No-Coding Strategies for Glucose Monitors: FreeStyle Lite��A Blood Glucose Meter That Requires No Coding

Background

Abbott Diabetes Care introduced the FreeStyle® Lite blood glucose monitoring system, which simplifies the management of diabetes. The FreeStyle Lite system relies on FreeStyle technology but eliminates the need for coding the meter for individual strip lots. The meter is precoded for the FreeStyle Lite strips. FreeStyle systems use coulometry technology where the glucose signal is calculated from the total charge generated as a result of the glucose reaction in the sample. FreeStyle strip calibration parameters can be controlled by controlling the sample volume. Coulometry technology is less sensitive to measurement conditions such as temperature and hematocrit. FreeStyle chemistry is less sensitive to interference from electroactive compounds. The ability to control calibration parameters coupled to a robust measurement technology enabled the development of a blood glucose monitoring system that does not require coding by the user.

Methods

Laboratory studies were performed to determine analytical performance, such as linearity, precision, and sensitivity to operating temperature. Clinical accuracy for finger tip capillary blood testing was assessed with five lots of FreeStyle Lite test strips. FreeStyle Lite results in these studies were compared to the plasma equivalent glucose values of finger tip blood samples measured by the Yellow Springs Instrument glucose analyzer.

Results

In the analytical performance evaluation, repeatability (within-run precision) of the FreeStyle Lite system showed an average standard deviation of 3.4 mg/dl (0.19 mmol/liter) at glucose concentrations <100 mg/dl (<5.56 mmol/liter) and an average coefficient of variation of 4.3% at glucose concentrations ≥100 mg/dl (≥5.56 mmol/liter). Linearity demonstrated across the measuring range of the FreeStyle Lite system was 20–500 mg/dl (1.1–27.8 mmol/liter) with r² > 0.99. The FreeStyle Lite system was also shown to maintain accuracy across the operating temperature range of 4 to 40°C.

Conclusions

The FreeStyle Lite system has good analytical performance and clinical accuracy. While simplifying the process of blood glucose monitoring, the FreeStyle Lite system continues to provide the performance that users have come to expect from FreeStyle products.     

Crohn��s Disease: A Surgeon��s Perspective

Crohn’s disease (CD) is known for wide anatomic distribution, different presentations, life-threatening complications, and multiple modalities of management. Its multiple implications are still unaddressed. Since all the patients do not show a good response to medical modalities of treatment, a significant percentage of these patients are referred to the surgeon for the palliation of complications or for the ultimate curative treatment. Since most surgeons come across such patients only rarely, it is sometimes difficult for them to choose the appropriate procedure at the time of need. Moreover, the various surgical modalities available for the different presentations and complications of the disease have not been adequately discussed. The aim of this review is to offer insight and a detailed account of the management of CD from a surgical perspective. This review offers an overview of the various surgical options available, their utility in context, and an approach to various scenarios of complicated CD.     

Approaches to Display of Multiple-Point Glucose Profiles: A UK Patient’s Perspective

Multiple-point glucose profiles are now acknowledged, in the diabetes literature, as a key way for people with diabetes to analyze and interpret blood glucose control (BGC).^1-3 Combined methods to visualize relevant blood glucose information are increasingly recognized as a more effective method of explaining actionable glucose profiles.^4,15(p564) This commentary is written from the perspective of a person with type 1 diabetes and might add value to the existing understanding about relevant ways to display BGC data. Through discussion of the limits to current multiple-point glucose displays, for example, AGP “dashboard,” a proposed alternative method of graphical display that brings together HbA1c and self-monitored blood glucose (SMBG) test data is presented.     

External Quality Assessment of Blood Glucose Monitors: Measurement Quality of Blood Glucose Meters: Is There a Need for an Institution with an Unbiased View?

