Subcutaneous Blood Glucose Research Articles

Wearable filamentary continuous sensor for interstitial glucose detection in diabetes management

The development of novel diabetes monitoring sensors is important for the diabetes management of millions of diabetic patients. This work reports a flexible filamentary continuous glucose monitoring (CGM) sensor. A multilayer CGM sensor has been constructed on titanium filament with low cost and ease of use. The sensor, made of flexible material, offers better adaptability and comfort than traditional rigid filament CGM sensors, allowing continuous monitoring of subcutaneous blood glucose levels to provide patients with treatment strategies. The performance and reliability of the sensor were verified through rat experiments. The trend of the increase and decrease of the detected current was generally consistent with the actual blood glucose, and the detected values were located in regions A and B of the Clarke error grid. The results show that the sensor has the advantages of high sensitivity, high accuracy and fast response speed, which is suitable for monitoring the blood glucose level for a long time and has a broad application prospect in diabetes monitoring, exercise monitoring, health management and clinical application.

The FreeStyle Libre flash glucose monitoring system: how it has improved glycaemic control for people with type 1 diabetes in Eastern Cheshire, UK.

Many people with type 1 diabetes continue to run high HbA1c levels with associated elevated risk of cardiovascular events and increased mortality. We describe here how use of the FreeStyle Libre flash monitor has improved the glycaemic control of many people with type 1 diabetes where the new technology has been intensively deployed. We report the outcomes of 92 consecutive adults (18 years of age or more) with type 1 diabetes who have begun using the FreeStyle Libre flash glucose monitor in East Cheshire, UK. Initiation was with education and support from one of the diabetes specialist nurses. An HbA1c of 60 mmol/mol (7.6%) was taken as the threshold for suboptimal glycaemic control. The mean cohort age was 43 years for men and 39 years for women (overall range 17-83 years). In 92 consecutive users, HbA1c decreased by an average of 10.7 mmol/mol (0.98%) after 3 months, and by 16.1 mmol/mol (1.47%) after 6 months. There was also a narrowing of the distribution of HbA1c, with many fewer people running high HbA1c ≥80 mmol/mol (9.5%). After the 6-month follow-up, two 2/92 users did not wish to continue with the monitoring. Flash glucose monitoring has great potential for the management of type 1 diabetes in the adult population and improving metabolic control/quality of life for people across the world. The technology provides significantly more data than the intermittent results obtained by traditional subcutaneous blood glucose monitoring, which may not capture intervals of extreme variability or nocturnal events.

Blood glucose concentration control for type 1 diabetic patients: a multiple‐model strategy

In this study, a multiple-model strategy is evaluated as an alternative closed-loop method for subcutaneous insulin delivery in type 1 diabetes. Non-linearities of the glucose-insulin regulatory system are considered by modelling the system around five different operating points. After conducting some identification experiments in the UVA/Padova metabolic simulator (accepted simulator by the US Food and Drug Administration (FDA)), five transfer functions are obtained for these operating points. Paying attention to some physiological facts, the control objectives such as the required settling time and permissible bounds of overshoots and undershoots are determined for any transfer functions. Then, five PID controllers are tuned to achieve these objectives and a bank of controllers is constructed. To cope with difficulties of the presence of delays in subcutaneous blood glucose (BG) measuring and in administration of insulin, a glucose-dependent setpoint is considered as the desired trajectory for the BG concentration. The performance of the obtained closed-loop glucose-insulin regulatory system is investigated on the in silico adult cohort of the UVA/Padova metabolic simulator. The obtained results show that the proposed multiple-model strategy leads to a closed-loop mechanism with limited hyperglycemia and no severe hypoglycemia.

Automatic blood glucose control for type 1 diabetes: A trade-off between postprandial hyperglycemia and hypoglycemia

