Efficacy of continuous glucose monitoring in improving glycemic control and reducing hypoglycemia: a systematic review and meta-analysis of randomized trials

Objective

We conducted a systematic review and meta-analysis to assess the efficacy of continuous glucose monitoring (CGM) in improving glycemic control and reducing hypoglycemia compared to self-monitored blood glucose (SMBG).

Methods

We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for randomized trials of adults and children with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed methodological quality, and extracted data. Meta-analytic estimates of treatment effects were generated using a random-effects model.

Results

Nineteen trials were eligible and provided data for meta-analysis. Overall, CGM was associated with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean difference (WMD) of -0.27% (95% confidence interval [CI] -0.44 to -0.10)]. This was true for adults with T1DM as well as T2DM [WMD -0.50% (95% CI -0.69 to -0.30) and -0.70 (95% CI, -1.14 to -0.27), respectively]. No significant effect was noted in children and adolescents. There was no significant difference in HbA1c reduction between studies of real-time versus non-realtime devices (WMD -0.22%, 95% CI, -0.59 to 0.15 versus -0.30%, 95% CI, -0.49 to -0.10; p for interaction 0.71). The quality of evidence was moderate due to imprecision, suggesting increased risk for bias. Data for the incidence of severe or nocturnal hypoglycemia were sparse and imprecise. In studies that reported patient satisfaction, users felt confident about the device and gave positive reviews.

Conclusion

Continuous glucose monitoring seems to help improve glycemic control in adults with T1DM and T2DM. The effect on hypoglycemia incidence is imprecise and unclear. Larger trials with longer follow-up are needed to assess the efficacy of CGM in reducing patient-important complications without significantly increasing the burden of care for patients with diabetes.     

Influence of Partial Pressure of Oxygen in Blood Samples on Measurement Performance in Glucose-Oxidase-Based Systems for Self-Monitoring of Blood Glucose

Background

Partial pressure of oxygen (pO₂) in blood samples can affect blood glucose (BG) measurements, particularly in systems that employ the glucose oxidase (GOx) enzyme reaction on test strips. In this study, we assessed the impact of different pO₂ values on the performance of five GOx systems and one glucose dehydrogenase (GDH) system. Two of the GOx systems are labeled by the manufacturers to be sensitive to increased blood oxygen content, while the other three GOx systems are not.

Methods

Aliquots of 20 venous samples were adjusted to the following pO₂ values: <45, ~70, and ≥150 mmHg. For each system, five consecutive measurements on each sample aliquot were performed using the same test strip lot. Relative differences between the mean BG results at pO₂ ~70 mmHg, which is considered to be similar to pO₂ in capillary blood samples, and the mean BG result at pO₂ <45 and ≥150 mmHg were calculated.

Results

For all tested GOx systems, mean relative differences in the BG measurement results were between 6.1% and 22.6% at pO₂ <45 mmHg and between -7.9% and -14.9% at pO₂ ≥150 mmHg. For both pO₂ levels, relative differences of all tested GOx systems were significant (p < .0001). The GDH system showed mean relative differences of -1.0% and -0.4% at pO₂ values <45 and ≥150 mmHg, respectively, which were not significant.

Conclusions

These data suggest that capillary blood pO₂ variations lead to clinically relevant BG measurement deviations in GOx systems, even in GOx systems that are not labeled as being oxygen sensitive.     

Effects of simulated altitude on blood glucose meter performance: implications for in-flight blood glucose monitoring

