Continuous monitoring of interstitial tissue oxygen using subcutaneous oxygen microsensors: In vivo characterization in healthy volunteers.

Measurements of regional tissue oxygen serve as a proxy to monitor local perfusion and have the potential to guide therapeutic decisions in multiple clinical disciplines. Transcutaneous oximetry (tcpO) is a commercially available noninvasive technique that uses an electrode to warm underlying skin tissue and measure the resulting oxygen tension at the skin surface. A novel approach is to directly measure interstitial tissue oxygen using subcutaneous oxygen microsensors composed of a biocompatible hydrogel carrier platform with embedded oxygen sensing molecules.

Intradermal insulin infusion achieves faster insulin action than subcutaneous infusion for 3-day wear.

Rapid uptake previously demonstrated by intradermal (ID) drug administration indicates compound delivery within the dermis may have clinical and pharmacological advantages for certain drug therapies. This study is the first clinical trial to evaluate continuous microneedle-based drug infusion, device wearability, and intradermal microneedle insulin kinetics over a multi-day (72 h) wear period. This was a single center, open-label, two-period crossover study in T1DM patients on continuous subcutaneous insulin infusion (CSII).

Pharmacokinetics and postprandial glycemic excursions following insulin lispro delivered by intradermal microneedle or subcutaneous infusion.

Background: Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery.

Method: The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design.

Use of subcutaneous interstitial fluid glucose to estimate blood glucose: revisiting delay and sensor offset.

Background: Estimates for delays in the interstitial fluid (ISF) glucose response to changes in blood glucose (BG) differ substantially among research groups. We review these findings along with arguments that continuous glucose monitoring (CGM) devices used to measure ISF delay contribute to the variability. We consider the impact of the ISF delay and review approaches to correct for it, including strategies pursued by the manufacturers of these devices.

Metabolic modelling and the closed-loop insulin delivery problem.

The approach used by Medtronic MiniMed to close the insulin delivery loop using the subcutaneous site for both glucose sensing and insulin delivery relies on modeling insulin action and beta-cell insulin secretion. This approach is contrasted with traditional control systems engineering.

Feasibility of automating insulin delivery for the treatment of type 1 diabetes.

An automated closed-loop insulin delivery system based on subcutaneous glucose sensing and subcutaneous insulin delivery was evaluated in 10 subjects with type 1 diabetes (2 men, 8 women, mean [+/-SD] age 43.4 +/- 11.4 years, duration of diabetes 18.

Evaluation of the effect of gain on the meal response of an automated closed-loop insulin delivery system.

A continuous closed-loop insulin delivery system using subcutaneous insulin delivery was evaluated in eight diabetic canines. Continuous glucose profiles were obtained by extrapolation of blood glucose measurements. Insulin delivery rate was calculated, using a model of beta-cell insulin secretion, and delivered with a Medtronic MiniMed subcutaneous infusion pump.

Closed-loop insulin delivery - what lies between where we are and where we are going?

Closed-loop insulin delivery in individuals with diabetes can potentially lead to near-normal glucose profiles. To this end, existing subcutaneous glucose sensors and external insulin pumps can be linked with an insulin delivery algorithm to create a completely automated closed-loop system. This paper reviews current research into the development of such a system, with particular emphasis on creating a system emulating the physiological properties of the beta-cell.

Evaluation of insulin sensitivity and beta-cell function indexes obtained from minimal model analysis of a meal tolerance test.

Modeling analysis of glucose, insulin, and C-peptide following a meal has been proposed as a means to estimate insulin sensitivity (S(i)) and beta-cell function from a single test. We compared the model-derived meal indexes with analogous indexes obtained from an intravenous glucose tolerance test (IVGTT) and hyperglycemic clamp (HGC) in 17 nondiabetic subjects (14 men, 3 women, aged 50 +/- 2 years [mean +/- SE], BMI 25.0 +/- 0.

Modeling beta-cell insulin secretion--implications for closed-loop glucose homeostasis.

Glucose sensing and insulin delivery technology can potentially be linked to form a closed-loop insulin delivery system. Ideally, such a system would establish normal physiologic glucose profiles. To this end, a model of beta-cell secretion can potentially provide insight into the preferred structure of the insulin delivery algorithm.

The role of the independent variable to glucose sensor calibration.

In vivo subcutaneous glucose sensor accuracy depends on the calibration method. Sensor accuracy was assessed during standard oral glucose tolerance tests in six non-diabetic subjects each wearing six subcutaneous glucose sensors (Medtronic MiniMed). Paired blood glucose (B(G)) and sensor current readings were used for retrospective sensor calibration using either B(G) or sensor current as the independent variable.

Determination of plasma glucose during rapid glucose excursions with a subcutaneous glucose sensor.

Continuous glucose monitoring has the potential to improve glucose management and reduce the risk of hypoglycemia in individuals with diabetes. Accurate sensors may also allow the development of a closed-loop insulin delivery system. The purpose of this work was to determine the delay time associated with a subcutaneous glucose sensor during rapidly changing glucose excursions.