Association of Fructosamine Levels With Glycemic Control in Children With Type 1 Diabetes as Determined by Continuous Glucose Monitoring: Results From the CGM TIME Trial.

OBJECTIVE: Our aim in this study was to determine the correlation between serum fructosamine and average blood glucose, as measured by continuous glucose monitoring (CGM) in children with type 1 diabetes. METHODS: Ninety-seven blood samples were collected from 70 participants in the Timing of Initiation of continuous glucose Monitoring in Established pediatric diabetes (CGM TIME) Trial. Each eligible participant had 3 weeks of CGM data with at least 60% CGM adherence before blood collection. Ordinary least-squares linear regression incorporating restricted cubic splines was used to determine the association between fructosamine levels and mean blood glucose. RESULTS: An association was found between fructosamine and mean blood glucose, with an F statistic of 9.543 (p<0.001). Data were used to create a formula and conversion chart for calculating mean blood glucose from fructosamine levels for clinical use. CONCLUSIONS: There is a complex relationship between average blood glucose, as determined by CGM and fructosamine. Fructosamine levels may be clinically useful for assessing short-term glycemic control when CGM is not available.

Socioeconomic representativeness of Australian, Canadian and British cohorts from the paediatric diabetes AdDIT study: comparisons to regional and national data.

BACKGROUND: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. METHODS: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national). RESULTS: Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001). CONCLUSIONS: Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials. TRIAL REGISTRATION: NCT01581476. Registered on 20 April 2012.

Increasing plasma glucose before the development of type 1 diabetes-the TRIGR study.

OBJECTIVE: The ß-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. RESEARCH DESIGN AND METHODS: A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. RESULTS: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp <0.001) and the development of diabetes (p < 0.002 resp <0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). CONCLUSIONS: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes.

Motivational Stage at Continuous Glucose Monitoring (CGM) Initiation in Pediatric Type 1 Diabetes Is Associated With Current Glycemic Control but Does Not Predict Future CGM Adherence or Glycemic Control.

OBJECTIVES: The Timing of Initiation of Continuous Glucose Monitoring in Established Pediatric Diabetes (CGM TIME) Trial is a multicenter, randomized controlled trial in children with type 1 diabetes, comparing simultaneous pump and CGM with CGM initiation 6 months later (Paradigm, Veo, Enlite Sensor, Medtronic Canada). This study addresses the ability of SOCRATES (Stages Of Change Readiness And Treatment Eagerness Scale) to classify children and parents into distinct motivational stages and identify the stages' association with glycated hemoglobin (A1C) at trial entry and outcomes 6 months after CGM initiation. METHODS: Ninety-eight of 99 eligible children 10 to 18 years of age and 137 of 141 eligible parents completed SOCRATES at trial entry and 6 months later. Parent-child agreement for motivational stage was determined by weighted kappa. Linear regression was used to examine association between motivational stage and i) A1C at trial entry and ii) change in A1C and CGM adherence 6 months after CGM initiation. RESULTS: More than 87% of children and 88% of parents were classified into distinct motivational stages, with weak parent-child agreement. At trial entry, motivational stage was associated with A1C, which was 1.02% higher for children in the Action stage than in the Precontemplation stage (p<0.0001). When compared with children of parents in Precontemplation, A1C for children of parents in the Maintenance and Action stages were 0.83% (p=0.02) and 0.36% (p=0.048) higher, respectively. Precontemplation was associated with shorter diabetes duration. Motivational stage at CGM initiation did not predict change in A1C or CGM adherence 6 months later. CONCLUSIONS: SOCRATES can categorize children with type 1 diabetes and their parents into motivational stages. Although motivational stage was associated with glycemic control at trial entry, it did not predict future diabetes-related behaviour or A1C.

Comparison of Clinical and Social Characteristics of Canadian Youth Living With Type 1 and Type 2 Diabetes.

