Diabetes management mediating effects between diabetes symptoms and health-related quality of life in adolescents and young adults with type 1 diabetes.

OBJECTIVES: The primary objective was to investigate the mediating effects of diabetes management in the relationship between diabetes symptoms and generic health-related quality of life (HRQOL) in adolescents and young adults (AYAs) with type 1 diabetes. The secondary objective explored patient health communication and perceived treatment adherence barriers as mediators in a serial multiple mediator model. METHODS: The PedsQL 3.2 Diabetes Module 15-item diabetes symptoms summary score, 18-item diabetes management summary score, and PedsQL 4.0 generic core scales were completed in a 10-site national field test study by 418 AYA aged 13 to 25 years with type 1 diabetes. Diabetes symptoms and diabetes management were tested for bivariate and multivariate linear associations with overall generic HRQOL. Mediational analyses were conducted to test the hypothesized mediating effects of diabetes management as an intervening variable between diabetes symptoms and generic HRQOL. RESULTS: The predictive effects of diabetes symptoms on HRQOL were mediated in part by diabetes management. In predictive analytics models utilizing multiple regression analyses, demographic and clinical covariates, diabetes symptoms, and diabetes management significantly accounted for 53% of the variance in generic HRQOL (P < 0.001), demonstrating a large effect size. Patient health communication and perceived treatment adherence barriers were significant mediators in an exploratory serial multiple mediator model. CONCLUSIONS: Diabetes management explains in part the effects of diabetes symptoms on HRQOL in AYA with type 1 diabetes. Patient health communication to healthcare providers and perceived treatment adherence barriers further explain the mechanism in the relationship between diabetes symptoms and overall HRQOL.

Diabetes symptoms predictors of health-related quality of life in adolescents and young adults with type 1 or type 2 diabetes.

OBJECTIVES: The objective was to investigate the patient-reported diabetes symptoms predictors of generic health-related quality of life (HRQOL) in adolescents and young adults (AYA) with type 1 or type 2 diabetes. METHODS: The 15-item PedsQL™ 3.2 Diabetes Module Diabetes Symptoms Summary Score and PedsQL™ 4.0 Generic Core Scales were completed in a 10-site national field test study by 513 AYA ages 13-25 years with type 1 (n = 424) or type 2 (n = 89) diabetes. Diabetes symptoms were tested for bivariate and multivariate linear associations with generic HRQOL. RESULTS: Diabetes symptoms were associated with decreased HRQOL in bivariate analyses. In predictive analytics models utilizing hierarchical multiple regression analyses controlling for relevant demographic and clinical covariates, diabetes symptoms accounted for 38 and 39% of the variance in patient-reported generic HRQOL for type 1 and type 2 diabetes, respectively, reflecting large effect sizes. The diabetes symptoms facets hyperglycemia symptoms, hypoglycemia symptoms, and nonspecific diabetes symptoms individually accounted for a significant percentage of the variance in separate exploratory predictive analytics models after controlling for demographic and clinical covariates, with small-to-large effect sizes. CONCLUSIONS: Diabetes symptoms are potentially modifiable predictors of generic HRQOL in AYA with diabetes. Identifying specific diabetes symptoms or symptoms facets that are the most important predictors from the patient perspective facilitates a patient-centered approach in clinical research, clinical trials, and practice designed to enhance overall generic HRQOL in AYA with diabetes.

Insulin pump use in young children in the T1D Exchange clinic registry is associated with lower hemoglobin A1c levels than injection therapy.

Insulin delivery via injection and continuous subcutaneous insulin infusion (CSII) via insulin pump were compared in a cross-sectional study (n = 669) and retrospective longitudinal study (n = 1904) of young children (<6 yr) with type 1 diabetes (T1D) participating in the T1D Exchange clinic registry. Use of CSII correlated with longer T1D duration (p < 0.001), higher parental education (p < 0.001), and annual household income (p < 0.006) but not with race/ethnicity. Wide variation in pump use was observed among T1D Exchange centers even after adjusting for these factors, suggesting that prescriber preference is a substantial determinant of CSII use. Hemoglobin A1c (HbA1c) was lower in pump vs. injection users (7.9 vs. 8.5%, adjusted p < 0.001) in the cross-sectional study. In the longitudinal study, HbA1c decreased after initiation of CSII by 0.2%, on average (p < 0.001). Frequency of a severe hypoglycemia (SH) event did not differ in pump vs. injection users (p = 0.2). Frequency of ≥1 parent-reported diabetic ketoacidosis (DKA) event in the prior year was greater in pump users than injection users (10 vs. 8%, p = 0.04). No differences between pump and injection users were observed for clinic-reported DKA events. Children below 6 yr have many unique metabolic characteristics, feeding behaviors, and care needs compared with older children and adolescents. These data support the use of insulin pumps in this youngest age group, and suggest that metabolic control may be improved without increasing the frequency of SH, but care should be taken as to the possibly increased risk of DKA.

