Pump It Up! A randomized clinical trial to optimize insulin pump self-management behaviors in adolescents with type 1 diabetes.

Individuals with type 1 diabetes (T1D) must engage in a variety of complex and burdensome self-management behaviors daily to maintain near normal blood glucose levels and prevent complications. There is a need for interventions to improve use of sophisticated diabetes technologies, such as insulin pumps, during adolescence - a very high-risk developmental period for individuals with T1D. All diabetes devices, including insulin pumps, store large amounts of behavioral data that can be downloaded and analyzed to evaluate adherence to recommended T1D self-management behaviors. The overall objective of the present study, Pump it Up!, was to use objectively downloaded insulin pump data to inform and test two interventions to optimize insulin pump use in adolescents with T1D and their caregivers. Multiphase Optimization Strategy (MOST) was used to achieve the overall goal of this study - to separately test the main effect of the Pump It Up! Personalized T1D Self-Management Behaviors Feedback Report and the main effect of Pump It Up! Problem-Solving Skills intervention to improve T1D self-management behaviors using a 2 × 2 factorial design. The purpose of this paper is to describe the Pump It Up! study design and rationale, and participant baseline characteristics. Longitudinal data analyses will be conducted, and moderating effects of psychosocial factors will be examined in relation to primary (insulin pump self-management behaviors) and secondary (A1C) outcomes.

Blood Glucose Monitoring Before and After Type 1 Diabetes Clinic Visits.

Objective: To determine patterns of blood glucose monitoring in children and adolescents with type 1 diabetes (T1D) before and after routine T1D clinic visits. Methods: Blood glucose monitoring data were downloaded at four consecutive routine clinic visits from children and adolescents aged 5-18 years. Linear mixed models were used to analyze patterns of blood glucose monitoring in patients who had at least 28 days of data stored in their blood glucose monitors. Results: In general, the frequency of blood glucose monitoring decreased across visits, and younger children engaged in more frequent blood glucose monitoring. Blood glucose monitoring increased before the T1D clinic visits in younger children, but not in adolescents. It declined after the visit regardless of age. Conclusions: Members of the T1D care team need to consider that a T1D clinic visit may prompt an increase in blood glucose monitoring when making treatment changes and recommendations. Tailored interventions are needed to maintain that higher level of adherence across time.

Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: A randomized trial.

BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin. OBJECTIVE: To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D). SUBJECTS: Children and adolescents (aged 1 to <18 years) with T1D. METHODS: A 16-week, phase 3b, treat-to-target, parallel-group, open-label, non-inferiority trial was conducted at 63 sites in 14 countries from October 2013 to November 2014. Patients were randomized 1:1 (age stratified: 1-<6 years; 6-<12 years; 12-<18 years) to IDegAsp once daily (OD) plus insulin aspart (IAsp) for remaining meals (IDegAsp + IAsp), or IDet OD or twice daily plus mealtime IAsp (IDet + IAsp). The primary end-point was HbA1c change from baseline at week 16. RESULTS: A total of 362 participants were randomized to IDegAsp + IAsp (n = 182) or IDet + IAsp (n = 180). HbA1c decreased from baseline to week 16 by 0.3% in both groups (estimated treatment difference: -0.04%-points [-0.23; 0.15]95%CI (-0.45 mmol/mol [-2.51; 1.60]95%CI ), confirming non-inferiority. There were no significant differences between treatment groups in fasting or self-measured plasma glucose. Confirmed hypoglycemia rates did not significantly differ between groups. There was a significant reduction in basal and total insulin dose with IDegAsp + IAsp vs IDet + IAsp (post hoc analysis). Mean number of injections/day was 3.6 and 4.9 with IDegAsp + IAsp and IDet + IAsp, respectively (post hoc analysis). A non-significant higher rate of severe hypoglycemia was observed with IDegAsp + IAsp vs IDet + IAsp. The most frequent adverse events in both groups were hypoglycemia, headache, and nasopharyngitis. CONCLUSIONS: IDegAsp + IAsp was non-inferior to IDet + IAsp regarding HbA1c, had similar hypoglycemia rates and required fewer injections.

A phase 3 multicenter, open-label, prospective study designed to evaluate the effectiveness and ease of use of nasal glucagon in the treatment of moderate and severe hypoglycemia in children and adolescents with type 1 diabetes in the home or school setting.

