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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.

Purpose: To examine youth and parent perspectives on the acceptability of Bright 1 Bodies, a group physical activity and coping intervention for adolescents with type 1 diabetes mellitus (T1DM)., Methods: Adolescents participated in 12 weekly sessions of moderate to vigorous physical activity and discussion with peers with T1DM. Adolescents completed an exit survey measuring satisfaction with the intervention on a 5-point Likert scale. Semistructured interviews were conducted with adolescents and at least one parent. Qualitative description was used to develop themes that summarize the acceptability of the intervention., Results: Mean scores for survey subscales were: 4.5 (SD = 0.39) for program components and strategies, 4.4 (SD = 0.44) for comfort with the intervention, and 4.3 (SD = 0.62) for instructors. Themes included: (1) adolescents and parents valued being around others with T1DM and their families, (2) the intervention helped adolescents gain knowledge and reinforce diabetes self-management behaviors, (3) challenges included convenience and sustaining participant engagement, and (4) adolescents intended to sustain physical activity and diabetes self-management behaviors after the intervention., Conclusions: Adolescents and parents viewed the intervention as acceptable across multiple domains. Participants valued the group aspect of the intervention, and future interventions would benefit from integrating social interactions with others with T1DM.

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., (©Garrett I Ash, Stephanie Griggs, Laura M Nally, Matthew Stults-Kolehmainen, Sangchoon Jeon, Cynthia Brandt, Barbara I Gulanski, Elias K Spanakis, Julien S Baker, Robin Whittemore, Stuart A Weinzimer, Lisa M Fucito. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 08.07.2021.)

Background: Despite significant advances in type 1 diabetes (T1D) management, achieving targeted glycemic control in pediatric patients remains a struggle. Continuous glucose monitoring (CGM) with remote access holds the promise to address this challenge by allowing caregivers to monitor glucose, even when the child is not directly under their supervision., Objective: To explore real-time and remote CGM practices in homes and schools, including caregiver expectations regarding this technology., Subjects: Parents and daytime caregivers., Methods: Respondents answered an anonymous survey assessing characteristics of CGM use. Cross-sectional data were collected and analyzed using quantitative and qualitative methods., Results: Thirty-three parents and 17 daytime caregivers responded. Threshold alerts (alerts when patients reached certain pre-set high or low limits) were used most frequently, followed by rate of change alerts. Most parents and daytime caregivers responded to low- and high-threshold CGM alerts by confirming with a glucose meter prior to treatment; while about one-third endorsed treating lows without a confirmatory test. Most parents expected their child's daytime caregiver to respond to CGM alerts and daytime caregivers felt the parent's expectations of them were reasonable. All parents and most caregivers reported decreased overall worry/stress. Parents felt positive about CGM use and daytime caregivers felt comfortable with CGM., Conclusion: The positive and collaborative management reported by parents and daytime caregivers sets the stage for CGM to play an important role in the management of children with T1D both in the home and in the school settings., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Measurement of glycated hemoglobin (HbA 1c ) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA 1c testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA 1c measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes., (© 2017 by the American Diabetes Association.)

Objective: To identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A 1c (HbA 1c ) based upon a review of the evidence, consensus from clinical experts, and input from researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work., Research and Methods: A Steering Committee-comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange-was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees., Results: The Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome's short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes-specific development is needed., Conclusions: The Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA 1c in the research, development, and evaluation of type 1 diabetes therapies., (© 2017 by the American Diabetes Association.)

After assessing previously published methods, we developed a practical approach to adjusting insulin doses using rtCGM trend arrows in pediatric patients with diabetes.

Background: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin., Methods: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7.4% ± 0.8%) underwent overnight pump suspension studies before and after treatment with canagliflozin (CANA). On both nights, basal insulin was suspended at 3 AM and plasma glucose (PG), β-hydroxybutyrate (BHB), free fatty acids (FFA), plasma insulin (PI), and glucagon were measured. Studies were terminated 6 h after suspension or if PG rose to >350 mg/dL or BHB >2.5 mmol/L., Results: PI levels at the start of suspension were reduced by 30% after CANA treatment (44 ± 11 uU/mL vs. 31 ± 10 uU/mL, P < 0.01), but baseline PG, BHB, FFA, and glucagon levels were not significantly different. During the suspension, PG rose from 104 ± 10 to 301 ± 21 mg/dL before treatment, but only from 109 ± 8 to 195 ± 14 mg/dL after treatment (P = 0.002 vs. pretreatment values). On the other hand, CANA treatment did not significantly affect the magnitude of increases in FFA, BHB, and glucagon levels during the suspension study., Conclusion: These data indicate that SGLT2i do not accelerate the rate of ketogenesis following the interruption of basal insulin infusion in T1D. Rather, the failure of patients to promptly recognize early metabolic decompensation relates to the much more gradual rise in PG levels.

