A weighted method for estimation of receptor occupancy for pharmacodynamic measurements in drug development.

Background: Flow cytometry-based receptor occupancy (RO) assessments for pharmacodynamic (PD) response measurements along with drug pharmacokinetic (PK) measurements represent a cornerstone in mechanism based PK/PD modeling of drugs against cell surface targets. This report describes the utility of using a "Free" and a "Bound" assay in combination to derive RO estimations through a weighted calculation method.

Methods: Data from a RO assay validation study in human samples was used to explore the performance of various RO data calculation methods.

Accuracy evaluation of a new real-time continuous glucose monitoring algorithm in hypoglycemia.

Background: The purpose of this study was to evaluate the performance of a new continuous glucose monitoring (CGM) calibration algorithm and to compare it with the Guardian(®) REAL-Time (RT) (Medtronic Diabetes, Northridge, CA) calibration algorithm in hypoglycemia.

Subjects And Methods: CGM data were obtained from 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. Data were obtained in two separate sessions using the Guardian RT CGM device.

Evaluation of an Algorithm for Retrospective Hypoglycemia Detection Using Professional Continuous Glucose Monitoring Data.

Background: People with type 1 diabetes (T1D) are unable to produce insulin and thus rely on exogenous supply to lower their blood glucose. Studies have shown that intensive insulin therapy reduces the risk of late-diabetic complications by lowering average blood glucose. However, the therapy leads to increased incidence of hypoglycemia.

An information and communication technology system to detect hypoglycemia in people with type 1 diabetes.

Continuous glucose monitoring (CGM) is a new technology with the potential to detect hypoglycemia in people with Type 1 diabetes. However, the inaccuracy of the device in the hypoglycemic range is unfortunately too large. The aim of this study was to develop an information and communication technology system for improving hypoglycemia detection in CGM.

Real-time hypoglycemia detection from continuous glucose monitoring data of subjects with type 1 diabetes.

Background: Hypoglycemia is a potentially fatal condition. Continuous glucose monitoring (CGM) has the potential to detect hypoglycemia in real time and thereby reduce time in hypoglycemia and avoid any further decline in blood glucose level. However, CGM is inaccurate and shows a substantial number of cases in which the hypoglycemic event is not detected by the CGM.

Professional continuous glucose monitoring in subjects with type 1 diabetes: retrospective hypoglycemia detection.

Background: An important task in diabetes management is detection of hypoglycemia. Professional continuous glucose monitoring (CGM), which produces a glucose reading every 5 min, is a powerful tool for retrospective identification of unrecognized hypoglycemia. Unfortunately, CGM devices tend to be inaccurate, especially in the hypoglycemic range, which limits their applicability for hypoglycemia detection.

QT Measurement and Heart Rate Correction during Hypoglycemia: Is There a Bias?

Introduction. Several studies show that hypoglycemia causes QT interval prolongation. The aim of this study was to investigate the effect of QT measurement methodology, heart rate correction, and insulin types during hypoglycemia.

Sources of glycemic variability--what type of technology is needed?

People on insulin therapy are challenged with evaluation of numerous factors affecting the blood glucose in order to select the optimal dose for reaching their glucose target. Following medical recommendations precisely still results in considerable blood glucose unpredictability, often resulting in frustration in the short term due to hypoglycemia and hyperglycemia, and, in the long term, will likely result in complications. The kinetics of insulin do indeed vary significantly and have become an important focus when developing new insulin analogues and delivery systems; however, numerous of other factors impact glycemic variability.

A physiological model of the effect of hypoglycemia on plasma potassium.

Background: Adrenaline release and excess insulin during hypoglycemia stimulate the uptake of potassium from the bloodstream, causing low plasma potassium (hypokalemia). Hypokalemia has a profound effect on the heart and is associated with an increased risk of malignant cardiac arrhythmias. It is the aim of this study to develop a physiological model of potassium changes during hypoglycemia to better understand the effect of hypoglycemia on plasma potassium.

Modeling the effect of blood glucose and physical exercise on plasma adrenaline in people with type 1 diabetes.

Background: Adrenaline is often studied in people with type 1 diabetes during hypoglycemic episodes. Adrenaline is difficult and costly to measure, and therefore a pharmacokinetic model of adrenaline can be a supportive tool that adds information and saves measurements resources.

Methods: We have developed a compartment model of adrenaline secretion and elimination.