Comparison of Insulin Pump Bolus Calculators Reveals Wide Variation in Dose Recommendations.

BACKGROUND: The introduction of insulin pumps with bolus calculators (BCs) has improved glycemic outcomes and quality of life for those with type 1 diabetes. Despite the increased reliance on BCs, the formulas used to derive recommended boluses are not standardized. Our objective was to examine whether recommendations from different pump BCs vary significantly for identical clinical scenarios. METHODS: Three commercially available insulin pump BCs were programmed with identical settings and then presented with combinations of blood glucose (BG) and carbohydrates (CHOs) to generate a 4-unit bolus. At one- and two-hour time points, while there was insulin-on-board (IOB) present, we simulated various BG and CHO scenarios in order to compare BC-recommended doses. RESULTS: Differences in suggested doses were noted between BCs, as well as within the same brand. The greatest variation was apparent when BG was below target. Doses suggested by one BC varied depending on whether the IOB resulted from a previous dose given for BG or CHO, while the other two BCs adjusted for total IOB regardless of the source. CONCLUSIONS: In this simulation study, there were large differences in recommended doses between BCs due to the unique way each manufacturer incorporates IOB into their formulas as well as the pharmacokinetics used to derive the IOB amount. Providers should be aware that identical pump settings will result in a different dose recommendation for each pump brand and advise patients accordingly.

Digital Diabetes Congress 2019.

New applications of digital health software and sensors for diabetes are rapidly becoming available. The link between healthcare, wearable or carryable devices, and the use of smartphones is increasingly being used by patients for timely information and by healthcare professionals to deliver information and personalized advice and to encourage healthy behavior. To assemble stakeholders from academia, industry, and government, Diabetes Technology Society and Sansum Diabetes Research Institute hosted the 3rd Annual Digital Diabetes Congress on May 14-15, 2019 in San Francisco. Physicians, entrepreneurs, attorneys, psychologists, and other leaders in the diabetes technology field came together to discuss current and future trends and applications of digital tools in diabetes. The meeting focused on eight topics: 1) User Interface/User Experience (UI/UX) for Digital Health, 2) clinical aspects, 3) marketing, 4) investment, 5) regulation, 6) who owns the data, 7) engagement, and 8) the future of digital health. This meeting report contains summaries of the meeting's eight plenary sessions and eight panel discussions, which were all focused on an important aspect of the development, use, and regulation of diabetes digital tools.

Diabetes Technology Society Report on the FDA Digital Health Software Precertification Program Meeting.

Diabetes Technology Society (DTS) convened a meeting about the US Food and Drug Administration (FDA) Digital Health Software Precertification Program on August 28, 2018. Forty-eight attendees participated from clinical and academic endocrinology (both adult and pediatric), nursing, behavioral health, engineering, and law, as well as representatives of FDA, National Institutes of Health (NIH), National Telecommunications and Information Administration (NTIA), and industry. The meeting was intended to provide ideas to FDA about their plan to launch a Digital Health Software Precertification Program. Attendees discussed the four components of the plan: (1) excellence appraisal and certification, (2) review pathway determination, (3) streamlined premarket review process, and (4) real-world performance. The format included (1) introductory remarks, (2) a program overview presentation from FDA, (3) roundtable working sessions focused on each of the Software Precertification Program's four components, (4) presentations reflecting the discussions, (5) questions to and answers from FDA, and (6) concluding remarks. The meeting provided useful information to the diabetes technology community and thoughtful feedback to FDA.

A Pilot Study of Use of a Software Platform for the Collection, Integration, and Visualization of Diabetes Device Data by Health Care Providers in a Multidisciplinary Pediatric Setting.

