Study of Glycemic Variability in Well-controlled Type 2 Diabetic Patients Using Continuous Glucose Monitoring System.

INTRODUCTION: The world has changed tremendously for patients suffering from diabetes mellitus with the development of cutting-edge technologies like continuous glucose monitoring and flash glucose monitoring systems. Now, the details of constant fluctuations of glucose in their blood can be monitored not only by medical professionals but also by patients, and this is called glycemic variability (GV). Traditional metrics of glycemic control measurement, such as glycated hemoglobin (HbA1c), fail to reflect various short-term glycemic changes like postprandial hyperglycemia and hypoglycemic episodes, paving the way to the occurrence of various diabetic complications even in asymptomatic, well-controlled diabetic patients. This need for advanced management of diabetes and effective monitoring of these swings in blood glucose can be met by using a continuous glucose monitoring system (CGMS). AIM AND OBJECTIVE: To evaluate the extent of GV in well-controlled type 2 diabetes mellitus (T2DM) patients using a flash CGMS and to assess the correlation between GV and HbA1c. MATERIALS AND METHODS: A hospital-based prospective observational study was carried out from May 2020 to Oct 2021 at the Department of Medicine, SMS Hospital, Jaipur, Rajasthan (India), after approval from the Ethics Committee of the institution. A total of 30 patients with well-controlled T2DM (HbA1c was ≥6.5, but ≤7.5) were included in the study using simple random techniques after written informed consent from patients. Patients were studied for glycemic excursions over a period of 7 days by using FreeStyle® Libre Pro™, which is a flash glucose monitoring system. The CGM sensor was attached to the left upper arm of the patient on day 0 and removed on day 7. The data recorded in the sensor was then retrieved using pre-installed computer software and analyzed using standard CGM metrics like standard deviation (SD), percentage coefficient of variation (%CV), time above range (TAR), time below range (TBR), and time in range (TIR), out of which %CV was used to quantify GV. %CV has been used to cluster patients into four cohorts from best to worst, namely: best/low CV ≤ 10%, intermediate CV from 10 to 20%, high CV from 20 to 30%, and very high CV of >30%. Scatterplots are used to establish correlations between various parameters. RESULT: Data from a total of 30 patients were analyzed using CGMS and thus used for calculating standard CGM metrics; glucose readings every 15 minutes were recorded consecutively for 7-day periods, making it a total of 672 readings for each patient. Interpreting the CGM data of all 30 patients, the following results were found: the mean blood glucose of all cases is 134.925 ± 22.323 mg/dL, the mean SD of blood glucose of all cases is 35.348 ± 9.388 mg/dL, the mean of %CV of all cases is 26.376 ± 6.193%. CGM parameters of time are used in the form of percentages, and the following results were found: the mean of TAR, TBR, and TIR is 14.425 ± 13.211, 5.771 ± 6.808, and 82.594 ± 12.888%, respectively. Clustering the patients into cohorts, the proportion of patients exhibiting best/low %CV (10%) is 0, intermediate %CV (10-20%) is 16.67% (five out of 30 patients), high %CV (20-30%) is 50% (15 out of 30 patients) and very high %CV (>30%) is 33.33% (10 out of 30 patients). Also, there is no significant correlation found between HbA1c and %CV (ρ = 0.076, p-value = 0.690); a significant negative correlation was found between %CV and TIR (ρ = -0.604, p < 0.001S); a positive correlation of %CV with TAR and TBR is significant (ρ = 0.816, p-value of <0.001). CONCLUSION: Using a flash CGMS device and considering %CV as the parameter and primary measure of GV, the study demonstrated the overall instability of a person's glycemic control, making note of unrecognized events of hypoglycemia and hyperglycemia in asymptomatic well-controlled T2DM patients, revealing the overall volatile glycemic control. The most important finding of this study is that even those diabetics who are considered well-controlled experience a great degree of GV as assessed by CGM-derived metrics. This study also demonstrated that there is no significant correlation between HbA1c and GV, suggesting that patients may not have optimal control of their diabetes despite having "normal HbA1c" values; hence, GV can be considered an HbA1c-independent danger factor, having more harmful effects than sustained hyperglycemia in the growth of diabetic complications. So, by using CGM-derived metrics, the measurement of GV has the potential to complement HbA1c data. In this manner, a more comprehensive assessment of glycemic excursions can be provided for better treatment decisions, thereby facilitating optimal glycemic control, which is essential for reducing overall complications and promoting good quality of life.

