Bedside monitoring of subcutaneous interstitial glucose in type 1 diabetic subjects using microdialysis and infrared spectrometry with optimal correlation to blood glucose concentrations

摘要

Infrared spectroscopy has been successfully employed in multi-component assays for the study of various biomedical samples. Two areas have found particular interest, i.e. in-vitro analysis in the clinical laboratory and point-of-care applications. With regard to the latter field, in-vivo blood glucose monitoring is an important topic for improving glycemic control in critically ill patients with non-adequate blood glucose regulation, similar to the situation faced for diabetic patients. For such application, a continuously operated mid-infrared spectroscopic system in combination with a subcutaneously implanted microdialysis probe and coupled by micro-fluidics has been developed. Using the dialysis process, the interstitial fluid matrix can be significantly simplified, since high molecular mass compounds such as proteins are separated. However, the micro-dialysis recovery rate is variable over time, so that a simultaneous determination of this parameter was implemented using the losses of an acetate marker from the perfusate across the dialysis membrane. Clinical measurements were carried out on type 1 diabetic subjects, with experiments lasting up to 28 hours. The concentrations of glucose, acetate and other components in the dialysates from interstitial body fluids were investigated. Two different multivariate calibration strategies, i.e. partial least squares (PLS) and classical least squares (CLS) regressions were applied. The results led to excellent correlation of the subcutaneous interstitial concentrations with those of laboratory blood glucose readings. Clarke-Error-Grid evaluations were employed for assessing the clinical applicability of the method.