Extending sleep to improve glycemia: The Family Routines Enhancing Adolescent Diabetes by Optimizing Management (FREADOM) randomized clinical trial protocol.

Sleep deficiencies amongst individuals with type 1 diabetes mellitus (T1DM) have been linked with dysregulated glycemic control and greater morbidities. Sleep extension (EXT) has been identified as a viable intervention target to improve adolescent outcomes. The intervention aims to emphasize collaborative work with families to engage in behaviors that increase the likelihood of the youth increasing their sleep duration consistently. This study will randomize up to 175 youth with T1DM and at least one caregiver to either an EXT intervention or a family routines support (FRS) consultation. It is hypothesized that the EXT condition will lead to improvements in sleep, which in turn, will contribute to improved glycemic control. The primary endpoint is improved glycemic control assessed via a continuous glucose monitor (CGM) to ascertain average glucose levels across a week, glycemic variability, and percent time in the target range at one month and HbA1c at three months. Analyses will control for co-morbid conditions, including sleep-disordered breathing and obesity. This study will provide the needed data to support addressing sleep as part of the standards of care in youth with T1DM.

Differences in sleep architecture according to body mass index in children with type 1 diabetes.

Slow wave sleep (SWS), or deep sleep, is thought to be the most restorative stage of sleep and may be of a particular interest in the pathophysiology of obesity. The aim of this study was to investigate differences in sleep architecture based on body mass index (BMI) among a pediatric population with type 1 diabetes mellitus (T1DM). We hypothesized that children with T1DM who are obese would have less SWS than those who are not obese. Of 105 children with T1DM (mean age 13.54 years, 49.5% females) in this study, 19% were obese, 22% were overweight, and 59% had a normal BMI (81% non-obese). The overall SWS% among the participants was 13.2%. In contrast to our hypothesis, there was no significant difference in SWS% between obese and non-obese participants. However, the percent of time spent in rapid eye movement (REM) sleep among obese participants was significantly lower than those who were not obese (P = .022), which remained after adjusting the result for multiple covariates. While we found no significant association between the SWS time and BMI, obese adolescents with T1DM spent less time in REM sleep than those who were not obese. This study adds to the growing body of evidence supporting the importance of addressing sleep in clinical care of youth with T1DM.

A 26-week, randomized trial of insulin detemir versus NPH insulin in children and adolescents with type 2 diabetes (iDEAt2).

There are limited studies evaluating the safety and efficacy of treatments in young people with type 2 diabetes (T2D). This study compared the efficacy and safety of insulin detemir versus neutral protamine Hagedorn (NPH) insulin, both in combination with metformin and lifestyle intervention, in children and adolescents with T2D. This randomized, open-label, phase 3 trial recruited patients (n = 42) aged 10-17 years diagnosed with T2D already receiving metformin ± other oral antidiabetic drugs ± basal insulin. Patients were randomized (1:1) to receive either insulin detemir or NPH insulin, both with the maximum tolerated dose of metformin, and lifestyle intervention, over 26 weeks. Enrollment terminated prematurely after 17 months due to a very slow recruitment rate (12% of the target met). After 26 weeks, the observed mean HbA1c value had decreased by 0.61% points in the insulin detemir group vs. 0.84% points in the NPH insulin group. The rate of symptomatic blood glucose-confirmed hypoglycemic episodes was 0.4 episodes/patient-year of exposure (PYE) for insulin detemir vs. 1.1 episodes/PYE for NPH insulin. CONCLUSION: No safety issues were revealed with either basal insulin. Due to the low number of patients recruited, no efficacy conclusions could be drawn. ClinicalTrials.gov identifier: NCT02131272. What is known: • There is a growing worldwide epidemic of type 2 diabetes in children and adolescents. • There is a lack of research and limited treatment options currently available in this population. What is new: • No safety issues with insulin detemir or neutral protamine Hagedorn insulin in children and adolescents with type 2 diabetes were observed. • Improving clinical trial recruitment, along with providing early, efficacious, and safe treatment options, in this population is critical.

Effect of cardiometabolic risk factors on the relationship between adiposity and bone mass in girls.

BACKGROUND/OBJECTIVE: Childhood obesity has been separately associated with cardiometabolic risk factors (CMRs) and increased risk of fracture. However, both augmented and compromised bone mass have been reported among overweight/obese children. Metabolic dysfunction, often co-existing with obesity, may explain the discrepancy in previous studies. The aim of this study was to examine whether the relationship between adiposity and dual-energy X-ray absorptiometry (DXA) derived bone mass differed in young girls with and without CMR(s). SUBJECTS/METHODS: Whole-body bone and body composition measures by DXA and measures of CMR (fasting glucose, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic and diastolic blood pressure, waist circumference (WC)) were obtained from 307, 9- to 12-year-old girls. Girls with 1 or ≥ 2 CMR(s) were considered to be at risk (vs. no CMR). Multiple linear regression was used to test the relationship of total fat mass with total body bone mineral content (BMC) after controlling for height, lean mass, CMR risk, and other potential confounders. RESULTS: There was a significant interaction between CMR risk and total body fat mass. When girls were stratified by CMR group, all groups had a significant positive relationship between fat mass and BMC (p < 0.05), however, girls with ≥ 2 CMRs had a lower BMC for a given level of body fat. Total body fat was not significantly related to bone mineral density (p > 0.05). CONCLUSION: Fat mass has a positive relationship with BMC even after controlling for lean mass. However, the positive relationship of fat mass with BMC may be attenuated if multiple CMRs are present.

