-free closed-loop basal insulin delivery

Variability of Insulin Requirements Over 12 Weeks of Closed-Loop Insulin Delivery in Adults With Type 1 Diabetes.

OBJECTIVE: To quantify variability of insulin requirements during closed-loop insulin delivery. RESEARCH DESIGN AND METHODS: We retrospectively analyzed overnight, daytime, and total daily insulin amounts delivered during a multicenter closed-loop trial involving 32 adults with type 1 diabetes. Participants applied hybrid day-and-night closed-loop insulin delivery under free-living home conditions over 12 weeks. The coefficient of variation was adopted to measure variability of insulin requirements in individual subjects. RESULTS: Data were analyzed from 1,918 nights, 1,883 daytime periods and 1,564 total days characterized by closed-loop use over 85% of time. Variability of overnight insulin requirements (mean [SD] coefficient of variation 31% [4]) was nearly twice as high as variability of total daily requirements (17% [3], P < 0.001) and was also higher than variability of daytime insulin requirements (22% [4], P < 0.001). CONCLUSIONS: Overnight insulin requirements were significantly more variable than daytime and total daily amounts. This may explain why some people with type 1 diabetes report frustrating variability in morning glycemia.Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity. We acknowledge support by the staff at the Addenbrooke’s Wellcome Trust Clinical Research Facility. Jasdip Mangat and John Lum (Jaeb Center) supported development and validation of the closed-loop system. Josephine Hayes (University of Cambridge) provided administrative support. Karen Whitehead (University of Cambridge) provided laboratory support. We acknowledge support by the staff at Profil Institut; Krisztina Schmitz-Grozs provided support as a research physician, Martina Haase supported the study as an insulin pump expert, and Maren Luebkert, Kirstin Kuschma and Elke Przetak provided administrative, coordinating and documentation support.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/dc15-262