Use of the site of subcutaneous insulin administration for the measurement of glucose in patients with type 1 diabetes

Abstract

OBJECTIVE To simplify and improve the treatment of patients with type 1 diabetes, we ascertained whether the site of subcutaneous insulin infusion can be used for the measurement of glucose. RESEARCH DESIGN AND METHODS Three special indwelling catheters (24-gauge microperfusion [MP] catheters) were inserted into the subcutaneous adipose tissue of subjects with type 1 diabetes (n = 10; all C-peptide negative). One MP catheter was perfused with short-acting insulin (100 units/ml, Aspart) and used for insulin delivery and simultaneous glucose sampling during an overnight fast and after ingestion of a standard glucose load (75 g). As controls, the further two MP catheters were perfused with an insulin-free solution (5% mannitol) and used for glucose sampling only. Plasma glucose was measured frequently at the bedside. RESULTS Insulin delivery with the MP catheter was adequate to achieve and maintain normoglycemia during fasting and after glucose ingestion. Tissue glucose concentrations derived with the insulin-perfused catheter agreed well with plasma glucose levels. Median correlation coefficient and median absolute relative difference values were found to be 0.93 (interquartile range 0.91-0.97) and 10.9%, respectively. Error grid analysis indicated that the percentage number of tissue values falling in the clinically acceptable range is 99.6%. Comparable analysis results were obtained for the two mannitol-perfused catheters. CONCLUSIONS Our data suggest that estimation of plasma glucose concentrations from the glucose levels directly observed at the site of subcutaneous insulin infusion is feasible and its quality is comparable to that of estimating plasma glucose concentrations from glucose levels measured in insulin-unexposed subcutaneous tissue.

Figure 1

Schematic of the experimental setup for assessing the feasibility of estimating plasma glucose concentrations from the ISF glucose levels observed at the insulin delivery site. A–C: Three MP catheters were inserted into subcutaneous adipose tissue of diabetic subjects (n = 10). One catheter (MP_I) was used for glucose sampling and simultaneous insulin delivery (A), and, as controls, two catheters (MP_M1 and MP_M2) were used for glucose sampling only (B and C). The catheter for glucose sampling and insulin delivery was perfused with a rapid-acting insulin solution (100 units/ml, Aspart) using two peristaltic pumps (A), with one attached to the inflow tubing and one to the outflow tubing (dual-pump operation mode). Insulin delivery rate was adjusted by adjusting the difference between the inflow and outflow rate of the catheter. The outflow conveying the extracted tissue glucose was collected in vials. The efficiency by which glucose was extracted via diffusion from the ISF of the tissue into the catheter (glucose recovery) was measured by applying the ionic reference technique (4,5). The catheters used for glucose sampling only (MP_M1 and MP_M2) were perfused with an insulin-free solution (5% mannitol) using either a single-pump operation mode where the inflow equaled the outflow rate (C) or a dual-pump operation mode (B) where the inflow and outflow rates equaled those applied in the insulin-perfused MP catheter (A).

Figure 2

Comparison of plasma and ISF-derived glucose concentrations observed during an overnight fast and OGTT in diabetic subjects. A: Average time course (n = 10, means ± SE) of plasma glucose concentration (●) and the tissue glucose concentration obtained with the MP catheter used for insulin delivery and simultaneous glucose sampling (MP_I, □). A also shows the average time course (n = 10, means ± SE) of the insulin delivery rate (bars) used to control glucose concentration during experiments. B and C: Average time course (n = 10, means ± SE) of plasma glucose (●) and the tissue glucose obtained with the mannitol-perfused MP catheters (MP_M1 and MP_M2, □). D: Error grid analysis results for the insulin-perfused MP catheter (MP_I): One of 268 data points (0.4%) fell outside of the clinically acceptable region A and B. E: Error grid analysis results for the mannitol-perfused catheter MP_M1: Two of 266 data points (0.8%) were outside of the clinically acceptable region A and B. F: Error grid analysis results for the mannitol-perfused catheter MP_M2: Three of 248 data points (1.2%) fell outside of the clinically acceptable region A and B. In A, the tendency toward lower tissue glucose concentrations than plasma glucose levels at the end of the OGTT is mainly caused by subject 8, whose tissue glucose concentration time course of the insulin-perfused catheter was an apparent outlier, with very low values during the last 4 h of the experiment (supplementary Fig. 1).