Impact of school-supervised ultra-long-acting basal insulin injections on ketosis in youth with T1D and elevated haemoglobin A1c: A pilot study.

BACKGROUND: In youth with type 1 diabetes (T1D), high haemoglobin A1c (HbA1c) levels are associated with an increased risk for diabetic ketoacidosis (DKA). AIMS: This study examined whether daily school-supervised basal insulin injections were feasible and if they reduced the risk of morning ketosis in children and adolescents with high HbA1c levels. We hypothesized that supervised glargine and degludec would reduce the risk of ketosis and that the prolonged action of degludec would protect from ketosis after consecutive days of unsupervised injections. MATERIALS & METHODS: After a 2-4-week run-in, youth (10-18 years, HbA1c ≥ 8.5%) managing T1D with injections were randomized to school-supervised administration of degludec or glargine for 4 months. School nurses observed daily blood ß-hydroxybutyrate (BHB) and glucose checks. During COVID closures, the research team supervised procedures remotely. RESULTS: Data from 28 youth (age 14.3 ± 2.3 years, HbA1c 11.4 ± 1.9%, 64% F) were analysed. School-supervised injections of both basal insulins for 1-4 days progressively lowered the percent of participants with elevated BHB. The percent of participants with elevated BHB (≥0.6 mmol/L) after 2 days of unsupervised basal insulin doses at home was greater in the glargine than degludec group but had a high p-value (17.2% vs. 9.0%, p = 0.3). HbA1c was unchanged in both groups. DISCUSSION: In youth with T1D at high risk for DKA, daily supervised long-acting insulin administration decreased the probability of elevated ketone levels on subsequent school days, regardless of basal insulin type. A larger sample size may have demonstrated that the longer action profile of degludec would offer additional protection from ketosis during days of not attending school. CONCLUSION: Engaging school-based caregivers in management of youth with T1D on injected insulin may decrease clinically significant ketosis and minimize acute complications of diabetes.

Personalized Digital Health Information to Substantiate Human-Delivered Exercise Support for Adults With Type 1 Diabetes.

OBJECTIVE: Pilot-test personalized digital health information to substantiate human-delivered exercise support for adults with type 1 diabetes (T1D). DESIGN: Single-group, 2-week baseline observation, then 10-week intervention with follow-up observation. SETTING: Community-based sample participating remotely with physician oversight. PARTICIPANTS: Volunteers aged 18 to 65 years with T1D screened for medical readiness for exercise intervention offerings. N = 20 enrolled, and N = 17 completed all outcomes with 88% to 91% biosensor adherence. INTERVENTION: Feedback on personalized data from continuous glucose monitoring (CGM), its intersection with other ecological data sets (exercise, mood, and sleep), and other informational and motivational elements (exercise videos, text-based exercise coach, and self-monitoring diary). MAIN OUTCOME MEASURES: Feasibility (use metrics and assessment completion), safety (mild and severe hypoglycemia, and diabetic ketoacidosis), acceptability (system usability scale, single items, and interview themes), and standard clinical and psychosocial assessments. RESULTS: Participants increased exercise from a median of 0 (Interquartile range, 0-21) to 64 (20-129) minutes per week ( P = 0.001, d = 0.71) with no severe hypoglycemia or ketoacidosis. Body mass index increased (29.5 ± 5.1 to 29.8 ± 5.4 kg/m 2 , P = 0.02, d = 0.57). Highest satisfaction ratings were for CGM use (89%) and data on exercise and its intersection with CGM and sleep (94%). Satisfaction was primarily because of improved exercise management behavioral skills, although derived motivation was transient. CONCLUSIONS: The intervention was feasible, safe, and acceptable. However, there is a need for more intensive, sustained support. Future interventions should perform analytics upon the digital health information and molecular biomarkers (eg, genomics) to make exercise support tools that are more personalized, automated, and intensive than our present offerings.

