Hala Hisham Mosli et al, 2021;5(4):1020–1028. International Journal of Medicine in Developing Countries https://doi.org/10.24911/IJMDC.51-1611360395

ORIGINAL ARTICLE Performance evaluation of egm1000™ non-invasive device in patients with type 2 and subjects with prediabetes Hala Hisham Mosli1* , Badr Mohammed Madani2

ABSTRACT Background: egm1000™ is a Conformité Européene-mark approved non-invasive glucose monitoring device intended for home use and in-door environment. The purpose of this post marketing clinical study is to demon- strate the performance of egm1000™ in measuring glucose levels in patients with and predi- abetic patients, when operated according to the manufacturer’s instructions for use, and by comparison to glucose levels using Accu-Chek® Performa. Methods: This is a combined, open label, prospective, comparative, single-center trial. The study was con- ducted at the Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, . One hundred and eighty-eight paired measurements from 36 type 2 diabetes patients and 11 prediabetic ones were performed and evaluated by Consensus Error Grid Analysis. The study duration was 2 months, and was conducted between July 2018 and August 2018. Results: Results showed that 100% of all egm1000™data points were within the clinically acceptable zones A and B. Furthermore, 100% of the performance evaluation participants’ data points were within the clinically acceptable zones of the Consensus Error Grid (A + B: 94.7% + 5.3%), respectively. Mean absolute relative dif- ference of the egm1000™ devices was found to be 13.8%. Conclusion: We conclude that our real-world study showed an overall accuracy, which is comparable to previ- ously published results from more standardized regulatory experiments. Keywords: Diabetes mellitus, , egm1000™, home monitoring.

Introduction

Diabetes is a long-term metabolic pathological condition device parts, such as strips, or inadequate blood sampling in which blood glucose level fluctuates above the normal operation causing clots, bubbles or inadequate amount of range and can lead to severe complications by affecting all blood [11-14]. vital organs. Therefore, self-monitoring of blood glucose Non-invasive glucose monitoring devices for home (SMBG) has an integral role in , to use aim to overcome the barriers of current invasive help achieve and maintain glycemic control and reduce glucose monitoring methods by offering a simple, diabetes-related complications [1,2] and their associated painless and convenient mean to measure glucose levels. costs [3]. Despite the clinical benefits of glucose self- monitoring, patient compliance is relatively limited for many reasons [4,5]. The low adherence may result from the discomfort associated with skin lancing and the Correspondence to: Hala H. Mosli relative complexity of test procedures [6-8]. *Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. Besides low adherence, the accuracy of the results given Email: [email protected] by a glucose meter depends on many factors, and among Full list of author information is available at the end of them the user’s skill (how well you perform the test) [9,10]. the article. It is reported that up to 97% of errors in blood glucose Received: 23 January 2021 | Accepted: 17 March 2021 measurements are related to the user’s mishandling of the

© IJMDC. https://www.ijmdc.com 1020 Performance evaluation of egm1000™ in patients with diabetes