OBJECTIVES: Our aim in this study was to describe the clinical and social characteristics of 2 Canadian cohorts of adolescents with diabetes. METHODS: Participants from the Improving renal Complications in Adolescents with type 2 diabetes through REsearch (iCARE) study (n=322) and the Early Determinants of Cardio-Renal Disease in Youth With Type 1 Diabetes (n=199) study were compared. RESULTS: Adolescents were 10 to 18 years of age (mean ± standard deviation: 14.8±2.4 years). The T2DM cohort had a shorter duration of diabetes. Both groups had glycated hemoglobin levels above target. The type 2 diabetes (T2D) cohort was comprised of predominantly Indigenous youth. The type 1 diabetes (T1D) cohort was 58.3% European/Caucasian, with a high proportion (41.7%) of visible minority groups (Afro-Caribbean, Asian/Pacific Islander, Hispanic). The prevalence of obesity, hypertension, left ventricular hypertrophy, albuminuria and hyperfiltration was higher in the T2D cohort. The T1D cohort was more socially and economically advantaged in all 4 dimensions of health inequality. CONCLUSIONS: There are significant differences in clinical and social characteristics of adolescents with T2D and T1D in Canada. Both have inadequate glycemic control with evidence of onset and progression of diabetes-related complications.

Fear of hypoglycemia in children with type 1 diabetes and their parents: Effect of pump therapy and continuous glucose monitoring with option of low glucose suspend in the CGM TIME trial.

To determine if pump therapy with continuous glucose monitoring offering low glucose suspend (LGS) decreases fear of hypoglycemia among children with type 1 diabetes and their parents. The CGM TIME trial is a multicenter randomized controlled trial that enrolled 144 children with type 1 diabetes for at least 1 year (mean duration 3.4 ± 3.1 years) starting pump therapy (MiniMed™ Veo™, Medtronic Canada). CGM (MiniMed™ Enlite™ sensor) offering LGS was introduced simultaneously or delayed for 6 months. Hypoglycemia Fear Scale (HFS) was completed by children ≥10 years old and all parents, at study entry and 12 months later. Simultaneous and Delayed Group participants were combined for all analyses. Subscale scores were compared with paired t-tests, and individual items with paired Wilcoxon tests. Linear regression examined association with CGM adherence. 121/140 parents and 91/99 children ≥10 years had complete data. Mean Behavior subscale score decreased from 21.1 (SD 5.9) to 17.2 (SD 6.1) (p < .001) for children, and 20.7 (SD 7.5) to 17.4 (7.4) (p < .001) for parents. Mean Worry subscale score decreased from 17.9 (SD 11.9) to 11.9 (SD 11.4) (p < .001) for children, and 23.1 (SD 13.2) to 17.6 (SD 10.4) (p < .001) for parents. Median scores for 10/25 child items and 12/25 parent items were significantly lower at 12 months (p < .001). Linear regression found no association between HFS scores and CGM adherence. Insulin pump therapy with CGM offering LGS significantly reduced fear of hypoglycemia not related to CGM adherence in children with type 1 diabetes and their parents.

Timing of CGM initiation in pediatric diabetes: The CGM TIME Trial.

OBJECTIVE: To determine whether timing of CGM initiation offering low glucose suspend (LGS) affects CGM adherence in children and youth starting insulin pump therapy. METHODS: A 5-site RCT of pump-naïve subjects (aged 5-18 years) with type 1 diabetes (T1D) for at least 1 year compared simultaneous pump and CGM initiation offering LGS vs standard pump therapy with CGM initiation delayed for 6 months. Primary outcome was CGM adherence (hours per 28 days) (MiniMed™ Paradigm™ Veo™ system; CareLink Pro™ software) over 6 months after CGM initiation. Secondary outcome HbA1c was measured centrally. Linear mixed-models and ordinary least squares models were fitted to estimate effect of intervention, and covariates baseline age, T1D duration, HbA1c, gender, ethnicity, hypoglycemia history, clinical site, and association between CGM adherence and HbA1c. RESULTS: The trial randomized 144/152 (95%) eligible subjects. Baseline mean age was 11.5 ± 3.3(SD) years, T1D duration 3.4 ± 3.1 years, and HbA1c 7.9 ± 0.9%. Six months after CGM initiation, adjusted mean difference in CGM adherence was 62.4 hours per 28 days greater in the Simultaneous Group compared to Delayed Group (P = .007). There was no difference in mean HbA1c at 6 months. However, for each 100 hours of CGM use per 28-day period, HbA1c was 0.39% (95% CI 0.10%-0.69%) lower. Higher CGM adherence was associated with reduced time with glucose >10 mmol/L (P < .001). CONCLUSION: CGM adherence was higher after 6 months when initiated at same time as pump therapy compared to starting CGM 6 months after pump therapy. Greater CGM adherence was associated with improved HbA1c.

A core outcome set for studies of gestational diabetes mellitus prevention and treatment.

AIMS/HYPOTHESIS: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM). METHODS: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised. RESULTS: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth). CONCLUSIONS/INTERPRETATION: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies. TRIAL REGISTRATION: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/.