Bayesian structural time series for biomedical sensor data: A flexible modeling framework for evaluating interventions.

The development of mobile-health technology has the potential to revolutionize personalized medicine. Biomedical sensors (e.g., wearables) can assist with determining treatment plans for individuals, provide quantitative information to healthcare providers, and give objective measurements of health, leading to the goal of precise phenotypic correlates for genotypes. Even though treatments and interventions are becoming more specific and datasets more abundant, measuring the causal impact of health interventions requires careful considerations of complex covariate structures, as well as knowledge of the temporal and spatial properties of the data. Thus, interpreting biomedical sensor data needs to make use of specialized statistical models. Here, we show how the Bayesian structural time series framework, widely used in economics, can be applied to these data. This framework corrects for covariates to provide accurate assessments of the significance of interventions. Furthermore, it allows for a time-dependent confidence interval of impact, which is useful for considering individualized assessments of intervention efficacy. We provide a customized biomedical adaptor tool, MhealthCI, around a specific implementation of the Bayesian structural time series framework that uniformly processes, prepares, and registers diverse biomedical data. We apply the software implementation of MhealthCI to a structured set of examples in biomedicine to showcase the ability of the framework to evaluate interventions with varying levels of data richness and covariate complexity and also compare the performance to other models. Specifically, we show how the framework is able to evaluate an exercise intervention's effect on stabilizing blood glucose in a diabetes dataset. We also provide a future-anticipating illustration from a behavioral dataset showcasing how the framework integrates complex spatial covariates. Overall, we show the robustness of the Bayesian structural time series framework when applied to biomedical sensor data, highlighting its increasing value for current and future datasets.

A Pilot Study of Youth With Type 1 Diabetes Initiating Use of a Hybrid Closed-Loop System While Receiving a Behavioral Economics Intervention.

OBJECTIVE: Many youth do not use the hybrid closed-loop system for type 1 diabetes effectively. This study evaluated the impact of financial incentives for diabetes-related tasks on use of the 670G hybrid closed-loop system and on glycemia. METHODS: At auto mode initiation and for 16 weeks thereafter, participants received a flat rate for wearing and calibrating the sensor ($1/day), administering at least 3 mealtime insulin boluses per day ($1/day), and uploading ($5/week). Weekly bonuses were given for maintaining at least 70% of the time in auto mode, which were increased for persistent auto mode use from $3/week to a maximum of $13/week. If a participant failed to maintain auto mode for a week, the rewards were reset to baseline. Data from 17 participants aged 15.9 years ± 2.5 years (baseline hemoglobin A1c [HbA1c] 8.6% ± 1.1%) were collected at 6, 12, and 16 weeks. The reinforcers were withdrawn at 16 weeks, with a follow-up assessment at 24 weeks. RESULTS: With reinforcers, the participants administered an average of at least 3 mealtime insulin boluses per day and wore the sensor over 70% of the time. However, auto mode use waned. HbA1c levels decreased by 0.5% after 6 weeks, and this improvement was maintained at 12 and 16 weeks (P < .05). Upon withdrawal of reinforcers, HbA1c levels increased back to baseline at 24 weeks. CONCLUSION: Compensation for diabetes-related tasks was associated with lower HbA1c levels, consistent administration of mealtime insulin boluses, and sustained sensor use. These results support the potential of financial rewards for improving outcomes in youth with type 1 diabetes.

The Influence of Health Mindset on Perceptions of Illness and Behaviors Among Adolescents.

