Background: Insulin jet injectors use a high-velocity jet to deliver insulin into the subcutaneous region without penetrating the skin with a needle. The pharmacodynamic and pharmacokinetic profile of rapid-acting insulin using this method of insulin administration is unknown.Methods: Euglycaemic glucose clamp tests were performed in 18 healthy volunteers (M/F 5/13; age 27±9 years, BMI 23.6±2.8 kg/m 2) after subcutaneous administration of 0.2 U/kg aspart insulin, either by jet injection or by conventional pen injection, using a double-blind, double-dummy cross-over study design.Results: The time to maximal exogenous glucose infusion rate (GIR) was 51±3 min with the jet injector versus 105±11 min with the insulin pen (P= 0.0001). There was no difference in the maximal GIR between the two modes of insulin administration (6.49±0.58 versus 6.09±0.56 mg/kg/min, P= 0.50), but the duration of the glucose …

A fringing field capacitive sensor has been used to measure the dielectric properties of human skin and underlying tissue in the MHz frequency range. It has recently been shown in clinical experimental studies that these dielectric properties can be related to the effects of in vivo glucose variations of the test subject. Previously, the relationship between electrical impedance and the glucose level has been established via statistical methods, such as the regression method. In this work, we explored a different approach, namely the resolution of the so-called inverse problem. First we applied the method on an artificial two-layer lossy system in order to test the sensitivity of the solution to forced changes in the layer properties and its stability to a constant setting. After validation of this method on artificial systems, a similar inverse problem was set and solved for dielectric measurements on human skin during an induced glucose excursion, where the skin is also modelled as a double-layer system. The changes of the measured permittivity and conductivity of the second layer versus the glucose changes are calculated for 22 study days. The statistical distribution shows that the median slopes of both dielectric properties are negative. These results can be used to test our hypothesis and to continue building potential explanations for the phenomena induced by the glucose changes on the skin layer dielectric parameters.

A wearable system incorporating sensors for dielectric and optical spectroscopy was used to study skin properties and their dependence on the cutaneous blood content (CBC). Simultaneous measurements with both modalities were carried out on the upper arm during blood perfusion-provoking exercises performed by four subjects in four separate sets of experiments. By relating changes in the attenuation of green (central wavelength λ(c) = 568 nm) and infrared (λ(c) = 798 nm) light, the ratio of mean pathlengths travelled by photons in the skin blood plexus was obtained. The pathlength for infrared light is found to be 3.85 times larger than for green. Combining signals of two wavelengths and accounting for pathlength difference, we quantitatively characterize the CBC as a cumulative optical thickness of red blood cells in the skin plexus. The dielectric spectra of skin in the MHz range were fitted with the Cole-Cole model and the changes of parameters were quantitatively related to the optically derived changes in CBC using a linear regression analysis. The positive correlation with CBC is obtained for the dispersion exponent (R(2) = 0.68), and the negative-for the dispersion time (R(2) = 0.40). Thus dielectric dispersion of the skin gets broader and shifts towards lower frequencies with an increase of CBC.

Impedance spectroscopy is a measurement technique that has been investigated in a wide variety of medical applications. An example is the measurement of the dielectric properties of the skin and underlying tissue using sensors placed in contact with human skin with capacitive fringing field electrodes. Electrodes with different characteristic geometries measure biophysical properties at separate penetration depths in the tissue and have therefore different sensitivities to e.g. physiological processes in the tissue. When the measured depth is in the dermis layer, the time series of the measured impedance at specific frequencies can be related to the effect of glucose changes. The aim of this work is to use finite element methods (FEM) for optimizing the sensor design to maximise its sensitivity to the dielectric changes of the dermis layer. This is achieved by evaluating FEM simulations for different electrode widths and distances to ground and searching for the geometries at which the information coming from the dermis layer reach a maximum. Experimental data supports the conclusions drawn from the simulation output.

Impedance spectroscopy has been shown to provide a great potential as a measuring technique for monitoring human blood glucose. The two major potential benefits are the ability to perform non-invasive and continuous measurements. Previous work has outlined the range of challenges of such an impedance based technique. Our impedance sensor is composed of several capacitive fringing field electrodes with various characteristic geometries to achieve the desired penetration depths in human skin and the underlying tissue. A comparison of the measurements made on reference materials of known dielectric properties with the results of electromagnetic field simulations allows sensor characterization to be achieved and provides the ability to optimize the sensor geometry. Such comparisons reveal that the measurements and simulations are in qualitative agreement with the expected impedance behavior, i.e. there is a larger sensitivity to changes in the dielectric properties of the deeper layer for electrodes with a deeper penetration of the electromagnetic field (EMF). Another conclusion is that, despite the approximations made in the simulation process, the measured and simulated quantities agree. This opens the possibility to use simulations to define the functional relation between the measured impedances and the layers dielectric parameters in order to correlate impedance changes with glucose concentration changes.

