Importance of FDA-Integrated Continuous Glucose Monitors to Ensure Accuracy of Continuous Glucose Monitoring.

Continuous glucose monitoring (CGM) has been shown to improve glycemic control and self-monitoring, as well as to reduce the risk of hypoglycemia. Integrated CGM (iCGM) FDA-cleared systems with published performance data are established nonadjunctive and accurate CGM tools that can directly inform decision-making in the treatment of diabetes (i.e., insulin dosing). Studies have assessed accuracy and safety data of CGMs that were eventually cleared for iCGM by the FDA and that informed the recommendation for their nonadjunctive use. Subsequent robust clinical trials and real-world studies demonstrated clinical effectiveness with improvements in a range of patient outcomes. In recent years, a number of non-iCGM-approved CGM devices have entered the market outside the United States worldwide. Some of these non-iCGM-approved CGM devices require additional user verification of blood glucose levels to be performed for making treatment decisions, termed adjunctive. Moreover, in many non-iCGM-approved CGM devices, accuracy studies published in peer-reviewed journals are scarce or have many limitations. Consequently, non-iCGM-approved CGM devices cannot be automatically perceived as having the same performance or quality standards than those approved for iCGM by the FDA. As a result, although these devices tend to cost less than iCGMs that carry FDA clearance and could therefore be attractive from the point of view of a health care payer, it must be emphasized that evaluation of costs should not be limited to the device (such as the usability preference that patients have for nonadjunctive sensors compared to adjunctive sensors) but to the wider value of the total benefit that the product provides to the patient.

Risks of peri- and postoperative complications with glucagon-like peptide-1 receptor agonists.

AIM: To assess whether adults with diabetes on oral hypoglycaemic agents undergoing general endotracheal anaesthesia during nine common surgical procedures who are glucagon-like peptide-1 receptor agonist (GLP1-RA) users, compared with non-users, are at increased risk of six peri- and post-procedure complications. MATERIALS AND METHODS: A retrospective observational cohort analysis of over 130 million deidentified US adults with diabetes (defined as being on oral hypoglycaemic agents) from a nationally representative electronic health dataset between 1 January 2015 and 1 April 2023 was analysed. Cohorts were matched by high-dimensionality propensity scoring. We compared the odds of six peri- and postoperative complications in GLP1-RA users and non-users. A sensitivity analysis compared these odds in GLP1-RA users to non-users with diabetes and obesity. We measured the odds of (a) a composite outcome of postoperative decelerated gastric emptying, including antiemetic use, ileus within 7 days post-procedure, gastroparesis diagnosis, gastric emptying study; (b) postoperative aspiration or pneumonitis; (c) severe respiratory failure; (d) postoperative hypoglycaemia; (e) inpatient mortality; and (f) 30-day mortality. RESULTS: Among 13 361 adults with diabetes, 16.5% were treated with a GLP1-RA. In the high-dimensionality propensity score-matched cohort, GLP1-RA users had a lower risk of peri- and postoperative complications for decelerated gastric emptying and antiemetic use compared with non-users. The risk of ileus within 7 days, aspiration/pneumonitis, hypoglycaemia and 30-day mortality were not different. A sensitivity analysis showed similar findings in patients with diabetes and obesity. CONCLUSION: No increased risk of peri- and postoperative complications in GLP1-RA users undergoing surgery with general endotracheal anaesthesia was identified.

Diabetes Technology Meeting 2023.

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

Advanced Glycation Endproducts: A Marker of Long-term Exposure to Glycemia.

This article examines the importance of advanced glycation endproducts (AGEs) and summarizes the structure of AGEs, pathological changes associated with AGEs, the contribution of AGEs to metabolic memory, and the value of AGEs as a predictor of diabetic complications and cardiovascular disease in people with and without diabetes. As a practical focus, skin autofluorescence (SAF) is examined as an attractive approach for estimating AGE burden. The measurement of AGEs may be of significant value to specific individuals and groups, including Black and Hispanic/Latino Americans, as they appear to have higher concentrations of hemoglobin A1c (HbA1c) than would be predicted by other metrics of mean glycemia. We hypothesize that if the amount of glycation of HbA1c is greater than expected from measured glucose levels, and if AGEs are accumulating, then this accumulation of AGEs might account for the increased rate of complications of diabetes in populations with high rates of vascular disease and other complications. Thus, identifying and modifying the burden of AGEs based on measurement of AGEs by SAF may turn out to be a worthwhile metric to determine individuals who are at high risk for the complications of diabetes as well as others without diabetes at risk of vascular disease. We conclude that available evidence supports SAF as both a clinical measurement and as a means of evaluating interventions aimed at reducing the risks of vascular disease and diabetic complications.