Testing an audit and feedback-based intervention to improve glycemic control after transfer to adult diabetes care: protocol for a quasi-experimental pre-post design with a control group.

BACKGROUND: When young adults transfer from pediatric to adult diabetes care they are at risk for deterioration of glycemic control, putting them at an increased risk of developing both acute and chronic complications. Despite increased awareness of these risks, there are gaps in care delivery during this vulnerable time and variability in the implementation of recommended transition practice. Audit and feedback (AF) interventions have a positive but variable effect on implementation of best practices. An expert group identified specific suggestions for optimizing the effectiveness of AF interventions. We aim to test an AF-based intervention incorporating these specific suggestions to improve transition practices and glycemic control in the first year after transfer from pediatric to adult diabetes care. METHODS: This is a pragmatic quasi-experimental study; a series of three cohort studies (pre-implementation, early-implementation, and post-implementation) to compare the baseline adjusted hemoglobin A1c (HbA1c) in the 12 months after the final pediatric visit in five pediatric diabetes centres within the Ontario Pediatric Diabetes Network in Ontario, Canada. The intervention includes three components: 1) centre-level feedback reports compiling data from chart abstraction, linked provincial administrative datasets, and patient-reported experience measures; 2) webinars for facilitated conversations/coaching about the feedback; and 3) online repository of curated transition resources for providers. The primary outcome will be analyzed using a multivariable linear regression model. We will conduct a qualitative process evaluation to understand intervention fidelity and to provide insight into the mechanisms of action of our results. DISCUSSION: There is a need to develop an innovative system-level approach to improve outcomes and the quality of care for young adults with type 1 diabetes during the vulnerable time when they transfer to adult care. Our research team, a collaboration of health services, implementation science, and quality improvement researchers, are designing, implementing, and evaluating an AF-based intervention using recommendations about how to optimize effectiveness. This knowledge will be generalizable to other care networks that aim to deliver uniformly high-quality care in diverse care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03781973. Registered 13 December 2018. Date of enrolment of the first participant to the trial: June 1, 2019.

Follow-up at 1 year and beyond of women with gestational diabetes treated with insulin and/or oral glucose-lowering agents: a core outcome set using a Delphi survey.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is linked with a higher lifetime risk for the development of impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, the metabolic syndrome, cardiovascular disease, postpartum depression and tumours. Despite this, there is no consistency in the long-term follow-up of women with a previous diagnosis of GDM. Further, the outcomes selected and reported in the research involving this population are heterogeneous and lack standardisation. This amplifies the risk of reporting bias and diminishes the likelihood of significant comparisons between studies. The aim of this study is to develop a core outcome set (COS) for RCTs and other studies evaluating the long-term follow-up at 1 year and beyond of women with previous GDM treated with insulin and/oral glucose-lowering agents. METHODS: The study consisted of three work packages: (1) a systematic review of the outcomes reported in previous RCTs of the follow-up at 1 year and beyond of women with GDM treated with insulin and/or oral glucose-lowering agents; (2) a three-round online Delphi survey with key stakeholders to prioritise these outcomes; and (3) a consensus meeting where the final COS was decided. RESULTS: Of 3344 abstracts identified and evaluated, 62 papers were retrieved and 25/62 papers were included in this review. A total of 121 outcomes were identified and included in the Delphi survey. Delphi round 1 was emailed to 835 participants and 288 (34.5%) responded. In round 2, 190 of 288 (65.9%) participants responded and in round 3, 165 of 190 (86.8%) participants responded. In total, nine outcomes were selected and agreed for inclusion in the final COS: assessment of glycaemic status; diagnosis of type 2 diabetes since the index pregnancy; number of pregnancies since the index pregnancy; number of pregnancies with a diagnosis of GDM since the index pregnancy; diagnosis of prediabetes since the index pregnancy; BMI; post-pregnancy weight retention; resting blood pressure; and breastfeeding. CONCLUSIONS/INTERPRETATION: This study identified a COS that will help bring consistency and uniformity to outcome selection and reporting in clinical trials and other studies involving the follow-up at 1 year and beyond of women diagnosed with GDM treated with insulin and/or oral glucose-lowering agents during pregnancy.

Evaluation of referrals for short stature: A retrospective chart review.

