Diabetes Without Needles: Non-invasive Diagnostics and Health Management

By Artur Rydosz

Diabetes Without Needles: Non-invasive Diagnostics and Health Management provides a comprehensive and objective compilation of the most promising noninvasive methods for glucose monitoring, including an in-depth analysis of their advantages and disadvantages in terms of biochemical processes. The latest advances in the field are discussed, including methods such as optical measurements, electrochemical measurements, exhaled breath analysis, direct measurements of glucose in the blood using noninvasive techniques, and the indirect analysis of biomarkers that are related to the glycemia. The book's author also presents recommendations for future research directions in this field.

This book is a valuable resource for researchers in the areas of diabetes, noninvasive methods and diagnostics development.

• Appeals to a multidisciplinary audience, including scientists, researchers and clinicians with an interest in noninvasive blood glucose monitoring technologies
• Features the latest advances in the field of noninvasive methods for diabetes monitoring, including recent results, perspectives and challenges
• Covers various noninvasive methods, including optical measurements, electrochemical, exhaled breath analysis, and more

• Language: English
• Publisher: Academic Press
• Release date: Jan 19, 2022
• ISBN: 9780323985291

Artur Rydosz

Artur Rydosz received his degrees in electronics engineering from the AGH University of Science and Technology, Krakow, Poland. In 2019 he obtained D.Sc. degree and since 2023 is a full professor at the Institute of Electronics AGH. His current research interests include gas sensors and organ-on-a-chip platforms. He's also interested in the PVD method of the fabrication of various sensing materials with a special emphasis on the detection of volatile organic compounds in exhaled human breath, for example, as a potential tool for the noninvasive measurement of several diseases, such as diabetes; as well as metallic layers for SPR-based sensors for gas-sensing and bio-sensing applications. Prof. Rydosz serves as the Vice-Chair of the Joint Chapter AP03/AES10/MTT17, IEEE Poland Section and is the Head of the Biomarkers Analysis LAB. In 2022, his book entitled Diabetes Without Needles (Elsevier) was published.

Book preview

Diabetes Without Needles

Non-invasive Diagnostics and Health Management

Artur Rydosz

Biomarkers Analysis LAB, Institute of Electronics, AGH University of Science and Technology, Krakow, Poland

President of NGO Foundation ‘Z cukrzyca na Ty’, Lesko, Poland

Table of Contents

Cover image

Title page

Copyright

About the author

Preface

Chapter 1. Introduction

1.1. Background and motivation

1.2. Prevention is better than cure

1.3. Wearable sensors in diabetes

1.4. Novel therapeutic techniques

1.5. Outline of the book

1.6. Conclusions

Chapter 2. Diabetes in general

2.1. Introduction

2.2. The history of diabetes

2.3. The classification of diabetes

2.4. What are the differences between type-1 and type-2?

2.5. The actual management of diabetes

2.6. Complications in diabetes

2.7. Prediabetes—how can it be recognized or detected?

2.8. Future clinical directions

2.9. Conclusions

Chapter 3. The basics of noninvasive methods

3.1. Introduction

3.2. The expectations of noninvasive methods

3.3. The main players of diabetes

3.4. The differences between various methods for noninvasive glucose measurements

3.5. Electrochemical measurements

3.6. Frequency measurements

3.7. Exhaled-biomarker measurements

3.8. Conclusions

Chapter 4. A review of noninvasive methods applied in diabetes management and treatment