Accuracy and Feasibility of Real-time Continuous Glucose Monitoring in Critically Ill Patients After Abdominal Surgery and Solid Organ Transplantation.

OBJECTIVE: Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery. RESEARCH DESIGN AND METHODS: We included patients undergoing pancreatic surgery and solid organ transplantation (liver, pancreas, islets of Langerhans, kidney) requiring an ICU stay after surgery. We used a Dexcom G6 sensor, placed in the infraclavicular region, for real-time CGM. Arterial blood glucose measured by the amperometric principle (ABL 800; Radiometer, Copenhagen, Denmark) served as a reference value and for calibration. Blood glucose was also routinely monitored by a StatStrip bedside glucose meter. Sensor accuracy was assessed by mean absolute relative difference (MARD), bias, modified Bland-Altman plot, and surveillance error grid for paired samples of glucose values from CGM and acid-base analyzer (ABL). RESULTS: We analyzed data from 61 patients and obtained 1,546 paired glucose values from CGM and ABL. Active sensor use was 95.1%. MARD was 9.4%, relative bias was 1.4%, and 92.8% of values fell in zone A, 6.1% fell in zone B, and 1.2% fell in zone C of the surveillance error grid. Median time in range was 78%, with minimum (<1%) time spent in hypoglycemia. StatStrip glucose meter MARD compared with ABL was 5.8%. CONCLUSIONS: Our study shows clinically applicable accuracy and reliability of Dexcom G6 CGM in postoperative ICU patients and a feasible alternative sensor placement site.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively, and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels are suggested that enable the collection of comparator data with these characteristics. This work is an important step toward establishing a future standard for the performance evaluation of CGM systems.

Emerging Biomarkers in the Laboratory and in Practice: A Novel Approach to Diagnosing Heart Failure in Diabetes.

The Biomarkers for the Diagnosis of Heart Failure in Diabetes webinar was hosted by Diabetes Technology Society on September 20, 2023, with the objective to review current evidence and management practices of biomarker screening for heart failure in people with diabetes. The webinar discussed (1) the four stages of heart failure, (2) diabetes and heart failure, (3) natriuretic peptide and troponin for diagnosing heart failure in diabetes, (4) emerging composite and investigational biomarkers for diagnosing heart failure, and (5) prevention of heart failure progression. Experts in heart failure from the fields of clinical chemistry, cardiology, and diabetology presented data about the importance of screening for heart failure as an often-unnoticed complication of people with type 1 and type 2 diabetes.

A Real-World Prospective Study of the Effectiveness and Safety of Automated Insulin Delivery Compared With Other Modalities of Type 1 Diabetes Treatment During Ramadan Intermittent Fasting.

OBJECTIVE: To compare the fasting experience and glycemic control during Ramadan among people with type 1 diabetes (PWT1D) who use automated insulin delivery (AID) versus other modalities of treatment. RESEARCH DESIGN AND METHODS: A total of 294 PWT1D who attempted fasting during Ramadan in 2022 were categorized on the basis of treatment modality into one of five groups: 1) AID (n = 62); 2) conventional pump + continuous glucose monitoring (CGM; n = 37); 3) pump + self-monitoring of blood glucose (SMBG; n = 8); 4) multiple daily injections (MDI) + CGM (n = 155); and 5) MDI + SMBG (n = 32). Predictors of fasting most days of Ramadan (i.e., breaking fast ≤2 days because of diabetes) were analyzed using uni- and multivariable logistic regression. RESULTS: The median numbers of days when fasting was broken because of diabetes were 2, 5, 3, 3.5, and 2.5 for AID, conventional pump + CGM, MDI + CGM, pump + SMBG, and MDI + SMBG users, respectively (P = 0.047). Users of AID had a significantly greater time in range (TIR) and lower glycemia risk index, time below range, and time above range compared with users of conventional pumps and MDI (both P < 0.05). Likewise, 53% of AID users attained the double target of 1) breaking fast ≤2 days because of diabetes and 2) maintaining TIR ≥70% during Ramadan compared with only 3% of the conventional pump users and 44% of the MDI + CGM users (both P < 0.05). Compared with MDI + CGM users, AID users were twice as likely to complete fasting most days of Ramadan. CONCLUSIONS: Use of AID is associated with the highest rates of fasting and best glycemic control during Ramadan fasting.

Optimal Screening for Predicting and Preventing the Risk of Heart Failure Among Adults With Diabetes Without Atherosclerotic Cardiovascular Disease: A Pooled Cohort Analysis.