The quality of self-monitoring of blood glucose (SMBG) with modern blood glucose meters is considered by many as not being a relevant topic anymore. However, in reality, a number of open questions about the quality of the measurement exists. Even if the meters fulfill the established quality criteria when they receive approval, there is no independent institution that performs a regular, critical comparison of the quality of the measurement of all blood glucose meters after their approval. Such an institute could also evaluate the quality of the different batches of test strips. In addition, it can evaluate the impact of other factors that are known to have an impact on the quality of measurement, e.g., the ambient temperature and the hematocrit. Such an institution will be very helpful to counterbalance complaints by the patients, physicians and authorities about an industry that earns a lot of money but does not provide solutions for the topics raised.     

Performance Evaluation of a New Blood Glucose Monitor That Requires No Coding: The OneTouch? Vita? System

Background

Improvements to blood glucose monitoring systems aim to simplify the testing process, reduce or eliminate errors, and provide additional information for patients with diabetes. New systems must continue to demonstrate high-quality analytical performance. The new OneTouch^® Vita™ System (LifeScan, Inc., Milpitas, CA) offers a no-code testing process and proven technology found in the OneTouch^® Ultra^® System. Comparative studies were conducted with the new and established systems to evaluate their precision and accuracy.

Methods

Within-run precision in blood, total precision with controls, and system accuracy were evaluated using three lots of OneTouch Vita Test Strips and one lot of OneTouch Ultra Test Strips. Accuracy was tested across a wide glucose range (38–520 mg/dl, 2.1–28.9 mmol/liter) using fingertip blood samples from 139 subjects. Reference plasma glucose values were obtained using the YSI 2300 STAT Plus Glucose & Lactate Analyzer (YSI Inc., Yellow Springs, OH). All studies were designed in accordance with requirements published by the International Organization for Standardization (ISO 15197).

Results

Precision testing (within-run and total) with both systems produced coefficients of variation (CVs) of <5% for all sample types and glucose levels. Within-run precision testing with blood showed CVs of <3.1% and <4.7% for the OneTouch Vita and OneTouch Ultra Systems respectively. Total precision with control samples gave CVs of <3.0% and <3.6% for the two systems. Consensus error grid analysis showed equivalent clinical accuracy with 98.4% (821/834) and 98.2% (273/278) of results within zone A. Both systems met the ISO acceptability requirements for system accuracy.

Conclusion

The OneTouch Vita System provides a simple no-code testing process with performance comparable to the OneTouch Ultra and OneTouch Ultra2 Systems.     

Consensus Report of the Coalition for Clinical Research��Self-Monitoring of Blood Glucose

The Coalition for Clinical Research—Self-Monitoring of Blood Glucose Scientific Board, a group of nine academic clinicians and scientists from the United States and Europe, convened in San Francisco, California, on June 11–12, 2008, to discuss the appropriate uses of self-monitoring of blood glucose (SMBG) and the measures necessary to accurately assess the potential benefit of this practice in noninsulin-treated type 2 diabetes mellitus (T2DM). Thirteen consultants from the United States, Europe, and Canada from academia, practice, and government also participated and contributed based on their fields of expertise. These experts represent a range of disciplines that include adult endocrinology, pediatric endocrinology, health education, mathematics, statistics, psychology, nutrition, exercise physiology, and nursing. This coalition was organized by Diabetes Technology Management, Inc. Among the participants, there was consensus that:

1. protocols assessing the performance of SMBG in noninsulin treated T2DM must provide the SMBG intervention subjects with blood glucose (BG) goals and instructions on how to respond to BG data in randomized controlled trials (RCTs);
2. intervention subjects in clinical trials of SMBG-driven interventions must aggressively titrate their therapeutic responses or lifestyle changes in response to hyperglycemia;
3. control subjects in clinical trials of SMBG must be isolated from SMBG-driven interventions and not be contaminated by physician experience with study subjects receiving a SMBG intervention;
4. the best endpoints to measure in a clinical trial of SMBG in T2DM include delta Hemoglobin A1c levels, hyperglycemic events, hypoglycemic events, time to titrate noninsulin therapy to a maximum necessary dosage, and quality of life indices;
5. either individual randomization or cluster randomization may be appropriate methods for separating control subjects from SMBG intervention subjects, provided that precautions are taken to avoid bias and that the sample size is adequate;
6. treatment algorithms for assessing SMBG in T2DM may include a dietary, exercise, and/or medication intervention, which are all titratable according to the SMBG values;
7. the medical literature contains very little information about the performance of SMBG in T2DM from RCTs in which treatment algorithms were used for dysglycemic values; and
8. research on the performance of SMBG in T2DM based on sound scientific principles and clinical practices is needed at this time.