Additionally, the innovative trend in glucose meters field focuses on reducing the user’s interaction in order to prevent the related errors. Evia Medical Technologies Limited has developed egm1000™, a non-invasive glucose monitoring device intended for people with type 2 diabetes or prediabetes for home and home-alike environments use [15]. In this non-invasive device glucose levels are measured from the earlobe using ultrasound (acoustic impedance of the tissue), electromagnetic (tissue electrical impedance), and thermal (heat transfer of the tissue) technologies. Thanks to the absence of both pain and incremental costs, egm1000™ aims to promote intensive structured SMBG, thereby improving glycemic Figure 1. egm1000™ non-invasive glucose monitoring device. control and the quality of life of over 400 million people (A) egm1000™. The device includes a MU and three different worldwide [16-18]. sensor pairs, one per each of the three technologies, all The purpose of this post-marketing clinical study is to located at the tip of an ear clip (EC). (B) Illustration of glucose demonstrate the safety and performance of egm1000™ measurement performance using egm1000™. The EC is clipped in measuring glucose levels in type 2 diabetic and to the earlobe for spot measurement. prediabetes patients in Saudi Arabia, when operated according to its instructions for use. This clinical study is conducted pursuant to previous clinical trials that were Device technology—principle of operation successfully performed in . The following study aims were explored: egm1000™ principle of operation is based on measuring • To demonstrate the accuracy of egm1000™ in physiological phenomena, which are correlated with monitoring glucose levels using the proportion glucose levels. The translation of the measured signals of egm1000™ measurements that fall within ± into glucose reading is achieved by individual calibration, 15 mg/dl of the reference values measured using which further minimizes the impact of the inter-individual the Accu-Check Performa device at glucose tissue variances, such as in thickness and structure, yet concentrations <100 mg/dl and within ±15% of the quasi-stable in the adult population. egm1000™ utilizes reference measurements at glucose concentrations three independent technologies, which work sequentially ≥100 mg/dl. to avoid mutual interference. • To demonstrate the device clinical performance egm1000™ combines the following technologies: and accuracy in monitoring glucose levels using • An ultrasound technology, which measures phase type 2 Consensus Error Grid Analysis: 99% of all shift as a function of signal propagation within the readings should fall within A and B zones of the tissue; Error Grid. • An electromagnetic technology, which measures • To assess users’ satisfaction regarding the device. the conductivity of the tissue; the earlobe is • To explore the eventual adverse effects, such as positioned between two electrodes which are skin reactions, skin irritation, or discomfort. connected to an electrical oscillating circuit; Materials • A thermal technology, which measures the heat capacity of the tissue. egm 1000™ The three independent readings are combined together by Brief presentation of the device a proprietary algorithm, which calculates their weighted average. From the user’s view, the measurement is carried In 2016, Evia Medical Technologies Limited received a out in one-step, and the end-result (reading) is displayed Conformité Européene mark approval for egm1000™, a on a large color screen and concomitantly announced non-invasive glucose monitoring device for individuals, verbally. Extreme values, pre-determined by the user, to be used at home and in-door environment. The device evoke visual and audible alerts. is battery operated and includes two subunits: (1) Main Device intended use Unit (MU) containing a color display and control touch- screen, a transmitter, a receiver and a processor and (2) egm1000™ is a non-invasive intermittent glucose an Ear Clip (EC) containing sensors and calibration monitoring device intended for home-use among adults electronics, that is attached (externally clipped) to the (aged 18 years and older) with type 2 diabetes or pre- earlobe. Figure 1 shows the device and illustrates how a diabetes. This age limitation is in relation with the ear measurement is performed. clip dimension being inappropriate with children’s

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earlobe. Additionally, medication intake and/or treatment of Medicine, Faculty of Medicine, King Abdulaziz decisions should not be based solely on egm1000™ University; P.O. Box 80215, Jeddah 21589, Saudi Arabia. measurements. egm1000™ is a glucose monitoring Population device and should not be used for diagnosis purposes. This trial included adult (age>18 years) individuals with Other device features type 2 diabetes and prediabetes, who were recruited and enrolled among patients following at the study center Extreme values, pre-determined by the user, evoke (convenience sampling). Other inclusion criteria applied visual, and audible alerts. for subjects who are able to complete and sign the informed consent form; as well as those who fulfil the The device does not require sterilization and does not following earlobe anatomical features: lobular diameter have any disposable components besides the EC, which 14-25 mm and earlobe thickness 3-6 mm. Exclusion should be replaced every 6 months. The EC lifetime is 6 criteria applied as follows: individuals on dialysis; those months from first use. diagnosed with human immunodeficiency viruses or viral Device specifications hepatitis infection; those with any condition that may interfere with good contact between the device ear clip and the earlobe, such as raised birthmarks and multiple Feature Specifications piercings; pregnant women; and patients with prior Operation modes Spot history of unawareness. Furthermore, Up to 3 users. Users patients with factors that may interfere with Accu-Chek EC for each user Performa measurement were excluded; these include Range 70-500 mg/dl (3.9-27.8 mmol/l) drugs such as anticoagulants, acetaminophen, ascorbate, Color-Touch Screen. mannitol, and dopamine [14]. Time, Date, Glucose Level (mg/dl or mmol/Liter - by User choice), Glucose Study procedure High/Low/Normal indication (preset Display by user), Battery Level, Low Battery After signing the informed consent, participants were indication, Replacement of EC Unit request, Re-Calibration request, User invited to attend the center 1 day prior to the trial day name, Memory use status for calibration, egm1000™ device was individually Turn On/Off Push button, “Home” Push calibrated with each participant in accordance with Controls button, Touch Screen control the manufacturer’s instructions, then participants were instructed to observe an 8-12 hours fasting prior to the Up to 1,000 last readings per user Memory (including level, date, time) scheduled trail date. On the trail day, fasting glucose measurement was carried out using egm1000™ device. USB for data downloading and charg- Interface ing Simultaneously, capillary blood glucose level was measured for the participants by Accu-Chek Performa Battery Li-Ion rechargeable glucose meter, the compared instrument, in accordance Working temp. +15ºC-+35ºC with the manufacturer’s instruction. Both results were Storage temp. −5ºC to +55ºC reported in a nominative patient report format. Afterward, Transportation patients benefitted of a standard meal consisting ofa −30ºC to +70ºC temperature single large croissant with cheese and olives and a bottle Relative Up to 95% of water. Postprandial measurements were performed at Adjusting/Pointing Tool, USB Cable, 30, 60, 90, 120, and 150 minutes after the standardized Accessories Charger, Case, Self-Test Aid meal, applying the same paired reading method. All measurements and calibration-related actions were Accu-Check performa performed by the investigators. Dropouts Accu-Chek Performa device (Roche Diagnostics) is a widely used home glucose monitoring device here in On the day of the trial, participants were informed of Saudi Arabia. The device complies with ISO 15197: the study procedure and advised regarding their freedom 2013, which justifies its use as a real-world comparison to withdraw from the study at any stage without any instrument in this study. consequence on their care at the center. Two participants Methods did not complete the trial, because their overnight fasting period was exceeding the protocol terms of 8-12 hours. Design and setting Study outcomes This was a combined, open label, prospective, Performance measures comparative, single-center trial. The present report was prepared to summarize the results obtained during egm1000™’s clinical accuracy was evaluated by this study. The study was conducted at the Department Consensus Error Grid Analysis (described in Appendix

