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.

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.

Transfer-printing-based integration of single-mode waveguide-coupled III-V-on-silicon broadband light emitters.

We present the first III-V opto-electronic components transfer printed on and coupled to a silicon photonic integrated circuit. Thin InP-based membranes are transferred to an SOI waveguide circuit, after which a single-spatial-mode broadband light source is fabricated. The process flow to create transfer print-ready coupons is discussed. Aqueous FeCl3 at 5°C was found to be the best release agent in combination with the photoresist anchoring structures that were used. A thin DVS-BCB layer provides a strong bond, accommodating the post-processing of the membranes. The resulting optically pumped LED has a 3 dB bandwidth of 130 nm, comparable to devices realized using a traditional die-to-wafer bonding method.

A noncontact approach for the evaluation of large artery stiffness: a preliminary study.

BACKGROUND: The time from carotid to femoral pulse wave propagation (pulse transit time (PTT)) is required to estimate the carotid-femoral pulse wave velocity (PWV), a reliable index for evaluating large artery stiffness. METHODS: In this work, we propose a novel, noncontact laser-based technique, named optical vibrocardiography (VCG), for evaluating PTT from synchronous recordings of the motion of the skin on the neck and the groin. These measurements, which have been demonstrated to be related to the radial displacement of the underlying blood vessels, were performed on 14 healthy subjects. As validation, applanation tonometry was performed to determine PTT between the carotid and the femoral artery. RESULTS: PTT evaluated by VCG was not different from applanation tonometry (74.86 +/- 8.63 ms vs. 75.85 +/- 8.61 ms, P = 0.377). CONCLUSIONS: Our preliminary results demonstrate that laser-based noncontact measurement in young healthy volunteers is feasible, and yields PTTs that are equivalent to those measured using arterial applanation tonometry. Its clinical application can overcome limitations inherent to a contact method like arterial tonometry.

Intracavity generation of radially polarized CO2 laser beams based on a simple binary dielectric diffraction grating.

We present experimental results on the intracavity generation of radially polarized light by incorporation of a polarization-selective mirror in a CO(2)-laser resonator. The selectivity is achieved with a simple binary dielectric diffraction grating etched in the backsurface of the mirror substrate. Very high polarization selectivity was achieved, and good agreement of simulation and experimental results is shown. The overall radial polarization purity of the generated laser beam was found to be higher than 90%.

Polarization-selective beam splitter based on a highly efficient simple binary diffraction grating.

A polarization beam splitter (PBS) based on a giant-reflection to zero-order (GIRO) grating is presented. The GIRO grating is a simple binary diffraction grating with parameters chosen such that the excited optical modes in the grating interfere constructively and destructively at the respective interfaces. This interference results in high-zero-order reflection (>99%) with a high polarization-selective extinction ratio (+/-30 dB). The grating shows a low aspect ratio. The GIRO PBS is theoretically and experimentally shown to be an adequate PBS for use as an optical isolator in combination with a quarter-wave plate in a CO2-laser system.

Rigorous electromagnetic analysis of dipole emission in periodically corrugated layers: the grating-assisted resonant-cavity light-emitting diode.

We study the grating-assisted light-emitting diode, an LED design for high brightness based on a resonant cavity containing one- or two-dimensionally periodically corrugated layers (grating). We give in detail a generally applicable electromagnetic analysis based on the rigorous coupled-wave theory to calculate the extraction efficiency of spontaneous emission in a periodically corrugated layer structure. This general model is then specified on the grating-assisted resonant-cavity LED, showing simulated efficiencies of more than 40%.