It has been shown that in vivo glucose level changes affect the dielectric characteristics of the skin and underlying tissue, which can be measured non-invasively by impedance spectroscopy (IS). For a successful implementation of such an impedance sensor it is necessary that the sensor, when placed in contact with human skin, has a sufficient field penetration depth so that it is not only sensitive to changes in the dielectric properties of the upper skin layer, but also has a higher sensitivity to changes in the deeper skin layers. This is due to the fact that the upper layers of the skin are poorly vascularised, therefore their dielectric properties have a low sensitivity to changes associated with blood and intravascular fluids. A simplified model of the human skin and underlying tissue has been developed using electromagnetic field finite element simulations. This model can be used to optimise the electrode design of the impedance sensor. Initially, the applicability of the simulation concepts has been tested by comparing simulations with measurements of reference materials using sensors of various sizes. Subsequently, simulations of the skin model are compared with measurements on human subjects using two experimental procedures. In the first procedure, the blood perfusion of the deeper skin layers is changed by the restriction of the blood outflow (using a pressure cuff). It is shown that the sensitivity to these changes is larger with the sensor with the deeper field penetration, in agreement with simulation results. Similar sensors are then used in a second procedure where the blood glucose concentration is changed. The largest sensitivity to this glucose change is again obtained with the sensor that has the deepest field penetration. Future work will concentrate on quantifying perturbing factors, their effects on the different electrode geometries and the differences between various skin types.

The aim of this work is to describe the ongoing development of a non-invasive continuous glucose monitoring system based on Impedance Spectroscopy (IS). Previous work has shown the importance of taking a multi-sensor approach to aid in the compensation of various potentially perturbing parameters, such as the impact of environmental/body temperature, changes in the blood perfusion of the measured skin, underlying tissue volume and changes in the sensor / skin contact due to movements. Here we describe how this multisensor concept has been implemented into an integrated functional model (FM). In our recent studies, this integrated FM has been tested in an experimental clinical study in subject groups with patients with Diabetes type I/II (D) and healthy subjects (ND). The relation between changes in the blood glucose concentration and the impedance of the skin / underlying tissue has been investigated under controlled clinical conditions. The clinical study protocol allowed the use of an intravenous glucose clamp technique to control the subject’s glucose concentration and enabled two hyperglycemic episodes to be achieved within a ten hour study day.

The aim of this work was to evaluate the performance of a novel non-invasive continuous glucose-monitoring system based on impedance spectroscopy (IS) in patients with diabetes. Ten patients with type 1 diabetes (mean+/-S.D., age 28+/-8 years, BMI 24.2+/-3.2 kg/m(2) and HbA(1C) 7.3+/-1.6%) and five with type 2 diabetes (age 61+/-8 years, BMI 27.5+/-3.2 kg/m(2) and HbA(1C) 8.3+/-1.8%) took part in this study, which comprised a glucose clamp experiment followed by a 7-day outpatient evaluation. The measurements obtained by the NI-CGMD and the reference blood glucose-measuring techniques were evaluated using retrospective data evaluation procedures. Under less controlled outpatient conditions a correlation coefficient of r=0.640 and a standard error of prediction (SEP) of 45 mg dl(-1) with a total of 590 paired glucose measurements was found (versus r=0.926 and a SEP of 26 mg dl(-1) under controlled conditions). Clark error grid analyses (EGA) showed 56% of all values in zone A, 37% in B and 7% in C-E. In conclusion, these results indicate that IS in the used technical setting allows retrospective, continuous and truly non-invasive glucose monitoring under defined conditions for patients with diabetes. Technical advances and developments are needed to expand on this concept to bring the results from the outpatient study closer to those in the experimental section of the study. Further studies will not only help to evaluate the performance and limitations of using such a technique for non non-invasive glucose monitoring but also help to verify technical extensions towards a IS-based concept that offers improved performance under real life operating conditions.

There is a requirement for the development of non-invasive continuous blood glucose monitoring devices to meet the clinical demands of the rapidly increasing number of people currently developing diabetes mellitus. Impedance spectroscopy is a technology that meets the requirements of such devices. An NI CGMD is being developed as a device that couples a sensor to the skin to form an RCL sensor. The reliability of such an RCL sensor model has been investigated by comparing electrodynamical simulations to in-vitro measurements of dielectrically "lossy" materials. The sensor has been modeled and simulated in FEMLAB (finite element modeling laboratory). In-vitro measurements are performed on hydrogels, representing the lossy material, by the aid of a Rohde & Schwarz VNA (vector network analyzer). From the quantitative agreement of the results we conclude, that the proposed qualitative model is appropriate for the characterization of the RCL sensor and suggests that more detailed models can be used to elucidate the behavior of human skin tissue.