Background: Automated insulin delivery systems, utilizing a control algorithm to dose insulin based upon subcutaneous continuous glucose sensor values and insulin pump therapy, will soon be available for commercial use. The objective of this study was to determine the preliminary safety and efficacy of initialization parameters with the Medtronic hybrid closed-loop controller by comparing percentage of time in range, 70-180 mg/dL (3.9-10 mmol/L), mean glucose values, as well as percentage of time above and below target range between sensor-augmented pump therapy and hybrid closed-loop, in adults and adolescents with type 1 diabetes., Methods: We studied an initial cohort of 9 adults followed by a second cohort of 15 adolescents, using the Medtronic hybrid closed-loop system with the proportional-integral-derivative with insulin feed-back (PID-IFB) algorithm. Hybrid closed-loop was tested in supervised hotel-based studies over 4-5 days., Results: The overall mean percentage of time in range (70-180 mg/dL, 3.9-10 mmol/L) during hybrid closed-loop was 71.8% in the adult cohort and 69.8% in the adolescent cohort. The overall percentage of time spent under 70 mg/dL (3.9 mmol/L) was 2.0% in the adult cohort and 2.5% in the adolescent cohort. Mean glucose values were 152 mg/dL (8.4 mmol/L) in the adult cohort and 153 mg/dL (8.5 mmol/L) in the adolescent cohort., Conclusions: Closed-loop control using the Medtronic hybrid closed-loop system enables adaptive, real-time basal rate modulation. Initializing hybrid closed-loop in clinical practice will involve individualizing initiation parameters to optimize overall glucose control., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose The first hybrid closed loop (HCL) system, which automates insulin delivery but requires user inputs, was approved for treatment of type 1 diabetes (T1D) by the US Food and Drug Administration in September 2016. The purpose of this study was to explore the benefits, expectations, and attitudes of individuals with T1D following a clinical trial of an HCL system. Methods Thirty-two individuals with T1D (17 adults, 15 adolescents) participated in focus groups after 4 to 5 days of system use. Content analysis generated themes regarding perceived benefits, hassles, and limitations. Results Some participants felt misled by terms such as "closed loop" and "artificial pancreas," which seemed to imply a more "hands-off" experience. Perceived benefits were improved glycemic control, anticipated reduction of long-term complications, better quality of life, and reduced mental burden of diabetes. Hassles and limitations included unexpected tasks for the user, difficulties wearing the system, concerns about controlling highs, and being reminded of diabetes. Conclusion Users are willing to accept some hassles and limitations if they also perceive health and quality-of-life benefits beyond current self-management. It is important for clinicians to provide a balanced view of positives and negatives to help manage expectations.

Aims: To describe the prevalence of overweight and obesity in adolescents with type 1 diabetes (T1D) and to examine the associations among socio-demographic, clinical, and self-management factors by weight status., Methods: We analyzed baseline data obtained from 5529 adolescents with T1D (mean age=15.4±1.4years, 51.8% male, 77.9% white, mean HbA1c=8.7±1.8%; 72mmol/mol) from the T1D Exchange Clinic Registry. We examined correlates of weight status using multinomial logistic regression analyses., Results: Overweight (22.9%) and obesity (13.1%) were prevalent in the overall sample and was highest among girls (40.8%) and adolescents of Hispanic/Latino race/ethnicity (46.1%). Female gender, older age, annual household income <$35,000 (vs. ≥$200,000), high school parental educational attainment (vs. ≥graduate degree), lower HbA1c, longer duration of T1D, higher amount of insulin, and a recent visit with an allied healthcare provider were independently and significantly associated with higher odds of overweight or obesity. Adolescents who self-rated their health as fair/poor (vs. excellent) had the highest odds of obesity (OR 3.92, 95% CI 2.53-6.06)., Conclusions: Overweight/obesity is prevalent among adolescents with T1D, especially among girls and those of diverse race/ethnicity. Some of these factors may be amenable to remediation and point to subgroups that can benefit from obesity prevention and management efforts., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated., Methods: Adolescents (n = 30, ages 14-21 years) and adults (n = 94, ages 22-75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed ® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase., Results: Adolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%-88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%-92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA 1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P < 0.001) and from 7.3% ± 0.9% to 6.8% ± 0.6% (P < 0.001, Wilcoxon signed-rank test), respectively. The proportion of overall in-target (71-180 mg/dL) sensor glucose (SG) values increased from 60.4% ± 10.9% to 67.2% ± 8.2% (P < 0.001) in adolescents and from 68.8% ± 11.9% to 73.8% ± 8.4% (P < 0.001) in adults. During the hotel stay, the proportion of in-target i-STAT ® blood glucose values was 67.4% ± 27.7% compared to SG values of 72.0% ± 11.6% for adolescents and 74.2% ± 17.5% compared to 76.9% ± 8.3% for adults. There were no severe hypoglycemic or diabetic ketoacidosis events in either cohort., Conclusions: HCL therapy was safe during in-home use by adolescents and adults and the study phase demonstrated increased time in target, and reductions in HbA 1c, hyperglycemia and hypoglycemia, compared to baseline., Trial Registration: Clinicaltrials.gov identifier: NCT02463097.