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A) of data points measured during the standardized In addition, AA was analyzed as the cumulative meal experiment. Performance was further assessed percentage of egm1000™ readings within 5%, 10%, by analyzing the mean and median absolute relative 15%, 20%, 30%, 40%, and above 40% deviation from differences (ARD) between egm1000™ readings and capillary blood glucose readings; this analysis was done paired capillary blood glucose readings, which were separately for readings ≥100 mg/dl and <100 mg/dl to computed using the following formulae: explore whether the accuracy of egm1000™ reading is impacted by the glucose level. Mean ARD (MARD) =

n Results 100 −×100 ∑ n=1( egmAccu Chek /Accu Chek [%]) N Participants’ characteristics egmA100 − ccu Chek Median ARD (Res n) = ×100 [%] Raw participants’ characteristics are provided in Appendix Accu Chek B. The study included 47 patients, 43 were males, mean (SD) age = 42.79 (11.16) years; of the total, 11 were Where Resn is the reading result, corresponding to prediabetes and 36 were type 2 diabetes diagnosed 1-15 different measurements in the same patients (Res1, Res2, years ago (Table 1). One hundred eighty-eight paired Res3… Resn). measurements of glucose level were obtained. Adequate performance of egm1000™ was assumed by an accuracy level that leads to clinical treatment decisions Safety assessment that are similar to those of the compared instrument in this study. No immediate adverse event, which is related to egm1000™, was observed among participants; and no Accuracy assessment injury or complication such as skin irritation, burning or discomfort were reported later. The accuracy assessment was carried out for further performance evaluation of the device. During this Performance measures evaluation, egm1000™ readings were classified into six cumulative categories (± 5%, ± 10%, ± 15%, ± 20%, ± Consensus error grid analysis 30%, + 40%) and one out-of-range category (beyond ± 40%), corresponding to the deviation of the egm1000™ Table 2 and Figure 2 summarize the Consensus Error readings from their respective pairs from the reference Grid statistics of egm1000™ performance by reference method. Subsequently, the percentage of egm1000™ to the Accu-Chek Performa for the 188 paired readings. readings that fallen within each deviation range was All 188 fasting and postprandial readings fell in the calculated. Consensus EG zone A or B, and 94.7% of these were in zone A, indicating high performance of the device and Regulatory approvals low error rate. These results demonstrate that the use of egm1000™ readings in clinical decision would lead The study protocol was submitted to and approved by the to an appropriate treatment, without raising any safety local institutional review board as well as other authorities concern. as required. Additionally, the study was conducted in accordance with all applicable local regulations and Absolute relative differences (ARD) standards. Table 3 depicts the mean and median ARD of the total During the clinical study, data of egm1000™ readings 188 egm1000™ readings, by reference to Accu-chek were collected and processed in a manner not to interfere with or compromise the standard care and clinical management of the participants. Given the study procedure and material, the estimated risk related to this Table 1. Summary of participants’ characteristics. study is very low. Parameter Category Frequency Percentage Statistical analysis Gender Male 43 91.0 Female 4 9.0 Prior the clinical evaluation, all devices were preloaded by Evia Company with most recent software version Age Mean, SD 42.79 11.16 -5.10.1. Weight Mean, SD 86.38 17.67 Clinical accuracy was determined using Consensus Error Status Prediabetes 11 23.4 Grid Analysis (as described in Appendix A). Statistical Diabetes 36 76.6 Duration mean, accuracy was demonstrated by the mean and median 3.83 1.15 (Res) ARD, with lower values demonstrating lesser range (years) difference between egm1000 and Accu-Chek readings, Reference Range (minimal, 80 283 thus indicating higher statistical accuracy. readings maximal), mg/dl