     

A Composite Model of Glucagon–Glucose Dynamics for In Silico Testing of Bihormonal Glucose Controllers

Background:

The utility of simulation environments in the development of an artificial pancreas for type 1 diabetes mellitus (T1DM) management is well established. The availability of a simulator that incorporates glucagon as a counterregulatory hormone to insulin would allow more efficient design of bihormonal glucose controllers.Existing models of the glucose regulatory system that incorporates glucagon action are difficult to identify without using tracer data. In this article, we present a novel model of glucagon–glucose dynamics that can be easily identified with standard clinical research data.

Methods:

The minimal model of plasma glucose and insulin kinetics was extended to account for the action of glucagon on net endogenous glucose production by incorporating a new compartment. An existing subcutaneous insulin absorption model was used to account for subcutaneous insulin delivery. The same model of insulin pharmacokinetics was employed to model the pharmacokinetics of subcutaneous glucagon absorption. Finally, we incorporated an existing gastrointestinal absorption model to account for meal intake. Data from a closed-loop artificial pancreas study using a bihormonal controller on T1DM subjects were employed to identify the composite model. To test the validity of the proposed model, a bihormonal controller was designed using the identified model.

Results:

Model parameters were identified with good precision, and an excellent fitting of the model with the experimental data was achieved. The proposed model allowed the design of a bihormonal controller and demonstrated its ability to improve glycemic control over a single-hormone controller.

Conclusions:

A novel composite model, which can be easily identified with standard clinical data, is able to account for the effect of exogenous insulin and glucagon infusion on glucose dynamics. This model represents another step toward the development of a bihormonal artificial pancreas.     

Faecal Calprotectin: A Novel Test for the Diagnosis of Colorectal Cancer?

Calprotectin, a prominent cytosol protein in neutrophil granulocytes, was present in increased concentrations in stools from 50 of 53 patients with colorectal cancer, 32 of 40 patients with colorectal polyps, and all of 18 patients with gastric cancer. After radical surgery, faecal calprotectin levels reverted to the normal range in all but one patient with colorectal cancer. Calprotectin determinations are simplified by the stability of this protein in stools. Reliable estimates can be obtained in samples of only 5 g. On the basis of data from the literature, the test for calprotectin seems better than that for occult blood for the detection of gastrointestinal neoplasms     

Sensors & Algorithms for Continuous Glucose Monitoring: Hypoglycemia Detection and Prediction Using Continuous Glucose Monitoring��A Study on Hypoglycemic Clamp Data

Motivation

The fear of hypoglycemia remains an important limiting factor in the ability of an individual with type 1 diabetes to tightly regulate glycemia. Continuous glucose monitors provide important feedback to improve glycemic control, but there remains a need for these devices to better alarm of possible impending hypoglycemia, particularly overnight or other periods when the individual is engaged in activities that take their focus away from glucose monitoring.

Methods

We have previously proposed an algorithm, based on the use of real-time glucose sensor signals and optimal estimation theory (Kalman filtering), to predict hypoglycemia; the algorithm was validated in simulation-based studies. In this article we further refine and validate the prediction algorithm based on the analysis of clinical hypoglycemic clamp data from 13 subjects. The sensitivity and specificity of the predictions are calculated with respect to reference blood glucose values obtained at the same sampling rate of the sensor.

Results

For a 30-minute prediction horizon and alarm threshold of 70 mg/dl, the sensitivity and specificity were 90 and 79%, respectively, indicating that a 21% false alarm rate must be tolerated to predict 90% of the hypoglycemic events 30 minutes ahead of time. Shorter prediction horizons yield a significant improvement in sensitivity and specificity.

Discussion

Sensitivity and specificity data as a function of prediction horizon and alarm threshold enable an individual to adjust the alarm to best meet their needs. Such decisions can be made depending on the subject''s risk for hypoglycemia, for example.     

