Periodic Extraction of Interstitial Fluid from the Site of Subcutaneous Insulin Infusion for the Measurement of Glucose: A Novel Single-Port Technique for the Treatment of Type 1 Diabetes Patients.
ABSTRACT Abstract Background: Treatment of type 1 diabetes patients could be simplified if the site of subcutaneous insulin infusion could also be used for the measurement of glucose. This study aimed to assess the agreement between blood glucose concentrations and glucose levels in the interstitial fluid (ISF) that is extracted from the insulin infusion site during periodic short-term interruptions of continuous subcutaneous insulin infusion (CSII). Subjects and Methods: A perforated cannula (24 gauge) was inserted into subcutaneous adipose tissue of C-peptide-negative type 1 diabetes subjects (n=13) and used alternately to infuse rapid-acting insulin (100 U/mL) and to extract ISF glucose during a fasting period and after ingestion of a standard oral glucose load (75 g). Results: Although periodically interrupted for extracting glucose (every hour for approximately 10 min), insulin infusion with the cannula was adequate to achieve euglycemia during fasting and to restore euglycemia after glucose ingestion. Furthermore, the ISF-derived estimates of plasma glucose levels agreed well with plasma glucose concentrations. Correlation coefficient and median absolute relative difference values were found to be 0.95 and 8.0%, respectively. Error grid analysis showed 99.0% of all ISF glucose values within clinically acceptable Zones A and B (83.5% Zone A, 15.5% Zone B). Conclusions: Results show that ISF glucose concentrations measured at the insulin infusion site during periodic short-term interruptions of CSII closely reflect blood glucose levels, thus suggesting that glucose monitoring and insulin delivery may be performed alternately at the same tissue site. A single-port device of this type could be used to simplify and improve glucose management in diabetes.
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ABSTRACT: Introduction: Insulin pump technology has advanced considerably over the past three decades, leading to more favorable metabolic control and less hypoglycemic events when compared with multiple daily injection therapy. The use of insulin pumps is increasing, particularly in children and adolescents with type 1 diabetes. Areas covered: This review outlines recent developments in insulin pump therapy from a pediatric perspective. 'Smart' pumps, sensor-augmented pump therapy and threshold-suspend feature of insulin pumps are reviewed in terms of efficacy, safety and psychosocial impact. The current status of closed-loop systems focusing on clinical outcomes is highlighted. Expert opinion: Closed-loop insulin delivery is gradually progressing from bench to the clinical practice. Longer and larger studies in home settings are needed to expand on short- to medium-term outpatient evaluations. Predictive low glucose management and overnight closed-loop delivery may be the next applications to be implemented in daily routine. Further challenges include improvements of control algorithms, sensor accuracy, duration of insulin action, integration and size of devices and connectivity and usability. Gradual improvements and increasing sophistication of closed-loop components lie on the path toward unsupervised hands-off fully closed-loop system.Expert Opinion on Drug Delivery 04/2014; DOI:10.1517/17425247.2014.910192 · 4.12 Impact Factor
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ABSTRACT: Because insulin promotes glucose uptake into adipocytes, it has been assumed that during measurement of glucose at the site of insulin delivery, the local glucose level would be much lower than systemic glucose. However, recent investigations challenge this notion. What explanations could account for a reduced local effect of insulin in the subcutaneous space? One explanation is that, in humans, the effect of insulin on adipocytes appears to be small. Another is that insulin monomers and dimers (from hexamer disassociation) might be absorbed into the circulation before they can increase glucose uptake locally. In addition, negative cooperativity of insulin action (a lower than expected effect of very high insulin concentrations)may play a contributing role. Other factors to be considered include dilution of interstitial fluid by the insulin vehicle and the possibility that some of the local decline in glucose might be due to the systemic effect of insulin. With regard to future research, redundant sensing units might be able to quantify the effects of proximity, leading to a compensatory algorithm. In summary, when measured at the site of insulin delivery, the decline in subcutaneous glucose level appears to be minimal, though the literature base is not large. Findings thus far support (1) the development of integrated devices that monitor glucose and deliver insulin and (2) the use of such devices to investigate the relationship between subcutaneous delivery of insulin and its local effects on glucose. A reduction in the number of percutaneous devices needed to manage diabetes would be welcome.Journal of diabetes science and technology 04/2014; DOI:10.1177/1932296814522805