BACKGROUND: Diabetes devices provide data for health care providers (HCPs) and people with type 1 diabetes to make management decisions. Extracting and viewing the data require separate, proprietary software applications for each device. In this pilot study, we examined the feasibility of using a single software platform (Tidepool) that integrates data from multiple devices. MATERIALS AND METHODS: Participating HCPs (n = 15) used the software with compatible devices in all patient visits for 6 months. Samples of registration desk activity and office visits were observed before and after introducing the software, and HCPs provided feedback by survey and focus groups. RESULTS: The time required to upload data and the length of the office visit did not change. However, the number of times the HCP referred to the device data with patients increased from a mean of 2.8 (±1.2) to 6.1 (±3.1) times per visit (P = 0.0002). A significantly larger proportion of children looked at the device data with the new application (baseline: 61% vs. study end: 94%, P = 0.015). HCPs liked the web-based user interface, integration of the data from multiple devices, the ability to remotely access data, and use of the application to initiate patient education. Challenges included the need for automated data upload and integration with electronic medical records. CONCLUSIONS: The software did not add to the time needed to upload data or the length of clinic visits and promoted discussions with patients about data. Future studies of HCP use of the application will evaluate clinical outcomes and effects on patient engagement and self-management.

Digital Diabetes Congress 2018.

Digital health is capturing the attention of the healthcare community. This paradigm whereby healthcare meets the internet uses sensors that communicate wirelessly along with software residing on smartphones to deliver data, information, treatment recommendations, and in some cases control over an effector device. As artificial intelligence becomes more widely used, this approach to creating individualized treatment plans will increase the opportunities for patients, even if they are in remote settings, to communicate with and learn from healthcare professionals. Simple design is needed to promote use of these tools, especially for the purpose of increased adherence to treatment. Widespread adoption by the healthcare industry will require better outcomes data, which will most likely be in the form of safety and effectiveness results from robust randomized controlled trials, as well as evidence of privacy and security. Such data will be needed to convince investors to direct resources into and regulators to clear new digital health tools. Diabetes Technology Society and William Sansum Diabetes Center launched the Digital Diabetes Congress in 2017 because of great interest in determining the potential benefits, metrics of success, and appropriate components of mobile applications for diabetes. The second annual meeting in this series took place on May 22-23, 2018 in San Francisco. This report contains summaries of the meeting's 4 plenary lectures and 10 sessions. This meeting report presents a summary of how 55 panelists, speakers, and moderators, who are leaders in healthcare technology, see the current and future landscape of digital health tools applied to diabetes.

Pilot Study of a Novel Application for Data Visualization in Type 1 Diabetes.

BACKGROUND: A novel software application, Blip, was created to combine and display diabetes data from multiple devices in a uniform, user-friendly manner. The objective of this study was to test the usability of this application by adults and caregivers of children with type 1 diabetes (T1D). METHODS: Patients (n = 35) and caregivers of children with T1D (n = 30) using an insulin pump for >1 year ± CGM were given access to the software for 3 months. Diabetes management practices and the use of diabetes data were assessed at baseline and at study end, and feedback was gathered in a concluding questionnaire. RESULTS: At baseline, 97% of participants agreed it was important for patients to know how to interpret glucose data. Most felt that clinicians and patients should share the tasks of reviewing data, finding patterns, and making changes to their insulin plans. However, despite valuing shared responsibility, at baseline, 43% of participants never downloaded pump data, and only 9% did so at least once per month. At study end, 72% downloaded data at least once during the 3-month study, and 38% downloaded at least once per month. Regarding the software application, participants liked the central repository of data and the user interface. Suggestions included providing tools for understanding and interpreting glucose patterns, an easier uploading process, and access with mobile devices. CONCLUSIONS: Collaboration between developers and researchers prompted iterative, rapid development of data visualization software and improvements in the uploading process and user interface, which facilitates clinical integration and future clinical studies.

Digital Diabetes Congress 2017.

The purpose of developing mobile applications for diabetes is generally to: (1) provide enhanced access to timely information for patients, health care professionals, and researchers; (2) facilitate remote monitoring and diagnosis of patients, often based on information delivered by wearable devices; (3) provide decision support to assist patients in selecting treatment; or (4) deliver timely recommendations for treatment to increase adherence to prescribed therapy. There is a perception that mobile applications can provide meaningful clinical benefits, however, there is only sparse convincing evidence to support this belief at the present time. Compounding this problem is the short life span of digital software, such that if a traditional type of randomized controlled trial is conducted on a product, by the time the study has been designed, approved by an IRB, conducted, and analyzed, the product might have significantly changed to a next generation system. Because of great interest in establishing what are the potential benefits, metrics of success, and appropriate components of mobile applications for diabetes, Diabetes Technology Society and William Sansum Diabetes Center launched the Digital Diabetes Congress, March 7-8, 2017, in San Francisco. This report contains summaries of the meeting's 12 sessions. Each summary was written by the session's moderator who helped develop the session prior to the event and keep it on track during the event. This meeting report presents a summary of how 57 panelists, speakers, and moderators, who are leaders in digital health, see the current and future landscape of digital health tools applied to diabetes.