BACKGROUND: Health mindsets can be viewed on a continuum of malleability from fixed (health cannot be altered) to growth (health can be affected by behavior). We propose that mindsets may influence the health perceptions of healthy adolescents as well as the health behaviors of adolescents with a chronic illness. METHODS: In Study 1, we surveyed healthy adolescents about their health mindsets and their judgments of illness in response to vignettes of fictional others. In Study 2, we measured the health mindsets and health behaviors of adolescents with type 1 diabetes RESULTS: In Study 1, healthy adolescents with a fixed health mindset were more likely to rate fictional others as being less healthy, less likely to recover, and more vulnerable to additional diseases. In Study 2, a growth mindset was associated with a greater frequency of glucose monitoring among younger, but not older, adolescents with type 1 diabetes. Further, growth mindset was associated with lower HbA1c levels for younger adolescents. CONCLUSIONS: Health mindsets may shape views of the implications of illness or injury for overall health and, in adolescents with a chronic condition, may interact with age to influence health behaviors and outcomes.

Wilderness Medical Society Clinical Practice Guidelines for Diabetes Management.

The Wilderness Medical Society convened an expert panel in 2018 to develop a set of evidence-based guidelines for the treatment of type 1 and 2 diabetes, as well as the recognition, prevention, and treatment of complications of diabetes in wilderness athletes. We present a review of the classifications, pathophysiology, and evidence-based guidelines for planning and preventive measures, as well as best practice recommendations for both routine and urgent therapeutic management of diabetes and glycemic complications. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks or burdens for each recommendation.

Integrated Strategies to Support Diabetes Technology in Pregnancy.

Managing diabetes in pregnancy can be overwhelming, with numerous dramatic physiologic changes taking place that require constant diligence and attention. Advances in diabetes technology have improved glycemic outcomes, well-being, and quality of life for people with type 1 diabetes of all ages. However, regulatory approval and access to diabetes technology in pregnancy has lagged behind these advancements, leaving many pregnant individuals without tools that could dramatically improve diabetes care before, during, and after gestation. Here, we review the benefits of continuous glucose monitors and automated insulin-delivery systems in pregnancy and highlight specific scientific and structural supports to help implement diabetes technology safely, effectively, and equitably in pregnancy.

Facilitating the Virtual Exercise Games for Youth with T1D (ExerT1D) Peer Intervention: Protocol Development and Feasibility.

Background: Barriers to moderate-to-vigorous physical activity (MVPA) for adolescents with type 1 diabetes (T1D) include physiology, transition to autonomy, and diabetes-specific stigma. Opportunities for T1D peer activities with T1D role model support are limited. To address this need, our single-arm pilot study tested the Home-based Virtual Activity Program for Youth with T1D (HAP-V-T1D) for feasibility. Methods: Participants (n=15) were mean age 15.6 [SD 1.5] years, 7 non-Hispanic white, 6 female, 2 non-binary, mean A1c 8.9%±2.2%. The program included an MVPA videogame, physician-led education regarding managing T1D around MVPA, objective habitual MVPA goal-setting , and T1D management skills guided by young adult instructors living with T1D. Results: For feasibility, 13/15 participants attended 10/12 sessions. Participants' perceptions of the program, comfort, instructors, and group cohesion were rated high/very high (4.2±0.5 to 4.8±0.3 out of 5).Motivation for the videogame was also high (4.1±0.4 out of 5). Instructor-adolescent interactions related to building T1D management skills were rated as excellent for 78% of sessions. Similarly, sharing knowledge and experiences were rated as excellent for 68% of sessions. However, adolescent-adolescent interactions were poor (communication 29% excellent, peer interactions 8% excellent). The most reported barriers to participation were negative mood and oversleeping. No participants experienced diabetic ketoacidosis, severe hypoglycemia, or injuries during the study period. Compared to baseline, glycemic metrics appeared to decrease during and post intervention (d= -0.72, -1.12). Conclusion: HAP-V-T1D facilitated unprecedented T1D peer support achievements by engaging diverse youth with T1D in an MVPA program led by T1D role models. Larger studies are needed to assess if this intervention can improve glycemic measures and reduce diabetes-specific stigma.

Navigating barriers to affording and obtaining insulin and diabetes supplies.