Objective: To assess whether snacking could be used with closed-loop (CL) insulin delivery to avoid exercise-induced reductions in plasma glucose (PG), as well as elevations in PG at the end of exercise., Research Design and Methods: Twelve type 1 diabetes (T1D) subjects (age 13-36 years, duration 10.7 ± 8.4 years, A1c 7.4% ± 0.8% [57 ± 8.7 mmol/mol]) underwent two 105-min exercise studies while under CL control: CL alone and CL+snack. Exercise, commenced at 3 PM, consisted of four 15-min periods of brisk treadmill walking to 65%-70% HR max (separated by three 5-min rest periods), followed by a 30-min recovery period. Fifteen to 30 g carbohydrate (Gatorade) was provided on snacking visits just before and midway through the exercise period. PG and insulin were measured every 15-20 min during the exercise studies., Results: Baseline PG levels were similar for CL alone (164 ± 16 mg/dL) versus CL+snack (172 ± 11 mg/dL). During exercise, PG levels fell by 53 ± 10 mg/dL without snacking versus a modest 10 ± 13 mg/dL increase in PG with snacking (P = 0.0005); similar differences in the change in PG levels were observed at the end of recovery period. Hypoglycemia requiring rescue treatment (PG ≤60 mg/dL) during exercise occurred in three nonsnacking visits versus none with snacking. During the 75-min exercise period, insulin delivered was 1.8 ± 0.4 U for the CL+snack admission compared to 0.7 ± 0.1 U during CL alone (P = 0.002)., Conclusion: These results support the use of a simple snacking strategy to avoid exercise-induced lowering of PG while on CL insulin delivery. Persistent insulin infusion during exercise with snacking also appears to be effective in limiting increases in PG at the end of exercise., Competing Interests: Author Disclosure Statement Medtronic Diabetes provided the pumps, sensors, infusion sets, reservoirs, and Android phones for the CL experiments. W.V.T. is a consultant for Medtronic Diabetes, NovoNordisk, and Sanofi. S.A.W. is a consultant for Medtronic Diabetes and Tandem, and serves on a Medical Advisory Board for Insulet. E.C. is a speaker for NovoNordisk. No other potential conflicts of interest relevant to this article were reported. No sponsor had any role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization-an architecture that is simultaneously highly segregated and integrated-the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034-4046, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to describe the experience of Hispanic adolescents with type 1 diabetes (T1DM) from the perspectives of adolescents and their diabetes clinicians., Methods: Nine Hispanic adolescents with T1DM and 7 clinicians at a tertiary academic medical center participated in in-depth individual semistructured interviews. Adolescents were purposively sampled to obtain a range in age and metabolic control. Based on interpretive descriptive methodology, data were coded and combined into themes, which were constructed separately for the 2 groups and then compared across groups. Data were analyzed concurrently with data collection., Results: Adolescents and clinicians reported similar themes related to (1) cultural aspects of living with T1DM; (2) finding the balance of: food, insulin, and exercise; being "perfect at diabetes" versus being a "normal teenager"; and being independent versus needing support, and (3) ways to improve life for Hispanic adolescents with T1DM. Although there were some key cultural distinctions, Hispanic adolescents with T1DM and their clinicians described life and daily management issues as being similar to those of their non-Hispanic peers., Conclusions: Hispanic adolescents with T1DM have unique experiences and beliefs that affect their living with T1DM, but in many respects, their experiences are similar to those of their non-Hispanic peers with T1DM. Hispanic adolescents with T1DM want their clinicians to learn about their personal lives. Preferably, clinicians and parents should speak the same language. If not possible, interpreters should be used instead of having adolescents translate during clinic appointments., (© 2016 The Author(s).)

Objective: Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-μg/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3-4 weeks of outpatient dose titration., Research Design and Methods: Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16-23 years; A1C 7.2 ± 0.6% [55 ± 6.6 mmol/mol]) completed two 24-h sessions: one on CL alone and one on CL plus 60-μg pramlintide (CL + P), after a 3-4-week outpatient dose escalation. Eleven subjects (age 18-27 years; A1C 7.5 ± 0.9% [58 ± 9.8 mmol/mol]) were studied before and after treatment with 1.8 mg liraglutide (CL + L) after a similar 3-4-week dose escalation period. Timing and content of meals during CL were identical within experiments; meals were not announced., Results: Pramlintide delayed the time to peak plasma glucose (PG) excursion (CL 1.6 ± 0.5 h vs. CL + P 2.6 ± 0.9 h, P < 0.001) with concomitant blunting of peak postprandial increments in PG (P < 0.0001) and reductions in postmeal incremental PG area under the curve (AUC) (P = 0.0002). CL + L also led to reductions in PG excursions (P = 0.05) and incremental PG AUC (P = 0.004), with a 28% reduction in prandial insulin delivery. Outpatient liraglutide therapy led to a weight loss of 3.2 ± 1.8 kg, with a 26% reduction in total daily insulin dose., Conclusions: Adjunctive pramlintide and liraglutide treatment mitigated postprandial hyperglycemia during CL control; liraglutide demonstrated the additional benefit of weight loss in an insulin-sparing manner. Further investigations of these and other adjunctive agents in long-term outpatient CL studies are needed., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Prior studies examining beta-cell preservation in type 1 diabetes have predominantly assessed stimulated C-peptide concentrations approximately 10 wk after diagnosis. We examined whether earlier assessments might aid in prediction of beta cell function over time., Methods: Using data from a multi-center randomized trial assessing the effect of intensive diabetes management initiated within 1 wk of diagnosis, we assessed which clinical factors predicted 90-min mixed-meal tolerance test (MMTT) stimulated C-peptide values obtained 2 and 6 wk after diagnosis. We also studied associations of these factors with C-peptide values at 1- and 2-year post-diagnosis. Data from intervention and control groups were pooled., Results: Among 67 study participants (mean age 13.3 ± 5.7 yr, range 7.8-45.7 yr) in multivariable analyses, C-peptide increased from baseline to 2 wks and then 6 wk. C-peptide levels at these times were significantly correlated with 1- and 2-yr C-peptide concentrations (all p < 0.001), with the strongest observed associations between 6-wk C-peptide and the 1- and 2-yr values (r = 0.66 and r = 0.61, respectively). In multivariable analyses, greater baseline and 6-wk C-peptide, and older age independently predicted greater 1- and 2-yr C-peptide concentrations., Conclusions: C-peptide assessments close to diagnosis were predictive of subsequent C-peptide production. Our data demonstrate a clear increase in C-peptide over the initial 6 wk after diabetes diagnosis followed by a plateau. Our data do not suggest that MMTT assessments performed closer to diagnosis than 6 wk would improve prediction of subsequent residual beta cell function., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4-10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims/hypothesis: The aim of this work was to assess the association between continuous glucose monitoring (CGM) data, HbA1c, insulin-dose-adjusted HbA1c (IDAA1c) and C-peptide responses during the first 2 years following diagnosis of type 1 diabetes., Methods: A secondary analysis was conducted of data collected from a randomised trial assessing the effect of intensive management initiated within 1 week of diagnosis of type 1 diabetes, in which mixed-meal tolerance tests were performed at baseline and at eight additional time points through 24 months. CGM data were collected at each visit., Results: Among 67 study participants (mean age [± SD] 13.3 ± 5.7 years), HbA1c was inversely correlated with C-peptide at each time point (p < 0.001), as were changes in each measure between time points (p < 0.001). However, C-peptide at one visit did not predict the change in HbA1c at the next visit and vice versa. Higher C-peptide levels correlated with increased proportion of CGM glucose values between 3.9 and 7.8 mmol/l and lower CV (p = 0.001 and p = 0.02, respectively) but not with CGM glucose levels <3.9 mmol/l. Virtually all participants with IDAA1c < 9 retained substantial insulin secretion but when evaluated together with CGM, time in the range of 3.9-7.8 mmol/l and CV did not provide additional value in predicting C-peptide levels., Conclusions/interpretation: In the first 2 years after diagnosis of type 1 diabetes, higher C-peptide levels are associated with increased sensor glucose levels in the target range and with lower glucose variability but not hypoglycaemia. CGM metrics do not provide added value over the IDAA1c in predicting C-peptide levels.

