Living with Insulin: The story of insulin from people with diabetes.

The history of insulin is rightly considered one of the most beautiful stories in medicine which goes even further than the extraordinary result of tens of millions of lives saved. Without a doubt, it constitutes a major achievement for medical science which, especially in the last 50 years, has led to an impressive acceleration in the succession of new treatment opportunities. We are going to describe the history of insulin therapy, the history we lived from two different angles as people living with type 1 diabetes, and obviously also as diabetologists, but as diabetologists with diabetes. Without a doubt, insulin and his story constitutes a major achievement for medical science which has led to an impressive acceleration in the succession of new treatment opportunities. Care opportunities that have not only allowed fundamental improvements in outcomes, but have also and above all impacted the quality of life of people with diabetes. Summarizing one hundred years of insulin is no simple endeavor. In our view, it would be easier, and probably more befitting, to focus on the last 50 years, namely the period we have lived closely and personally together with insulin. More to the point, these last 50 years have witnessed a dramatic acceleration of research and innovation. In our opinion, it is precisely the innovations in insulin therapy introduced from the last decades that fully justify the description of events in this incredible period as "the miracle of insulin". We'll describe how the most important innovations introduced in the last decades had impact on what we have nowadays, as patients and diabetologits: today, we can finally adapt insulin therapy to the patient's life or lifestyle, reversing what was the perception of patients until 20 years, when insulin was considered, by the most, as an obstacle, which seemed insurmountable to some, to a free and unconstrained life.

Optoacoustic imaging in endocrinology and metabolism.

Imaging is an essential tool in research, diagnostics and the management of endocrine disorders. Ultrasonography, nuclear medicine techniques, MRI, CT and optical methods are already used for applications in endocrinology. Optoacoustic imaging, also termed photoacoustic imaging, is emerging as a method for visualizing endocrine physiology and disease at different scales of detail: microscopic, mesoscopic and macroscopic. Optoacoustic contrast arises from endogenous light absorbers, such as oxygenated and deoxygenated haemoglobin, lipids and water, or exogenous contrast agents, and reveals tissue vasculature, perfusion, oxygenation, metabolic activity and inflammation. The development of high-performance optoacoustic scanners for use in humans has given rise to a variety of clinical investigations, which complement the use of the technology in preclinical research. Here, we review key progress with optoacoustic imaging technology as it relates to applications in endocrinology; for example, to visualize thyroid morphology and function, and the microvasculature in diabetes mellitus or adipose tissue metabolism, with particular focus on multispectral optoacoustic tomography and raster-scan optoacoustic mesoscopy. We explain the merits of optoacoustic microscopy and focus on mid-infrared optoacoustic microscopy, which enables label-free imaging of metabolites in cells and tissues. We showcase current optoacoustic applications within endocrinology and discuss the potential of these technologies to advance research and clinical practice.

Improving pediatric endocrinology trainees' knowledge about insulin pumps and continuous glucose monitors with online spaced education: Technology Knowledge Optimization in T1D (TeKnO T1D).

OBJECTIVE: We explored the impact of TeKnO T1D, an online, case-based, spaced education curriculum about insulin pump and continuous glucose monitor (CGM) use in pediatric type 1 diabetes management. METHODS: Pediatric endocrinology fellows (n = 64) were randomized to receive an educational curriculum focused on either insulin pumps or CGMs. Fellows received interactive questions twice weekly via email or mobile app. Median time to completion was 76.5 days. The primary outcome was change in knowledge as measured by performance on multiple-choice questions (MCQ) from the pre-test to the post-test. RESULTS: Forty-eight of 64 (75%) learners completed the curriculum and assessments. The pump group improved from 35.0 ± 15% on the pre-test MCQs to 61.1 ± 17% on the post-test, a 12.2 absolute percentage point greater improvement on pump-specific items than the CGM group (P = .03). The CGM group improved from 30.3 ± 15% on the pre-test MCQs to 61.4 ± 21% on the post-test, a 28.7 absolute percentage point greater improvement on CGM-specific items than the pump group (P < .001). Both groups were more likely to report an appropriate level of understanding of their respective technologies after completing the corresponding curriculum. In thematic analysis of qualitative data, fellows indicated that knowledge gains led to improved patient care. There was universal agreement about enjoyment and effectiveness of the curricula. CONCLUSIONS: TeKnO T1D proved to be an engaging, effective way to improve endocrinology fellows' knowledge and confidence about insulin pumps and CGM use in the management of pediatric type 1 diabetes.