Implementation research: a protocol for two three-arm pragmatic randomised controlled trials on continuous glucose monitoring devices in people with type 1 diabetes in South Africa and Kenya.

BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.

[Erratum in "Point-of-Care Blood Glucose Testing: Post-Market Performance Assessment of the Accu-Chek Inform II Hospital-Use Glucose Meter" (DOI: 10.26442/00403660.2023.12.202522)].

In the article "Point-of-care blood glucose testing: post-market performance assessment of the Accu-Chek Inform II hospital-use glucose meter," published in the Terapevticheskii Arkhiv journal, Vol. 95, No.12, 2023 (DOI: 10.26442/00403660.2023.12.202522), errors were made: the term "measurements at the place of treatment" was changed, as well as the section "Conflict of interest." At the request of the authors' team, errors in the conflict of interest and the wording of the term have been corrected, and the section "Information about the authors" has been updated. The publisher replaced the original version of the published article with the corrected one; the information on the website was also corrected. Correct text of the section "Conflict of interest": Conflict of interest. All authors are not employees or consultants of Roche Diagnostics and have not received any compensation from Roche Diagnostics. Correct wording of the term in Russian: "измерения по месту лечения". Changes were made to the title of the article in Russian: "Измерения глюкозы по месту лечения: пострегистрационное испытание госпитального глюкометра Акку-Чек Информ II", the text of the abstract, keywords, citation, in the text of the article, and abbreviations. Information of the place of work has been updated: Center for Laboratory Diagnostics of the Russian Children Clinical Hospital, a Branch of the Pirogov Russian National Research Medical University. The publisher apologizes to readers and authors for the errors and is confident that the correction of errors will ensure the correct perception and interpretation of the results of the study described in the text.

An integrated wearable differential microneedle array for continuous glucose monitoring in interstitial fluids.

Monitoring biomarkers in human interstitial fluids (ISF) using microneedle sensors has been extensively studied. However, most of the previous studies were limited to simple in vitro demonstrations and lacked system integration and analytical performance. Here we report a miniaturized, high-precision, fully integrated wearable electrochemical microneedle sensing device that works with a customized smartphone application to wirelessly and in real-time monitor glucose in human ISF. A microneedle array fabrication method is proposed which enables multiple individually addressable, regionally separated sensing electrodes on a single microneedle system. As a demonstration, a glucose sensor and a differential sensor are integrated in a single sensing patch. The differential sensing electrodes can eliminate common-mode interference signals, thus significantly improving the detection accuracy. The basic mechanism of microneedle penetration into the skin was analyzed using the finite element method (FEM). By optimizing the structure of the microneedle, the puncture efficiency was improved while the puncture force was reduced. The electrochemical properties, biocompatibility, and system stability of the microneedle sensing device were characterized before human application. The test results were closely correlated with the gold standard (blood). The platform can be used not only for glucose detection, but also for various ISF biomarkers, and it expands the potential of microneedle technology in wearable sensing.

Practical considerations for continuous glucose monitoring in elite athletes with type 1 diabetes mellitus: A narrative review.

Type 1 diabetes mellitus (T1DM) refers to a metabolic condition where a lack of insulin impairs the usual homeostatic mechanisms to control blood glucose levels. Historically, participation in competitive sport has posed a challenge for those with T1DM, where the dynamic changes in blood glucose during exercise can result in dangerously high (hyperglycaemia) or low blood glucoses (hypoglycaemia) levels. Over the last decade, research and technological development has enhanced the methods of monitoring and managing blood glucose levels, thus reducing the chances of experiencing hyper- or hypoglycaemia during exercise. The introduction of continuous glucose monitoring (CGM) systems means that glucose can be monitored conveniently, without the need for frequent fingerpick glucose checks. CGM devices include a fine sensor inserted under the skin, measuring levels of glucose in the interstitial fluid. Readings can be synchronized to a reader or mobile phone app as often as every 1-5 min. Use of CGM devices is associated with lower HbA1c and a reduction in hypoglycaemic events, promoting overall health and athletic performance. However, there are limitations to CGM, which must be considered when being used by an athlete with T1DM. These limitations can be addressed by individualized education plans, using protective equipment to prevent sensor dislodgement, as well as further research aiming to: (i) account for disparities between CGM and true blood glucose levels during vigorous exercise; (ii) investigate the effects of temperature and altitude on CGM accuracy, and (iii) explore of the sociological impact of CGM use amongst sportspeople without diabetes on those with T1DM.

