Continuous glucose monitoring system for early detection of graft dysfunction in allogenic islet transplant recipients.

BACKGROUND: There are no effective indicators of graft dysfunction in islet transplantation. This study evaluated the role of the Continuous Glucose Monitoring System (CGMS) as an early indicator of graft dysfunction in islet transplant recipients. METHODS: In 5 islet allograft recipients, we retrospectively determined the date of graft dysfunction: 3 fasting blood glucose levels >7.8 mmol/L (140 mg/dL) and/or 3 postprandial blood glucose levels >10 mmol/L (180 mg/dL) in 1 week. We then determined 2 time points in respect to graft dysfunction, 5 to 9 months before (time point A) and 2 to 3 months before (time point B). For these 2 time points, we assessed the following: HbA1c, C-peptide (CP), C-peptide glucose ratio (CPGR), 90-minute glucose from mixed meal tolerance test, and percentage of capillary blood glucose levels >7.8 mmol/L (%CBG >7.8) in a 15-day interval (1 week before and after CGMS placement). From the CGMS recordings, we calculated the glucose variability and the percentage of time spent in hyperglycemia >7.8 mmol/L (%HGT >7.8) and >10 mmol/L (%HGT >10). RESULTS: No difference was found between time points A and B for the following parameters: HbA1c, CP, CPGR, 90-minute glucose, %CBG >7.8, and %HGT >10. We observed a statistically significant increase from time point A to time point B in glucose variability (1.1 +/- 0.5 mmol/L to 1.6 +/- 0.6 mmol/L; P = .004), and in the %HGT >7.8 (11 +/- 12% to 22 +/- 18%; P = .036). CONCLUSION: Glucose variability and %HGT >7.8 determined using CGMS are useful as early indicators of graft dysfunction in islet transplant recipients. Further studies with larger sample sizes will help validate these observations.

Performance evaluation of the MiniMed continuous glucose monitoring system during patient home use.

BACKGROUND: The recent availability of a continuous glucose monitor offers the opportunity to match the demands of intensive diabetes management with a period of equally intensive blood glucose monitoring. The present study evaluates the performance of the MiniMed continuous glucose monitoring system (CGMS) in patients with diabetes during home use. METHODS: Performance data and demographic information were obtained from 135 patients who were (mean +/- SD) 40.5+/-14.5 years old, had an average duration of diabetes of 18.0+/-9.8 years, 50% were female, 90% were Caucasian, and 87% of whom had been diagnosed with type 1 diabetes. Patients were selected by their physician, trained on the use of the CGMS and wore the device at home for 3 days or more. The performance of the CGMS was evaluated against blood glucose measurements obtained using each patient's home blood glucose meter. Evaluation statistics included correlation, linear regression, mean difference and percent absolute difference scores, and Clarke error grid analysis. RESULTS: The CGMS values were compared to 2477 SMBG tests (r = 0.91, slope = 0.93, intercept = 14.5 mg/dL, mean absolute difference = 18.0%+/-19.8%). Clarke error grid analysis showed 96.2% of the data pairs falling within the clinically acceptable regions (zones A and B). CONCLUSIONS: These results demonstrate the agreement of the CGMS to blood glucose meter values, under conditions of home use, in patients selected by their physicians as candidates for continuous monitoring. The detailed glucose information provided by the CGMS should make successful management of diabetes more easily achieved.

Subcutaneous glucose predicts plasma glucose independent of insulin: implications for continuous monitoring.

The present study investigated the relationship between blood and subcutaneous interstitial fluid (ISF) glucose by employing an amperometric glucose sensor specifically developed for 3-day continuous glucose monitoring. The apparent sensor sensitivity and ISF glucose equilibration delay were estimated on separate days during hyperglycemic clamps in four dogs in which insulin was either suppressed with somatostatin, allowed to change, or increased with an exogenous infusion. A 2-h sensor "settling-in" period was allowed before the clamps. During insulin deficiency, the sensor sensitivity and ISF glucose delay were 0.23 +/- 0.03 nA per mg/dl and 4.4 +/- 0. 8 min. Sensitivity was not affected by increases in endogenous (0.30 +/- 0.04 vs. 0.28 +/- 0.04 nA per mg/dl) or exogenous insulin (0.18 +/- 0.01 vs. 0.16 +/- 0.01 nA per mg/dl) nor was the delay (3.3 +/- 1.2 vs. 5.7 +/- 1.1 and 9.2 +/- 2.6 vs. 12.3 +/- 1.7 min; P > 0.05 for all). Sensor glucose accurately predicted plasma glucose without correcting for delays <10 min (r > 0.9 for all), whereas for longer delays a digital corrective filter was used (r = 0.91 with filter). We conclude that the relationship between blood and ISF glucose is not affected by insulin and that delays in ISF glucose equilibration can be corrected with digital filters.