Artificial pancreas (AP) systems perform automated insulin delivery to subjects with type 1 diabetes mellitus (T1DM). In this paper, a nonlinear suboptimal controller is designed to make a trade-off between the elimination of hypoglycemia events and the limitation of postprandial hyperglycemia. All the in silico simulations are performed using the distribution version of the UVA/Padova type 1 diabetes (T1D) simulator. The proposed nonlinear AP system is based on an individualized control law which is designed in three steps. At first, a nonlinear model of the glucose–insulin regulatory system is identified based on the data collected from some safe experiments. Then, using the personalized models for all the patients of the simulator and a nonlinear technique called state-dependent Riccati equation (SDRE), suboptimal controllers are designed in which a trade-off between the abilities to correct hyperglycemia and to minimize hypoglycemia is made by considering variable weighting matrices for the controller. Since the SDRE controller has a state-feedback structure, unscented Kalman filter (UKF) is employed to generate estimations for unmeasured state variables from the measured subcutaneous blood glucose level. To assess the performance of the proposed AP system, several scenarios are considered for 33 in silico patients (11 adults, 11 adolescents, and 11 children). The obtained results are analyzed and compared with two other AP systems. Patients’ blood glucose concentrations are maintained in safe levels in all the simulated scenarios and very limited hyperglycemia and no hypoglycemia are observed even in a challenging scenario. The promising results are so encouraging and the proposed AP system is worthy to be tested in vivo.

Empirical Dynamic Model Identification for Blood-Glucose Dynamics in Response to Physical Activity.

In this paper, the dynamic response of blood glucose concentration in response to physical activity of people with Type 1 Diabetes Mellitus (T1DM) is captured by subspace identification methods. Activity (input) and subcutaneous blood glucose measurements (output) are employed to construct a personalized prediction model through semi-definite programming. The model is calibrated and subsequently validated with non-overlapping data sets from 15 T1DM subjects. This preliminary clinical evaluation reveals the underlying linear dynamics between blood glucose concentration and physical activity. These types of models can enhance our capabilities of achieving tighter blood glucose control and early detection of hypoglycemia for people with T1DM.

Neural Inverse Optimal Control via Passivity for Subcutaneous Blood Glucose Regulation in Type 1 Diabetes Mellitus Patients

This paper deals with subcutaneous blood glucose level control. Inverse optimal trajectory tracking for discrete time non-linear positive systems is applied. The scheme is developed for MIMO (multi-input, multi-output) affine systems. The control law calculates the subcutaneous insulin delivery rate in order to prevent hyperglycemia and hypoglycemia events. A neural model is obtained from an on-line neural identifier, which uses a recurrent neural network, trained with the extended Kalman filter (EKF); this neural model has an affine form, which permits the applicability of inverse optimal control scheme. The proposed algorithm is tuned to follow a desired trajectory; this trajectory reproduces the glucose absorption of a healthy person. Then this model is used to synthesize an inverse optimal controller in order to regulate the subcutaneous blood glucose level for a Type 1 Diabetes Mellitus patient the applicability of the proposed scheme is illustrated via simulation using a recurrent neural network in ...

Severe gastroparesis associated recurrent hypoglycemic unconsciousness in diabetic neuropathy

The gastric emptying rate has a decisive role in the regulation of blood glucose in diabetic patients. In some cases the gastric hypomotility might result an insufficient glucose absorption leading to extreme metabolic instability. Here we describe the diagnostic and the therapeutic strategy of this motility disorder. A 45 years old man was admitted to the department of neurology with severe recurrent convulsions and transient unconsciousness. His pancreatic diabetes developed 10 years before when the head of the pancreas was removed due to a pseudocyst. As the neurological diagnostic procedures did not reveal any organic central nervous disorder and the glucose levels were unstable, he was transfered to our clinic. The careful analysis of the daily blood glucose profile revealed severe recurrent hypoglycemias after breakfast besides the gradual reduction of the pre-breakfast insulin. Although he did not have digestive symptoms, a scintigraphic gastric emptying was done. The half-time of gastric emptying (HTE) after breakfast was extremely long (HTE: 487.6min, normal range: ≤67.6min.). The cardiovascular reflex tests reflected a severe autonomic neuropathy (score: 8, normal range: ≤2), with a dominance of parasympathetic dysfunction. The subcutaneous blood glucose was measured via an inserted electrode on 6 consecutive days by the application of a continuous blood glucose measuring system (CGMS). On all of the 6 days the post-breakfast glucose was much lower than the fasting value and on 2 of the 6 days it fell down to the hypoglycemic range. Parenteral, later oral metoclopramid and alpha lipoic acid were administered with oral pancreatic enzyme substitution. The insulin treatment and the diet were also adjusted. 6 months later the patient was hypoglycemia- and symptom-free, the HTE was less longer (245.8min.), the CGMS did not reveal post-breakfast glucose lowering while the autonomic neuropathy remained severe (score: 10). Conclusions: The measurement of the gastric emptying might be a part of the differenzial diagnostics of newly appearing convulsive disorder in diabetic patients with long-term disease. The application of cardiovascular tests and a CGMS method strengthens the diagnostic accuracy. The treatment of gastric hypomotility, neuropathy and exocrine insufficiency ensures a stable metabolism and an improvement in quality of life.