Feasibility and Performance of Continuous Glucose Monitoring to Guide Computerized Insulin Infusion Therapy in Cardiovascular Intensive Care Unit.

BACKGROUND: We evaluated the feasibility of real-time continuous glucose monitoring (CGM) for titrating continuous intravenous insulin infusion (CII) to manage hyperglycemia in postoperative individuals in the cardiovascular intensive care unit and assessed their accuracy, nursing acceptance, and postoperative individual satisfaction. METHODS: Dexcom G6 CGM devices were applied to 59 postsurgical patients with hyperglycemia receiving CII. A hybrid approach combining CGM with periodic point-of-care blood glucose (POC-BG) tests with two phases (initial-ongoing) of validation was used to determine CGM accuracy. Mean and median absolute relative differences and Clarke Error Grid were plotted to evaluate the CGM accuracy. Surveys of nurses and patients on the use of CGMs experience were conducted and results were analyzed. RESULTS: In this cohort (mean age 64, 32% female, 32% with diabetes) with 864 paired POC-BG and CGM values analyzed, mean and median absolute relative difference between POC-BG and CGM values were 13.2% and 9.8%, respectively. 99.7% of paired CGM and POC-BG were in Zones A and B of the Clarke Error Grid. Responses from nurses reported CGMs being very or quite convenient (n = 28; 93%) and it was favored over POC-BG testing (n = 28; 93%). Majority of patients (n = 42; 93%) reported their care process using CGM as being good or very good. CONCLUSION: This pilot study demonstrates the feasibility, accuracy, and nursing convenience of adopting CGM via a hybrid approach for insulin titration in postoperative settings. These findings provide robust rationale for larger confirmatory studies to evaluate the benefit of CGM in postoperative care to improve workflow, enhance health outcomes, and cost-effectiveness.

Association Between Treatment Adherence and Continuous Glucose Monitoring Outcomes in People With Diabetes Using Smart Insulin Pens in a Real-World Setting.

OBJECTIVE: To evaluate the association of insulin injection adherence, smart insulin pen engagement, and glycemic control using real-world data from 16 countries from adults self-administering basal insulin degludec and bolus insulin with a smart insulin pen (NovoPen 6 or NovoPen Echo Plus) alongside continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS: Data were aggregated over 14-day periods. Treatment adherence was defined according to the number of missed basal and missed bolus insulin doses and smart pen engagement according to the number of days with data uploads. RESULTS: Data from 3,945 adults, including 25,157 14-day periods with ≥70% CGM coverage, were analyzed. On average, 0.2 basal and 6.0 bolus insulin doses were missed over 14 days. The estimated probability of missing at least one basal insulin dose over a 14-day period was 17.6% (95% CI 16.5, 18.7). Missing one basal or bolus insulin dose per 14 days was associated with a significant decrease in percentage of time with glucose levels in range (TIR) (3.9-10.0 mmol/L), of -2.8% (95% CI -3.7, -1.8) and -1.7% (-1.8, -1.6), respectively; therefore, missing two basal or four bolus doses would decrease TIR by >5%. Smart pen engagement was associated positively with glycemic outcomes. CONCLUSIONS: This combined analysis of real-world smart pen and CGM data showed that missing two basal or four bolus insulin doses over a 14-day period would be associated with a clinically relevant decrease in TIR. Smart insulin pens provide valuable insights into treatment injection behaviors.

Development of sensor system and data analytic framework for non-invasive blood glucose prediction.

