Zeinab Mahmoudi

Professional continuous glucose monitoring in subjects with type 1 diabetes: retrospective hypoglycemia detection.

Background: An important task in diabetes management is detection of hypoglycemia. Professional continuous glucose monitoring (CGM), which produces a glucose reading every 5 min, is a powerful tool for retrospective identification of unrecognized hypoglycemia. Unfortunately, CGM devices tend to be inaccurate, especially in the hypoglycemic range, which limits their applicability for hypoglycemia detection. The objective of this study was to develop an automated pattern recognition algorithm to detect hypoglycemic events in retrospective, professional CGM. Method: Continuous glucose monitoring and plasma glucose (PG) readings were obtained from 17 data sets of 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. The CGM readings were automatically classified into a hypoglycemic group and a nonhypoglycemic group on the basis of different features from CGM readings and insulin injection. The classification was evaluated by comparing the automated classification with PG using sample-based and event-based sensitivity and specificity measures. Results: With an event-based sensitivity of 100%, the algorithm produced only one false hypoglycemia detection. The sample-based sensitivity and specificity levels were 78% and 96%, respectively. Conclusions: The automated pattern recognition algorithm provides a new approach for detecting unrecognized hypoglycemic events in professional CGM data. The tool may assist physicians and diabetologists in conducting a more thorough evaluation of the diabetes patients glycemic control and in initiating necessary measures for improving glycemic control.

A multistep algorithm for processing and calibration of microdialysis continuous glucose monitoring data

BACKGROUND The deviation of continuous subcutaneous glucose monitoring (CGM) data from reference blood glucose measurements is substantial, and adequate signal processing is required to reduce the discrepancy between subcutaneous glucose and blood glucose values. The purpose of this study was to develop a multistep algorithm for the processing and calibration of continuous subcutaneous glucose monitoring data with high accuracy and short delay. Algorithm PRESENTATION The algorithm comprises three steps: rate-limiting filtering, selective smoothing, and robust calibration. Initially, the algorithm detects nonphysiological glucose rate-of-change and corrects it with a weighted local polynomial. Noisy signal parts that require smoothing are then detected based on zero crossing count of the sensor signal first-order differences, and an exponentially weighted moving average smooths the noisy parts of the signal afterward. Finally, calibration is performed using a first-order polynomial as the conversion function, with coefficients being estimated using robust regression with a bi-square weight function. ALGORITHM PERFORMANCE: The performance of the algorithm was evaluated on 16 patients with type 1 diabetes mellitus. To compare the algorithm with state-of-the-art CGM data denoising and calibration, the rate-limiting filter and selective smoothing were replaced with an adaptive Kalman filter, and the calibration method was replaced with the calibration algorithm presented in one of the Medtronic (Northridge, CA) CGM patents. The median (mean) of the absolute relative deviation (ARD) of the sensor glucose values processed by the newly developed algorithm from capillary reference blood glucose measurements was 14.8% (22.6%), 10.6% (14.6%), and 8.9% (11.7%) in hypoglycemia, euglycemia, and hyperglycemia, respectively, whereas for the alternative algorithm, the median (mean) was 22.2% (26.9%), 12.1% (15.9%), and 8.8 (11.3%), respectively. The median (mean) ARD in all ranges was 10.3% (14.7%) for the new algorithm and 11.5% (15.8%) for the alternative algorithm. The new algorithm had an average delay of 2.1 min across the patients, and the alternative algorithm had an average delay of 2.9 min. CONCLUSIONS The presented algorithm may increase the accuracy of CGM data.

Comparison between one-point calibration and two-point calibration approaches in a continuous glucose monitoring algorithm

Background: The purpose of this study was to investigate the effect of using a 1-point calibration approach instead of a 2-point calibration approach on the accuracy of a continuous glucose monitoring (CGM) algorithm. Method: A previously published real-time CGM algorithm was compared with its updated version, which used a 1-point calibration instead of a 2-point calibration. In addition, the contribution of the corrective intercept (CI) to the calibration performance was assessed. Finally, the sensor background current was estimated real-time and retrospectively. The study was performed on 132 type 1 diabetes patients. Results: Replacing the 2-point calibration with the 1-point calibration improved the CGM accuracy, with the greatest improvement achieved in hypoglycemia (18.4% median absolute relative differences [MARD] in hypoglycemia for the 2-point calibration, and 12.1% MARD in hypoglycemia for the 1-point calibration). Using 1-point calibration increased the percentage of sensor readings in zone A+B of the Clarke error grid analysis (EGA) in the full glycemic range, and also enhanced hypoglycemia sensitivity. Exclusion of CI from calibration reduced hypoglycemia accuracy, while slightly increased euglycemia accuracy. Both real-time and retrospective estimation of the sensor background current suggest that the background current can be considered zero in the calibration of the SCGM1 sensor. Conclusions: The sensor readings calibrated with the 1-point calibration approach indicated to have higher accuracy than those calibrated with the 2-point calibration approach.