BACKGROUND: Referrals to paediatric endocrine clinics for short stature are common. Height velocity (HV) is an essential component of the evaluation of short stature as growth deceleration often reflects an underlying paediatric endocrine diagnosis (PED). Access to previous measurements facilitates prompt calculation of HV. OBJECTIVE: To determine the availability of previous measurements at time of referral for short stature and to determine predictors of a PED. METHODS: A retrospective chart review was performed on all referrals for short stature to a single paediatric endocrinologist between January 2008 and December 2014. Standard practice following receipt of a referral for short stature included repeated requests to the referring physician for previous measurements. RESULTS: A total of 324 charts of patients aged 11 months to 18 years were reviewed and 286 were eligible for inclusion. Previous measurements were available in 72.4%, and 44.8% of these were found to have a PED. There was a significant relation between HV<25th percentile and a PED (P<0.0001) and between height deficit (HD) and a PED (P<0.0001). Logistic regression analysis showed that a HV<25th percentile and a HD>2 standard deviations, increased the odds of PED by a factor of 5.12 (P<0.001) and 1.39 (P<0.005), respectively. CONCLUSION: HV is a significant predictor of a PED. Our higher rate of previous measurement availability is likely due to our effective referral screening protocol. The availability of these measurements, which are essential for HV calculation, are likely to reduce delays in diagnosis and management.

Closing the Gap: Results of the Multicenter Canadian Randomized Controlled Trial of Structured Transition in Young Adults With Type 1 Diabetes.

OBJECTIVE: To determine if a structured transition program for young adults with type 1 diabetes improves clinic attendance, glycemic control, diabetes-related distress, quality of life, and satisfaction with care. RESEARCH DESIGN AND METHODS: In this multicenter randomized controlled trial, young adults (17-20 years) with type 1 diabetes were randomly assigned to a transition program with a transition coordinator or to standard care. The intervention lasted 18 months (6 in pediatric and 12 in adult care). The primary outcome was the proportion of participants who failed to attend at least one adult diabetes clinic visit during the 12-month follow-up after completion of the intervention. RESULTS: We randomized 205 participants, 104 to the transition program and 101 to standard care. Clinic attendance was improved in the transition program (mean [SD] number of visits 4.1 [1.1] vs. 3.6 [1.2], P = 0.002), and there was greater satisfaction with care (mean [SD] score 29.0 [2.7] vs. 27.9 [3.4], P = 0.032) and less diabetes-related distress (mean [SD] score 1.9 [0.8] vs. 2.1 [0.8], P = 0.049) reported than in standard care. There was a trend toward improvement in mean HbA1c (8.33% [68 mmol/mol] vs. 8.80% [73 mmol/mol], P = 0.057). During the 12-month follow-up, there was no difference in those failing to attend at least one clinic visit (P = 0.846), and the mean change in HbA1c did not differ between the groups (P = 0.073). At completion of follow-up, the groups did not differ with respect to satisfaction with care or diabetes-related distress and quality of life. CONCLUSIONS: Transition support during this 18-month intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but these benefits were not sustained 12 months after completion of the intervention.

Elevated Leukocyte Azurophilic Enzymes in Human Diabetic Ketoacidosis Plasma Degrade Cerebrovascular Endothelial Junctional Proteins.

OBJECTIVE: Diabetic ketoacidosis in children is associated with vasogenic cerebral edema, possibly due to the release of destructive polymorphonuclear neutrophil azurophilic enzymes. Our objectives were to measure plasma azurophilic enzyme levels in children with diabetic ketoacidosis, to correlate plasma azurophilic enzyme levels with diabetic ketoacidosis severity, and to determine whether azurophilic enzymes disrupt the blood-brain barrier in vitro. DESIGN: Prospective clinical and laboratory study. SETTING: The Children's Hospital, London Health Sciences Centre. SUBJECTS: Pediatric type 1 diabetes patients; acute diabetic ketoacidosis or age-/sex-matched insulin-controlled. MEASUREMENTS AND MAIN RESULTS: Acute diabetic ketoacidosis in children was associated with elevated polymorphonuclear neutrophils. Plasma azurophilic enzymes were elevated in diabetic ketoacidosis patients, including human leukocyte elastase (p < 0.001), proteinase-3 (p < 0.01), and myeloperoxidase (p < 0.001). A leukocyte origin of human leukocyte elastase and proteinase-3 in diabetic ketoacidosis was confirmed with buffy coat quantitative real-time polymerase chain reaction (p < 0.01). Of the three azurophilic enzymes elevated, only proteinase-3 levels correlated with diabetic ketoacidosis severity (p = 0.002). Recombinant proteinase-3 applied to human brain microvascular endothelial cells degraded both the tight junction protein occludin (p < 0.05) and the adherens junction protein VE-cadherin (p < 0.05). Permeability of human brain microvascular endothelial cell monolayers was increased by recombinant proteinase-3 application (p = 0.010). CONCLUSIONS: Our results indicate that diabetic ketoacidosis is associated with systemic polymorphonuclear neutrophil activation and degranulation. Of all the polymorphonuclear neutrophil azurophilic enzymes examined, only proteinase-3 correlated with diabetic ketoacidosis severity and potently degraded the blood-brain barrier in vitro. Proteinase-3 might mediate vasogenic edema during diabetic ketoacidosis, and selective proteinase-3 antagonists may offer future vascular- and neuroprotection.