Highlights Our study suggests that people with diabetes (PWD) face issues of affording and obtaining insulin and diabetes supplies, even in a population predominantly on private health insurance. Financially independent young adults reported increased compensatory strategies and resulting perilous behaviors to ration or obtain insulin and supplies, indicating that additional issues may arise once transitioning into adulthood. This study suggests that improved access and affordability of insulin and diabetes supplies is needed to reduce the financial burden and prevent adverse outcomes among PWD.

Technology Utilization in Black Adolescents with Type 1 Diabetes: Exploring the Decision-Making Process.

Background: Significant disparities in diabetes device (DD) use exist for Black adolescents with type 1 diabetes (T1D), meriting further exploration. We sought to describe how Black adolescents with T1D and their parents make decisions about using DDs and understand personal, familial, and cultural beliefs that may influence use. Materials and Methods: Nineteen Black adolescents with T1D and 17 parents participated in individual qualitative semistructured interviews. Adolescents were purposively sampled for a range of socioeconomic and clinical demographics. Interview data were recorded, transcribed, and coded for thematic analysis, analyzed separately for parents and adolescents, and then compared across groups. Data collection continued until thematic saturation was achieved. Results: Adolescents and parents reported similar themes related to the (1) intersectionality of multiple identities: T1D experience of Black adolescents; (2) decision to use DDs: complexities of T1D management and easing the burden; and (3) reasons for differential uptake of DDs in Black adolescents. Adolescents reported lacking peers with T1D "who look like me," leading to stigmatization, exacerbated by device visibility and alarms. Cultural and familial traditions as well as individual factors were described as both facilitators and barriers in DD use. Lack of familiarity with T1D, limited exposure to DDs, and mistrust of the medical community, both historically and currently, were brought up as reasons for inequities in DD use. Conclusions: Understanding the decision-making process surrounding DDs in one sample of Black adolescents and their parents is critical to guide further research to improve equity in DD use and glycemic outcomes.

Feasibility and Preliminary Safety of Smartphone-Based Automated Insulin Delivery in Adolescents and Children With Type 1 Diabetes.

BACKGROUND: A smartphone-based automated insulin delivery (AID) controller device can facilitate use of interoperable components and acceptance in adolescents and children. METHODS: Pediatric participants (N = 20, 8F) with type 1 diabetes were enrolled in three sequential age-based cohorts: adolescents (12-<18 years, n = 8, 5F), school-age (8-<12 years, n = 7, 2F), and young children (2-<8 years, n = 5, 1F). Participants used the interoperable artificial pancreas system (iAPS) and zone model predictive control (MPC) on an unlocked smartphone for 48 hours, consumed unrestricted meals of their choice, and engaged in various unannounced exercises. Primary outcomes and stopping criteria were defined using fingerstick blood glucose (BG) data; secondary outcomes compared continuous glucose monitoring (CGM) data with preceding sensor augmented pump (SAP) therapy. RESULTS: During AID, there was no more than one BG <50 mg/dL except in one young child participant; no instance of more than two episodes of BG ≥300 mg/dL lasting longer than 2 hours; and no adverse events. Despite large meals (total of 404.9 grams of carbs) and unannounced exercise (total of 182 minutes), overall CGM percent time in range (TIR) of 70 to 180 mg/dL during AID was statistically similar to SAP (63.5% vs 57.3%, respectively, P = .145). Overnight glucose standard deviation was 43 mg/dL (vs SAP 57.9 mg/dL, P = .009) and coefficient of variation was 25.7% (vs SAP 34.9%, P < .001). The percent time in closed-loop mode and connected to the CGM was 92.7% and 99.6%, respectively. Surveys indicated that participants and parents/guardians were satisfied with the system. CONCLUSIONS: The smartphone-based AID was feasible and safe in sequentially younger cohorts of adolescents and children. CLINICALTRIALS.GOV: NCT04255381 (https://clinicaltrials.gov/ct2/show/NCT04255381).