Evaluation of Pump Discontinuation and Associated Factors in the T1D Exchange Clinic Registry.

BACKGROUND: The objectives of this study were to examine factors associated with insulin pump discontinuation among children and adults followed longitudinally for 1 year in the multicenter T1D Exchange clinic registry, and to provide participant-reported reasons for stopping pump therapy. METHODS: We longitudinally followed 8935 participants of all ages using an insulin pump at the time of registry enrollment. Logistic regressions were used to identify demographic and clinical factors associated with pump discontinuation. Pump discontinuation was self-reported by participants on a first annual follow-up survey. RESULTS: The overall frequency of pump discontinuation was 3%. Discontinuation was higher in adolescents (4%) and young adults (4%) than in younger children (3%) or older adults (1%). In multivariate analysis of children between 6 and <13 and 13 and <18 years, participants who discontinued pump use were more likely to have higher HbA1c levels at baseline (adjusted P < .001 for both). The top participant-reported reasons for discontinuing the pump included problems with wearability (57%), disliking the pump or feeling anxious (44%), and problems with glycemic control (30%). CONCLUSIONS: In T1D Exchange registry participants, insulin pump discontinuation is uncommon, but more prevalent among adolescents and young adults, and youth with poor glycemic control. Given the known benefits of pump therapy, these populations should be targeted for support and education on troubleshooting pump use. Common reasons for discontinuation should also be considered in future device design and technological improvement.

A case study in open source innovation: developing the Tidepool Platform for interoperability in type 1 diabetes management.

OBJECTIVE: Develop a device-agnostic cloud platform to host diabetes device data and catalyze an ecosystem of software innovation for type 1 diabetes (T1D) management. MATERIALS AND METHODS: An interdisciplinary team decided to establish a nonprofit company, Tidepool, and build open-source software. RESULTS: Through a user-centered design process, the authors created a software platform, the Tidepool Platform, to upload and host T1D device data in an integrated, device-agnostic fashion, as well as an application ("app"), Blip, to visualize the data. Tidepool's software utilizes the principles of modular components, modern web design including REST APIs and JavaScript, cloud computing, agile development methodology, and robust privacy and security. DISCUSSION: By consolidating the currently scattered and siloed T1D device data ecosystem into one open platform, Tidepool can improve access to the data and enable new possibilities and efficiencies in T1D clinical care and research. The Tidepool Platform decouples diabetes apps from diabetes devices, allowing software developers to build innovative apps without requiring them to design a unique back-end (e.g., database and security) or unique ways of ingesting device data. It allows people with T1D to choose to use any preferred app regardless of which device(s) they use. CONCLUSION: The authors believe that the Tidepool Platform can solve two current problems in the T1D device landscape: 1) limited access to T1D device data and 2) poor interoperability of data from different devices. If proven effective, Tidepool's open source, cloud model for health data interoperability is applicable to other healthcare use cases.

A Minority of Patients with Type 1 Diabetes Routinely Downloads and Retrospectively Reviews Device Data.

BACKGROUND: In type 1 diabetes (T1D), periodic review of blood glucose and insulin dosing should be performed, but it is not known how often patients review these data on their own. We describe the proportion of patients with T1D who routinely downloaded and reviewed their data at home. MATERIALS AND METHODS: A cross-sectional survey of 155 adults and 185 caregivers of children with T1D at a single academic institution was performed. "Routine Downloaders" (downloaded four or more times in the past year) were also considered "Routine Reviewers" if they reviewed their data most of the time they downloaded from devices. Logistic regression was used to identify factors associated with being a Routine Reviewer. RESULTS: Only 31% of adults and 56% of caregivers reported ever downloading data from one or more devices, whereas 20% and 40%, respectively, were considered Routine Downloaders. Only 12% of adults and 27% of caregivers were Routine Reviewers. Mean hemoglobin A1c was lower in Routine Reviewers compared with non-Routine Reviewers (7.2±1.0% vs. 8.1±1.6% [P=0.03] in adults and 7.8±1.4% vs. 8.6±1.7% [P=0.001] in children). In adjusted analysis of adults, the odds ratio of being a Routine Reviewer of one or more devices for every 10-year increase in age was 1.5 (95% confidence interval, 1.1, 2.1 [P=0.02]). For every 10 years since diabetes diagnosis, the odds ratio of being a Routine Reviewer was 1.7 (95% confidence interval, 1.2, 2.4 [P=0.01]). For caregivers, there were no statistically significant factors associated with being a Routine Reviewer. CONCLUSIONS: A minority of T1D patients routinely downloads and reviews data from their devices on their own. Further research is needed to understand obstacles, provide better education and tools for self-review, and determine if patient self-review is associated with improved glycemic control.