7. Diabetes Technology: Standards of Medical Care in Diabetes-2020.

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

System Accuracy Assessment of a Blood Glucose Meter With Wireless Internet Access Associated With Unusual Hypoglycemia Patterns in Clinical Trials.

BACKGROUND: In recent randomized clinical trials, an unusual reporting pattern of glycemic data and hypoglycemic events potentially related to an internet enabled blood glucose meter (MyGlucoHealth, BGM) was observed. Therefore, this clinical study was conducted to evaluate the system accuracy of the BGM in accordance with the ISO15197:2015 guidelines with additional data collection. METHODS: To investigate system accuracy, 10 of 3088 devices and 6 of 23 strip lots, used in the trials, were selected by a randomization procedure and a standard repeatability assessment. YSI 2300 STAT Plus was used as the standard reference method. The samples were distributed as per the ISO15197:2015 recommendations with 20 additional samples in the hypoglycemic range. Each sample was tested with 6 devices and 6 strip lots with double determinations. RESULTS: Overall, 121 subjects with blood glucose values 26-423 mg/dL were analyzed, resulting in 1452 data points. In all, 186/1452 readings (12.8%) did not meet the ISO acceptance criteria. Data evaluated according to the FDA guidelines showed that 336/1452 (23.1%) readings did not meet the acceptance criteria. A clear bias toward elevated values was observed for BG <100 mg/dL (MARD: 11.0%). CONCLUSIONS: The results show that the BGM, although approved according to standard regulatory guidelines, did not meet the level of analytical accuracy required for clinical treatment decisions according to ISO 15197:2015 and FDA requirements. In general, caution should be exercised before selection of BGMs for patients and in clinical trials.

Clinical endocrinology and hormones quantitation: the increasing role of mass spectrometry.

Clinical endocrinology has always had a close relationship with laboratory medicine. In fact, the quantification of hormones is of great importance for diagnosis, treatment, recurrence and patient's prognosis of endocrine disorders. This review dealt with the role of the laboratory in diagnosing endocrine pathologies related to adrenal gland, pituitary, gonads and thyroid. The measurements of the main hormones (17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulphate, testosterone, estradiol, cortisol, aldosterone, metanephrines, thyroglobulin and insulin-like-growth factor-1) were described considering analytical characteristics but also some aspects of preanalytical and postanalytical steps. Traditionally, hormonal quantification is performed with immunoassays (IMAs), which have several advantages (i.e. limited training of technicians, high throughput, widely spread worldwide), but also some limitations on the accuracy of the results due mainly to cross-reactivity of IMA antibodies (i.e. steroid measurements) and protein interferences (i.e. heterophilic antibodies, antithyroglobulin antibodies in Tg measurements, etc.). In order to meet the need for clinicians to obtain ever more accurate results from laboratories, in recent decades, mass spectrometry (MS) has been developed. MS, in particular Liquid Chromatography-Tandem MS (LC-MS/MS), is a more complex but also more flexible technique able to guarantee greater specificity. It also provides multi-parameter quantification in the same analytical session delineating steroid profiles and, in some cases, defining the appropriate reference range for each hormone. Similar to IMAs, LC-MS/MS shows some inter-method variability, limiting the goal of standardization. However, several studies have recently demonstrated the possibility of reaching harmonization of this technology with good expectations for the future.

Computer-assisted reproductive surgery: why it matters to reproductive endocrinology and infertility subspecialists.

