Development of a prototype toe sensor for detection of diabetic peripheral small fiber neuropathy.

Diabetic peripheral neuropathy (DPN) affects a large proportion of people with diabetes, and early detection is essential to prevent further progression. Widespread clinical testing relies on simplicity and cost-effectiveness of examination. Early signs of DPN may be detected by assessing the sudomotor nerves, and sudomotor activity can be measured by bioimpedance. We present a prototype toe probe for DPN detection including sensors for measuring skin AC conductance, skin temperature and humidity. The prototype was tested on five participants with DPN and five healthy age-matched controls in a pilot study. Sudomotor sensor responses to a simple deep breathing test were very weak or absent in the DPN group, with all controls having larger responses than the DPN group. Evaporation was lower for the DPN group, and skin temperature was higher on average. For the same foot, the results for sudomotor responses were in agreement with sensory neurography amplitudes from the sural nerve whereas the monofilament test gave normal results for two of the DPN participants. If sufficient detection accuracy is confirmed in larger studies, the method may provide a simple and cost-effective tool to support clinical examination. Clinical Relevance- We present the early realization and testing of a simple device to support early detection of diabetic peripheral neuropathy.

Quantification of aerosol dispersal from suspected aerosol-generating procedures.

BACKGROUND: Oxygen-delivering modalities like humidified high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV) are suspected of generating aerosols that may contribute to transmission of disease such as coronavirus disease 2019. We sought to assess if these modalities lead to increased aerosol dispersal compared to the use of non-humidified low-flow nasal cannula oxygen treatment (LFNC). METHODS: Aerosol dispersal from 20 healthy volunteers using HFNC, LFNC and NIV oxygen treatment was measured in a controlled chamber. We investigated effects related to coughing and using a surgical face mask in combination with the oxygen delivering modalities. An aerodynamic particle sizer measured aerosol particles (APS3321, 0.3-20 µm) directly in front of the subjects, while a mesh of smaller particle sensors (SPS30, 0.3-10 µm) was distributed in the test chamber. RESULTS: Non-productive coughing led to significant increases in particle dispersal close to the face when using LFNC and HFNC but not when using NIV. HFNC or NIV did not lead to a statistically significant increase in aerosol dispersal compared to LFNC. With non-productive cough in a room without air changes, there was a significant drop in particle levels between 100 cm and 180 cm from the subjects. CONCLUSIONS: Our results indicate that using HFNC and NIV does not lead to increased aerosol dispersal compared to low-flow oxygen treatment, except in rare cases. For a subject with non-productive cough, NIV with double-limb circuit and non-vented mask may be a favourable choice to reduce the risk for aerosol spread.

A multiparameter model for non-invasive detection of hypoglycemia.

OBJECTIVE: Severe hypoglycemia is the most serious acute complication for people with type 1 diabetes (T1D). Approximately 25% of people with T1D have impaired ability to recognize impending hypoglycemia, and nocturnal episodes are feared. APPROACH: We have investigated the use of non-invasive sensors for detection of hypoglycemia based on a mathematical model which combines several sensor measurements to identify physiological responses to hypoglycemia. Data from randomized single-blinded euglycemic and hypoglycemic glucose clamps in 20 participants with T1D and impaired awareness of hypoglycemia was used in the analyses. MAIN RESULTS: Using a sensor combination of sudomotor activity at three skin sites, ECG-derived heart rate and heart rate corrected QT interval, near-infrared and bioimpedance spectroscopy; physiological responses associated with hypoglycemia could be identified with an F1 score accuracy up to 88%. SIGNIFICANCE: We present a novel model for identification of non-invasively measurable physiological responses related to hypoglycemia, showing potential for detection of moderate hypoglycemia using a wearable sensor system.

Author Correction: Evaluation of Hypoglycaemia with Non-Invasive Sensors in People with Type 1 Diabetes and Impaired Awareness of Hypoglycaemia.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Measuring Blood Pulse Wave Velocity with Bioimpedance in Different Age Groups.

In this project, we have studied the use of electrical impedance cardiography as a possible method for measuring blood pulse wave velocity, and hence be an aid in the assessment of the degree of arteriosclerosis. Using two different four-electrode setups, we measured the timing of the systolic pulse at two locations, the upper arm and the thorax, and found that the pulse wave velocity was in general higher in older volunteers and furthermore that it was also more heart rate dependent for older subjects. We attribute this to the fact that the degree of arteriosclerosis typically increases with age and that stiffening of the arterial wall will make the arteries less able to comply with increased heart rate (and corresponding blood pressure), without leading to increased pulse wave velocity. In view of these findings, we conclude that impedance cardiography seems to be well suited and practical for pulse wave velocity measurements and possibly for the assessment of the degree of arteriosclerosis. However, further studies are needed for comparison between this approach and reference methods for pulse wave velocity and assessment of arteriosclerosis before any firm conclusions can be drawn.

Non-invasive prediction of blood glucose trends during hypoglycemia.