Objective: To investigate whether type 1 diabetes affects white matter (WM) structure in a large sample of young children., Research Design and Methods: Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance imaging scans in this multisite neuroimaging study. Participants with type 1 diabetes were assessed for HbA1c history and lifetime adverse events, and glucose levels were monitored using a continuous glucose monitor (CGM) device and standardized measures of cognition., Results: Between-group analysis showed that children with type 1 diabetes had significantly reduced axial diffusivity (AD) in widespread brain regions compared with control subjects. Within the type 1 diabetes group, earlier onset of diabetes was associated with increased radial diffusivity (RD) and longer duration was associated with reduced AD, reduced RD, and increased fractional anisotropy (FA). In addition, HbA1c values were significantly negatively associated with FA values and were positively associated with RD values in widespread brain regions. Significant associations of AD, RD, and FA were found for CGM measures of hyperglycemia and glucose variability but not for hypoglycemia. Finally, we observed a significant association between WM structure and cognitive ability in children with type 1 diabetes but not in control subjects., Conclusions: These results suggest vulnerability of the developing brain in young children to effects of type 1 diabetes associated with chronic hyperglycemia and glucose variability.

Background: The ability to lie still in an MRI scanner is essential for obtaining usable image data. To reduce motion, young children are often sedated, adding significant cost and risk., Objective: We assessed the feasibility of using a simple and affordable behavioral desensitization program to yield high-quality brain MRI scans in sedation-free children., Materials and Methods: 222 children (4-9.9 years), 147 with type 1 diabetes and 75 age-matched non-diabetic controls, participated in a multi-site study focused on effects of type 1 diabetes on the developing brain. T1-weighted and diffusion-weighted imaging (DWI) MRI scans were performed. All children underwent behavioral training and practice MRI sessions using either a commercial MRI simulator or an inexpensive mock scanner consisting of a toy tunnel, vibrating mat, and video player to simulate the sounds and feel of the MRI scanner., Results: 205 children (92.3%), mean age 7 ± 1.7 years had high-quality T1-W scans and 174 (78.4%) had high-quality diffusion-weighted scans after the first scan session. With a second scan session, success rates were 100% and 92.5% for T1-and diffusion-weighted scans, respectively. Success rates did not differ between children with type 1 diabetes and children without diabetes, or between centers using a commercial MRI scan simulator and those using the inexpensive mock scanner., Conclusion: Behavioral training can lead to a high success rate for obtaining high-quality T1-and diffusion-weighted brain images from a young population without sedation.

Objective: An integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2 h if patients fail to respond to low-glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low glucose levels detected by sensor could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2 h in the overnight period would not lead to clinically important increases in blood β-hydroxybutyrate levels despite widely varying glucose values prior to the suspension., Research Design and Methods: Subjects measured blood glucose and blood β-hydroxybutyrate levels using a meter each night at 9:00 p.m., then fasted until the next morning. On control nights, the usual basal rates were continued; on experimental nights, the basal insulin infusion was reprogrammed for a 2-h zero basal rate at random times after 11:30 p.m., Results: In 17 type 1 diabetic subjects (mean age 24 ± 9 years, diabetes duration 14 ± 11 years, A1C level 7.3 ± 0.5% [56 mmol/mol]), blood glucose and blood β-hydroxybutyrate levels were similar at 9:00 p.m. on suspend nights (144 ± 63 mg/dL and 0.09 ± 0.07 mmol/L) and nonsuspend nights (151 ± 65 mg/dL and 0.08 ± 0.06 mmol/L) (P = 0.39 and P = 0.47, respectively). Fasting morning blood glucose levels increased after suspend nights compared with nonsuspend nights (191 ± 68 vs. 141 ± 75 mg/dL, P < 0.0001), and the frequency of fasting hypoglycemia decreased the morning following suspend nights (P < 0.0001). Morning blood β-hydroxybutyrate levels were slightly higher after suspension (0.13 ± 0.14 vs. 0.09 ± 0.11 mmol/L, P = 0.053), but the difference was not clinically important., Conclusions: Systems that suspend basal insulin for 2 h are safe and do not lead to clinically significant ketonemia even if the blood glucose level is elevated at the time of the suspension.