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Table 2. Consensus error grid analysis of 94 egm1000™ Table 4. Cumulative percentage of egm1000™ readings within readings by reference to 94 paired Accu-Chek Performa paired 5%, 10%, 15%, 20%, 30% and 40% deviation of capillary blood measurements. glucose readings.

Reference method Accu-Chek Performa readings Deviation from Cumulative percentage of readings reference Consensus EG zone n % within the range method (range) A 178 94.7% Readings ≥100 mg/ Readings <100 mg/ B 10 5.3% dl (n = 168) dl (n = 20) A+B 188 100% ± 5% 20.2 40.0 C 0 0 ± 10% 41.7 55.0 D 0 0 ± 15% 61.3 70.0 E 0 0 ± 20% 81.0 80.0 Total 188 100% ± 30% 92.9 85.0 ± 40% 97.0 90.0 Beyond ± 40% 3.0 10.0

poor glycemic control. While some studies [7] have shown that SMBG did not improve overall glycemic control, other evidence demonstrated significant benefits in improving glycemic control [8-13]. This study is an extension to the previous studies highlighting the importance of SMBG, and compares a real-world, invasive technique to a non-invasive egm1000™ system. The findings of this study demonstrate the safety, effectiveness and the reliability of the egm1000™ device as a glucose monitoring device, compared with one of the most commonly used glucose meters locally. The user-friendly nature along with the non-invasive mode of action of egm1000™ constitute a favorable option for the participants in this study. Another highlight of this study is the absence of any Figure 2. Consensus error grid of the Accu-Chek-calibrated notable complications while using the device, which is egm1000™. another added advantage to the egm1000™. egm1000™ results showed that 100% of the performance Table 3. ARD between egm1000™ and Accu-Chek readings. evaluation participants’ data points are within the Reference method MARD (%) Median ARD (%) clinically accepted zones of the Consensus Error Grid A + B zones (94.7% + 5.3%, respectively), when compared Accu-Chek Performa 13.8 11.4 to the Accu-Chek Performa. MARD of the egm1000™ devices was found to be 13.8%. These findings show an overall accuracy of egm1000™ that is comparable to that observed in more standardized regulatory experiments, Performa readings. These showed low mean and median notably those performed in Germany, which showed ARD. 100% of the cases in Consensus A + B zones (85.2% + 14.8%, respectively) and MARD of 18.1%, by reference Accuracy assessment analysis to YSI Stat 2,300 plus instrument [15]. Consequently, the use of Accu-Chek Performa as the comparison method, Cumulative percentage of egm1000™ readings within in the present study, may be questioned given the error 5%, 10%, 15%, 20%, 30%, and 40% deviation of levels reported in such glucometer devices, which may capillary blood glucose readings are presented in Table 4; limit their usage for clinical decisions [16]. reading ≥100 mg/dl and those <100 mg/dl are presented in separate columns. By comparison, two other noninvasive devices that measure blood glucose in the fingertip and earlobe were Discussion assessed by reference to YSI Stat 2300 plus. The first device (fingertip) was studied among a population of 36 One of the major dilemmas facing primary care physicians patients, including 14 healthy individuals and 6 type 1 and endocrinologists with their diabetic patients is the and 16 type 2 diabetes patients, and showed that 100% of