Continuous glucose monitoring used to adjust diabetes therapy improves glycosylated hemoglobin: a pilot study.

A 5-week pilot study was conducted to determine if continuous glucose monitoring could be used to improve glycemic control. A total of nine subjects with type 1 diabetes and HbA1c values greater than 8.5% completed the study. Subjects wore a continuous glucose monitor for two 1-week periods during the study. After each sensor use, changes to diet, insulin dosage and self-monitored blood glucose (SMBG) schedule were made. HbA1c decreased from 9.9% (S.D. = 1.1%) at baseline to 8.8% (S.D. = 1.0%) 5 weeks after baseline (P = 0.0006), but daily insulin usage was unchanged over the same period of time (P = 0.428). The glucose sensors performed accurately, with a median correlation of 0.92 and a mean absolute difference of 19.1% (S.D. = 9.0%). The continuous glucose profiles allowed identification of glucose patterns and excursions that helped direct changes in therapy. These treatment changes would not have been made on the basis of meter data alone and were effective in improving glucose control. Additional studies are needed to validate these findings. This pilot study highlights the potential for continuous glucose monitoring to provide the valuable information necessary to make therapy adjustments that can dramatically improve patients' glycemic control and reduce the risk of long-term complications.

Rigid and flexible thin-film multielectrode arrays for transmural cardiac recording.

Thin-film transmural cardiac multielectric arrays were fabricated using integrated-circuit processing techniques. Several substantial improvements were achieved over conventional handmade arrays such as a smaller cross-sectional area, a larger number of recording sites per needle, more accurately controlled size and spacing of the recording sites, smaller bipolar spacings, and higher throughout yield. These advantages allow for a higher density of closely spaced bipolar electrodes capable of monitoring complex voltage and gradient fields present during ventricular fibrillation and defibrillation. Both rigid and flexible arrays were fabricated and used in the acquisition of transmural electrical signals. The rigid multielectrode arrays were made of gold electrodes on a molybdenum substate, and the flexible arrays of silver and gold electrodes on a polyimide substrate. In vitro and in vivo testing of the thin-film transmural cardiac multielectrode arrays indicates that there are no adhesion or delamination problems observed during acute studies, no implantation difficulties, and that unipolar and bipolar recordings during normal sinus rhythm and injury potentials in unipolar recordings are similar to those obtained using the handmade electrodes.

In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue.

Cleanroom processing techniques have been used to mass-produce flexible, electroenzymatic glucose sensors designed for implantation in subcutaneous tissue. In vitro characterization studies have shown the sensor's performance to be acceptable. Initial in vivo studies were conducted with the sensor implanted in the subcutaneous tissue of rabbits. Sensors implanted in the subcutaneous tissue of normal human subjects showed an excellent correlation between glucose concentrations measured by the sensor and capillary finger sticks measured with a commercial analyzer.

A new sock electrode for recording epicardial activation from the human heart: one size fits all.

Simultaneous recording of epicardial activation from multiple sites during open heart surgery is essential for studying unstable ventricular arrhythmias. A previously described sock electrode array for this purpose requires custom-woven nylon sock material and expensive machined button electrodes. The limited compliance and elasticity of nylon requires that a new sock be individually fitted for each heart. Despite careful fitting, 17-20% of electrodes do not make satisfactory epicardial contact in dogs. Further, electrodes frequently dislodge from the sock and wires break at the button electrode solder joint. Recognizing these limitations, we formed a new sock from Xspan tubular dressing material and devised electrodes that attach securely to the sock. In six dogs, 90% +/- 3% of electrodes made satisfactory contact using the same Xspan sock, significantly (p less than .01) more than with the nylon sock despite far less labor. The same size X span sock with 60 snap electrodes was used to record from 27 human hearts of widely different dimensions. Satisfactory epicardial contact was obtained in 90% +/- 14% of electrodes in the 18 patients with Wolff-Parkinson-White syndrome (WPW) and 75% +/- 15% of electrodes in the nine patients with coronary artery disease. In no case did an accessory pathway fail to conduct following sock placement. The hemodynamic effect of the Xspan sock was evaluated in four dogs and was found to be minimal. Both the Xspan sock and the snap electrodes are easily made from inexpensive, readily available materials. The same Xspan sock accommodates a wide range of heart sizes, and the electrodes supported by the Xspan sock record significantly better and with less dislodgement and wire breakage than previous socks.