Relative contributions of lean and fat mass to bone strength in young Hispanic and non-Hispanic girls.

BACKGROUND: With the high prevalence of childhood obesity, especially among Hispanic children, understanding how body weight and its components of lean and fat mass affect bone development is important, given that the amount of bone mineral accrued during childhood can determine osteoporosis risk later in life. The aim of this study was to assess the independent contributions of lean and fat mass on volumetric bone mineral density (vBMD), geometry, and strength in both weight-bearing and non-weight-bearing bones of Hispanic and non-Hispanic girls. METHODS: Bone vBMD, geometry, and strength were assessed at the 20% distal femur, the 4% and 66% distal tibia, and the 66% distal radius of the non-dominant limb of 326, 9- to 12-year-old girls using peripheral quantitative computed tomography (pQCT). Total body lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). Multiple linear regression was used to assess the independent relationships of fat and lean mass with pQCT bone measures while adjusting for relevant confounders. Potential interactions between ethnicity and both fat and lean mass were also tested. RESULTS: Lean mass was a significant positive contributor to all bone outcomes (p < 0.05) with the exception of vBMD at diaphyseal sites. Fat mass was a significant contributor to bone strength at weight bearing sites, but did not significantly contribute to bone strength at the non-weight bearing radius and was negatively associated with radius cortical content and thickness. Bone measures did not significantly differ between Hispanic and non-Hispanic girls, although there was a significant interaction between ethnicity and fat mass with total bone area at the femur (p = 0.02) and 66% tibia (p = 0.005) as well as bone strength at the femur (p = 0.03). CONCLUSION: Lean mass is the main determinant of bone strength for appendicular skeletal sites. Fat mass contributes to bone strength in the weight-bearing skeleton but does not add to bone strength in non-weight-bearing locations and may potentially be detrimental. Bone vBMD, geometry, and strength did not differ between Hispanic and non-Hispanic girls; fat mass may be a stronger contributor to bone strength in weight-bearing bones of Hispanic girls compared to non-Hispanic.

Personalized exercise for adolescents with diabetes or obesity.

OBJECTIVE: This study examined adherence to a personalized, community-based exercise intervention by sedentary adolescents with type 1 or type 2 diabetes or those with obesity. RESEARCH DESIGN AND METHODS: We conducted a pretest-posttest investigation to explore the application of an individualized exercise prescription based upon current fitness level for 39 adolescents (20 with type 1 diabetes, 9 with type 2 diabetes, and 10 obese) over 16 weeks in community settings. Subjects were recruited from a university-based pediatric endocrinology clinic in the southwestern United States. Adherence to the exercise prescription was monitored using accelerometers over the entire intervention period. RESULTS: Moderate-to-vigorous physical activity (MVPA) levels significantly increased over sedentary baseline values (p < .001), but the average of 42.5 ± 22.1 min/day of MVPA determined at the end of the study was still less than the recommended 60 min/day. Perceptions of health were significantly increased for the total group following the intervention (p = .008). For those with type 1 diabetes, there was a significant association between MVPA duration and percentage change in HbA1c (r = -.526, p = .02). CONCLUSIONS: Recruitment and retention of adolescent participation in daily exercise is challenging. Personalized approaches that include adolescent choices with family support and ongoing motivation can improve individual exercise adherence and a sense of personal health.

Sleep, glucose, and daytime functioning in youth with type 1 diabetes.

UNLABELLED: STUDY HYPOTHESES: 1) Youth with evidence of SDB (total apnea-hypopnea index [Total-AHI] ≥ 1.5) would have significantly worse glucose control than those without SDB; 2) Elevated self-reported sleepiness in youth with T1DM would be related to compromised psychosocial functioning; and 3) Youth with T1DM would have significantly less slow wave sleep (SWS) than controls. DESIGN: The study utilized home-based polysomnography, actigraphy, and questionnaires to assess sleep, and continuous glucose monitors and hemoglobin A1C (HbA1C) values to assess glucose control in youth with T1DM. We compared sleep of youth with T1DM to sleep of a matched control sample. SETTING: Diabetic participants were recruited in a pediatric endocrinology clinic. PARTICIPANTS: Participants were youth (10 through 16 years) with T1DM. Controls, matched for sex, age, and BMI percentile, were from the Tucson Children's Assessment of Sleep Apnea study. RESULTS: Participants with a Total-AHI ≥ 1.5 had higher glucose levels. Sleepiness and/or poor sleep habits correlated with reduced quality of life, depressed mood, lower grades, and lower state standardized reading scores. Diabetic youth spent more time (%) in stage N2 and less time in stage N3. Findings related to sleep architecture included associations between reduced SWS and higher HbA1C, worse quality of life, and sleepiness. More time (%) spent in stage N2 related to higher glucose levels/hyperglycemia, behavioral difficulties, reduced quality of life, lower grades, depression, sleep-wake behavior problems, poor sleep quality, sleepiness, and lower state standardized math scores.