1024 Performance evaluation of egm1000™ in patients with diabetes

results within consensus error grid zone A (96.6%) or B Funding (3.4%) along with a MARD of 14.4% [17]. The second Evia medical technology limited is a UK based company that device (earlobe) was studied among a population of 27 develops, manufactures and distributes medical devices for individuals with type 2 diabetes (n = 20) or prediabetes (n the field of diabetes care, the limited funding for this study = 7), and showed 100% of measurements within clinically was mainly directed towards providing the tools of Blood accepted zone; however, only 62.4% fell in zone A versus sugar measurements " accu chek test strips, providing snacks 37.6% in zone B, and MARD was 19.7% [18]. for the participants" , neither the author nor the co-author has claimed any incentives from the funder. Financially, although costing about 2,300 USD, compared to Accu-Chek Performa strips box that Consent to participate costs approximately 17–26 USD, egm1000™ cost- All proprietary information, including Evia Medical effectiveness is demonstrated over the long-term use by Technologies Limited operations, patent application, considering the number of strips boxes needed, e.g., over formulas, manufacturing processes, basic scientific data a 5-year period, versus one-time purchase and no strips and formulation information provided to the investigator or needed for egm1000™. Additionally, egm1000™ can be the methodologies used in this study, as well as proprietary shared by up to three users with personalized profile for information obtained during the course of the study are each user, which further enables up to 3-fold cost saving confidential and should remain the sole property of Evia in a household comprising many diabetic patients. Medical Technologies Limited. The Principal Investigator The ease of use of the device, combined to its accuracy agrees not to disclose any proprietary information supplied that is comparable to commonly used glucometers, makes by Evia Medical Technologies Limited without prior written it a better alternative for patients who require frequent permission. monitoring and do not tolerate finger pricks. Further The data obtained during this study is confidential and studies are warranted to demonstrate the effect of using should not be disclosed to third parties, with the following egm1000™ in improving adherence to and frequency of exceptions: SMBG. • When the data is needed by the subject’s personal Another potential benefit of the non-invasive nature of physician or other medical personnel responsible the device is the reduction of the risk of contamination for the subject’s health. and infection, notably in clinics, schools, and , by bypassing the intrusion of epidermal barrier and • For data inspection and verification by Evia exposure to contaminated blood. Medical Technologies Limited or designated personnel, regulatory authority auditors or by the The main limitation of this study is the use of a non- IRB or ethics committee. standard instrument as the reference method to calculate egm1000™ accuracy; however, this use is might be Any manuscript or abstract produced by the investigator defended by the highly frequent use of Accu-Chek must be provided to Evia Medical Technologies Limited Performa in the study setting, thereby providing a for review 30 days prior to submission. Individual subject real-world comparison. Other limitation includes the identity should not be divulged in any publication. relatively small sample size along with being a single- Ethical approval center trial. Ethical approval was granted by Ethics Committee via Conclusion reference number Ref 416-18 dated: 05/06/2018. Informed consent This trial demonstrated adequate performance of All participants have signed an informed consent. egm1000™ device in SMBG and correlated well with finger prick method using Accu-Chek Performa. Data availability However, more studies are needed to evaluate the Study records including subject source documents, case egm1000™ device with a more standardized method of report forms, all test results and signed informed consent blood glucose monitoring. In this real-world study, results forms must be archived by the investigator for at least 15 were comparable to previous published results from years. All IRB correspondence including notification of more standardized regulatory experiments. Additionally, protocol and consent form approval and all annual reports egm1000™ is well tolerated and provides a safe use with along with the final report to the IRB/Ethics Committee must absence of inconveniences and adverse events. be retained. Other documents pertaining to the conduct of the study including laboratory normal values, laboratory List of Abbreviations certification, monitor logs and telephone reports and all EC Ear clip written correspondence must also be kept as part of the MARD Mean absolute relative differences permanent record. MU Main unite If the PI relocates, retires, or for any reason cannot archive SMBG Self-monitoring of blood glucose the study records, the records may be transferred to Conflict of interest an acceptable designee or submitted to Evia Medical The authors declare that they have no competing interests. Technologies Limited. Evia Medical Technologies Limited