4.1. Introduction

4.2. The route from discovery to clinical application

4.3. Recent developments of minimally invasive methods in diabetes

4.4. Recent developments of noninvasive methods in diabetes

4.5. The review of optical methods

4.6. Review of nonoptical methods

4.7. Review of breath biomarker detection

4.8. Review of the multisensing approach

4.9. A novel battery-free biosensors

4.10. Conclusions

Chapter 5. Further perspectives and challenges

5.1. Introduction

5.2. Interpretation of data analysis and results

5.3. Beta cells—the secret players of diabetes

5.4. Telehealth systems for diabetes

5.5. Advanced glucose-sensing technologies for clinical decision-making

5.6. Screening scenarios due to the obesity pandemic

5.7. The artificial pancreas—when will sci-fi become reality?

5.8. The challenges for diabetes management in the post-COVID-19 pandemic

5.9. Conclusions

Chapter 6. Conclusion

6.1. Challenges in diabetes therapy

6.2. Challenges in diabetes monitoring

6.3. Future directions

6.4. Conclusions

Index

Copyright

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Notices

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About the author

Photo credit: Guillermo Orts.

Prof. Artur Rydosz is an young, talented researcher who devoted his research on making diabetes without needles as soon as possible in terms of glucose or other biomarkers monitoring for keeping normoglycemia. He started his research on noninvasive exhaled breath analysis almost twodecades ago. He is working at AGH University of Science and Technology, where he obtained MSc (2009), PhD (2014), and DSc (2019). He was also studying at Technische Universitaet Ilmenau (Germany) and Stanford University (USA). In 2019, he got the professor position at the Institute of Electronics AGH, where he established his own research group—Biomarkers Analysis Lab (www.lab.agh.edu.pl). The group is working on various applications for biomarkers analysis including in-vitro and in-vivo applications. LAB is cooperating with several national and international teams. In 2020, Prof. Rydosz cofounded a start-up spin-off company—Advanced Diagnostic Equipment (www.adediabetics.pl) to commercialize the developed sensing systems. Currently, ADE is working on exhaled ketone analyzer, and clinical trials will be launched in 2022 under the project cofinanced by the National Research and Development Center. Apart from the scientific work, Prof. Rydosz is CEO and cofounder of a nongovernment organization—Foundation Z cukrzyca na Ty (the English translation would be Say hello to your diabetes), where he is serving for diabetes society including diabetic patients and their families. He propagates the knowledge about diabetes and novel technical developments such as closing-loop systems and continuous glucose monitors for better glycaemic monitoring. The Foundation offers also the financial support for those who cannot afford for these novel devices (www.zcukrzycanaty.pl). Prof. Rydosz is also a member of various international societies, and he was granted the START-2015 and START-2016 stupendous from the Foundation for Polish Science, the stupendous from the Ministry of Science and Higher Education for young talented researchers. He was Principal Investigator in several projects focused on novel devices for diabetes, and the obtained results pave the wave for truly noninvasive glycemia monitoring in the near future.

Preface

Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.

Marie Curie-Skłodowska, Nobel Prize Winner in 1903 and 1911.

This book is the result of over 10years of endeavors to understand the complexity of glucose detection via noninvasive methods that could be applied in daily clinical practice. However, the development process of noninvasive methods began 5decades ago and it is still ongoing. In the meantime, the evolution of technology has enabled numerous pioneering achievements. As a result of cooperation between engineers from various disciplines such as electronics, bioengineering, material science, pharmacy, and medicine, changes in diabetes management have emerged and have been implemented in international recommendations for daily clinical routines.

In the case of diabetes, the advent of self-monitored blood glucose devices has been followed by recently released continuous glucose monitors that do not require finger picks. Therefore, the obvious question addresses how far we are from truly noninvasive device for glucose monitoring dedicated for both nondiabetic and diabetic patients. At the same time, insulin pumps are being developed to increase glycemic control and improve the quality of life. The combination of these two technological achievements paves the way for fully closed-loop systems, which require almost no action from the patient. Recently, such systems have started to become available. In addition, routes for the noninvasive administration of insulin are being considered and the results are very promising. Thus, the key question is whether it is possible to manage diabetes in a fully noninvasive way, including both glucose measurement and the administration of insulin or other antidiabetic drugs.