Dynamic regulation of plasma matrix metalloproteinases in human diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) in children is associated with cerebrovascular-related complications. We recently reported that DKA facilitates leukocyte adherence to the brain microvascular endothelium. Adhered leukocytes can release enzymes that instigate vascular dysfunction. Our aims were to measure plasma levels of leukocyte-derived matrix metalloproteinases (MMPs) from DKA patients and to correlate plasma MMP concentrations with DKA severity. METHODS: Plasma was obtained from children with type 1 diabetes, either in DKA (n = 16) or insulin controlled (CON; n = 16). Antibody microarray and gelatin zymography were used to quantify plasma MMPs and their endogenous tissue inhibitors (TIMPs). MMP concentrations were correlated with DKA severity (blood pH). Quantitative PCR of leukocyte mRNA was used to help determine the origin of plasma MMPs. RESULTS: DKA was associated with altered plasma levels of ↓MMP-2 (P < 0.001), ↑MMP-8 (P < 0.001), ↑MMP-9 (P < 0.05), and ↑TIMP-4 (P < 0.001), as compared with CON. Elevated MMP-8 and MMP-9 were both positively correlated with DKA severity (P < 0.05). DKA was associated with increased leukocyte mRNA for MMP-8, MMP-9, and TIMP-4 (P < 0.005). CONCLUSION: MMPs are dynamically regulated during DKA. Plasma MMP-8 and MMP-9 concentrations correlate with DKA severity and are known to degrade brain microvascular endothelial cell tight junctions. Thus, leukocyte-derived MMPs might contribute to DKA-associated cerebrovascular complications.

Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis.

OBJECTIVE: Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system. RESEARCH DESIGN AND METHODS: In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight. RESULTS: Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis. CONCLUSIONS: In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher.

The Health Initiative Program for Kids (HIP Kids): effects of a 1-year multidisciplinary lifestyle intervention on adiposity and quality of life in obese children and adolescents--a longitudinal pilot intervention study.

BACKGROUND: Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents. METHODS: Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted of fifteen 90-minute educational sessions led by a dietitian, exercise specialist, and social worker. Anthropometric measures, body composition, and QoL (Pediatric Quality of Life Inventory 4.0), were assessed at baseline, 3 months, and 12 months. Laboratory values were measured at baseline and 12 months. The primary outcome measures were change in BMI and BMI z-score, secondary outcome measures included change in QoL and body composition. A paired sample t-test was used to assess within-group differences and 95% confidence intervals were reported for the mean differences. RESULTS: 42 obese children and adolescents (21 girls) completed the 1-year intervention (mean age 12.8 ± 3.14 years). Mean baseline BMI was 31.96 ± 5.94 kg/m(2) and BMI z-score was +2.19 ± 0.34. Baseline QoL (self-assessments and parental assessments) was impaired: mean baseline scores were 74.5 ± 16.5 and 63.7 ± 19.4 for physical functioning and 69.0 ± 14.9 and 64.0 ± 18.3 for emotional functioning, respectively. At 12 months, BMI z-score had decreased (-0.07 ± 0.11, 95% CI: -0.11 to -0.04). BMI (0.80 ± 1.57 kg/m(2), 95% CI 0.31 to 1.29) and fat-free mass (4.02 ± 6.27 kg, 95% CI 1.90 to 6.14) increased, but % body fat and waist circumference did not. Both the parent-reported physical (11.3 ± 19.2, 95% CI 4.7 to 17.9) and emotional (7.7 ± 15.7, 95% CI 2.3 to 13.0) functioning QoL scores and the children's self-reported physical (5.3 ± 17.1, 95% CI 0.5 to 11.1) and emotional (7.9 ± 14.3, 95% CI 3.2 to 12.7) functioning scores significantly improved. CONCLUSIONS: Following a 1-year intervention, the participants' BMI z-scores and QoL improved, while other adiposity-related measures of body composition remained unchanged. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000015622 .