BACKGROUND: The optimal approach to identify individuals with diabetes who are at a high risk for developing heart failure (HF) to inform implementation of preventive therapies is unknown, especially in those without atherosclerotic cardiovascular disease (ASCVD). METHODS: Adults with diabetes and no HF at baseline from 7 community-based cohorts were included. Participants without ASCVD who were at high risk for developing HF were identified using 1-step screening strategies: risk score (WATCH-DM [Weight, Age, Hypertension, Creatinine, HDL-C, Diabetes Control, QRS Duration, MI, and CABG] ≥12), NT-proBNP (N-terminal pro-B-type natriuretic peptide ≥125 pg/mL), hs-cTn (high-sensitivity cardiac troponin T ≥14 ng/L; hs-cTnI ≥31 ng/L), and echocardiography-based diabetic cardiomyopathy (echo-DbCM; left atrial enlargement, left ventricular hypertrophy, or diastolic dysfunction). High-risk participants were also identified using 2-step screening strategies with a second test to identify residual risk among those deemed low risk by the first test: WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, NT-proBNP/echo-DbCM. Across screening strategies, the proportion of HF events identified, 5-year number needed to treat and number needed to screen to prevent 1 HF event with an SGLT2i (sodium-glucose cotransporter 2 inhibitor) among high-risk participants, and cost of screening were estimated. RESULTS: The initial study cohort included 6293 participants (48.2% women), of whom 77.7% without prevalent ASCVD were evaluated with different HF screening strategies. At 5-year follow-up, 6.2% of participants without ASCVD developed incident HF. The 5-year number needed to treat to prevent 1 HF event with an SGLT2i among participants without ASCVD was 43 (95% CI, 29-72). In the cohort without ASCVD, high-risk participants identified using 1-step screening strategies had a low 5-year number needed to treat (22 for NT-proBNP to 37 for echo-DbCM). However, a substantial proportion of HF events occurred among participants identified as low risk using 1-step screening approaches (29% for echo-DbCM to 47% for hs-cTn). Two-step screening strategies captured most HF events (75-89%) in the high-risk subgroup with a comparable 5-year number needed to treat as the 1-step screening approaches (30-32). The 5-year number needed to screen to prevent 1 HF event was similar across 2-step screening strategies (45-61). However, the number of tests and associated costs were lowest for WATCH-DM/NT-proBNP ($1061) compared with other 2-step screening strategies (NT-proBNP/hs-cTn: $2894; NT-proBNP/echo-DbCM: $16 358). CONCLUSIONS: Selective NT-proBNP testing based on the WATCH-DM score efficiently identified a high-risk primary prevention population with diabetes expected to derive marked absolute benefits from SGLT2i to prevent HF.

The Launch of the iCoDE-2 Standard Project: Integration of Connected Diabetes Device Data Into the Electronic Health Record.

INTRODUCTION: Diabetes Technology Society virtually hosted the first meeting of the Integration of Connected Diabetes Device Data Into the Electronic Health Record #2 (iCoDE-2) Standards Project on May 31, 2023, via Zoom. METHODS: Clinicians, patients, data aggregators, informaticists, manufacturers, attorneys, and cybersecurity experts discussed dosing data currently available from insulin delivery devices and data aggregators and the types of information that patients and clinicians want to see. This information along with technical and regulatory aspects of (1) data standards and (2) integration into the electronic health record (EHR) are the basis of iCoDE-2. RESULTS: Six sessions were hosted discussing themes including (1) What's Currently Available: The Continuous Glucose Monitor Experience; (2) What's Currently Available: The Aggregator Experience; (3) What's Currently Available: The Insulin Pump Experience; (4) What's Currently Available: The Insulin Pen Experience; (5) What Do Clinicians and Patients Want Out of iCoDE-2 Data?; and (6) Technical and Regulatory Aspects of Data Aggregation. CONCLUSION: Additional working group meetings to discuss data standard and clinical workflow will be held to create additional technical specifications and clinical workflows to aid in insulin dosing data integration into the EHR. A mid-project meeting will convene in the second half of 2023.

Use of Continuous Glucose Monitors Upon Hospital Discharge of People With Diabetes: Promise, Barriers, and Opportunity.

Continuous glucose monitors (CGMs) have increasingly been used in ambulatory and inpatient or hospital settings to improve glycemic outcomes for people with diabetes. Given their capacity to aid individuals in avoiding hypo- and hyperglycemia, they may also be useful when transitioning from hospital to home by reducing rates of hospital readmissions and emergency department visits. Several types of barriers presently exist that make the deployment of CGMs at the time of hospital discharge problematic, including (1) regulatory, (2) behavioral, (3) logistical, (4) technical, (5) staffing, and (6) systemic issues. In this commentary, we review the literature, discuss these barriers, and propose possible solutions to facilitate the use of CGMs in people with diabetes at the time of hospital discharge.