Objective: This study was undertaken to investigate the effect of an insulin infusion site warming device, the InsuPatch(40)(™) (IP(40)) (InsuLine Medical Ltd., Petach-Tikvah, Israel), on insulin aspart pharmacodynamics (PD) and pharmacokinetics (PK) in adolescents with type 1 diabetes., Subjects and Methods: Seventeen subjects with type 1 diabetes (age, 15±1 years; hemoglobin A1c, 7.5±0.2% [58±2.2 mmol/mol]) underwent two euglycemic clamps performed on separate mornings with and without IP(40) activation with warming temperature at 40°C. On both days, the basal infusion was suspended, and glucose levels were maintained between 90 and 100 mg/dL by a variable rate dextrose infusion for up to 5 h after a 0.2 U/kg bolus of insulin aspart., Results: Time to peak insulin action and time to half-maximal action occurred earlier with a greater early glucodynamic effect (area under the curve [AUC] for glucose infusion rate from 0 to 30 min) with IP(40) than without the IP(40), whereas the AUC for the time-action profile and the peak action did not differ with and without infusion site warming. PK parameters were in agreement with PD parameters, namely, a significantly earlier time to reach the maximum increment in insulin concentrations and greater early bioavailability (AUC for the change in insulin concentration from 0 to 30 min) with the IP(40). The tail of the plasma insulin response curve was also shortened with infusion site warming, with the time to reach baseline insulin concentration occurring significantly earlier (P=0.04)., Conclusions: Our data demonstrate that skin warming around the infusion site to 40°C with the IP(40) is an effective means to accelerate absorption and action of rapid-acting insulin. These improvements in time-action responses have the potential to enhance the performance of open- and closed-loop insulin delivery systems.

Objective: To assess effectiveness of inpatient hybrid closed-loop control (HCLC) followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7 days of diagnosis of type 1 diabetes on the preservation of β-cell function at 1 year., Research Design and Methods: Sixty-eight individuals (mean age 13.3 ± 5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP therapy (intensive group; N = 48) or to the usual-care group treated with multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C-peptide concentrations during mixed-meal tolerance tests at 12 months., Results: Intensive-group participants initiated HCLC a median of 6 days after diagnosis for a median duration of 71.3 h, during which median participant mean glucose concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at 12 months, only 33% of intensive participants averaged sensor use ≥6 days/week. In the usual-care group, insulin pump and CGM use were initiated prior to 12 months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in both groups throughout the study. At 12 months, the geometric mean (95% CI) of C-peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide concentration ≥0.2 pmol/mL (P = 0.30)., Conclusions: In new-onset type 1 diabetes, HCLC followed by SAP therapy did not provide benefit in preserving β-cell function compared with current standards of care.

Objective: Afternoon exercise increases the risk of nocturnal hypoglycemia (NH) in subjects with type 1 diabetes. We hypothesized that automated feedback-controlled closed-loop (CL) insulin delivery would be superior to open-loop (OL) control in preventing NH and maintaining a higher proportion of blood glucose levels within the target blood glucose range on nights with and without antecedent afternoon exercise., Research Design and Methods: Subjects completed two 48-h inpatient study periods in random order: usual OL control and CL control using a proportional-integrative-derivative plus insulin feedback algorithm. Each admission included a sedentary day and an exercise day, with a standardized protocol of 60 min of brisk treadmill walking to 65-70% maximum heart rate at 3:00 p.m., Results: Among 12 subjects (age 12-26 years, A1C 7.4±0.6%), antecedent exercise increased the frequency of NH (reference blood glucose<60 mg/dL) during OL control from six to eight events. In contrast, there was only one NH event each on nights with and without antecedent exercise during CL control (P=0.04 vs. OL nights). Overnight, the percentage of glucose values in target range was increased with CL control (P<0.0001). Insulin delivery was lower between 10:00 p.m. and 2:00 a.m. on nights after exercise on CL versus OL, P=0.008., Conclusions: CL insulin delivery provides an effective means to reduce the risk of NH while increasing the percentage of time spent in target range, regardless of activity level in the mid-afternoon. These data suggest that CL control could be of benefit to patients with type 1 diabetes even if it is limited to the overnight period.