Trained fertility specialists possess a unique clinical perspective and an extensive medical and technological armamentarium to overcome reproductive dysfunction: it is their privilege and ethical duty to lead the field of reproductive surgery. However, modern reproductive surgery can no longer exist outside of the realm of advanced laparoscopy. This has been a major hurdle to the thriving of surgery within our subspecialty, owing to the time and effort required to achieve and maintain proficiency in the anti-ergonomic environment of conventional laparoscopy. Computer-assisted surgery minimizes aptitudinal restrictions to the adoption of advanced laparoscopy. As such, it promotes strategy over technique and may hold the key to the continued success of high-specialty reproductive surgery.

Video games for diabetes self-management: examples and design strategies.

The July 2012 issue of the Journal of Diabetes Science and Technology includes a special symposium called "Serious Games for Diabetes, Obesity, and Healthy Lifestyle." As part of the symposium, this article focuses on health behavior change video games that are designed to improve and support players' diabetes self-management. Other symposium articles include one that recommends theory-based approaches to the design of health games and identifies areas in which additional research is needed, followed by five research articles presenting studies of the design and effectiveness of games and game technologies that require physical activity in order to play. This article briefly describes 14 diabetes self-management video games, and, when available, cites research findings on their effectiveness. The games were found by searching the Health Games Research online searchable database, three bibliographic databases (ACM Digital Library, PubMed, and Social Sciences Databases of CSA Illumina), and the Google search engine, using the search terms "diabetes" and "game." Games were selected if they addressed diabetes self-management skills.

Designing serious video games for health behavior change: current status and future directions.

Serious video games for health are designed to entertain while changing a specific health behavior. This article identifies behavioral principles that can guide the development of serious video games focused on changing a variety of health behaviors, including those attempting to decrease risk of obesity and type 2 diabetes. Guidelines discussed include how to develop video games that provide a solid foundation for behavior change by enhancing a player's knowledge and skill, ways in which personal mastery experiences can be incorporated into a video game environment, using game characters and avatars to promote observational learning, creating personalized experiences through tailoring, and the importance of achieving a balance between "fun-ness" and "seriousness." The article concludes with suggestions for future research needed to inform this rapidly growing field.

No loss of chance of diabetic retinopathy screening by endocrinologists with a digital fundus camera.

OBJECTIVE: To compare the efficacy of the diabetic retinopathy (DR) screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of "loss of chance." RESEARCH DESIGN AND METHODS: In a cross-sectional study, 500 adult diabetic patients (1,000 eyes) underwent three-field retinal photography with a digital fundus camera following pupillary dilatation. Five endocrinologists and two ophthalmology residents underwent 40 h of training on screening and grading of DR and detection of associated retinal findings. A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists. Screening efficiency of endocrinologists was evaluated in terms of "loss of chance," i.e., missed diagnoses that required ophthalmologist referrals. RESULTS: The mean weighted κ of DR screening performed by endocronologists was similar to that of ophthalmology residents (0.65 vs. 0.73). Out of 456 DR eyes, both endocrinologists and ophthalmology residents misdiagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral. There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training. CONCLUSIONS: The endocrinologist with specific training for DR detection using a three-field digital fundus camera with pupillary dilatation can perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.

A comprehensive evaluation of commonly used accelerometer energy expenditure and MET prediction equations.

Numerous accelerometers and prediction methods are used to estimate energy expenditure (EE). Validation studies have been limited to small sample sizes in which participants complete a narrow range of activities and typically validate only one or two prediction models for one particular accelerometer. The purpose of this study was to evaluate the validity of nine published and two proprietary EE prediction equations for three different accelerometers. Two hundred and seventy-seven participants completed an average of six treadmill (TRD) (1.34, 1.56, 2.23 ms(-1) each at 0 and 3% grade) and five self-paced activities of daily living (ADLs). EE estimates were compared with indirect calorimetry. Accelerometers were worn while EE was measured using a portable metabolic unit. To estimate EE, 4 ActiGraph prediction models were used, 5 Actical models, and 2 RT3 proprietary models. Across all activities, each equation underestimated EE (bias -0.1 to -1.4 METs and -0.5 to -1.3 kcal, respectively). For ADLs EE was underestimated by all prediction models (bias -0.2 to -2.0 and -0.2 to -2.8, respectively), while TRD activities were underestimated by seven equations, and overestimated by four equations (bias -0.8 to 0.2 METs and -0.4 to 0.5 kcal, respectively). Misclassification rates ranged from 21.7 (95% CI 20.4, 24.2%) to 34.3% (95% CI 32.3, 36.3%), with vigorous intensity activities being most often misclassified. Prediction equations did not yield accurate point estimates of EE across a broad range of activities nor were they accurate at classifying activities across a range of intensities (light <3 METs, moderate 3-5.99 METs, vigorous ≥ 6 METs). Current prediction techniques have many limitations when translating accelerometer counts to EE.