Accuracy Evaluation of a New Real-Time Continuous Glucose Monitoring Algorithm in Hypoglycemia

BACKGROUND The purpose of this study was to evaluate the performance of a new continuous glucose monitoring (CGM) calibration algorithm and to compare it with the Guardian(®) REAL-Time (RT) (Medtronic Diabetes, Northridge, CA) calibration algorithm in hypoglycemia. SUBJECTS AND METHODS CGM data were obtained from 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. Data were obtained in two separate sessions using the Guardian RT CGM device. Data from the same CGM sensor were calibrated by two different algorithms: the Guardian RT algorithm and a new calibration algorithm. The accuracy of the two algorithms was compared using four performance metrics. RESULTS The median (mean) of absolute relative deviation in the whole range of plasma glucose was 20.2% (32.1%) for the Guardian RT calibration and 17.4% (25.9%) for the new calibration algorithm. The mean (SD) sample-based sensitivity for the hypoglycemic threshold of 70 mg/dL was 31% (33%) for the Guardian RT algorithm and 70% (33%) for the new algorithm. The mean (SD) sample-based specificity at the same hypoglycemic threshold was 95% (8%) for the Guardian RT algorithm and 90% (16%) for the new calibration algorithm. The sensitivity of the event-based hypoglycemia detection for the hypoglycemic threshold of 70 mg/dL was 61% for the Guardian RT calibration and 89% for the new calibration algorithm. Application of the new calibration caused one false-positive instance for the event-based hypoglycemia detection, whereas the Guardian RT caused no false-positive instances. The overestimation of plasma glucose by CGM was corrected from 33.2 mg/dL in the Guardian RT algorithm to 21.9 mg/dL in the new calibration algorithm. CONCLUSIONS The results suggest that the new algorithm may reduce the inaccuracy of Guardian RT CGM system within the hypoglycemic range; however, data from a larger number of patients are required to compare the clinical reliability of the two algorithms.

Evaluation of an Algorithm for Retrospective Hypoglycemia Detection Using Professional Continuous Glucose Monitoring Data

Background: People with type 1 diabetes (T1D) are unable to produce insulin and thus rely on exogenous supply to lower their blood glucose. Studies have shown that intensive insulin therapy reduces the risk of late-diabetic complications by lowering average blood glucose. However, the therapy leads to increased incidence of hypoglycemia. Although inaccurate, professional continuous glucose monitoring (PCGM) can be used to identify hypoglycemic events, which can be useful for adjusting glucose-regulating factors. New pattern classification approaches based on identifying hypoglycemic events through retrospective analysis of PCGM data have shown promising results. The aim of this study was to evaluate a new pattern classification approach by comparing the performance with a newly developed PCGM calibration algorithm. Methods: Ten male subjects with T1D were recruited and monitored with PCGM and self-monitoring blood glucose during insulin-induced hypoglycemia. A total of 19 hypoglycemic events occurred during the sessions. Results: The pattern classification algorithm detected 19/19 hypoglycemic events with 1 false positive, while the PCGM with the new calibration algorithm detected 17/19 events with 2 false positives. Conclusions: We can conclude that even after the introduction of new calibration algorithms, the pattern classification approach is still a valuable addition for improving retrospective hypoglycemia detection using PCGM.

An ensemble nonlinear model predictive control algorithm in an artificial pancreas for people with type 1 diabetes

This paper presents a novel ensemble nonlinear model predictive control (NMPC) algorithm for glucose regulation in type 1 diabetes. In this approach, we consider a number of scenarios describing different uncertainties, for instance meals or metabolic variations. We simulate a population of 9 patients with different physiological parameters and a time-varying insulin sensitivity using the Medtronic Virtual Patient (MVP) model. We augment the MVP model with stochastic diffusion terms, time-varying insulin sensitivity and noise-corrupted CGM measurements. We consider meal challenges where the uncertainty in meal size is ± 50%. Numerical results show that the ensemble NMPC reduces the risk of hypoglycemia compared to standard NMPC in the case where the meal size is overestimated or correctly estimated at the expense of a slightly increased number of hyperglycemia. Therefore, ensemble MPC-based algorithms can improve the safety of the AP compared to the classical MPC-based algorithms.

Comparison of three nonlinear filters for fault detection in continuous glucose monitors

The purpose of this study is to compare the performance of three nonlinear filters in online drift detection of continuous glucose monitors. The nonlinear filters are the extended Kalman filter (EKF), the unscented Kalman filter (UKF), and the particle filter (PF). They are all based on a nonlinear model of the glucose-insulin dynamics in people with type 1 diabetes. Drift is modelled by a Gaussian random walk and is detected based on the statistical tests of the 90-min prediction residuals of the filters. The unscented Kalman filter had the highest average F score of 85.9%, and the smallest average detection delay of 84.1%, with the average detection sensitivity of 82.6%, and average specificity of 91.0%.The purpose of this study is to compare the performance of three nonlinear filters in online drift detection of continuous glucose monitors. The nonlinear filters are the extended Kalman filter (EKF), the unscented Kalman filter (UKF), and the particle filter (PF). They are all based on a nonlinear model of the glucose-insulin dynamics in people with type 1 diabetes. Drift is modelled by a Gaussian random walk and is detected based on the statistical tests of the 90-min prediction residuals of the filters. The unscented Kalman filter had the highest average F score of 85.9%, and the smallest average detection delay of 84.1%, with the average detection sensitivity of 82.6%, and average specificity of 91.0%.