OBJECTIVE: This multicenter, open-label study was designed to evaluate real-world effectiveness and ease of use of nasal glucagon (NG) in treating moderate or severe hypoglycemic events in children and adolescents with type 1 diabetes (T1D). METHODS: Caregivers were trained to administer NG (3 mg) to the child/adolescent with T1D during spontaneous, symptomatic moderate or severe hypoglycemic events, observe treatment response (defined as awakening or returning to normal status within 30 minutes), and measure blood glucose (BG) levels every 15 minutes. Data regarding adverse events and ease of use were solicited using questionnaires. RESULTS: The analysis population included 14 patients who experienced 33 moderate hypoglycemic events with neuroglycopenic symptoms and BG level ≤70 mg/dL. Patients returned to normal status within 30 minutes of NG administration in all 33 events. Mean BG levels increased from 55.5 mg/dL (range 42-70 mg/dL) at baseline to 113.7 mg/dL (range 79-173 mg/dL) within 15 minutes of NG administration. In most hypoglycemic events (93.9%), caregivers reported that NG administration was easy or very easy; they could administer NG within 30 seconds in 60.6% of events. There were no serious adverse events. CONCLUSIONS: A single 3-mg dose of NG was effective in treating moderate, symptomatic, hypoglycemic events in children and adolescents with T1D in a real-world setting. It was easy-to-use and reasonably well tolerated. NG shows promise as an effective, needle-free, and user-friendly alternative to injectable glucagon.

White Coat Adherence Occurs in Adolescents With Type 1 Diabetes Receiving Intervention to Improve Insulin Pump Adherence Behaviors.

BACKGROUND: To assess the occurrence of white coat adherence, defined as an increase in adherence to treatment regimens prior to a study appointment, in adolescents with type 1 diabetes (T1D) using insulin pumps and participating in a randomized adherence intervention trial. METHODS: Blood glucose monitoring (BGM) readings, carbohydrate inputs, and insulin boluses delivered were downloaded from the insulin pumps of adolescents, aged 10-18 years, at 3 consecutive T1D study visits. Linear mixed models were used to analyze patterns of BGM, carbohydrate inputs, and insulin boluses delivered in patients who had 40 consecutive days of data stored in their insulin pumps prior to the study visit. RESULTS: Stratified linear mixed models revealed that adolescents randomized to the Tailored Feedback Intervention group increased their blood glucose monitoring ( P < .01), carbohydrate inputs ( P < .0001), and insulin bolusing ( P < .0001) prior to study appointments. In contrast, white coat adherence did not occur in adolescents randomized to the Treatment as Usual group ( Ps > .42). CONCLUSIONS: White coat adherence may occur in adolescents participating in clinical trials. Meter and insulin pump data downloads representing the 1- to 2-week period prior to a study visit are likely to overestimate actual adherence during the time frame between study visits.

White Coat Adherence in Pediatric Patients With Type 1 Diabetes Who Use Insulin Pumps.

BACKGROUND: The purpose was to assess the occurrence of white coat adherence, defined as an increase in adherence to treatment regimens prior to a clinic appointment, in children and adolescents with type 1 diabetes (T1D) who use insulin pumps. METHODS: Blood glucose monitoring (BGM) data, carbohydrate inputs, and insulin boluses delivered were downloaded from the insulin pumps of children and adolescents, aged 7-19 years with T1D, at 2 consecutive routine diabetes clinic visits. Linear mixed models were used to analyze patterns of BGM, carbohydrate inputs, and insulin boluses delivered in patients who had ≥28 days of data stored in their insulin pumps. RESULTS: In general, younger children engaged in more frequent BGM, carbohydrate inputs, and insulin boluses delivered than older children and adolescents. White coat adherence occurred with frequency of BGM, carbohydrate inputs, and insulin boluses delivered, but only in younger children. CONCLUSIONS: Diabetes care providers need to be aware that white coat adherence may occur, particularly in young children. Providers routinely download meter and insulin pump data for the 1- to 2-week period before the clinic visit. For patients exhibiting white coat adherence, their data will overestimate the patient's actual adherence.

Are children with type 1 diabetes safe at school? Examining parent perceptions.

OBJECTIVE: To describe parent perceptions of children's diabetes care at school including: availability of licensed health professionals; staff training; logistics of provision of care; and occurrence and treatment of hypo- and hyperglycemia; and to examine parents' perceptions of their children's safety and satisfaction in the school environment. RESEARCH DESIGN AND METHODS: A survey was completed by parents of children with type 1 diabetes from permissive (trained, non-medical school personnel permitted to provide diabetes care; N = 237) and non-permissive (only licensed health care professionals permitted to provide diabetes care; N = 198) states. RESULTS: Most parents reported that schools had nurses available for the school day; teachers and coaches should be trained; nurses, children, and parents frequently provided diabetes care; and hypo- and hyperglycemia occurred often. Parents in permissive states perceived children to be as safe and were as satisfied with care as parents in non-permissive states. CONCLUSIONS: Training non-medical staff will probably maximize safety of children with diabetes when a school nurse is not available.