NIH Fifth Artificial Pancreas Workshop 2023: Meeting Report: The Fifth Artificial Pancreas Workshop: Enabling Fully Automation, Access, and Adoption.

The Fifth Artificial Pancreas Workshop: Enabling Fully Automation, Access, and Adoption was held at the National Institutes of Health (NIH) Campus in Bethesda, Maryland on May 1 to 2, 2023. The organizing Committee included representatives of NIH, the US Food and Drug Administration (FDA), Diabetes Technology Society, Juvenile Diabetes Research Foundation (JDRF), and the Leona M. and Harry B. Helmsley Charitable Trust. In previous years, the NIH Division of Diabetes, Endocrinology, and Metabolic Diseases along with other diabetes organizations had organized periodic workshops, and it had been seven years since the NIH hosted the Fourth Artificial Pancreas in July 2016. Since then, significant improvements in insulin delivery have occurred. Several automated insulin delivery (AID) systems are now commercially available. The workshop featured sessions on: (1) Lessons Learned from Recent Advanced Clinical Trials and Real-World Data Analysis, (2) Interoperability, Data Management, Integration of Systems, and Cybersecurity, Challenges and Regulatory Considerations, (3) Adaptation of Systems Through the Lifespan and Special Populations: Are Specific Algorithms Needed, (4) Development of Adaptive Algorithms for Insulin Only and for Multihormonal Systems or Combination with Adjuvant Therapies and Drugs: Clinical Expected Outcomes and Public Health Impact, (5) Novel Artificial Intelligence Strategies to Develop Smarter, More Automated, Personalized Diabetes Management Systems, (6) Novel Sensing Strategies, Hormone Formulations and Delivery to Optimize Close-loop Systems, (7) Special Topic: Clinical and Real-world Viability of IP-IP Systems. "Fully automated closed-loop insulin delivery using the IP route," (8) Round-table Panel: Closed-loop performance: What to Expect and What are the Best Metrics to Assess it, and (9) Round-table Discussion: What is Needed for More Adaptable, Accessible, and Usable Future Generation of Systems? How to Promote Equitable Innovation? This article summarizes the discussions of the Workshop.

A narrative commentary about interoperability in medical devices and data used in diabetes therapy from an academic EU/UK/US perspective.

People living with diabetes have many medical devices available to assist with disease management. A critical aspect that must be considered is how systems for continuous glucose monitoring and insulin pumps communicate with each other and how the data generated by these devices can be downloaded, integrated, presented and used. Not only is interoperability associated with practical challenges, but also devices must adhere to all aspects of regulatory and legal frameworks. Key issues around interoperability in terms of data ownership, privacy and the limitations of interoperability include where the responsibility/liability for device and data interoperability lies and the need for standard data-sharing protocols to allow the seamless integration of data from different sources. There is a need for standardised protocols for the open and transparent handling of data and secure integration of data into electronic health records. Here, we discuss the current status of interoperability in medical devices and data used in diabetes therapy, as well as regulatory and legal issues surrounding both device and data interoperability, focusing on Europe (including the UK) and the USA. We also discuss a potential future landscape in which a clear and transparent framework for interoperability and data handling also fulfils the needs of people living with diabetes and healthcare professionals.

Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial.

BACKGROUND: ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes. METHODS: This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin [HbA1c] <10·0% [86 mmol/mol]) were randomly assigned (1:1) to once-weekly icodec or once-daily degludec, both in combination with insulin aspart (two or more daily injections). The primary endpoint was change in HbA1c from baseline to week 26, tested for non-inferiority (0·3 percentage point margin) in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04848480, and is now complete. FINDINGS: Between April 30 and Oct 15, 2021, of 655 participants screened, 582 participants were randomly assigned to icodec (n=290) or degludec (n=292). At week 26, from baseline values of 7·59% (icodec) and 7·63% (degludec), estimated mean changes in HbA1c were -0·47 percentage points and -0·51 percentage points, respectively (estimated treatment difference 0·05 percentage points [95% CI -0·13 to 0·23]), confirming non-inferiority of icodec to degludec (p=0·0065). Overall rate of combined clinically significant or severe hypoglycaemia (baseline to week 26) was statistically significantly higher with icodec than degludec (19·9 vs 10·4 events per patient-year of exposure; estimated rate ratio 1·9 [95% CI 1·5 to 2·3]; p<0·0001). The rate was also statistically significantly higher with icodec than degludec when evaluated over 57 weeks (52 weeks plus a 5-week follow-up period). 39 serious adverse events were reported in 24 (8%) participants receiving icodec, and 25 serious adverse events were reported in 20 (7%) participants receiving degludec. One participant in the icodec group died; this was judged unlikely to be due to the trial product. INTERPRETATION: In adults with type 1 diabetes, once-weekly icodec showed non-inferiority to once-daily degludec in HbA1c reduction at week 26, with statistically significantly higher rates of combined clinically significant or severe hypoglycaemia. For icodec, time below 3·0 mmol/L (<54 mg/dL) was at the threshold of the internationally recommended target (<1%) during weeks 22-26 and below target during weeks 48-52. FUNDING: Novo Nordisk.