Diabetes Without Needles was conceived to address and recognize the expertise and efforts of countless people of multiple disciplines from all over the world, devoted to improving the lives of people with diabetes. International collaboration using large and varied cohorts with increasingly sophisticated technologies enables a better understanding of the factors contributing to the onset of diabetes, including the common types of diabetes and the newly introduced type-3c. In 2021, we celebrate the 100th anniversary of the discovery of insulin and its clinical use, which was one of the pivotal moments in diabetes treatment. Due to the molecular experiments that have been conducted over recent years, our knowledge of insulin resistance and the regulation of insulin secretion has increased.

You may ask why did I write this book when there as so many research papers and books devoted to diabetes, including noninvasive methods. I would like to share with you the synergy of progress in this field because the progress of the development of noninvasive methods has accelerated over the last 2decades. The number of papers in which noninvasive, diabetes, and glucose detection keywords have been used is over 100,000 and is constantly increasing. However, some papers on noninvasive approaches have been omitted after critical assessment for reasons including a lack of clinical validation and controversial calibration methods. I have tried to avoid repetition wherever possible; however, in some parts of the book, the same information is provided to aid the flow of reading and to reduce the reader's need to continually refer back to previous sections. In addition, if the reader decides to treat each chapter as a self-contained work rather than read them consecutively, all the appropriate information is provided with references to other chapters where required.

It is important to stress that while every effort has been made to make this entire book as up to date as possible, many details and excellent work from other researchers have been omitted. Unfortunately, there is only so much space one can fill, and my apologies go out to those whose work I may have overlooked or details I have not fully described.

Finally, I would like to express my gratitude to my family who have supported me during the demanding challenge that is writing a book. Special thanks go to my wife, Ewelina, my lovely daughters, Zosia and Hania, and my parents, Grażyna and Ryszard, who always believed in me.

Krakow, Poland

Artur Rydosz

Chapter 1: Introduction

Abstract

In this introductory chapter, which sets the scene for this book, the background of diabetes and glucose monitoring is provided. It is important to stress that while every effort has been made to make this entire book as up to date as possible, the reader should bear in mind that progress in all areas of noninvasive measurement is dynamic—including those targeted at diabetes—and that the process of writing and publishing a book is notoriously lengthy. The problem of truly noninvasive systems for diagnosis and monitoring diabetes has become well known over the last fourdecades when similar devices have started to appear on the market. However, to date, regardless of the numerous marketing news as well as published research papers, clinically accepted devices have not yet become commercially available. The general outline of this issue is highlighted, and it will be presented in detail in the following chapters.

Keywords

Diabetes education; Glucose monitors; Noninvasive measurements; The development of glucose monitoring

1.1. Background and motivation

Each scientific epoch regardless of its length has its own pressing problems, for example, dealing with the civilization diseases such as acquired immunodeficiency syndrome (AIDS), hypertension, osteoporosis, cancers, obesity, and diabetes. Moreover, in many countries all over the world, the expectancy of life has been on the increase for many years. According to the data provided by the World Health Organization (WHO), the global average life expectancy was 31 years in 1900, and it is expected to be around 80 years by 2030 [1]. According to the estimations provided by the United Nations, by 2050, one out of every six people in the world will be over 65 years old; the population over 60 years will have almost doubled between 2015 and 2050 [2].