BACKGROUND: Most manufacturers of blood glucose monitoring equipment do not give advice regarding the use of their meters and strips onboard aircraft, and some airlines have blood glucose testing equipment in the aircraft cabin medical bag. Previous studies using older blood glucose meters (BGMs) have shown conflicting results on the performance of both glucose oxidase (GOX)- and glucose dehydrogenase (GDH)-based meters at high altitude. The aim of our study was to evaluate the performance of four new-generation BGMs at sea level and at a simulated altitude equivalent to that used in the cabin of commercial aircrafts. Methodology/Principal Findings: Blood glucose measurements obtained by two GDH and two GOX BGMs at sea level and simulated altitude of 8000 feet in a hypobaric chamber were compared with measurements obtained using a YSI 2300 blood glucose analyzer as a reference method. Spiked venous blood samples of three different glucose levels were used. The accuracy of each meter was determined by calculating percentage error of each meter compared with the YSI reference and was also assessed against standard International Organization for Standardization (ISO) criteria. Clinical accuracy was evaluated using the consensus error grid method. The percentage (standard deviation) error for GDH meters at sea level and altitude was 13.36% (8.83%; for meter 1) and 12.97% (8.03%; for meter 2) with p = .784, and for GOX meters was 5.88% (7.35%; for meter 3) and 7.38% (6.20%; for meter 4) with p = .187. There was variation in the number of time individual meters met the standard ISO criteria ranging from 72-100%. Results from all four meters at both sea level and simulated altitude fell within zones A and B of the consensus error grid, using YSI as the reference. CONCLUSIONS: Overall, at simulated altitude, no differences were observed between the performance of GDH and GOX meters. Overestimation of blood glucose concentration was seen among individual meters evaluated, but none of the results obtained would have resulted in dangerous failure to detect and treat blood glucose errors or in giving treatment that was actually contradictory to that required.     

Historical achievements of self-monitoring of blood glucose technology development in Japan

Japanese companies were the first in the world to achieve a colorimetric glucose measurement meter back in 1973. Over the following 40 or so years, they succeeded in achieving a much greater level of user-friendliness and performance and in so doing, have contributed to the spread of self-monitoring of blood glucose. This article aims to unravel the history of blood glucose measurement's technological developments; to look at the direction and features of the development path Japan is taking; as well as to introduce some Japanese products that are on the market.     

Benefits of blinded continuous glucose monitoring during a randomized clinical trial

Background:

Real-time, personal continuous glucose monitoring (CGM) is a validated technology that can help patients improve glycemic control. Blinded CGM is a promising technology for obtaining retrospective data in clinical research where the quantity and quality of blood glucose information is important. This study was designed to investigate the use of novel procedures to enhance data capture from blinded CGM.

Methods:

Following a 4-week run-in, 46 patients with type 1 diabetes were randomized to one of two prandial insulins for a 12-week treatment period, after which they were crossed over to the alternate treatment for 12 weeks. Continuous glucose monitoring was implemented at the end of run-in (practice only) and during the last 2 weeks of each treatment period. Eighty percent of 288 possible daily glucose values were required for at least three days. Continuous glucose monitoring was extended for an additional week if these criteria were not met, and patients were allowed to insert sensors at home when necessary. Continuous glucose monitoring results were compared to reference eight-point self-monitoring of blood glucose (SMBG).

Results:

Higher than expected sensor failure rate was approximately 25%. During run-in, 12 of 45 attempted profiles failed adequacy criteria. However, treatment periods had only 1 of 82 attempted profiles considered inadequate (6 cases required an additional week of CGM). Using SMBG as reference, 93.7% of 777 CGM values were in Clarke error grid zones A+B.

Conclusions:

With appropriate training, adequate practice, and opportunity to repeat blinded CGM as needed, nearly 100% of attempted profiles can be obtained successfully.     

Performance of the DIDGET blood glucose monitoring system in children, teens, and young adults

Background

This study evaluated the performance of the DIDGET® blood glucose monitoring system (BGMS) in the hands of its intended users: children, teens, and young adults with diabetes.

Methods

Finger stick capillary blood samples were tested in duplicate by subjects (with parent/guardian assistance, if needed) and health care professionals using the DIDGET BGMS, and results were compared with those obtained using a Yellow Springs Instruments (YSI) glucose analyzer. Modified venous blood samples (i.e., glycolyzed or spiked with glucose) were used to analyze meter performance under extreme glucose concentrations. Accuracy was assessed using International Organization for Standardization (ISO) 15197:2003 guidelines (i.e., 95% of meter results within ±15 mg/dl or ±20% of reference values).

Results

A total of 123 subjects aged 4 to 24 years with type 1 or type 2 diabetes were enrolled. The DIDGET meter achieved accuracy according to ISO 15197:2003 criteria: >97% of meter results were within ±15 mg/dl or ±20% of reference values. Regression analyses showed a high degree of correlation between meter and YSI results: coefficient of determination (R²) = 98.2% for all samples combined and 97.2% for capillary samples only. Clinical accuracy for combined samples was demonstrated by Parkes consensus error grid analyses; 100% of meter results were in zone A (98.5%) or zone B (1.5%). There was no difference in performance or accuracy across age subsets. Hematocrit values did not affect meter blood glucose results.