Over the last four decades, there has been a pursuit for a non-invasive solution for glucose measurement, but there is not yet any viable product released. Of the many sensor modalities tried, the combination of electrical and optical measurement is among the most promising for continuous measurements. Although non-invasive prediction of exact glucose levels may seem futile, prediction of their trends may be useful for certain applications. Hypoglycemia is the most serious of the acute complications in type-1 diabetes highlighting the need for a reliable alarm, but little is known about the performance of this technology in predicting hypoglycemic glucose levels and associated trends. We aimed to assess such performance on the way to develop a multisensor system for detection of hypoglycemia, based on near-infrared (NIR), bioimpedance and skin temperature measurements taken during hypoglycemic and euglycemic glucose clamps in 20 subjects with type-1 diabetes. Performance of blood glucose prediction was assessed by global partial least squares and neural network regression models using repeated double cross-validation. Best trend prediction was obtained by including all measurements in a neural network model. Prediction of glucose level was inaccurate for threshold-based detection of hypoglycemia, but the trend predictions may provide useful information in a multisensor system. Comparing NIR and bioimpedance measurements, NIR seems to be the main predictor of blood glucose while bioimpedance may act as correction for individual confounding properties.

Bioimpedance and NIR for Non-invasive Assessment of Blood Glucose.

Sixteen volunteers each drank 700 ml sugar-containing soft drink during two successive periods and the blood sugar was measured at 10 min intervals together with electrical impedance spectroscopy and near infrared spectroscopy (NIR). A maximum correlation of 0.46 was found for the electrical measurements but no clear separation between low and high blood glucose levels were found in the NIR measurements. The latter was attributed to the experimental design where the NIR probe was removed from the skin between each measurement.

Age-related Differences in the Morphology of the Impedance Cardiography Signal.

Impedance cardiography (ICG) is a non-invasive method of hemodynamic measurement, mostly known for estimation of stroke volume and cardiac output based on characteristic features of the signal. Compared with electrocardiography, the knowledge on the morphology of the ICG signal is scarce, especially with respect to age-dependent changes in ICG waveforms. Based on recordings from ten younger (20-29 years) and ten older (60-79) healthy human subjects after three different levels of physical activity, the typical interbeat ICG waveforms were derived based on ensemble averages. Comparison of these waveforms between the age groups indicates the following differences: a later initial upward deflection for the younger group, an additional hump in the waveform from many older subjects not presented in the younger group, and a more pronounced second wave in the younger group. The explanation for these differences is not clear, but may be related to arterial stiffness. Further studies are suggested to determine whether these morphological differences have clinical value.

Evaluation of Hypoglycaemia with Non-Invasive Sensors in People with Type 1 Diabetes and Impaired Awareness of Hypoglycaemia.

People with type 1 diabetes and impaired awareness of hypoglycaemia (IAH) are prone to severe hypoglycaemia. Previous attempts to develop non-invasive hypoglycaemia alarm systems have shown promising results, but it is not known if such alarms can detect severe hypoglycaemia in people with IAH. We aimed to explore whether a combination of non-invasive sensors could reliably evaluate hypoglycaemia (plasma glucose (PG) minimum 2.5 mmol/L) in people with IAH. Twenty participants with type 1 diabetes and IAH underwent randomly ordered, single blinded hyperinsulinemic euglycaemic and hyperinsulinemic hypoglycaemic clamps. Sweating, skin temperature, ECG, counterregulatory hormones and symptoms of hypoglycaemia were assessed. Overall, we were not able to detect clamp-induced hypoglycaemia with sufficient sensitivity and specificity for further clinical use. As a post-hoc analysis, we stratified participants according to their ability to identify hypoglycaemic symptoms during hypoglycaemic clamps. Five out of 20 participants could identify such symptoms. These participants had a significantly higher adrenaline response to hypoglycaemia (p < 0.001) and were reliably identified by sensors. Based on our observations, a non-invasive alarm system based on measurement of sweating responses and ECG changes during hypoglycaemia might provide an alert at a plasma glucose concentration around 2.5 mmol/L if an adequate sympatho-adrenal reaction is elicited.

Detection of sympathoadrenal discharge by parameterisation of skin conductance and ECG measurement.

Detection of sympathoadrenal discharge is valuable for stress monitoring, but measuring the circulating adrenaline level directly is inconvenient, making non-invasive physiological sensors an attractive alternative. Little is known however, about their performance in detecting different adrenaline levels. In this study, adrenaline measurements over time from 20 subjects × 2 trials were compared with skin conductance (SC) from different skin sites and ECG recordings from which the heart rate and QT interval were derived. The frequency of sudomotor responses (FSR) was derived from the SC recording, and a new composite parameter for amplification of synchronous changes in multiple sensor signals was calculated for different combinations of FSR from different skin sites, heart rate and QT interval. The single and composite parameters were evaluated for detection performance of adrenaline levels above 1000, 1500 and 2000 pmol/L. The best prediction performance was indicated for the composite parameter using the FSR from the abdomen, FSR from the forehead and the heart rate, with a ROC area under the curve of 0.93 for the 2000 pmol/L threshold. In conclusion, detection of strong sympathoadrenal discharges is feasible with good accuracy during resting conditions in comfortable room temperature.