Nowadays, we are bearing witness to the fourth industrial revolution, which results in transition within all industrial branches, including the transition of medicine to medicine 4.0—this is schematically illustrated in Fig. 1.1. The evolution of medicine can be simplified as four stages, where medicine 1.0 is defined by the treatment in the era of germ and virus infections without pharmacological support. The development of antibiotics, vaccines, and other drugs paved the way for medicine 2.0, where hospitals with specialists appeared. The inventions of simple medical devices and physicians' equipment began. In addition, preventative strategies and society education became more enhanced. Then, medicine 3.0 arose with advanced medical devices, mostly thanks to technological development in many fields, with a special emphasis on electronics and bioengineering. Within medicine 3.0, diagnostic methods shifted, and formalized healthcare systems started to become common practice. In terms of diabetes, the progress of glucose-monitoring systems and insulin-dosing administration methods needs to be stressed. Medicine 3.0 represents the diagnostic and management method that we recognize as being the period prior to around 2000–2010 when the transition to medicine 4.0 began. This is a generally a slow process, but we have witnessed a definite acceleration in the last 2–4 years, depending on the specialization [3–5]. Precision medicine, artificial intelligence support, and telemedicine (e-Health, m-Health) systems were introduced into clinical practice. In 2021, the 3D vision, surgical operations conducted with the support of machines and with the utilization of robotics are increasingly common. Emerging technologies in diabetes are continuous glucose monitors and insulin pumps with dedicated algorithms that enable the prevention of hypo- and hyperglycemia. However, for diabetic patients, the most important date is 1921 when insulin was discovered and since that time, deaths directly related to diabetes have greatly reduced as a direct result of the discovery (more information is in Chapter 2). Despite the obvious progress over the last century, the World Health Organization has shown that 1.5 deaths worldwide were directly caused by diabetes in 2019, and more than two million deaths were attributed to high blood glucose [6]. Therefore, the death risks related to diabetes have not been fully eliminated, and due to the high prices of novel devices and drugs, it will probably never happen. Recently, Ioppolo et al. [4] summarized the current challenges that are facing medicine at the end of this period of transition to medicine 4.0 with smart technology, artificial intelligence, and the Internet of things (IoT) sensors constantly detecting a number of signals. It can be said that at some point, the transition to medicine 5.0 will come.

Figure 1.1 Evolution of medicine: the transition from medicine 1.0 to medicine 4.0.

In 2020, the COVID-19 pandemic situation completely redesigned the approach to disease detection, especially chronic diseases. When the medical staff were focused on the fight with SARS-cov-2, ¹ other diseases were forced to take a back seat. Therefore, the development of novel techniques for early detection of these illnesses started to become important as never before. The issue of diabetes treatment in the context of COVID-19 is discussed in Chapter 5.

The motivation for developing a noninvasive method started years before COVID-19, in fact, it began in the early 1970s after a number of breakthrough papers that were published at that time. This started in 1969 when Tassopoulos, Barnett, and Fraser measured the breath acetone of 251 diabetics subjects using the gas chromatography technique [7]. Simultaneously, venous β-hydroxybutyrate and blood-glucose values were analyzed, and the obtained results confirmed that the concentration of breath acetone is correlated with both venous β-hydroxybutyrate and blood glucose [8]. In 1971, Pauling et al. [9] reported that experimental results on volatile organic compounds present in exhaled breath indicated a possible method for the detection of biomarkers of several diseases; this was followed by Jellum et al. in 1973 [9]. The authors concluded "If one were able to identify and determine the concentration of all compounds inside the human body, including high molecular weight as well as low molecular weight substances, one would probably find that almost every known disease would result in characteristic changes of the biochemical composition of the cells and of the body fluids."

In the case of diabetes, 1982 is a pivot moment when John Whitehead, grandson of the founder of the world's largest clinical laboratory instrument company (Technicon Instruments), was visibly excited when he was holding a wristwatch, displaying Blood Glucose=107. "Wouldn't that be great! he babbled, No more trips for diabetics to the doctor to measure blood sugar, no more need to stick a needle in your finger to make measurements at home." The only problem in 1982, as well as in 2022, is that it still does not work to a satisfactory degree. However, the progress in the diagnosis and management of diabetes is tremendous and brings new hope for noninvasive measurements [10].