The Scientific Knowledge of Bard and ChatGPT in Endocrinology, Diabetes, and Diabetes Technology: Multiple-Choice Questions Examination-Based Performance.

BACKGROUND: The present study aimed to investigate the knowledge level of Bard and ChatGPT in the areas of endocrinology, diabetes, and diabetes technology through a multiple-choice question (MCQ) examination format. METHODS: Initially, a 100-MCQ bank was established based on MCQs in endocrinology, diabetes, and diabetes technology. The MCQs were created from physiology, medical textbooks, and academic examination pools in the areas of endocrinology, diabetes, and diabetes technology and academic examination pools. The study team members analyzed the MCQ contents to ensure that they were related to the endocrinology, diabetes, and diabetes technology. The number of MCQs from endocrinology was 50, and that from diabetes and science technology was also 50. The knowledge level of Google's Bard and ChatGPT was assessed with an MCQ-based examination. RESULTS: In the endocrinology examination section, ChatGPT obtained 29 marks (correct responses) of 50 (58%), and Bard obtained a similar score of 29 of 50 (58%). However, in the diabetes technology examination section, ChatGPT obtained 23 marks of 50 (46%), and Bard obtained 20 marks of 50 (40%). Overall, in the entire three-part examination, ChatGPT obtained 52 marks of 100 (52%), and Bard obtained 49 marks of 100 (49%). ChatGPT obtained slightly more marks than Bard. However, both ChatGPT and Bard did not achieve satisfactory scores in endocrinology or diabetes/technology of at least 60%. CONCLUSIONS: The overall MCQ-based performance of ChatGPT was slightly better than that of Google's Bard. However, both ChatGPT and Bard did not achieve appropriate scores in endocrinology and diabetes/diabetes technology. The study indicates that Bard and ChatGPT have the potential to facilitate medical students and faculty in academic medical education settings, but both artificial intelligence tools need more updated information in the fields of endocrinology, diabetes, and diabetes technology.

Clinical Performance Evaluation of Continuous Glucose Monitoring Systems: A Scoping Review and Recommendations for Reporting.

The use of different approaches for design and results presentation of studies for the clinical performance evaluation of continuous glucose monitoring (CGM) systems has long been recognized as a major challenge in comparing their results. However, a comprehensive characterization of the variability in study designs is currently unavailable. This article presents a scoping review of clinical CGM performance evaluations published between 2002 and 2022. Specifically, this review quantifies the prevalence of numerous options associated with various aspects of study design, including subject population, comparator (reference) method selection, testing procedures, and statistical accuracy evaluation. We found that there is a large variability in nearly all of those aspects and, in particular, in the characteristics of the comparator measurements. Furthermore, these characteristics as well as other crucial aspects of study design are often not reported in sufficient detail to allow an informed interpretation of study results. We therefore provide recommendations for reporting the general study design, CGM system use, comparator measurement approach, testing procedures, and data analysis/statistical performance evaluation. Additionally, this review aims to serve as a foundation for the development of a standardized CGM performance evaluation procedure, thereby supporting the goals and objectives of the Working Group on CGM established by the Scientific Division of the International Federation of Clinical Chemistry and Laboratory Medicine.

Lipohypertrophy and Insulin: An Update From the Diabetes Technology Society.

Lipohypertrophy is a common skin complication associated with insulin-treated diabetes. The impact of lipohypertrophy as a contributing factor to suboptimal glycemic control, glucose variability, and hypoglycemia is often under-recognized by health care professionals. In a recent Webinar on April 26, 2023, Diabetes Technology Society asked international experts to provide updates on the latest knowledge related to lipohypertrophy for practicing clinicians and educators, researchers, and industries involved in insulin delivery. A recording of the Webinar is freely available on the Diabetes Technology Society Web site (https://www.diabetestechnology.org/).