Importance of manually entering blood glucose readings when wireless-compatible meters are not being used with an insulin pump.

BACKGROUND: The objective was to determine if there were differences in blood glucose monitoring (BGM) data downloaded from insulin pumps of patients who use meters that wirelessly transmit data to their insulin pumps (i.e., wireless group) and those who do not (i.e., nonwireless group). METHODS: Blood glucose monitoring data were downloaded from the meters and insulin pumps of 47 children and adolescents with type 1 diabetes mellitus. Independent and paired t tests compared BGM data downloaded from meters and BGM data downloaded from insulin pumps. RESULTS: There were significant differences in BGM data downloaded from the insulin pumps of patients using wireless meters compared to those using nonwireless meters. Wireless patients appeared to engage in more BGM, had more low and in-range BG readings and fewer very high BG readingss than nonwireless patients. However, a comparison of BGM data downloaded from meters and insulin pumps of nonwireless patients indicated that their insulin pump data significantly underestimated the number of BGM readings conducted, as well as the number of low and in-range readings, while overestimating the number of very high BGM readings. CONCLUSIONS: Because patients who use nonwireless-compatible meters do not manually enter their low and in-range BGM readings into the insulin pump, BGM data downloaded only from pumps may provide an incomplete representation of BGM frequency or results. It is recommended that patients use meters that directly communicate with pumps or perform bolus calculations. Patients should be educated about the importance of manually entering all BGM readings if they do not use a wireless-compatible meter with their insulin pump.

Insulin bolusing software: the potential to optimize health outcomes in type 1 diabetes mellitus.

BACKGROUND: Insulin bolusing calculators alleviate the burden of having to calculate insulin bolus doses for patients with type 1 diabetes mellitus (T1DM). Three important pieces of information are needed: a blood glucose monitoring (BGM) result, carbohydrates to be consumed, and the amount of insulin bolus delivered. The purpose of this study was to describe insulin pump adherence behaviors associated with the use of bolus calculators in youth who use Medtronic insulin pumps. METHODS: Data were downloaded from the MiniMed Paradigm insulin pumps (Medtronic) of 31 youth with T1DM. Areas of adherence that were evaluated included fundamental insulin pump adherence behaviors (e.g., BGM, carbohydrate entry, and insulin bolusing), decisions about Wizard® recommendations, and three Wizard steps: BGM result-carbohydrate input-insulin bolus. RESULTS: On average, patients conducted BGM ≥4 times/day on 69% of days, inputted carbohydrates ≥3 times/day on 63% of days, and insulin bolused ≥3 times/day on 85% of days. Participants generally followed Wizard recommendations. Finally, participants completed all three Wizard steps (BGM, carbohydrate input, insulin bolus) within 30 min for an average of 29% of boluses. Almost 3% of boluses that were preceded by Wizard use were delivered without conducting BGM or inputting carbohydrates. CONCLUSION: There was substantial variability in insulin pump adherence behaviors (e.g., days when no BGM occurred, reliance on basal insulin). Interventions targeting insulin pump adherence behaviors have the potential to optimize diabetes health outcomes and glycemic control. Improving insulin pump software reports is one promising avenue for improving adherence.

Impact of a telemedicine system with automated reminders on outcomes in women with gestational diabetes mellitus.

BACKGROUND: Health information technology has been proven to be a successful tool for the management of patients with multiple medical conditions. The purpose of this study was to examine the impact of an enhanced telemedicine system on glucose control and pregnancy outcomes in women with gestational diabetes mellitus (GDM). SUBJECTS AND METHODS: We used an Internet-based telemedicine system to also allow interactive voice response phone communication between patients and providers and to provide automated reminders to transmit data. Women with GDM were randomized to either the telemedicine group (n=40) or the control group (n=40) and asked to monitor their blood glucose levels four times a day. Women in the intervention group transmitted those values via the telemedicine system, whereas women in the control group maintained paper logbooks, which were reviewed at prenatal visits. Primary outcomes were infant birth weight and maternal glucose control. Data collection included blood glucose records, transmission rates for the intervention group, and chart review. RESULTS: There were no significant differences between the two groups (telemedicine vs. controls) in regard to maternal blood glucose values or infant birth weight. However, adding telephone access and reminders increased transmission rates of data in the intervention group compared with the intervention group in our previous study (35.6±32.3 sets of data vs.17.4±16.9 sets of data; P<0.01). CONCLUSIONS: Our enhanced telemedicine monitoring system increased system utilization and contact between women with GDM and their healthcare providers but did not impact upon pregnancy outcomes.

