Comprehensive Review on Wearable Sweat-Glucose Sensors for Continuous Glucose Monitoring

The incidence of diabetes is increasing at an alarming rate, and regular glucose monitoring is critical in order to manage diabetes. Currently, glucose in the body is measured by an invasive method of blood sugar testing. Blood glucose (BG) monitoring devices measure the amount of sugar in a small sample of blood, usually drawn from pricking the fingertip, and placed on a disposable test strip. Therefore, there is a need for non-invasive continuous glucose monitoring, which is possible using a sweat sensor-based approach. As sweat sensors have garnered much interest in recent years, this study attempts to summarize recent developments in non-invasive continuous glucose monitoring using sweat sensors based on different approaches with an emphasis on the devices that can potentially be integrated into a wearable platform. Numerous research entities have been developing wearable sensors for continuous blood glucose monitoring, however, there are no commercially viable, non-invasive glucose monitors on the market at the moment. This review article provides the state-of-the-art in sweat glucose monitoring, particularly keeping in sight the prospect of its commercialization. The challenges relating to sweat collection, sweat sample degradation, person to person sweat amount variation, various detection methods, and their glucose detection sensitivity, and also the commercial viability are thoroughly covered.

Titration of Long-Acting Insulin Using Continuous Glucose Monitoring and Smart Insulin Pens in Type 1 Diabetes: A Model-Based Carbohydrate-Free Approach

ObjectiveMultiple daily injections (MDI) therapy is the most common treatment for type 1 diabetes (T1D), consisting of long-acting insulin to cover fasting conditions and rapid-acting insulin to cover meals. Titration of long-acting insulin is needed to achieve satisfactory glycemia but is challenging due to inter-and intra-individual metabolic variability. In this work, a novel titration algorithm for long-acting insulin leveraging continuous glucose monitoring (CGM) and smart insulin pens (SIP) data is proposed.MethodsThe algorithm is based on a glucoregulatory model that describes insulin and meal effects on blood glucose fluctuations. The model is individualized on patient’s data and used to extract the theoretical glucose curve in fasting conditions; the individualization step does not require any carbohydrate records. A cost function is employed to search for the optimal long-acting insulin dose to achieve the desired glycemic target in the fasting state. The algorithm was tested in two virtual studies performed within a validated T1D simulation platform, deploying different levels of metabolic variability (nominal and variance). The performance of the method was compared to that achieved with two published titration algorithms based on self-measured blood glucose (SMBG) records. The sensitivity of the algorithm to carbohydrate records was also analyzed.ResultsThe proposed method outperformed SMBG-based methods in terms of reduction of exposure to hypoglycemia, especially during the night period (0 am–6 am). In the variance scenario, during the night, an improvement in the time in the target glycemic range (70–180 mg/dL) from 69.0% to 86.4% and a decrease in the time in hypoglycemia (<70 mg/dL) from 10.7% to 2.6% was observed. Robustness analysis showed that the method performance is non-sensitive to carbohydrate records.ConclusionThe use of CGM and SIP in people with T1D using MDI therapy has the potential to inform smart insulin titration algorithms that improve glycemic control. Clinical studies in real-world settings are warranted to further test the proposed titration algorithm.SignificanceThis algorithm is a step towards a decision support system that improves glycemic control and potentially the quality of life, in a population of individuals with T1D who cannot benefit from the artificial pancreas system.

Continuous Glucose Monitoring Initiation Within First Year of Type 1 Diabetes Diagnosis Is Associated With Improved Glycemic Outcomes: 7-Year Follow-Up Study

OBJECTIVE To evaluate long-term glycemic outcomes of continuous glucose monitoring (CGM) initiation within the first year of type 1 diabetes diagnosis. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (N = 396) were divided into three groups: 1) CGM (CGM use within 1 year of diabetes diagnosis and continued through the study); 2) no-CGM (no CGM use throughout the study); and 3) new-CGM (CGM use after 3 years since diabetes diagnosis). Patients were followed up to 7 years. RESULTS A1c was significantly lower in the CGM compared with the no-CGM group throughout 7 years of follow-up (least squares mean A1c values: 6 months, 7.3% vs. 8.1%; 1 year, 7.4% vs. 8.6%; 2 years, 7.7% vs. 9.1%; 3 years, 7.6% vs. 9.3%; 4 years, 7.4% vs. 9.6%; 5 years, 7.6% vs. 9.7%; 6 years, 7.5% vs. 10.0%; and 7 years, 7.6% vs. 9.8%; for all, P < 0.001) adjusting for age at diagnosis, sex, and insulin delivery method. CONCLUSION CGM initiation within first year of type 1 diabetes diagnosis results in long-term improvement in A1c.

In Vitro Evaluation of Miniaturized Amperometric Enzyme Sensor Based on the Direct Electron Transfer Principle for Continuous Glucose Monitoring

Background: The bacterial derived flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenase (FADGDH) is the most promising enzyme for the third-generation principle-based enzyme sensor for continuous glucose monitoring (CGM). Due to the ability of the enzyme to transfer electrons directly to the electrode, recognized as direct electron transfer (DET)-type FADGDH, although no investigation has been reported about DET-type FADGDH employed on a miniaturized integrated electrode. Methods: The miniaturized integrated electrode was formed by sputtering gold (Au) onto a flexible film with 0.1 mm in thickness and divided into 3 parts. After an insulation layer was laminated, 3 openings for a working electrode, a counter electrode and a reference electrode were formed by dry etching. A reagent mix containing 1.2 × 10−4 Unit of DET-type FADGDH and carbon particles was deposited. The long-term stability of sensor was evaluated by continuous operation, and its performance was also evaluated in the presence of acetaminophen and the change in oxygen partial pressure (pO2) level. Results: The amperometric response of the sensor showed a linear response to glucose concentration up to 500 mg/dL without significant change of the response over an 11-day continuous measurement. Moreover, the effect of acetaminophen and pO2 on the response were negligible. Conclusions: These results indicate the superb potential of the DET-type FADGDH-based sensor with the combination of a miniaturized integrated electrode. Thus, the described miniaturized DET-type glucose sensor for CGM will be a promising tool for effective glycemic control. This will be further investigated using an in vivo study.

Optimal Data Collection Period for Continuous Glucose Monitoring to Assess Long-Term Glycemic Control: Revisited

Background and Objective: It is not clear how the short-term continuous glucose monitoring (CGM) sampling time could influence the bias in estimating long-term glycemic control. A large bias could, in the worst case, lead to incorrect classification of patients achieving glycemic targets, nonoptimal treatment, and false conclusions about the effect of new treatments. This study sought to investigate the relation between sampling time and bias in the estimates. Methods: We included a total of 329 type 1 patients (age 14-86 years) with long-term CGM (90 days) data from three studies. The analysis calculated the bias from estimating long-term glycemic control based on short-term sampling. Time in range (TIR), time above range (TAR), time below range (TBR), correlation, and glycemic target classification accuracy were assessed. Results: A sampling time of ten days is associated with a high bias of 10% to 47%, which can be reduced to 4.9% to 26.4% if a sampling time of 30 days is used ( P < .001). Correct classification of patients archiving glycemic targets can also be improved from 81.5% to 91.9 to 90% to 95.2%. Conclusions: Our results suggest that the proposed 10-14 day CGM sampling time may be associated with a high correlation with three-month CGM. However, these estimates are subject to large intersubject bias, which is clinically relevant. Clinicians and researchers should consider using assessments of longer durations of CGM data if possible, especially when assessing time in hypoglycemia or while testing a new treatment.