Early feasibility study with an implantable near-infrared spectroscopy sensor for glucose, ketones, lactate and ethanol.

OBJECTIVE: To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. RESEARCH DESIGN AND METHODS: This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40-400 mg/dL, 2.2-22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4-8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. RESULTS: The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. CONCLUSIONS: The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. TRIAL REGISTRATION: Clinical trial identifier: NCT04782934.

Effect of nationwide reimbursement of real-time continuous glucose monitoring on HbA1c, hypoglycemia and quality of life in a pediatric type 1 diabetes population: The RESCUE-pediatrics study.

Objective: Real-time continuous glucose monitoring (RT-CGM) can improve metabolic control and quality of life (QoL), but long-term real-world data in children with type 1 diabetes (T1D) are scarce. Over a period of 24 months, we assessed the impact of RT-CGM reimbursement on glycemic control and QoL in children/adolescents with T1D treated with insulin pumps. Research design and methods: We conducted a multicenter prospective observational study. Primary endpoint was the change in HbA1c. Secondary endpoints included change in time in hypoglycemia, QoL, hospitalizations for hypoglycemia and/or ketoacidosis and absenteeism (school for children, work for parents). Results: Between December 2014 and February 2019, 75 children/adolescents were followed for 12 (n = 62) and 24 months (n = 50). Baseline HbA1c was 7.2 ± 0.7% (55 ± 8mmol/mol) compared to 7.1 ± 0.8% (54 ± 9mmol/mol) at 24 months (p = 1.0). Participants with a baseline HbA1c ≥ 7.5% (n = 27, mean 8.0 ± 0.3%; 64 ± 3mmol/mol) showed an improvement at 4 months (7.6 ± 0.7%; 60 ± 8mmol/mol; p = 0.009) and at 8 months (7.5 ± 0.6%; 58 ± 7mmol/mol; p = 0.006), but not anymore thereafter (endpoint 24 months: 7.7 ± 0.9%; 61 ± 10mmol/mol; p = 0.2). Time in hypoglycemia did not change over time. QoL for parents and children remained stable. Need for assistance by ambulance due to hypoglycemia reduced from 8 to zero times per 100 patient-years (p = 0.02) and work absenteeism for parents decreased from 411 to 214 days per 100 patient-years (p = 0.03), after 24 months. Conclusion: RT-CGM in pump-treated children/adolescents with T1D showed a temporary improvement in HbA1c in participants with a baseline HbA1c ≥ 7.5%, without increasing time in hypoglycemia. QoL was not affected. Importantly, RT-CGM reduced the need for assistance by ambulance due to hypoglycemia and reduced work absenteeism for parents after 24 months. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02601729].

Trends of glucose, lactate and ketones during anaerobic and aerobic exercise in subjects with type 1 diabetes: The ACTION-1 study.

BACKGROUND: Exercise is part of type 1 diabetes (T1D) management due to its cardiovascular and metabolic benefits. However, despite using continuous glucose monitoring, many patients are reluctant to exercise because of fear for hypoglycaemia. AIMS: We assessed trends in glucose, lactate and ketones during anaerobic and aerobic exercise in people with T1D and compared incremental area under the curve (AUC) between both exercises. METHODS: Twenty-one men with T1D (median [IQR]: age 29 years [28-38], body mass index (BMI) 24.4 kg/m2 [22.3-24.9], HbA1c 7.2% [6.7-7.8]), completed a cardiopulmonary exercise test (CPET) and a 60-min aerobic exercise (AEX) at 60% VO2 peak on an ergometer bicycle within a 6-week period. Subjects consumed a standardised breakfast (6 kcal/kg, 20.2 g CHO/100 ml) before exercise without pre-meal insulin and basal insulin for pump users. RESULTS: During CPET, glucose levels increased, peaking at 331 mg/dl [257-392] 1-3 h after exercise and reaching a nadir 6 h after exercise at 176 mg/dl [118-217]. Lactate levels peaked at 6.0 mmol/L [5.0-6.6] (max 13.5 mmol/L). During AEX, glucose levels also increased, peaking at 305 mg/dl [245-336] 80 min after exercise and reaching a nadir 6 h after exercise at 211 mg/dl [116-222]. Lactate levels rose quickly to a median of 4.3 mmol/L [2.7-6.7] after 10 min. Ketone levels were low during both tests (median ≤ 0.2 mmol/L). Lactate, but not glucose or ketone AUC, was significantly higher in CPET compared to AEX (p = 0.04). CONCLUSIONS: Omitting pre-meal insulin and also basal insulin in pump users, did prevent hypoglycaemia but induced hyperglycaemia due to a too high carbohydrate ingestion. No ketosis was recorded during or after the exercises. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05097339.

The road from intermittently scanned continuous glucose monitoring to hybrid closed-loop systems. Part B: results from randomized controlled trials.

BACKGROUND: Advances in diabetes technology have been exponential in the last few decades. With evolution in continuous glucose monitoring (CGM) systems and its progressive automation in control of insulin delivery, these advances have changed type 1 diabetes mellitus (T1DM) management. These novel technologies have the potential to improve glycated haemoglobin (HbA1c), reduce hypoglycaemic events, increase time spent in range and improve quality of life (QoL). Our aim was to evaluate the sustained effects in free-living unsupervised conditions of CGM systems (intermittently scanned and real time) and insulin delivery [from multiple daily injections, via sensor-augmented pump therapy and (predictive) low-glucose insulin suspension to hybrid closed-loop systems] on glucose control and QoL in adults and children with T1DM. METHODS: We performed a systematic review of randomized controlled trials (RCTs), using PubMed and the Cochrane library up to 30 May 2019. Inclusion of RCTs was based on type of intervention (comparing glucose-monitoring devices and insulin-delivery devices), population (nonpregnant adults and children with T1DM), follow-up (outpatient setting for at least 8 weeks) and relevant outcomes [HbA1c, time in range (TIR), time in target, time in hypoglycaemia and QoL]. Exclusion of RCTs was based on intervention (exercise, only overnight use). The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were used to score the quality of the papers and for the final selection of the articles. RESULTS: Our search resulted in 214 articles, of which 19 were eligible. Studies on advanced use in adults and children with T1DM reported increased TIR (all 9 studies); decreased time in hypoglycaemia (13 out of 15 studies); lowered HbA1c levels (5 out of 15 studies); improved QoL (10 of 16 studies) and treatment satisfaction (7 studies). CONCLUSIONS: Recent technologies have dramatically changed the course of T1DM. They are proving useful in controlling glycaemia in patients with T1DM, without increasing the treatment burden.

The road from intermittently scanned glucose monitoring to hybrid closed-loop systems: Part A. Keys to success: subject profiles, choice of systems, education.

Managing type 1 diabetes (T1DM) is challenging and requires intensive glucose monitoring and titration of insulin in order to reduce the risk of complications. The use of continuous glucose monitoring (CGM) systems, either flash or intermittently scanned glucose monitoring (isCGM) or real-time (RT) CGM, has positively affected the management of type 1 diabetes with the potential to lower HbA1c, enhance time spent in range, reduce frequency and time spent in hypoglycemia and hyperglycemia, lower glycemic variability, and improve quality of life. In recent years, both CGM and pump technology have advanced, with improved functional features and integration, including low glucose suspend (LGS), predictive low glucose suspend (PLGS), and hybrid closed-loop (HCL) systems. In this review, we highlight the benefits and limitations of use of isCGM/RT-CGM for open-loop control and recent progress in closed-loop control systems. We also discuss different subject profiles for the different systems, and focus on educational aspects that are key to successful use of the systems.