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must be notified in writing of the name and address of the 10. Polonsky WH, Fisher L, Schikman CH, Hinnen DA, Parkin person designated to retain the study records. CG, Jelsovsky Z, et al. Structured self-monitoring of blood glucose significantly reduces A1C levels in poorly Author details controlled, noninsulin-treated type 2 diabetes: results Hala Hisham Mosli1, Badr Mohammed Madani2 from the structured testing program study. Diabetes Care. 1. Department of Medicine, College of Medicine, King 2011;34:262–7. https://doi.org/10.2337/dc10-1732 Abdulaziz University, Jeddah, Saudi Arabia 11. Schwedes U, Siebolds M, Mertes G; SMBG Study Group. 2. Department of Family and Community Medicine, College Meal-related structured self-monitoring of blood glucose: of Medicine, University of Jeddah, Jeddah, Saudi Arabia effect on diabetes control in non--treated type 2 diabetic patients. Diabetes Care. 2002;25:1928–32. References https://doi.org/10.2337/diacare.25.11.1928 1. The DCCT Research Group. The absence of a 12. Ciudin A, Hernandez C, Simo R. Non-invasive methods glycemic threshold for the development of long-term of glucose measurement: current status and future complications: the perspective of the diabetes control perspectives. Curr Diabetes Rev. 2012;8:48–54. https:// and complications trial. Diabetes. 1996;45:1289–98. doi.org/10.2174/157339912798829197 https://doi.org/10.2337/diab.45.10.1289 13. Durán A, Martín P, Runkle I, Pérez N, Abad R, Fernández 2. The DCCT Research Group. The relationship of glycemic M, et al. Benefits of self-monitoring blood glucose in the exposure (HbA1c) to the risk development and management of new-onset Type 2 diabetes mellitus: the progression of retinopathy in the diabetes control and St Carlos Study, a prospective randomized clinic-based complications trial. Diabetes. 1995;44:968–83. https:// interventional study with parallel groups. J Diabetes. doi.org/10.2337/diab.44.8.968 2010;2:203-11. https://doi.org/10.1111/j.1753-0407. 3. Martin S, Schneider B, Heinemann L, Lodwig V, Kurth HJ, 2010.00081.x Kolb H, et al. Self-monitoring of blood glucose in type 2 14. Tonyushkina K, Nichols JH. Glucose meters: a review diabetes and long-term outcome: an epidemiological of technical challenges to obtaining accurate results. cohort study. Diabetologia. 2006;49:271–8. https://doi. J Diabetes Sci Technol. 2009;3(4):971–80. https://doi. org/10.1007/s00125-005-0083-5 org/10.1177/193229680900300446 4. Dorchy H, Roggemans MP. Improvement of the 15. Pfützner A. Evaluation of the non-invasive glucose compliance with blood glucose monitoring in young monitoring device egm1000 in patients with type 2 insulin-dependent diabetes mellitus patients by the diabetes and subjects with prediabetes; data presented Sensorlink system. Diabetes Res Clin Pract. 1997;36:77– (poster presentation). Bethesda, MA: Diabetes 82. https://doi.org/10.1016/S0168-8227(97)00034-X Technology Meeting; 2016. 5. Jones PM, Remley C, Engberg RA. Development and 16. Kermani SK, Khatony A, Jalali R, Rezaei M, Abdi A. Accuracy testing of the barriers to self-monitoring blood glucose and precision of measured blood sugar values by three scale. Diabetes Educ. 1996;22:609–16. https://doi. glucometers compared to the standard technique. J Clin org/10.1177/014572179602200610 Diagn Res. 2017;11(4):OC05. https://doi.org/10.7860/ 6. American Diabetes Association. Standards of medical care JCDR/2017/23926.9613 in diabetes 2016. Diabetes Care. 2016;39(Suppl.1):S1– 17. Pfützner A, Strobl S, Demircik F. Evaluation of a new S112. https://doi.org/10.2337/dc16-S003 noninvasive glucose monitoring device by means 7. O'Kane MJ, Bunting B, Copeland M, Coates VE; ESMON of standardized meal experiments. J Diabetes Sci study group. Efficacy of self monitoring of blood glucose Technol. 2018;12(6):1178–83. https://doi.org/10.1177/ in patients with newly diagnosed type 2 diabetes (ESMON 1932296818758769 study): randomised controlled trial. BMJ. 2008;336:1174– 18. Pfützner A, Sachsenheimer D, Hanna MR, Lier A, Anke 7. https://doi.org/10.1136/bmj.39534.571644.BE H. Evaluation of the non-invasive glucose monitoring 8. Bosi E, Scavini M, Ceriello A, Cucinotta D, Tiengo A, device egm1000 in patients with type 2 diabetes and Marino R, et al. Intensive structured self-monitoring of subjects with prediabetes. J Diabetes Metab Manage. blood glucose and glycemic control in noninsulin-treated 2019. Accessed on Nov 2020. Available from: https:// type 2 diabetes: the PRISMA randomized trial. Diabetes grfpublishers.com/article/view/OTc=/Evaluation-of-the- Care. 2013;36:2887–94. https://doi.org/10.2337/dc13- Non-Invasive-Glucose-Monitoring-Device-egm-1000- 0092 TM-in-Patients-with-Type-2-Diabetes-and-Subjects-with- Prediabetes 9. Karter AJ, Ackerson LM, Darbinian JA, D'Agostino RB Jr, Ferrara A, Liu J, et al. Self-monitoring of blood glucose 19. Parkes JL, Slatin SL, Pardo S, Ginsberg BH. A new levels and glycemic control: the Northern California Kaiser consensus error grid to evaluate the clinical significance permanente diabetes registry. Am J Med. 2001;111:1–9. of inaccuracies in the measurement of blood glucose. https://doi.org/10.1016/S0002-9343(01)00742-2 Diabetes Care. 2000 Aug;23(8):1143-8. doi: 10.2337/ diacare.23.8.1143.