Performance of the DIDGET blood glucose monitoring system in children, teens, and young adults.

BACKGROUND: This study evaluated the performance of the DIDGET® blood glucose monitoring system (BGMS) in the hands of its intended users: children, teens, and young adults with diabetes. METHODS: Finger stick capillary blood samples were tested in duplicate by subjects (with parent/guardian assistance, if needed) and health care professionals using the DIDGET BGMS, and results were compared with those obtained using a Yellow Springs Instruments (YSI) glucose analyzer. Modified venous blood samples (i.e., glycolyzed or spiked with glucose) were used to analyze meter performance under extreme glucose concentrations. Accuracy was assessed using International Organization for Standardization (ISO) 15197:2003 guidelines (i.e., 95% of meter results within ±15 mg/dl or ±20% of reference values). RESULTS: A total of 123 subjects aged 4 to 24 years with type 1 or type 2 diabetes were enrolled. The DIDGET meter achieved accuracy according to ISO 15197:2003 criteria: >97% of meter results were within ±15 mg/dl or ±20% of reference values. Regression analyses showed a high degree of correlation between meter and YSI results: coefficient of determination (R(2)) = 98.2% for all samples combined and 97.2% for capillary samples only. Clinical accuracy for combined samples was demonstrated by Parkes consensus error grid analyses; 100% of meter results were in zone A (98.5%) or zone B (1.5%). There was no difference in performance or accuracy across age subsets. Hematocrit values did not affect meter blood glucose results. CONCLUSION: The DIDGET BGMS provided accurate test results across all age ranges in children, teens, and young adults with diabetes.

International Forum for the Advancement of Diabetes Research and Care, April 29-30, 2011, Athens, Greece.

The International Forum for the Advancement of Diabetes Research and Care brought together distinguished international experts in diabetes to discuss diverse trends and emerging issues in diabetes therapy and management. The plenary sessions on the first day focused on trends in insulin therapy, the role of glucagon-like peptide-1 receptor agonists in diabetes treatment, the relationship between diabetes and cardiovascular risk, and the challenges associated with the development of clinically relevant treatment guidelines. Interactive breakout sessions addressed the following topics: microvascular complications of diabetes; the need for a team approach to patient education; optimal management of Asian people with diabetes; the role of continuous glucose monitoring in assessing glucose variability; and lessons learned from biosimilar drugs. The plenary sessions on the second day covered self-monitoring of blood glucose, treatment and prevention of type 1 diabetes, and future directions for diabetes therapy. The meeting represented an excellent forum for the presentation of new research and the exchange of ideas aimed at improving outcomes for people with diabetes.

Does blood glucose monitoring increase prior to clinic visits in children with type 1 diabetes?

OBJECTIVE: To assess the occurrence of white coat adherence in families with children who have type 1 diabetes. RESEARCH DESIGN AND METHODS: Blood glucose data were downloaded from meters of 72 children, aged 2-11 years, with type 1 diabetes at four consecutive clinic visits. Generalized estimating equations were used to analyze patterns of blood glucose monitoring (BGM) during the 28 days before each clinic visit. RESULTS: More frequent BGM was associated with better glycemic control. Evidence of a white coat adherence effect, with BGM frequency increasing before a clinic visit, was found only among children with low A1C levels. CONCLUSIONS: Highly motivated families who frequently monitor their child's blood glucose increased the frequency of BGM before the child's clinic visit. The additional monitoring may benefit the child by providing the physician with a wealth of blood glucose information to guide recommendations.

Ease of use and preference for a new disposable self-injection pen compared with a reusable pen for administering recombinant human growth hormone: A multicenter, 2-month, single-arm, open-label clinical trial in patient-caregiver dyads.