Conclusion

The DIDGET BGMS provided accurate test results across all age ranges in children, teens, and young adults with diabetes.     

The effect of an instant hand sanitizer on blood glucose monitoring results

Background

People with diabetes mellitus are instructed to clean their skin prior to self-monitoring of blood glucose to remove any dirt or food residue that might affect the reading. Alcohol-based hand sanitizers have become popular when soap and water are not available. The aim of this study was to determine whether a hand sanitizer is compatible with glucose meter testing and effective for the removal of exogenous glucose.

Methods

We enrolled 34 nonfasting subjects [14 male/20 female, mean ages 45 (standard deviation, 9.4)] years, 2 with diagnosed diabetes/32 without known diabetes]. Laboratory personnel prepared four separate fingers on one hand of each subject by (1) cleaning the second finger with soap and water and towel drying (i.e., control finger), (2) cleaning the third finger with an alcohol-based hand sanitizer, (3) coating the fourth finger with cola and allowing it to air dry, and (4) coating the fifth finger with cola and then cleaning it with the instant hand sanitizer after the cola had dried. Finger sticks were performed on each prepared finger and blood glucose was measured. Several in vitro studies were also performed to investigate the effectiveness of the hand sanitizer for removal of exogenous glucose.z

Results

Mean blood glucose values from fingers cleaned with instant hand sanitizer did not differ significantly from the control finger (p = .07 and .08, respectively) and resulted in 100% accurate results. Blood glucose data from the fourth (cola-coated) finger were substantially higher on average compared with the other finger conditions, but glucose data from the fifth finger (cola-coated then cleaned with hand sanitizer) was similar to the control finger. The data from in vitro experiments showed that the hand sanitizer did not adversely affect glucose meter results, but when an exogenous glucose interference was present, the effectiveness of the hand sanitizer on glucose bias (range: 6% to 212%) depended on the surface area and degree of dilution.

Conclusions

In our study, use of an instant hand sanitizer was compatible with the results of a blood glucose monitor and did not affect finger stick blood glucose results. However, depending on surface area, hand sanitizers may not be adequate for cleaning the skin prior to glucose meter testing.     

Integrated self-monitoring of blood glucose system: handling step analysis

Self-monitoring of blood glucose (SMBG) implicates a number of handling steps with the meter and the lancing device. Numerous user errors can occur during SMBG, and each step adds to the complexity of use. This report compares the required steps to perform SMBG of one fully integrated (the second generation of the Accu-Chek® Mobile), three partly integrated (Accu-Chek Compact Plus, Ascensia® Breeze®2, and Accu-Chek Aviva), and six conventional (Bayer Contour®, Bayer Contour USB, BGStar™, FreeStyle Lite®, OneTouch® Ultra® 2, and OneTouch Verio™Pro) systems. The results show that the fully integrated system reduces the number of steps to perform SMBG. The mean decrease is approximately 70% compared with the other systems. We assume that a reduction of handling steps also reduces the risk of potential user errors and improves the user-friendliness of the system.     

Evaluation of the analytical performance of the coulometry-based Optium Omega blood glucose meter

Background

The goal of diabetes treatment is maintaining near normoglycemia based on self-monitoring of blood glucose (SMBG). In this study, an evaluation of the analytical performance of the coulometry-based Optium Omega™ glucose meter designed for SMBG has been carried out.

Methods

The assessment of precision and between-lot variability was based on glucose measurements in ethylene-diaminetetraacetic acid venous blood samples. Glucose concentrations measured in 289 fresh capillary blood samples using the Omega glucose meter and the Biosen C_line analyzer were compared.

Results

Within-run imprecision coefficient of variation for the lower and higher glucose concentrations amounted to 5.09 and 2.1%, respectively. The relative lot-dependent differences found for the lower and higher glucose concentrations were equal to 6.8 and 2.6%, respectively. The glucose meter error calculated for various concentration ranges amounted from 2.22 to 4.48%. The glucose meter error met the accuracy criteria recommended by the International Organization for Standardization and the American Diabetes Association. The Passing-Bablok agreement test and error grid analysis with 96% of results in zone A indicated good concordance of results, including glucose concentrations below 100 mg/dl.