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Appendix A. Consensus error grid analysis. diabetes were included and the corresponding grid version was used for the analysis. The following table and figure The Consensus error grid was suggested by Parkes et describes the properties of the Consensus error grid. al. (2000), who constructed it with the participation of Description of consensus error grid zones a team of 100 physicians, as an alternative to Clarke's grid. The definitions of the risk zones in the Consensus error grid correspond to the definitions of risk zones Zone Description in Consensus Error Grid. The consensus error grid has A No effect on clinical action no discontinuities of risk at the boundaries (i.e., all Altered clinical action or little or no effect on clinical B boundaries separate regions that are adjacent in both outcome proximity on the graph and severity of risk) as further Altered clinical action - likely to affect clinical out- C elucidated by Pfützner et al. (2013). This stands in come contrast with the CEG, which has several boundaries Altered clinical action - could have significant med- D separating nonadjacent categories. ical risk Altered clinical action - could have dangerous con- Parkes et al. (2000) presented two grids, one per each E diabetes type. In this evaluation only patients with type 2 sequences

(A) Consensus error grid for people with , (B) Consensus error grid for people with type 2 diabetes.

Appendix B. Patient characteristics.

Subject # Diabetes Gender Age [year] Weight [kg] DM duration [years] 1 Pre M 36 77 - 2 Pre M 40 110 - 3 Type 2, MDI M 65 95 NA 4 Type 2 F 63 95 NA 5 Type 2 M 45 145 NA 6 Type 2, MDI M 32 67 NA 7 Type 2 M 44 95 NA 8 Pre M 21 68 - 9 Pre M 36 84 - 10 Type 2 M 65 90 NA 11 Pre M 30 71 -

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Subject # Diabetes Gender Age [year] Weight [kg] DM duration [years] 12 Pre M 37 81 - 13 Type 2 F 56 78 NA 14 Type 2 M 35 120 NA 15 Pre M 38 125 - 16 Pre M 36 100 - 17 Type 2 F 47 92 15 18 Type 2 M 19 70 NA 19 Type 2, MDI M 34 82 2 20 Pre M 30 83 1 21 Type 2, MDI M 52 73 1 22 Type 2, MDI M 37 83 5 23 Type 2, MDI M 49 98 15 24 Type 2 M 63 66 NA 25 Type 2, MDI M 52 84 1 26 Type 2 M 37 66 4 27 Type 2 M 42 122 NA 28 Type 2, MDI M 44 81 5 29 Type 2, MDI M 36 71 6 30 Type 2 M 40 80 NA 31 Type 2, MDI M 39 86 2 32 Type 2 M 53 88 2 33 Type 2, MDI M 29 58 3 34 Type 2 M 40 86 1 35 Type 2, MDI M 31 100 1 36 Type 2, MDI M 51 82 1 37 Type 2, MDI M 42 102 4 38 Type 2 M 38 86 1 39 Type 2, MDI M 37 76 1 40 Type 2 M 56 98 1 41 Type 2 M 49 56 12 42 Type 2 M 58 74 1 43 Type 2, MDI M 48 79 3 44 Type 2 M 62 79 NA 45 Type 2 M 33 100 NA 46 Pre M 37 87 - 47 Pre F 47 71 -

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