In the case of diabetes, the possibility to measure glucose in the blood and to conduct primary oral glucose tolerance tests (OGTT) with the utilization of noninvasive methods is also highly anticipated in point-of-care testing (POCT). Mass screening with an OGTT is generally not recommended due to the invasive nature of the measurement, and it does not work well for cohort studies. The currently used scenario includes a questionnaire analysis to select subjects who are at a high risk of diabetes and then conduct the OGTT if needed. To date, numerous risk scores have been developed [11], included age, height, body mass index, waist circumference, and systolic and diastolic blood pressure. In Europe, a well-known risk study is the FINRISK study [12] developed in 1992, in which the risk assessment form has eight questions: (1) age; (2) body mass index; (3) waist circumference measured below the ribs; (4) physical activity; (5) consumption of fruit and vegetables; (6) the regular taking of antihypertensive medication; (7) high blood glucose episodes; (8) family history of diabetes. Each question has a proper number of points, and the total risk score is calculated on the basis of answers given by the subjects. Recently, Krabbe et al. compared the diabetes risk scores and HbA1c values in terms of type-2 diabetes mellitus (T2DM) prediction in population-based cohort studies [11]. The obtained results confirmed that this provides a good prediction of the risk of T2DM. In remote areas, a simple test that could indicate low, medium, high level of glucose in blood would also be very helpful for screening scenarios.

Throughout the last fivedecades, the progress of the development of blood-glucose monitoring methods considerably increased with the primary goal of making diabetes patients' lives easier, and at the same time safer, including routine disease screening, diagnosis, and long-term management. However, to a certain extent, this progress can be summarized as incremental work. Currently, disruptive innovations are expected, where a whole new principle will replace the traditional approach and enable quantum leaps in this field. There are four main conditions for advanced technologies to be suitable for clinical applications, as is illustrated in Fig. 1.2. In Europe, such research projects are financially supported by the European Research Council (ERC) every year under several programs. In Poland, the Foundation for Polish Science (FNP), the National Science Centre Poland (NCN), and the National Research and Development Centre (NCBR) offer grants for such groundbreaking innovations.

Figure 1.2 The requirements for clinically approved technologies.

Usually, after very promising results are obtained in the laboratory environment, the correlation with reference methods (accuracy, linearity, specificity) is not systematically accomplished. One of the key factors is long-term stability. Interestingly, currently used glucose sensors in continuous glucose monitoring operate for a short period of time, mostly from 10 to 14 days; however, even 10 days without several finger-pricking measurements bring relief for all diabetic patients, with a special emphasis on type-1 diabetes. It has to be stressed that within type-1, the number of daily tests vary between 8 and 12 or even more at the beginning. Therefore, there is no surprise that type-1 diabetes patients are the main target for noninvasive glucose monitors. However, for type-2 diabetes sufferers, using continuous glucose monitors for 2weeks enables the possibility to learn how their body manages the insulin–glucose relationship and therefore provides crucial information about the metabolism condition. In other types of diabetes, the pros are similar; therefore, several agencies/societies such as the American Diabetes Association (ADA), the European Association for Study of Diabetes (EASD), and the American Association of Clinical Endocrinologist (AACE) have supported the use of CGMs [13]. Due to the increased number of patients using CGMs every day, the International Federation of Clinical Chemistry and Laboratory Medicine (IPCC) has set up a working group (WG) on CGMs [14]. The WG is focused on developing a new standard to be fulfilled by all continuous glucose monitor devices to deliver equivalent results. Four major tasks were defined in details: (1) defining the measurand (substance, unit, matrix); (2) defining the traceability—measurement uncertainty according to ISO17511; (3) defining the procedures for the assessment of the analytical performance of CGMs; (4) defining the minimum acceptance criteria for the analytical performance of CGMs. Recently (2021), Freckmann et al . presented the status of the working group's activities with a discussion about the importance of defining the traceability and performance of continuous glucose monitors in terms of continuous use [15]. A comprehensive review of the currently available continuous glucose monitor systems (2021) was given by Kubihal et al. [13] including information about shelf life, calibration, mean absolute relative difference (MARD), and price. However, every year, it can be expected that a new device or modification of a current device is released on the market. Additionally, the progress of the WG's work should be reported, and readers are encouraged to follow the news in this field.