Conclusions

The evaluated Optium Omega glucose meter fits the analytical requirements for its use in blood glucose monitoring in diabetes patients.     

Effects of a structured self-monitoring of blood glucose method on patient self-management behavior and metabolic outcomes in type 2 diabetes mellitus

Background

The purpose of this study was to evaluate the effect of structured self-monitoring of blood glucose (SMBG) on patient self-management behavior and metabolic outcomes in patients with type 2 diabetes mellitus (T2DM).

Methods

From January to June 2009, 30 patients with basic diabetes education were followed for a period of 90 days. To provide assessment of glycemic control and frequency of dysglycemia, patients, underwent 3 consecutive days of seven-point SMBG during each month for 3 consecutive months, using the ACCU-CHEK 360° View tool. Glucose profiles of the first and third month were used for comparison.

Results

Hemoglobin A1c (HbA1c) improved significantly during the 90-day period in all patients [confidence interval (CI) 95%, 0.32–1.64%, p < .05] and those with poor metabolic control (group B; CI 95%, 0.86–2.64%, p < .05). Mean blood glucose (MBG) values decreased significantly in group B (CI 95%, 0.56–24.78 mg/dl, p < .05) and all cases (CI 95%, 1.61–19.73 mg/dl, p < .05). Meanwhile, there was an average decrease of 15.7 mg/dl in fasting blood sugar (FBS) levels in the whole subjects. Mean postprandial blood glucose levels (MPP) decreased by 19.3 and 11.3 mg/dl in group B and in all cases, respectively. However, there were no significant changes in HbA1c, MBG, FBS, and MPP in people with good metabolic control.

Conclusion

A structured SMBG program improves HbA1c, FBS, MPP, and MBG in people with poorly controlled diabetes. This improvement shows the importance of patient self-management behavior on metabolic outcomes in T2DM.     

Accuracy of point-of-care glucose measurements

Control of blood glucose (BG) in an acceptable range is a major therapy target for diabetes patients in both the hospital and outpatient environments. This review focuses on the state of point-of-care (POC) glucose monitoring and the accuracy of the measurement devices. The accuracy of the POC glucose monitor depends on device methodology and other factors, including sample source and collection and patient characteristics. Patient parameters capable of influencing measurements include variations in pH, blood oxygen, hematocrit, changes in microcirculation, and vasopressor therapy. These elements alone or when combined can significantly impact BG measurement accuracy with POC glucose monitoring devices (POCGMDs). In general, currently available POCGMDs exhibit the greatest accuracy within the range of physiological glucose levels but become less reliable at the lower and higher ranges of BG levels. This issue raises serious safety concerns and the importance of understanding the limitations of POCGMDs. This review will discuss potential interferences and shortcomings of the current POCGMDs and stress when these may impact the reliability of POCGMDs for clinical decision-making.     

Self-Monitoring of Blood Glucose in Type 2 Diabetes: Recent Studies

The increasing role for structured and personalized self-monitoring of blood glucose (SMBG) in management of type 2 diabetes has been underlined by randomized and prospective clinical trials. These include Structured Testing Program (or STeP), St. Carlos, Role of Self-Monitoring of Blood Glucose and Intensive Education in Patients with Type 2 Diabetes Not Receiving Insulin, and Retrolective Study Self-Monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (or ROSSO)-in-praxi follow-up. The evidence for the benefit of SMBG both in insulin-treated and non-insulin-treated patients with diabetes is also supported by published reviews, meta-analyses, and guidelines. A Cochrane review reported an overall effect of SMBG on glycemic control up to 6 months after initiation, which was considered to subside after 12 months. Particularly, the 12-month analysis has been criticized for the inclusion of a small number of studies and the conclusions drawn. The aim of this article is to review key publications on SMBG and also to put them into perspective with regard to results of the Cochrane review and current aspects of diabetes management.     