Objective: A pilot study was undertaken to determine whether establishment of a Spanish Language Diabetes Clinic (SLDC) for Spanish-speaking families conducted by a team of Spanish-speaking, Hispanic and nonHispanic clinicians provides a means to improve control of type 1 diabetes (T1D)., Methods: The first 21 Hispanic pediatric patients with T1D who enrolled in the SLDC were matched to 21 Hispanic patients treated in the English Language Diabetes Clinic (ELDC) based on age and duration of diabetes. The two groups did not differ significantly with respect to gender, body mass index (BMI), or glycated hemoglobin (HbA1c). Patients in both groups were followed for 12 months., Results: The mean (± standard deviation) baseline glycated hemoglobin (HbA1c) level in the SLDC group (8.4 ± 1.0%) was similar to that in the ELDC group (8.6 ± 1.4%, P = .83). HbA1c levels fell by 0.5 ± 1.0% (P = .01) during the year following enrollment in the SLDC but did not change significantly from baseline during the year of follow-up in the ELDC group (decrease of 0.2 ± 0.9%, P = .1). At the start of the study, only 5 patients (23%) in the SLDC group and 7 patients (33%) in the ELDC group met the ≤7.5% target HbA1c level. After 1 year, 10 of the SLDC patients (48%) and 4 of ELDC patients (19%) had HbA1c levels ≤7.5% (P = .01)., Conclusions: Our preliminary findings support the hypothesis that overcoming language barriers by the establishment of a SLDC can be an effective means of improving metabolic control in youth with T1D in Hispanic families with limited English language skills.

Background: Hyperglycemia is a significant problem for critically ill children. Treatment for hyperglycemia remains controversial. This study explores the effect of controlling blood glucose (BG) in hyperglycemic critically ill children., Methods: A retrospective cohort of nondiabetic critically ill children (defined as requiring mechanical ventilation and/or vasopressors) with BG persistently ≥ 150 mg/dl and treated with insulin (treatment group) were compared with a historical cohort of similar children who did not receive interventions to control hyperglycemia (baseline group)., Results: There were 130 children in the treatment group and 137 children in the baseline group. Mean BG in the treatment group was 140 ± 24 mg/dl compared with 179 ± 47 mg/dl in the baseline group (p < .001). After adjusting for patient characteristics, cointerventions, and glucose metrics, patients in the treatment group had 2.5 fewer intensive care unit (ICU)-free days (i.e., number of days alive and discharged from ICU within 28 days after inclusion) than the baseline group (p = .023). Glucose control was not independently associated with duration of ICU stay, ventilator-free days, vasopressor-free days, or mortality., Conclusions: Blood glucose control appears associated with worse outcomes in critically ill children. Our data combined with conflicting results in adults leads us to strongly advocate for the conduct of randomized trials on glucose control in critically ill children., (© 2013 Diabetes Technology Society.)

Background: This article describes our experience with inpatient hybrid closed-loop control (HCLC) initiated shortly after the diagnosis of type 1 diabetes in a randomized trial designed to assess the effectiveness of inpatient HCLC followed by outpatient sensor-augmented pump (SAP) therapy on the preservation of β-cell function., Subjects and Methods: Forty-eight individuals with newly diagnosed type 1 diabetes and positive pancreatic autoantibodies (7.8-37.7 years old) received inpatient HCLC therapy for up to 93 h, initiated within 7 days of diagnosis., Results: On initiation of HCLC, mean glucose concentration was 240±100 mg/dL. During the first day of HCLC, median of the participant's mean glucose concentrations fell rapidly to 146 mg/dL, a level of control that was sustained on Days 2 and 3 (138 mg/dL and 139 mg/dL, respectively). By Day 3, the median percentage of glucose values >250 and <60 mg/dL was <1%. During the first 2 weeks of SAP treatment at home, the median participant mean glucose level was 126 mg/dL (interquartile range, 117, 137 mg/dL), and the median percentage of values between 71 and 180 mg/dL was 85% (interquartile range, 80%, 90%)., Conclusions: Inpatient HCLC followed by outpatient SAP therapy can provide a safe and effective means to rapidly reverse glucose toxicity and establish near-normal glycemic control in patients with newly diagnosed type 1 diabetes.

Background and Objective: Subcutaneously injected rapid-acting insulin analogs do not replicate physiologic insulin action due to delays in their onset and peak action resulting in postprandial glucose excursions. The InsuPatch (IP) is a novel insulin infusion site warming device developed to accelerate insulin action by increasing blood flow to the area of insulin absorption. Thirteen adolescents with type 1 diabetes (T1D, mean age 14 ± 4 yr) were enrolled in this study to investigate the effect of the IP on the pharmacodynamics and pharmacokinetics of a 0.2 unit/kg bolus dose of aspart insulin using the euglycemic clamp technique., Research Design and Methods: Each subject underwent two euglycemic clamp procedures on separate occasions: one with IP and one without IP activation in random order., Results: When the insulin bolus was given with IP activation as compared to without IP activation, time to reach maximum insulin action (T(GIRmax)) and to reach 50% maximum action (T(50%GIRmax)) were 35 and 18 min earlier (125 ± 8 min vs. 90 ± 6 min, p = 0.002 and 58 ± 5 min. vs. 40 ± 3 min, p = 0.01, respectively), and the area under curve, AUC(GIR 0-90 min), reflecting early glucodynamic action, was significantly greater (p = 0.001). IP activation also accelerated the rise in plasma insulin levels after the bolus (p = 0.03) and resulted in a higher peak (p = 0.04) and greater overall increase (p = 0.02) in plasma insulin levels., Conclusions: Our results show that insulin infusion site warming with IP activation accelerates the time action profile of aspart insulin which may be of benefit to current open-loop and future closed-loop insulin delivery in patients with T1D., (© 2012 John Wiley & Sons A/S.)