Periodic quantification of blood glucose levels is performed using painful, invasive methods. The proposed work presents the development of a noninvasive glucose-monitoring device with two sensors, i.e., finger and wrist bands. The sensor system was designed with a near-infrared (NIR) wavelength of 940 nm emitter and a 900-1700 nm detector. This study included 101 diabetic and non-diabetic volunteers. The obtained dataset was subjected to pre-processing, exploratory data analysis (EDA), data visualization, and integration methods. Ambiguities such as the effects of skin color, ambient light, and finger pressure on the sensor were overcome in the proposed 'niGLUC-2.0v'. niGLUC-2.0v was validated with performance metrics where accuracy of 99.02%, mean absolute error (MAE) of 0.15, mean square error (MSE) of 0.22 for finger, and accuracy of 99.96%, MAE of 0.06, MSE of 0.006 for wrist prototype with ridge regression (RR) were achieved. Bland-Altman analysis was performed, where 98% of the data points were within ± 1.96 standard deviation (SD), 100% were under zone A of the Clarke Error Grid (CEG), and statistical analysis showed p < 0.05 on evaluated accuracy. Thus, niGLUC-2.0v is suitable in the medical and personal care fields for continuous real-time blood glucose monitoring.

A self-powered and supercapacitive microneedle continuous glucose monitoring system with a wide range of glucose detection capabilities.

Continuous detection of sudden changes in blood glucose is essential for individuals with diabetes who have difficulty in maintaining optimal control of their blood glucose levels. Hypoglycemic shock or a hyperglycemic crisis are likely to occurs in patients with diabetes and poses a significant threat to their lives. Currently, commercial continuous glucose monitoring (CGM) has limits in the glucose concentration detection range, which is 40-500 mg/dL, making it difficult to prevent the risk of hyperglycemic shock. In addition, current CGMs are invasive, cause pain and irritation during usage, and expensive. In this research, we overcome these limitations by introducing a novel mechanism to detect glucose concentration using supercapacitors. The developed CGM, which is self-powered and minimally invasive due to the use of microneedles, can detect a wider range of glucose concentrations than commercial sensors. In addition, efficacy and stability were proven through in vitro and in vivo experiments. Thus, this self-powered, microneedle and supercapacitive-type CGM can potentially prevent both hypoglycemic and complications of hyperglycemia without pain and with less power consumption than current commercial sensors.

Changes in glucometric parameters in people living with diabetes users of the free-style libre 2 system before and after the update possibility to real-time glucose readings in real world practice.

In Spain, from October 10th, 2023, the FreeStyle Libre 2 system offers the possibility to automatically changed from isCGM to rtCGM with a system update. Our study aimed to evaluate the glucometric before and after that date. We didn't find significant changes in TIR, however time of use increased and TBR decreased.

Research progress on the association between glycemic variability index derived from CGM and cardiovascular disease complications.

Currently, glycated hemoglobin A1c (HbA1c) has been widely used to assess the glycemic control of patients with diabetes. However, HbA1c has certain limitations in describing both short-term and long-term glycemic control. To more accurately evaluate the glycemic control of diabetes patients, the continuous glucose monitoring (CGM) technology has emerged. CGM technology can provide robust data on short-term glycemic control and introduce new monitoring parameters such as time in range, time above range, and time below range as indicators of glycemic fluctuation. These indicators are used to describe the changes in glycemic control after interventions in clinical research or treatment modifications in diabetes patient care. Recent studies both domestically and internationally have shown that these indicators are not only associated with microvascular complications of diabetes mellitus but also closely related to cardiovascular disease complications and prognosis. Therefore, this article aims to comprehensively review the association between CGM-based glycemic parameters and cardiovascular disease complications by analyzing a large number of domestic and international literature. The purpose is to provide scientific evidence and guidance for the standardized application of these indicators in clinical practice, in order to better evaluate the glycemic control of diabetes patients and prevent the occurrence of cardiovascular disease complications. This research will contribute to improving the quality of life for diabetes patients and provide important references for clinical decision-making.

Comparing Clinical Accuracy and Analytical Accuracy Between Continuous Glucose Monitors.

This study compares performance between two continuous glucose monitors (CGMs). The study design contains a mix of laboratory results (CGM vs YSI) and home results (CGM vs glucose meter). Analysis is provided for both clinical accuracy and analytical accuracy of CGM glucose measurements. Both types of accuracy are important. Error grid analysis informs about clinical accuracy. Analytical error is important as most users would prefer a CGM with a smaller spread of CGM versus reference differences. The authors provide the percentage of time that no result was obtained. Study design, data analysis, and editorial support were provided by a manufacturer of one of the products studied. This study provides a template for comparisons.