1.1.1. Noninvasive methods—what is needed?

In the case of developing truly noninvasive glucose monitors, interdisciplinary teams need to cover the knowledge of several disciplines such as engineering (physics, bioengineering, electronics, chemical engineering, mechanical engineering, computer sciences, etc.), biochemistry (glucose, insulin, glucagon, amylin, and their detection possibility), physiology (the distribution of important molecules in fluids and tissues), metabolism (glucose–insulin relationship), endocrinology, and diabetes within clinical practice since without feedback from end users, the innovation will never become successful. The abovementioned aspects are covered in detail in Chapters 2 and 3.

There are also two important elements that play a crucial role when noninvasive methods are under development: (1) knowledge about the history of noninvasive measurement techniques including failures as well as those that have been successful; (2) current regulations and standards that need to be fulfilled to launch the device on the market as a medical device. It has to be underlined that in the case of diabetes, there is always a pressing need to deliver the device for millions of people who are suffering from diabetes globally; this need serves as a driving force and motivation for researchers all over the world.

The advent of truly noninvasive measurements will shift our knowledge about diabetes and will also change the diabetic lifestyle including needle phobia, which is mostly exhibited by children who refuse the testing. In addition, the apprehension of possible infections will be removed. Recently, in 2021, Patel and Priefer reviewed reports regarding infections associated with diabetic-care devices, including glucose monitors and insulin delivery systems. As the authors concluded "although cases exist of infections, either by pathogen transmission or direct inoculation of the prick site, these are a very small percentage and thus should not undermine the confidence in diabetes management" [16].

Fig. 1.3 illustrates the four types of glucose monitoring systems, such as capillary glucose monitoring (also called self-management blood glucose, SMBG), invasive glucose monitoring (used only in the clinical/hospital environment), minimal invasive glucose monitoring (in this case, known as continuous glucose monitors), and noninvasive glucose monitoring. It is obvious that noninvasive blood-glucose measurements that will fulfill all requirements for medical devices will revolutionize the diabetes diagnosis and the management of millions of diabetics forever, including commercial success. According to the data reported by one manufacturer, more than two million users used its CGM device in 2020 [17].

Schematics of various glucose monitoring approaches are provided in Fig. 1.4. Starting with invasive glucose monitoring, where venous blood samples are used for calibration and measurement and in fact, the devices give venous-equivalent glucose values. The minimally invasive glucose monitors can be divided into three subgroups, where venous calibration, capillary calibration, and interstitial fluid calibration are used; these provide venous-equivalent glucose values, capillary-equivalent glucose values, and interstitial fluid glucose values, respectively. Algorithms, data processing, and compartment compensation are used to the physiologic differences such as lag time. However, in the case of noninvasive glucose measurements, nothing has been confirmed thus far. Since various methods are the subject of research, there is no confirmation about what kind of calibration is needed or what kind of measurement should be conducted (e.g., via optical, nonoptical, or a combination of various techniques). In terms of truly noninvasive glucose monitoring systems, there remain more questions than answers, and in the next chapters, some of these will be addressed.

Figure 1.3 Sampling arrangements of different types of glucose monitoring approaches including capillary glucose monitoring, invasive glucose monitoring, minimally invasive glucose monitoring, and noninvasive glucose monitoring. 

Reprinted with permission from Ref. [16].

1.2. Prevention is better than cure

Diabetes is a heterogeneous disease of varying manifestations and risks of complications. More details about diabetes background, common types, and subtypes are commented upon in the next chapters. All types are characterized by hyperglycemia. However, the origin of hyperglycemia can arise due to multiple complex etiological processes that can vary between individuals.