Plasmapheresis as an Early Treatment for Severe Hypertriglyceridemia, Acute Pancreatitis, and Diabetic Ketoacidosis.

OBJECTIVE: Severe hypertriglyceridemia (SHTG; plasma triglycerides >1000 mg/dL) is a rare but serious complication in children who develop diabetic ketoacidosis (DKA) from uncontrolled or new-onset type 1 diabetes. METHODS: We present the case of a severely malnourished 16-year-old with a 10-month history of presumed type 2 diabetes managed with lifestyle modifications and metformin, who presented with SHTG, acute pancreatitis, and DKA. On examination, there was no evidence of lipemia retinalis, cutaneous xanthomas, or xanthelasma. He was initially treated with an insulin infusion and intravenous fluids. Despite this treatment, his pancreatitis symptoms worseneed and lipase level increased, necessitating 2 courses of plasmapheresis that immediately resolved his symptoms and dramatically improved his clinical status. He was discharged on hospital day 5. During his hospital admission, islet cell antigen 512, insulin, glutamic acid decarboxylase 65, and zinc transporter 8 autoantibodies were positive in the presence of insulinopenia, consistent with type 1 diabetes. RESULTS: Hypertriglyceridemia and hypercholesterolemia did not recur during follow-up, suggesting that the underlying mechanism for SHTG was insulin deficiency. CONCLUSION: This report of SHTG, DKA, and pancreatitis in an adolescent highlights the safe, early initiation of plasmapheresis as an effective treatment. To our knowledge, plasmapheresis has rarely been used so early in the course of treatment for an adolescent with SHTG, DKA, and acute pancreatitis.

Evaluation of Web-Based and In-Person Methods to Recruit Adults With Type 1 Diabetes for a Mobile Exercise Intervention: Prospective Observational Study.

BACKGROUND: Our clinical trial of a mobile exercise intervention for adults 18 to 65 years old with type 1 diabetes (T1D) occurred during COVID-19 social distancing restrictions, prompting us to test web-based recruitment methods previously underexplored for this demographic. OBJECTIVE: Our objectives for this study were to (1) evaluate the effectiveness and cost of using social media news feed advertisements, a clinic-based approach method, and web-based snowball sampling to reach inadequately active adults with T1D and (2) compare characteristics of enrollees against normative data. METHODS: Participants were recruited between November 2019 and August 2020. In method #1, Facebook and Instagram news feed advertisements ran for five 1-to-8-day windows targeting adults (18 to 64 years old) in the greater New Haven and Hartford, Connecticut, areas with one or more diabetes-related profile interest. If interested, participants completed a webform so that the research team could contact them for eligibility screening. In method #2, patients 18 to 24 years old with T1D were approached in person at clinical visits in November and December 2019. Those who were interested immediately completed eligibility screening. Older patients could not be approached due to clinic restrictions. In method #3, snowball sampling was conducted by physically active individuals with T1D contacting their peers on Facebook and via email for 48 days, with details to contact the research staff to express interest and complete eligibility screening. Other methods referred participants to the study similarly to snowball sampling. RESULTS: In method #1, advertisements were displayed to 11,738 unique viewers and attracted 274 clickers (2.33%); 20 participants from this group (7.3%) volunteered, of whom 8 (40%) were eligible. Costs averaged US $1.20 per click and US $95.88 per eligible volunteer. Men had lower click rates than women (1.71% vs 3.17%; P<.001), but their responsiveness and eligibility rates did not differ. In method #2, we approached 40 patients; 32 of these patients (80%) inquired about the study, of whom 20 (63%) volunteered, and 2 of these volunteers (10%) were eligible. Costs including personnel for in-person approaches averaged US $21.01 per inquirer and US $479.79 per eligible volunteer. In method #3, snowball sampling generated 13 inquirers; 12 of these inquirers (92%) volunteered, of whom 8 (67%) were eligible. Incremental costs to attract inquirers were negligible, and total costs averaged US $20.59 per eligible volunteer. Other methods yielded 7 inquirers; 5 of these inquirers (71%) volunteered, of whom 2 (40%) were eligible. Incremental costs to attract inquirers were negligible, and total costs averaged US $34.94 per eligible volunteer. Demographic overrepresentations emerged in the overall cohort (ie, optimal glycemic control, obesity, and low exercise), among those recruited by news feed advertisements (ie, obesity and older age), and among those recruited by snowball sampling (ie, optimal glycemic control and low exercise). CONCLUSIONS: Web-based advertising and recruitment strategies are a promising means to attract adults with T1D to clinical trials and exercise interventions, with costs comparing favorably to prior trials despite targeting an uncommon condition (ie, T1D) and commitment to an intervention. These strategies should be tailored in future studies to increase access to higher-risk participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT04204733; https://clinicaltrials.gov/ct2/show/NCT04204733.