Sensor-based detection and estimation of meal carbohydrates for people with diabetes

Abstract People with type 1 diabetes (T1D) must estimate the carbohydrate (CHO) content in meals to compute the bolus insulin correctly. To release T1D patients from the cumbersome task of counting CHO, we develop a method for detecting meals that can be used in blood glucose (BG) control. The algorithm detects a meal and estimates the meal onset and the amount of CHO. The inputs of the meal detector are the continuous glucose monitoring (CGM) data and the insulin infusion rate. We use second-order linear input-output models for insulin to subcutaneous glucose dynamics and for CHO to subcutaneous glucose dynamics. The models are converted to a linear discrete-time state-space model. A white noise double integrator models the unknown meal disturbances. The state-space model is augmented with the unknown meal disturbance (CHO ingestion rate) and a Kalman filter (KF) estimates the CHO rate (g/min). The algorithm uses two tests to announce a meal. The first test is a cumulative sum algorithm that detects changes in the KF innovation and estimates the onset of change. The second test is comparison of the estimated CHO rate with a threshold to detect a change in the rate. If both tests simultaneously detect a change, an optimal smoother estimates the meal-size. If the estimated meal-size reaches a certain amount, the algorithm announces a meal. Furthermore, we integrate a bolus calculator (BC) with the meal detector. We test the algorithm for nine virtual T1D patients. In total, the patients eat 45 meals in 13.5 days. The detection sensitivity is 93% and the detection delay has a median of 40 min. The median of the meal onset estimation bias is 5 min. Out of 42 detected meals, the algorithm underestimates 26 meals with a median bias of −19 g, and it overestimates 16 meals with a median bias of 21 g. The meal detector with the BC reduces the BG postprandial peak from 274 mg/dL (unbolused meals) to 207 mg/dL, and it increases the mean time in euglycemia from 50% to 79%. The meal detector combined with the BC improves glycemia for the virtual patients in this study.

Application of the continuous-discrete extended Kalman filter for fault detection in continuous glucose monitors for type 1 diabetes

The purpose of this study is the online detection of faults and anomalies of a continuous glucose monitor (CGM). We simulated a type 1 diabetes patient using the Medtronic virtual patient model. The model is a system of stochastic differential equations and includes insulin pharmacokinetics, insulin-glucose interaction, and carbohydrate absorption. We simulated and detected two types of CGM faults, i.e., spike and drift. A fault was defined as a CGM value in any of the zones C, D, and E of the Clarke error grid analysis classification. Spike was modelled by a binomial distribution, and drift was modelled by a Gaussian random walk. We used a continuous-discrete extended Kalman filter for the fault detection, based on the statistical tests of the filter innovation and the 90-min prediction residuals of the sensor measurements. The spike detection had a sensitivity of 93% and a specificity of 100%. Also, the drift detection had a sensitivity of 80% and a specificity of 85%. Furthermore, with 100% sensitivity the proposed method was able to detect if the drift overestimates or underestimates the interstitial glucose concentration.

Effect of continuous glucose monitoring accuracy on clinicians' retrospective decision making in diabetes: a pilot study

Background: The use of continuous glucose monitoring (CGM) in clinical decision making in diabetes could be limited by the inaccuracy of CGM data when compared to plasma glucose measurements. The aim of the present study is to investigate the impact of CGM numerical accuracy on the precision of diabetes treatment adjustments. Method: CGM profiles with maximum 5-day duration from 12 patients with type 1 diabetes treated with a basal-bolus insulin regimen were processed by 2 CGM algorithms, with the accuracy of algorithm 2 being higher than the accuracy of algorithm 1, using the median absolute relative difference (MARD) as the measure of accuracy. During 2 separate and similar occasions over a 1-month interval, 3 clinicians reviewed the processed CGM profiles, and adjusted the dose level of basal and prandial insulin. The precision of the dosage adjustments were defined in terms of the interclinician agreement and the intraclinician reproducibility of the decisions. The Cohen’s kappa coefficient was used to assess the precision of the decisions. The study was based on retrospective and blind CGM data. Results: For the interclinician agreement, in the first occasion, the kappa of algorithm 1 was .32, and that of algorithm 2 was .36. For the interclinician agreement, in the second occasion, the kappas of algorithms 1 and 2 were .17 and .22, respectively. For the intraclinician reproducibility of the decisions, the kappas of algorithm 1 were .35, .22, and .80 and the kappas of algorithm 2 were .44, .52, and .32, for the 3 clinicians, respectively. For the interclinician agreement, the relative kappa change from algorithm 1 to algorithm 2 was 86.06%, and for the intraclinician reproducibility, the relative kappa change from algorithm 1 to algorithm 2 was 53.99%. Conclusions: Results indicated that the accuracy of CGM algorithms might potentially affect the precision of the CGM-based insulin adjustments for type 1 diabetes patients. However, a larger study with several clinical centers, with higher number of clinicians and patients is required to validate the impact of CGM accuracy on decisions precision.