A New Metabolite Panel Test for Identification of Patients With Impaired Glucose Tolerance? Analysis of the Article by Cobb et al

The article by Cobb et al represents solid research work applying the most sophisticated laboratory technologies, a very sound clinical research methodology, and valid statistical analysis procedures. The authors have identified a combination of metabolites suitable to replace the oral glucose tolerance test procedure in the identification of patients with impaired glucose tolerance (IGT) from a fasting blood draw. However, the discussed pathophysiological, clinical, and economic aspects may induce mechanisms restricting the probability of a global acceptance of this test for daily routine.     

Application of the Glucose Hydrogen Breath Test for the Detection of Bacterial Overgrowth in Patients with Cystic Fibrosis––A Reliable Method?

Patients with cystic fibrosis (CF) have recently been deemed highly susceptible for bacterial intestinal overgrowth (BIO). We aimed to define the prevalence of BIO in children with CF by applying the H₂-glucose breath test. Forty children with CF and ten healthy children received 1 g/kg D-glucose orally. Breath samples for H₂ content (ppm) were collected for 3 h. BIO was suspected if the breath hydrogen content increased by more than 20 ppm or if baseline concentrations topped 20 ppm. In 27 of 40 CF children (68%), breath hydrogen content exceeded 20 ppm. Whereas the breath hydrogen exhalation persisted above 20 ppm in almost all these children throughout the sampling period, none of the remaining children increased above this threshold. The high rate of CF children with elevated fasting hydrogen breath concentrations indicates that this phenomenon is less a sign of BIO rather than a consequence of global malabsorption and intestinal dysmotility.     

Continuous Glucose Monitors and the Burden of Tight Glycemic Control in Critical Care: Can They Cure the Time Cost?

Background

Tight glycemic control (TGC) in critical care has shown distinct benefits but has also proven to be difficult to obtain. The risk of severe hypoglycemia (<40 mg/dl) raises significant concerns for safety. Added clinical burden has also been an issue. Continuous glucose monitors (CGMs) offer frequent automated measurement and thus the possibility of using them for early detection and intervention of hypoglycemic events. Additionally, regular measurement by CGM may also be able to reduce clinical burden.

Aim

An in silico study investigates the potential of CGM devices to reduce clinical effort in a published TGC protocol.

Methods

This study uses retrospective clinical data from the Specialized Relative Insulin Nutrition Titration (SPRINT) TGC study covering 20 patients from a benchmark cohort. Clinically validated metabolic system models are used to generate a blood glucose (BG) profile for each patient, resulting in 33 continuous, separate BG episodes (6881 patient hours). The in silico analysis is performed with three different stochastic noise models: two Gaussian and one first-order autoregressive. The noisy, virtual CGM BG values are filtered and used to drive the SPRINT TGC protocol. A simple threshold alarm is used to trigger glucose interventions to avert potential hypoglycemia. The Monte Carlo method was used to get robust results from the stochastic noise models.

Results

Using SPRINT with simulated CGM noise, the BG time in an 80–110 mg/dl band was reduced no more than 4.4% to 45.2% compared to glucometer sensors. Antihypoglycemic interventions had negligible effect on time in band but eliminated all recorded hypoglycemic episodes in these simulations. Assuming 4–6 calibration measurements per day, the nonautomated clinical measurements are reduced from an average of 16 per day to as low as 4. At 2.5 min per glucometer measurement, a daily saving of ∼25–30 min per patient could potentially be achieved.

Conclusions

This paper has analyzed in silico the use of CGM sensors to provide BG input data to the SPRINT TGC protocol. A very simple algorithm was used for early hypoglycemic detection and prevention and tested with four different-sized intravenous glucose boluses. Although a small decrease in time in band (still clinically acceptable) was experienced with the addition of CGM noise, the number of hypoglycemic events was reduced. The reduction to time in band depends on the specific CGM sensor error characteristics and is thus a trade-off for reduced nursing workload. These results justify a pilot clinical trial to verify this study.