The general assumption is made that 10–15% of all cases result from the autoimmune destruction of beta cells, commonly known as type-1 diabetes mellitus (T1DM), latent autoimmune destruction (LADA), and rare monogenic diabetes types such as maturity-onset diabetes of young (MODY). The remaining 85–90% are considered to have type-2 diabetes mellitus with multiple underlying etiologies that result from the combined effects of numerous genetic and environmental risk factors [18]. However, a clear-cut definition that will allow all patients to be classified as T1DM, T2DM, LADA, or MODY is not that simple. Ahlqvist, Prasad, and Groop recently proposed an intermediary model for diabetes classification taking into account major clinical parameters; the model assumes that diabetes is caused by many overlapping mechanisms [19]. Therefore, in all cases, where the risk factors are different from genetic and autoimmune destruction, diabetes can be prevented, and thus major efforts in all healthcare systems (globally) should be directed toward restraining the diabetes pandemic.

Figure 1.4 Schematics of various glucose-measurement approaches. Drop symbols indicate samples of capillary blood (red [black in print version]), venous blood (blue [white in print version]), and interstitial fluid (ISF) (orange [gray in print version]). Black rectangles denote data processing steps typically performed by algorithms in the CGM system to compensate for lag time and compartment differences, and the gray flash indicates a step that is not possible with the current technology. 

Adapted with permission from Ref. [16].

1.2.1. Diabetes education

Diabetes education is as important as tailor-made treatment. In general, diabetes education can be divided into two groups: (1) education of diabetes patients regardless of the diabetes type; (2) education about diabetes in general. Both approaches are important since in the former, the diabetic patient is equipped with all necessary information about how to manage diabetes, how to control glycemia level, how to avoid glucose highs and lows, how to calculate the dose of insulin (type-1 diabetes), etc. General knowledge about diabetes is crucial for preventing diabetes complications since diabetes is a slow-killing disease. Early stages of diabetes are usually without symptoms, and thus a part of the population is undiagnosed or suffers from prediabetes (more details in the next chapter).

The first symptoms should never be neglected; the symptoms are natural responses of our body. However, due to a lack of knowledge, symptoms such as polydipsia (excessive thirst or excess drinking), polyphagia (an abnormally strong sensation of hunger or desire to eat), and polyuria (excessive or an abnormally large production or passing of urine). Polydipsia, polyphagia, and polyuria—also known as 3Ps—are the symptoms commonly associated with diabetes mellitus (more details are provided in Chapter 2).

Diabetes educational programs should start with the youngest, who will learn how to avoid diabetes (type-2) and their complications by choosing carbs carefully, maintaining an optimal body mass index, getting enough sleep, and being active. Diet, physical activity, and the ability to manage stress and get enough sleep are the primary habits that could halt the diabetes pandemic.

In addition to education on prevention, educators should focus on the importance of frequent blood-glucose measurement, especially in the case of T1DM. Recently, results presented on cohort studies have shown that 10% of type-1 diabetes and 97.5% of type-2 diabetes are not following their healthcare professionals' directions in terms of the frequency of blood-glucose measurement (3–4 times per day). When questioned about their reasons for poor adherence, the cohort indicated that it was due to the painful (29.2%), uncomfortable (33.8%), or inconvenient nature of testing (36.9%) [20]. The International Diabetes Federation (IDF) offers the training of medical workers and specialists in the field of diabetes called IDF Diabetes School [21].

Novel diagnostic tools that enable the reduction of direct blood-glucose measurement will open the possibility to increase self-control and reduce diabetes complications in all diabetes types. Meanwhile, healthcare has evolved from the traditional to telemedicine, connected-health, e-health, mobile health, and smart-health. The growth of ICT (information and communication technologies) and IoT has had a great impact on the healthcare sector, including diabetes management. The achievements in the field of ICT, IoT, and sensors in general are moving the data handling process forward. A number of data collected by the sensors, including body monitoring as well as environmental features (e.g., air quality), requires additional