Early stimulation and late inhibition of extracellular signal-regulated kinase 1/2 phosphorylation by IGF-I: a potential mechanism mediating the switch in IGF-I action on skeletal muscle cell differentiation.

IGF-I has a unique biphasic effect on skeletal muscle cell differentiation. Initially, IGF-I inhibits differentiation and promotes proliferation of skeletal myoblasts. Subsequently, IGF-I switches to stimulating differentiation of these cells. The mechanisms responsible for this switch in IGF action remain unknown. We have examined the role of extracellular signal-regulated kinase (Erk)1/2 signaling in mediating the early inhibitory and late stimulatory effects of IGF-I on the gene expression of myogenin, a skeletal muscle-specific transcription factor essential for myogenic differentiation. We find that, concurrent with its early inhibitory and late stimulatory effects on myogenin mRNA, IGF-I has a biphasic but opposite effect on phosphorylation of Erk1/2: initially, IGF-I increases and subsequently decreases the phosphorylation of Erk1/2 in comparison to untreated cells. Cotreatment with an inhibitor of Erk1/2 activation prevents the early IGF-I-stimulation of Erk1/2 phosphorylation and partially reverses IGF-I-inhibition of myogenin mRNA. Conversely, preventing the late IGF-I-induced decrease in Erk1/2 phosphorylation blocks IGF-I-stimulation of myogenin mRNA. Our data indicate that the time-dependent, opposing effects of IGF-I on skeletal muscle cell differentiation are mediated, at least in part, by biphasic but opposite effects on activation of the Erk1/2 MAPK signaling pathway.

Akt phosphorylation is not sufficient for insulin-like growth factor-stimulated myogenin expression but must be accompanied by down-regulation of mitogen-activated protein kinase/extracellular signal-regulated kinase phosphorylation.

IGF-I has a unique biphasic effect on skeletal muscle differentiation. Initially, IGF-I inhibits expression of myogenin, a skeletal muscle-specific regulatory factor essential for myogenesis. Subsequently, IGF-I switches to stimulating expression of myogenin. The mechanisms that mediate this switch in IGF action are incompletely understood. Several laboratories have demonstrated that the phosphatidylinositol-3-kinase/Akt signaling pathway is essential for myogenic differentiation and have suggested that this pathway mediates IGF-I stimulation of myogenin mRNA expression, an early critical step in the differentiation process. These studies, however, did not address concurrent Akt and MAPK/ERK1/2 phosphorylation, the latter of which is also known to regulate myogenic differentiation. In the present study in rat L6E9 muscle cells, we have manipulated ERK1/2 phosphorylation with either an upstream inhibitor or activator and examined concurrent levels of Akt and ERK1/2 phosphorylation and of myogenin mRNA expression in response to treatment with IGF-I. We find that even in the presence of phosphorylated Akt, it is only when ERK1/2 phosphorylation is inhibited that IGF-I can stimulate myogenin mRNA expression. Thus, although Akt phosphorylation may be necessary, it is not sufficient for induction of myogenic differentiation by IGF-I and must be accompanied by a decrease in ERK1/2 phosphorylation.

Cardio-facio-cutaneous syndrome: clinical features, diagnosis, and management guidelines.

Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care.

Real-time continuous glucose monitoring among participants in the T1D Exchange clinic registry.

OBJECTIVE: To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]). RESEARCH DESIGN AND METHODS: Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days. RESULTS: Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ≥26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P < 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P < 0.001) and adults (7.7% vs. 7.9%, P < 0.001). In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year. CONCLUSIONS: CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.

Type 1 diabetes mellitus in adolescents.

The diagnosis and management of type 1 diabetes in adolescents present special challenges related to the unique hormonal and emotional milieu in the teenage years. Management of type 1 diabetes requires a multitude of life-long daily tasks that the child and/or family must perform to maintain a relatively healthy metabolism and glycemic control. Although in younger children these tasks are performed primarily by the care givers, in the teenage years the burden of diabetes management falls on the adolescents themselves. This review focuses on some of the unique aspects in the diagnosis and management of type 1 diabetes in adolescents, and the impact of pubertal changes on diabetes control, and presents an overview of general guidelines to aid health care providers in the acute and long-term care of these patients.