BACKGROUND: Improved ease of use of drug-delivery devices may enhance compliance. Development of an easier-to-use device for administration of recombinant human growth hormone (rhGH) may thus be beneficial for patients and their caregivers. OBJECTIVE: This study compared ease of use and preference for a new disposable rhGH injection pen relative to previous experience with the currently available reusable pen in standard practice. Both pens deliver the same formulation of rhGH. METHODS: This multicenter, single-arm, open-label study assessed ease of use and preference for the 2 injection pens in patient-caregiver dyads. Eligible children were aged 8 through 18 years, were currently being treated with rhGH, and had been compliant with use of the current reusable pen for ≥ 3 months before study entry. A validated self-reported Injection Pen Assessment Questionnaire was administered twice during the study-at baseline (to assess perceptions of the reusable pen) and after 2 months of use of the new disposable pen-to assess ease of use of the individual pens (rated on a 5-point Likert-type scale), the comparative ease of use of the 2 pens, and pen preference. The primary end point was the proportion of dyads who rated the new pen as no different or easier to use than the current pen. Regardless of treatment or suspected causal relationship to the investigational product, all observed or volunteered adverse events (AEs) were recorded and rated as mild, moderate, or severe. RESULTS: Of 137 screened dyads, 136 (91 boys, 45 girls) were included in the safety population and 133 were included in the efficacy population. The children had a mean age of 12.3 years, a mean weight of 42.2 kg, a mean height of 145.9 cm, and a mean body mass index of 19.3 kg/m(2); 84.6% of the children were white. The majority (82.4%) of adult dyad members were subjects' mothers. The adult dyad members were more likely than the child members to be responsible for preparing the injection (82.0%) and administering the injection (72.9%). Overall, 73.7% of dyads rated the new disposable pen no different or easier to use than the reusable pen (95% CI, 66.2%-81.2%), and 65.2% rated the disposable pen no different or preferable to the reusable pen (95% CI, 57.0%-73.3%). Overall, 60 all-causality AEs occurred in 28 subjects (20.6%), most of them (93.3%) either mild or moderate in intensity. Eight device-related AEs occurred in 7 subjects (5.1%) (injection-site hematoma in 3 and injection-site pain in 5). The most common AEs were headache (7 events), injection-site pain (5), upper respiratory tract infection (4), and pyrexia (4). No deaths or serious AEs were reported. CONCLUSIONS: Nearly three quarters of patients and caregivers reported that the new disposable pen was no different or easier to use than the reusable pen, and nearly two thirds preferred the disposable pen. No safety concerns were identified. The findings suggest that the improvements in the new pen were recognized by patients and caregivers.

Risk factors associated with depressive symptoms in caregivers of children with type 1 diabetes or cystic fibrosis.

OBJECTIVE: Evaluate depressive symptoms in caregivers of children with type 1 diabetes (T1D) or cystic fibrosis (CF) and identify associated risk factors. METHODS: A total of 195 caregivers completed demographic, stress, and depressive symptoms questionnaires. Children's health status was obtained from medical records. RESULTS: Approximately 33% of caregivers reported elevated symptoms of depression (i.e., exceeded clinical cutoff of 16 on the Center for Epidemiological Studies-Depression Scale). For caregivers of children with T1D, elevations were associated with less caregiver education, more family stress, older child age, and worse glycemic control. For caregivers of children with CF, more family stress and lack of employment outside of the home were associated with elevated depressive symptoms. CONCLUSIONS: Many caregivers of children with T1D or CF experience depressive symptoms, although risk factors may differ in these two populations. Screening of caregiver depressive symptoms as part of routine clinic visits may provide opportunities for needed intervention.

Predictors of study completion and withdrawal in a randomized clinical trial of a pediatric diabetes adherence intervention.

PURPOSE: Loss of participants in randomized clinical trials threatens the validity of study findings. The purpose of this study was to determine pre-randomization predictors of study completion status throughout the course of a randomized clinical trial involving young children with type 1 diabetes and their primary caregivers. METHODS: An intervention to improve adherence to the diabetes treatment regimen was delivered as part of the child's regular 3-month diabetes clinic visit. The study protocol involved 7 clinic visits across 18 months for the Immediate Treatment group and 9 clinic visits across 24 months for the Delayed Treatment group. Among those who completed the study and regardless of treatment group, participants were categorized into two groups: On-Time Completers (n=41) and Late Completers (n=39). Demographic, disease, and psychosocial characteristics of children and their primary caregivers measured prior to study randomization were tested for their association with the participants' completion status (i.e., On-Time Completers, Late Completers, or Withdrawals). RESULTS: Of the 108 participants, 28 (25.9%) withdrew and 80 (74.1%) completed the study. On-Time Completers (i.e., study completed within 4 months of expected date) were more likely to have private insurance and primary caregivers with some college education. Late Completers (i.e., study completion took longer than 4 months) were more likely to be boys and to have primary caregivers who reported mild to moderate levels of depression. Children who subsequently withdrew from the study reported poorer diabetes-related quality of life and poorer school-related quality of life at study inception and were more likely to have primary caregivers who did not work outside the home. CONCLUSIONS: Pre-randomization screening of participants on both demographic and psychological variables may help identify those at greatest risk for study withdrawal or poor study protocol adherence, permitting the investigators to develop retention strategies aimed at this high-risk group.