Clinical review: Realistic expectations and practical use of continuous glucose monitoring for the endocrinologist.

CONTEXT: Real-time continuous glucose monitoring (CGM) has been available for type 1 diabetes for several years. This paper is a status report on our early experiences with this next technology. EVIDENCE ACQUISITION: The two major sources of data acquisition included PubMed search strategies and personal experience of the author from clinical experience. EVIDENCE SYNTHESIS: Data assessing CGM accuracy, short-term outcomes (12 wk), and longer term outcomes (6 months) are reported. Potential strategies for successful and efficient use in an office or clinic setting are also discussed. Practical aspects of CGM use (alarm settings, using glycemic trending information) are also reviewed. CONCLUSIONS: Accuracy of this technology has improved in the short amount of time it has been available. Six-month data suggest that patient selection is a key for success. Patients who do not understand or practice the basics of intensive insulin therapy have the greatest challenges. Those who do best watch the receiver frequently, continue with frequent home blood glucose monitoring, use the trending information to make insulin adjustments, and understand the limitations of the technology. With insurance reimbursement improving, CGM is gaining acceptance as an important tool for the management of type 1 diabetes. Like home blood glucose monitoring and insulin pump therapy, this technology by itself is not a panacea for diabetes control. However, it further adds to our ability to improve the lives of people with diabetes. Long-term, the hope is that this technology will pave the way for a "closed-loop" device.

Liquid chromatography tandem-mass spectrometry (LC-MS/MS)--technique and applications in endocrinology.

In recent years, liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as an innovative analytical technology applicable to a wide number of analyses in the endocrinology laboratory. Compared to the "traditional" technique of gas chromatography-mass spectrometry (GC-MS), LC-MS/MS is easier to use and is applicable for a substantially larger number of relevant analytes. With the development of LC-MS/MS, the widespread application of the proven principle of isotope dilution mass spectrometry is now feasible not only in research but also for routine applications. The aim of this review is to explain the basic technical principles of LC-MS/MS, to describe the general characteristics of analytical LC-MS/MS applications and to comprehensively discuss the application of this technology in the field of endocrinology.

Insulin pen injection devices for management of patients with type 2 diabetes: considerations based on an endocrinologist's practical experience in the United States.

OBJECTIVE: To review the features of several insulin pens currently available in the United States, discuss the validity of concerns about certain pen devices, and provide specific training information for clinicians to increase the accuracy of insulin administration and patient satisfaction with the use of insulin pens. METHODS: The published literature on insulin pens and Internet-available, product-specific information are reviewed. In addition, special practical considerations regarding insulin pen selection based on personal experience in a high-volume endocrinology practice are high-lighted by presentation of case vignettes. RESULTS: For some patients with diabetes, the need for performance of self-injection can be a barrier to acceptance of insulin therapy. Insulin pen devices provide a delivery option that may be more acceptable and more convenient to use in comparison with traditional vials and syringes and thus may promote patient compliance, which can enhance the ability to achieve and maintain glycemic control. When choosing a specific insulin pen for an individual patient, the clinician should consider the patient's insulin regimen, lifestyle, and factors that may affect the ability to use a particular device, such as motor dexterity and visual acuity. CONCLUSION: Insulin pens offer convenience and can potentially increase patient satisfaction and compliance with therapy. Because certain characteristics of a given insulin pen may make it preferable for specific patients, it is important for clinicians to be aware of individual needs. Provision of thorough training for patients in the correct use of insulin pens is important because user error can affect pen performance and accuracy of the dose administered. Manufacturers should be notified of any recurring problems.