Establishing a Global Standard for Wearable Devices in Sport and Exercise Medicine: Perspectives from Academic and Industry Stakeholders.

Millions of consumer sport and fitness wearables (CSFWs) are used worldwide, and millions of datapoints are generated by each device. Moreover, these numbers are rapidly growing, and they contain a heterogeneity of devices, data types, and contexts for data collection. Companies and consumers would benefit from guiding standards on device quality and data formats. To address this growing need, we convened a virtual panel of industry and academic stakeholders, and this manuscript summarizes the outcomes of the discussion. Our objectives were to identify (1) key facilitators of and barriers to participation by CSFW manufacturers in guiding standards and (2) stakeholder priorities. The venues were the Yale Center for Biomedical Data Science Digital Health Monthly Seminar Series (62 participants) and the New England Chapter of the American College of Sports Medicine Annual Meeting (59 participants). In the discussion, stakeholders outlined both facilitators of (e.g., commercial return on investment in device quality, lucrative research partnerships, and transparent and multilevel evaluation of device quality) and barriers (e.g., competitive advantage conflict, lack of flexibility in previously developed devices) to participation in guiding standards. There was general agreement to adopt Keadle et al.'s standard pathway for testing devices (i.e., benchtop, laboratory, field-based, implementation) without consensus on the prioritization of these steps. Overall, there was enthusiasm not to add prescriptive or regulatory steps, but instead create a networking hub that connects companies to consumers and researchers for flexible guidance navigating the heterogeneity, multi-tiered development, dynamicity, and nebulousness of the CSFW field.

A Feasibility Study to Detect Neonatal Hypoglycemia in Infants of Diabetic Mothers Using Real-Time Continuous Glucose Monitoring.

BACKGROUND: Infants born to mothers with diabetes commonly experience asymptomatic hypoglycemia after birth. Continuous glucose monitors (CGM) can detect asymptomatic hypoglycemia in this population without the need for painful glucose checks. METHODS: Infants born after 34 weeks of gestation to mothers with diabetes had a CGM placed after birth. One group of infants was remotely monitored in real-time by research staff during the hospitalization, whereas another group wore a blinded CGM. In both groups, hospital standard-of-care (SOC) glucose checks were performed. Clinical staff and families were blinded to CGM data. For CGM readings <45 mg/dL, research staff requested a verification blood glucose (BG) using the point-of-care glucometer. RESULTS: Sixteen infants were studied; 4 with a blinded CGM and 12 with remote monitoring (RM). When there were confirmatory hospital glucometer readings, the sensitivity of the CGM to detect hypoglycemia was 86% and the specificity was 91%. The positive predictive value was 55% and the negative predictive value was 98%. In the full cohort, hypoglycemia (<45 mg/dL) was confirmed in 12 of 16 infants with 30 events at <12 hours of life (HOL), 3 events between 12 and 24 HOL, and 1 event at >48 HOL. In the RM group, CGM detected hypoglycemia five times when the infant was not due for a BG check based on the SOC. Overall, the CGM detected five false-positive alerts and six true-positive alerts for hypoglycemia. Only one hypoglycemic episode was missed by CGM in the RM group. Barriers to recruitment included fear of pain with glucose checks, concerns with CGM use, satisfaction with the hospital SOC, personal reasons independent of the study, and lack of interest in participating in research. CONCLUSIONS: Although there were barriers to recruitment and retention in the study, we conclude that CGM can provide added benefit for detecting hypoglycemia when used early after birth.

Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature.

Background Neonatal severe hyperparathyroidism (NSHPT) is commonly treated with either parathyroidectomy or pharmacologic agents with varying efficacy and numerous side effects. Reports of using cinacalcet for NSHPT have increased, however, the effective dose for pediatric patients from the onset of symptoms through infancy has not been established. Case presentation We describe the clinical course of a newborn with a de novo R185Q mutation in the calcium-sensing receptor (CASR) gene, causing NSHPT. The infant received cinacalcet from the first days of life until 1 year of age. Conclusions Cinacalcet therapy effectively controlled the patient's serum calcium, phosphorus, and parathyroid hormone (PTH) levels without side effects.

Pharmacologic treatment options for type 1 diabetes: what's new?

INTRODUCTION: The expanding variety of insulins, including biosynthetic human insulin and rapid and long-acting insulin analogs, have dramatically transformed the management of type 1 diabetes (T1D) over the past 25 years. Moreover, increasing interest in the use of novel drugs developed for the treatment of type 2 diabetes (T2D) as adjunctive therapies for T1D remains a work in progress. Areas Covered: We reviewed articles published up to December 2018 in PubMed and ClinicalTrials.gov for recent developments in the pharmacologic treatment of T1D, including inhaled insulin, ultrafast and ultralong-acting insulins and adjunctive therapies including pramlintide, metformin, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2, and SGLT1/2 inhibitors. Expert Opinion: With the creation of ultrafast-acting insulin analogs and very prolonged duration of action of basal insulins, it is possible to more closely mimic physiologic insulin secretion. Adjunctive therapies, likewise, may also overcome some of the abnormal physiology that is a hallmark of T1D. Therefore, individualized consideration of the efficacy of these agents must be measured alongside the potential adverse effects when choosing an adjunctive therapy.

Clinical utility of an ultrasensitive urinary free cortisol assay by tandem mass spectrometry.

BACKGROUND: 24 h urinary free cortisol measurement is a clinically important first-line screening test for Cushing's syndrome (CS). Tandem mass spectrometry (LC-MS/MS) assays have superior sensitivity and specificity compared to immunoassays. Our goal was to improve and validate a LC-MS/MS method to measure urinary free cortisol in both adult and pediatric patients and to characterize its clinical diagnostic performance of CS by chart review. METHODS: We improved a LC-MS/MS method previously reported for urinary free cortisol to be able to measure urinary and salivary cortisol in the same batch for increased efficiency. The sample preparation was by liquid-liquid extraction using dichloromethane followed by stepwise washing with acidic, basic and neutral solutions. The assay's analytical performance was characterized, and a retrospective patient chart review was conducted to evaluate the assay's clinical performance in diagnosing CS. RESULTS: The LC-MS/MS assay demonstrated enhanced sensitivity and was linear within an analytical measurement range of 10-10,000 ng/dL. Assay accuracy was satisfactory as determined by spike and recovery studies and highly correlated with a reference LC-MS/MS method. The assay's clinical diagnostic sensitivity and specificity in detecting CS was 96% and 91%, respectively, when compared to a urinary cortisol excretion of at least 50 µg/24 h. CONCLUSIONS: The improved LC-MS/MS method is both sensitive and specific with enhanced analytical performance and clinical diagnostic utility to screen for CS. The clinical diagnostic sensitivity and specificity were superior based on retrospective patient chart review.