Measuring Glucose Concentrations: Daily Practice, Current and Future Developments

Self-monitoring of blood glucose (SMBG) by means of modern glucose meters is of relevance for all patients with diabetes. It not only provides important information about the effect of therapeutic interventions on metabolic control, but about the effect of exercise and meals as well. Therefore, it is an essential part of diabetes therapy. However, it has received little interest from academia in the last 10 years. This is in sharp contrast to the massive increase in SMBG use in the last decades and its economic impact on health care systems. Many physicians and patients believe that SMBG and the measurement technologies behind it are a no-brainer nowadays, i.e., that the measurement provides reliable results in practically all cases. In reality, it appears as if patients have only mediocre knowledge about the appropriate handling of the procedure and subsequent therapeutic action. Also, evaluation of the measurement quality of blood glucose meters is not studied adequately in many cases. Such studies should also take into account handling by the patients themselves under daily life conditions. Unfortunately, most of such studies are initiated and sponsored by the manufacturers of blood glucose meters/test strips, and not by an independent institution. In view of the costs and risks combined with SMBG, we should consider that all patients participate in a course that ends with a little examination and provides them with a “driver''s license” for this diagnostic measure.     

Patient Perceptions of Different Lancing Sites for Self-Monitoring of Blood Glucose: A Comparison of Fingertip Site with Palm Site Using the OneTouch? Ultra? Blood Glucose Monitoring System

Background

Alternate-site testing (AST) for self-monitoring of blood glucose leads to improved glycemic control for treatment of diabetes mellitus. The aim of this randomized, open-label, two-period, crossover study was to compare the comfort of two different lancing sites, fingertip and palm sites, for AST in diabetes patients.

Methods

Patients injected insulin four times a day. Self-monitoring of blood glucose was carried out more than thrice daily with fingertip measurements for at least three months using apparatuses except the OneTouch^®Ultra^®Blood Glucose Monitoring System (OneTouch) before examination. The comfort of two lancing sites using OneTouch were compared. In two randomized groups that used one fingertip lancing site for one week followed by the alternate lancing site for another week, patients completed 11-item questionnaires assessing usability of the site before and after each week. Each item was scored on a visual analogue scale from –100 (most negative) to +100 (most positive).

Results

Most patients desired to continue AST, which was insignificantly different between the two lancing sites (fingertip and palm AST) in 43 diabetes patients aged 57.3 ± 13.8 years, body mass index of 23.1 ± 2.5 kg/m², diabetes duration of 19.6 ± 9.7 years, and hemoglobin A1c of 7.4 ± 1.1%. However, patients were less (p < .01) satisfied with using the palm lancing site as compared to the fingertip lancing site because of difficulties in inserting the needle, drawing blood samples, and applying enough blood into the test strip.

Conclusions

These results suggest that patients desire to use the palm for AST, but more technological advances in AST of a palm site is required to reduce patient discomfort.     

Evaluation of a Blood Glucose Monitoring System with Automatic High- and Low-Pattern Recognition Software in Insulin-Using Patients: Pattern Detection and Patient-Reported Insights

Background

This study aimed to evaluate the performance of a glucose pattern recognition tool incorporated in a blood glucose monitoring system (BGMS) and its association with clinical measures, and to assess user perception and understanding of the pattern messages they receive.

Methods

Participants had type 1 or type 2 diabetes mellitus and were self-adjusting insulin doses for ≥1 year. During a 4-week home testing period, participants performed ≥6 daily self-tests, adjusted their insulin regimen based on BGMS results, and recorded pattern messages in the logbook. Participants reflected on usability of the pattern tool in a questionnaire.

Results

Study participants (n = 101) received a mean ± standard deviation of 4.5 ± 1.9 pattern messages per week (3.6 ± 1.8 high glucose patterns and 0.9 ± 1.3 low glucose patterns). Most received ≥1 high (96.5%) and/or ≥1 low (46.0%) pattern message per week. The average number of high- and low-pattern messages per week was associated with higher and lower, respectively, baseline hemoglobin A1c (p < .01) and fasting plasma glucose (p < .05). Participants found high- and low-pattern messages clear and easy to understand (84.2% and 83.2%, respectively) and considered the frequency of low (82.0%) and high (63.4%) pattern messages about right. Overall, 71.3% of participants indicated they preferred to use a meter with pattern messages.

Conclusions

The on-device Pattern tool identified meaningful blood glucose patterns, highlighting potential opportunities for improving glycemic control in patients who self-adjust their insulin.