Assessment of habitual physical activity in adolescents with type 1 diabetes.

OBJECTIVE: To evaluate habitual physical activity in a cohort of adolescents with type 1 diabetes in relation to similarly aged control subjects. METHODS: A cross-sectional case control study of 54 healthy adolescents and 66 patients with type 1 diabetes, 14 to 18 years of age, was conducted. Subjects were surveyed using the Habitual Activity Estimation Scale, a validated self-report instrument to assess activity levels in teens. Subjects' time was classified into categories ranging from inactive (lying down, resting) to very active (increased heart rate and diaphoresis). Active time, described in relative (%) and absolute hours per day was determined for each individual. Age, sex, weight, height and body mass index were recorded for all participants, and the charts of subjects with type 1 diabetes were reviewed for most recent levels of glycated hemoglobin, low-density lipoproteins, high-density lipoproteins, total cholesterol, triglycerides and blood pressure. A regression analysis was performed to determine factors associated with hours spent being active. RESULTS: Subjects with type 1 diabetes spent similar hours being very active (3.4 hours vs. 3.5 hours, p=0.49) but reported more time being inactive than controls (2.0 hours vs. 1.3 hours, p=0.002). In both groups, female gender was associated with more hours spent being active. Metabolic control as assessed by glycated hemoglobin worsened with activity. In the group with type 1 diabetes, more hours spent being active were associated with lower systolic blood pressure, lower serum triglyceride levels, lower total cholesterol and higher high-density lipoproteins, whereas inactivity correlated with higher low-density lipoproteins and total cholesterol. CONCLUSIONS: Adolescents with type 1 diabetes reported significantly more time being inactive than did healthy controls. In patients with type 1 diabetes, activity was associated with improved cardiovascular risk profile.

The JDRF CCTN CGM TIME Trial: Timing of Initiation of continuous glucose Monitoring in Established pediatric type 1 diabetes: study protocol, recruitment and baseline characteristics.

BACKGROUND: Continuous glucose monitoring (CGM) has been shown to improve glucose control in adults with type 1 diabetes. Effectiveness of CGM is directly linked with CGM adherence, which can be challenging to maintain in children and adolescents. We hypothesize that initiating CGM at the same time as starting insulin pump therapy in pump naïve children and adolescents with type 1 diabetes will result in greater CGM adherence and effectiveness compared to delaying CGM introduction by 6 months, and that this is related to greater readiness for making behaviour change at the time of pump initiation. METHODS/DESIGN: The CGM TIME Trial is a multicenter randomized controlled trial. Eligible children and adolescents (5-18 years) with established type 1 diabetes were randomized to simultaneous initiation of pump (Medtronic Veo©) and CGM (Enlite©) or to standard pump therapy with delayed CGM introduction. Primary outcomes are CGM adherence and hemoglobin A1C at 6 and 12 months post pump initiation. Secondary outcomes include glycemic variability, stage of readiness, and other patient-reported outcomes with follow-up to 24 months. 144 (95%) of the 152 eligible patients were enrolled and randomized. Allowing for 10% withdrawals, this will provide 93% power to detect a between group difference in CGM adherence and 86% power to detect a between group difference in hemoglobin A1C. Baseline characteristics were similar between the treatment groups. Analysis of 12 month primary outcomes will begin in September 2014. DISCUSSION: The CGM TIME Trial is the first study to examine the relationship between timing of CGM initiation, readiness for behaviour change, and subsequent CGM adherence in pump naïve children and adolescents. Its findings will advance our understanding of when and how to initiate CGM in children and adolescents with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrial.gov NCT01295788. Registered 14 February 2011.

Hyperosmolar hyperglycemic state without ketosis in a toddler with type 1 diabetes.

We present a thin toddler whose initial presentation with type 1 diabetes was hyperglycemic hyperosmolar syndrome without diabetic ketoacidosis after ingestion of copious quantities of high-sugar beverages. Increasing consumption of high-sugar beverages may make this presentation of type 1 diabetes mellitus more common. Emergency care physicians must be aware of this potential clinical constellation in the very young, as management differs significantly from that accepted for diabetic ketoacidosis in children.