When a person consumes ethanol, the body quickly begins to convert it to acetic acid, which circulates in the blood and can serve as a source of energy for the brain and other organs. This study used 13C magnetic resonance spectroscopy to test whether chronic heavy drinking is associated with greater brain uptake and oxidation of acetic acid, providing a potential metabolic reward or adenosinergic effect as a consequence of drinking. Seven heavy drinkers, who regularly consumed at least 8 drinks per week and at least 4 drinks per day at least once per week, and 7 light drinkers, who consumed fewer than 2 drinks per week were recruited. The subjects were administered [2-13C]acetate for 2 hours and scanned throughout that time with magnetic resonance spectroscopy of the brain to observe natural 13C abundance of N-acetylaspartate (NAA) and the appearance of 13C-labeled glutamate, glutamine, and acetate. Heavy drinkers had approximately 2-fold more brain acetate relative to blood and twice as much labeled glutamate and glutamine. The results show that acetate transport and oxidation are faster in heavy drinkers compared with that in light drinkers. Our finding suggests that a new therapeutic approach to supply acetate during alcohol detoxification may be beneficial.

Objective: Even under closed-loop (CL) conditions, meal-related blood glucose (BG) excursions frequently exceed target levels as a result of delays in absorption of insulin from the subcutaneous site of infusion. We hypothesized that delaying gastric emptying with preprandial injections of pramlintide would improve postprandial glycemia by allowing a better match between carbohydrate and insulin absorptions., Research Design and Methods: Eight subjects (4 female; age, 15-28 years; A1C, 7.5 ± 0.7%) were studied for 48 h on a CL insulin-delivery system with a proportional integral derivative algorithm with insulin feedback: 24 h on CL control alone (CL) and 24 h on CL control plus 30-μg premeal injections of pramlintide (CLP). Target glucose was set at 120 mg/dL; timing and contents of meals were identical on both study days. No premeal manual boluses were given. Differences in reference BG excursions, defined as the incremental glucose rise from premeal to peak, were compared between conditions for each meal., Results: CLP was associated with overall delayed time to peak BG (2.5 ± 0.9 vs. 1.5 ± 0.5 h; P < 0.0001) and reduced magnitude of glycemic excursion (88 ± 42 vs. 113 ± 32 mg/dL; P = 0.006) compared with CL alone. Pramlintide effects on glycemic excursions were particularly evident at lunch and dinner, in association with higher premeal insulin concentrations at those mealtimes., Conclusions: Pramlintide delayed the time to peak postprandial BG and reduced the magnitude of prandial BG excursions. Beneficial effects of pramlintide on CL may in part be related to higher premeal insulin levels at lunch and dinner compared with breakfast.

Background: Closed-loop (CL) insulin delivery systems utilizing proportional-integral-derivative (PID) controllers have demonstrated susceptibility to late postprandial hypoglycemia because of delays between insulin delivery and blood glucose (BG) response. An insulin feedback (IFB) modification to the PID algorithm has been introduced to mitigate this risk. We examined the effect of IFB on CL BG control., Methods: Using the Medtronic ePID CL system, four subjects were studied for 24 h on PID control and 24 h during a separate admission with the IFB modification (PID + IFB). Target glucose was 120 mg/dl; meals were served at 8:00 AM, 1:00 PM, and 6:00 PM and were identical for both admissions. No premeal manual boluses were given. Reference BG excursions, defined as incremental glucose rise from premeal to peak, and postprandial BG area under the curve (AUC; 0-5 h) were compared. Results are reported as mean ± standard deviation., Results: The PID + IFB control resulted in higher mean BG levels compared with PID alone (153 ± 54 versus 133 ± 56 mg/dl; p < .0001). Postmeal BG excursions (114 ± 28 versus 114 ± 47 mg/dl) and AUCs (285 ± 102 versus 255 ± 129 mg/dl/h) were similar under both conditions. Total insulin delivery averaged 57 ± 20 U with PID versus 45 ± 13 U with PID + IFB (p = .18). Notably, eight hypoglycemic events (BG < 60 mg/dl) occurred during PID control versus none during PID + IFB., Conclusions: Addition of IFB to the PID controller markedly reduced the occurrence of hypoglycemia without increasing meal-related glucose excursions. Higher average BG levels may be attributable to differences in the determination of system gain (Kp) in this study. The prevention of postprandial hypoglycemia suggests that the PID + IFB algorithm may allow for lower target glucose selection and improved overall glycemic control., (© 2012 Diabetes Technology Society.)

Objective: Mixing rapid acting insulin analogs with detemir insulin to minimize daily injections has been adopted as a common regimen, especially for some children with type 1 diabetes, despite the manufacturing company's caution against mixing these analogs in the same syringe. The effect of this practice on the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied. This crossover, randomized study was undertaken to determine whether mixing aspart with detemir insulin has an adverse effect on the early glucodynamic action of rapid-acting insulin analog in humans., Research Design and Methods: Eight adolescents with type 1 diabetes (age 17.3 ± 0.6 years and A1C 7.3 ± 0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4 units/kg detemir insulin were injected either as a separate or single mixed injection in random order., Results: Mixing the two insulins diminished the peak and overall early aspart insulin action with significantly lower maximum glucose infusion rate (GIR(max) separate 6.1 ± 0.7 mg/kg/min vs. mix 4.5 ± 0.5 mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h of the insulin action study (separate 757 ± 105 mg/kg vs. mix 491 ± 66 mg/kg; P = 0.04)., Conclusions: These data demonstrate that mixing aspart with detemir insulin markedly lowers the early PD action of aspart and prolongs its time-action profile as compared with the separate injection of these analogs. These changes in insulin PD should be weighed against the added convenience of mixing when considering such unlicensed use of these insulins in youth with type 1 diabetes.