Linear Quadratic Gaussian-Based Closed-Loop Control of Type 1 Diabetes

We investigated the applicability of linear quadratic Gaussian (LQG) methodology to the subcutaneous blood glucose regulation problem. We designed an LQG-based feedback control algorithm using linearization of a previously published metabolic model of type 1 diabetes. A key feature of the controller is a Kalman filter used to estimate metabolic states of the patient based on continuous glucose monitoring. Insulin infusion is computed from linear quadratic regulator feedback gains applied to these estimates, generally seeking to minimize squared deviations from a target glucose concentration and basal insulin rate. We evaluated in silico subject-specific LQG control and compared it to preexisting proportional-integral-derivative control.

Real-Time Continuous Glucose Monitoring in Pediatric Patients During and After Cardiac Surgery

Given the demonstrated benefit of euglycemia in critically ill patients as well as the risk for hypoglycemia during insulin infusion in children, we sought to validate a subcutaneous sensor for real-time continuous glucose monitoring in pediatric patients during and after cardiac surgery. Children up to 36 months of age who were undergoing cardiac bypass surgery were recruited. After anesthetic induction, a continuous glucose-monitoring system sensor (CGMS, Medtronic Minimed, Northridge, CA) was inserted subcutaneously. Sensors remained in place for up to 72 hours. Arterial blood glucose was measured intermittently in the central laboratory (Bayer Rapidlab 860, Tarrytown, NY). Sensor data, after prospective calibration with 6-hourly laboratory values using the proprietary Medtronic Minimed Guardian RT algorithm, were compared with all laboratory glucose values. Statistical analysis was performed to test whether sensor performance was affected by body temperature, inotrope dose, or body-wall edema. Twenty patients were enrolled in the study for a total of 40 study days and 246 paired sensor and laboratory glucose values. Consensus error grid analysis demonstrated that 72.0% of sensor value comparisons were within zone A (no effect on clinical action), and 27.6% of comparisons were within zone B (altered clinical action of little or no effect on outcome), with a mean absolute relative deviation of 17.6% for all comparisons. One comparison (0.4%) was in zone C (altered clinical action likely to affect outcome). No significant correlations were found between sensor performance and body temperature, inotrope dose, or body-wall edema. All patients tolerated the sensors well without bleeding or tissue reaction. Guardian RT real-time subcutaneous blood glucose measurement is safe and potentially useful for continuous glucose monitoring in critically ill children. Subcutaneous sensors performed well in the setting of hypothermia, inotrope use, and edema. These sensors facilitate identifying and following the effects of interventions to control blood glucose.

Continuous Glucose Monitoring in Normal Mice and Mice with Prediabetes and Diabetes

It is well established that the key to minimizing diabetes-associated complications, in both type 1 and type 2 diabetes, is tight regulation of blood glucose levels. Currently the major approach to regulating blood glucose levels in patients with diabetes relies on external blood glucose monitors. However, poor patient compliance usually results in limited insights into the dynamic range of blood glucose levels (i.e., hyperglycemia vs. hypoglycemia), and inadequate prediction and control of blood glucose levels in these patients. Implantable glucose sensors hold promise for controlling blood glucose levels, but currently these sensors have only limited in vivo life span. Recently we have developed an extremely robust murine model for implantable glucose sensors. In the present study, we have extended this model by developing a complete system for real-time continuous glucose monitoring in normal mice and mice with prediabetes and diabetes (type 1). These studies demonstrated that (1) glucose sensors can be implanted and maintained subcutaneously in the mice; (2) continuous glucose sensor data can be obtained for at least 5 days; and (3) subcutaneous blood glucose sensing paralleled blood glucose levels in normal mice and mice with prediabetes and diabetes. Subcutaneous blood glucose sensing also successfully tracked changes in blood glucose levels induced in the mice with diabetes by administration of oral glucose or insulin. These results mirror the results for subcutaneous blood glucose sensing seen in both normal subjects and patients with diabetes, and therefore validate both our continuous glucose monitoring system in the mouse, and the use of the mouse as a model for implantable glucose sensing in vivo.