Purpose of Review: The availability of glucose sensors and insulin pumps has enabled the development of devices and software to partially or completely automate insulin delivery. Over the last 2 years, the number of centers developing and evaluating such systems, as well as the number of reports of these studies in the literature, have expanded dramatically. The purpose of this review is to highlight the progress along multiple fronts to develop automated systems to improve control of type 1 diabetes., Recent Findings: Multiple approaches, including automated suspension for actual or impending hypoglycemia, automated augmentation for hyperglycemia, as well as hybrid and full closed-loop control, are in parallel development. So far, early hypoglycemia prevention studies and small inpatient feasibility studies have demonstrated the potential for reducing hypoglycemia and improving overall diabetes control., Summary: Current sensors, pumps, and control algorithms show promise for use in a closed-loop system but have been limited to inpatient studies. The next phase of development should focus on their evaluation in controlled short-term outpatient safety and efficacy trials.

Background: Optimizing a closed-loop insulin delivery algorithm for individuals with type 1 diabetes can be potentially facilitated by a mathematical model of the patient. However, model simulation studies that evaluate changes to the control algorithm need to produce conclusions similar to those that would be obtained from a clinical study evaluating the same modification. We evaluated the ability of a low-order identifiable virtual patient (IVP) model to achieve this goal., Methods: Ten adult subjects (42.5 ± 11.5 years of age; 18.0 ± 13.5 years diabetes; 6.9 ± 0.8% hemoglobin A1c) previously characterized with the IVP model were studied following the procedures independently reported in a pediatric study assessing proportional-integral-derivative control with and without a 50% meal insulin bolus. Peak postprandial glucose levels with and without the meal bolus and use of supplemental carbohydrate to treat hypoglycemia were compared using two-way analysis of variance and chi-square tests, respectively., Results: The meal bolus decreased the peak postprandial glucose levels in both the adult-simulation and pediatricclinical study (231 ± 38 standard deviation to 205 ± 33 mg/dl and 226 ± 51 to 194 ± 47 mg/dl, respectively; p = .0472). No differences were observed between the peak postprandial levels obtained in the two studies (clinical and simulation study not different, p = .57; interaction p = .83) or in the use of supplemental carbohydrate (3 occurrences in 17 patient days of closed-loop control in the clinical-pediatric study; 7 occurrences over 20 patient days in the adult-simulation study, p = .29)., Conclusions: Closed-loop simulations using an IVP model can predict clinical study outcomes in patients studied independently from those used to develop the model., (© 2012 Diabetes Technology Society.)

Objective: Maintenance of appropriate A1C values and minimization of hyperglycemic excursions are difficult for many pediatric patients with type 1 diabetes. Continuous glucose monitoring (CGM) sensor-augmented pump (SAP) therapy is an alternative to multiple daily injection (MDI) therapy in this population., Research Design and Methods: Sensor-augmented pump therapy for A1C reduction (STAR 3) was a 1-yr trial that included 82 children (aged 7-12) and 74 adolescents (aged 13-18) with A1C values ranging from 7.4 to 9.5% who were randomized to either SAP or MDI therapy. Quarterly A1C values were obtained from all subjects. CGM studies were carried out at baseline, 6 months, and 12 months to quantify glycemic excursions [calculated as area under the glucose concentration-time curve (AUC)] and variability. In the SAP group, sensor compliance was recorded., Results: Baseline A1C values were similar in subjects randomized to the SAP (8.26 ± 0.55%) and MDI groups (8.30 ± 0.53%). All subsequent A1C values showed significant (p < 0.05) treatment group differences favoring SAP therapy. Compared with the MDI group, subjects in the SAP group were more likely to meet age-specific A1C targets and had lower AUC values for hyperglycemia with no increased risk of hypoglycemia. Glucose variability improved in the SAP group compared to the MDI group. Children wore CGM sensors more often and were more likely to reach age-specific A1C targets than adolescents., Conclusions: SAP therapy allows both children and adolescents with marginally or inadequately controlled type 1 diabetes to reduce A1C values, hyperglycemic excursions, and glycemic variability in a rapid, sustainable, and safe manner., (© 2011 John Wiley & Sons A/S.)

Objective: Continuous glucose monitoring (CGM) has been demonstrated to improve glycemic control in adults with type 1 diabetes but less so in children. We designed a study to assess CGM benefit in young children aged 4 to 9 years with type 1 diabetes., Research Design and Methods: After a run-in phase, 146 children with type 1 diabetes (mean age 7.5 ± 1.7 years, 64% on pumps, median diabetes duration 3.5 years) were randomly assigned to CGM or to usual care. The primary outcome was reduction in HbA(1c) at 26 weeks by ≥0.5% without the occurrence of severe hypoglycemia., Results: The primary outcome was achieved by 19% in the CGM group and 28% in the control group (P = 0.17). Mean change in HbA(1c) was -0.1% in each group (P = 0.79). Severe hypoglycemia rates were similarly low in both groups. CGM wear decreased over time, with only 41% averaging at least 6 days/week at 26 weeks. There was no correlation between CGM use and change in HbA(1c) (r(s) = -0.09, P = 0.44). CGM wear was well tolerated, and parental satisfaction with CGM was high. However, parental fear of hypoglycemia was not reduced., Conclusions: CGM in 4- to 9-year-olds did not improve glycemic control despite a high degree of parental satisfaction with CGM. We postulate that this finding may be related in part to limited use of the CGM glucose data in day-to-day management and to an unremitting fear of hypoglycemia. Overcoming the barriers that prevent integration of these critical glucose data into day-to-day management remains a challenge.