Carbohydrate Beta Cell Function and Glucose Control in Children With Diabetes

Change in C-peptide 2-h area under the curve after a mixed-meal tolerance test (ΔCP).

From continuous glucose monitoring (CGM) - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.

Calculated based on percent children with insulin dose corrected HbA1c (IDAA1c) <9.

From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.

From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.

From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation 2-week increments.

From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.

From CGM - will be computed throughout study participation in 2-week increments.

From CGM - will be computed by dividing glucose standard deviation by glucose average throughout study participation in 2-week increments.

From CGM - will be computed using published formula throughout study participation in 2-week increments.

From insulin administration device uploads - will be computed in units per kg throughout study participation in 2-week increments.

Calculated from fasting blood draw [fasting insulin (µU/ml) × fasting plasma glucose (mg/dl)]/405.

Weight divided by height squared.

Fasting blood - total, LDL and HDL cholesterol, and triglycerides.

Fasting blood

Fasting blood

Interleukins 1β, 17, 23, 6, 10; high sensitivity c-reactive protein; tumor necrosis factor α, interferon gamma

Extraction and sequencing will be performed by Qiagen PowerSoil DNA extraction using Qiagen's DNeasy 96 PowerSoil Pro QIAcube HT Kit (480), followed by whole genome sequencing (WGS) using a miniaturized version of the NEBNext Ultra FS II method.

Blood samples will be processed using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). The LC-MS analyses will be carried out on a Sciex triple quadrupole mass spectrometer couple to an Exion ultra-performance LC system. The targeted analysis will utilize the Biocrates Q500 targeted metabolomics assay which quantifies more than 500 metabolites over 26 chemical classes (Biocrates Inc., Innsbruck, Austria). Data processing to yield metabolite concentrations in micromolar units will utilize the Biocrates MetIDQ software. The NMR data will be acquired on a Bruker Avance NEO 700 MHz NMR equipped with a TCI cryoprobe and a SampleXPress automatic sample changer. The data will be processed using the Chenomx NMR Processor and Profiler packages (Chenomx, Edmonton, CA) to yield quantitative data in millimolar units.

Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate greater burden.

Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate greater burden.

Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate better quality of life.

Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate better quality of life.

Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate less problems.

Validated questionnaire, scored according to published standards. Scores range 0-100, higher scores indicate less problems.

Validated questionnaire, scored according to published standards. Scores range 0-42, higher scores are worse.

Questionnaire to assess participants' and caregivers' perceptions of the influence of the diet on their diabetes management.

Interviews will be held with children and caregivers separately after implementation and completion of the intervention.

Interviews will be held with children and caregivers separately after implementation and completion of the intervention.

From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.

From CGM - percent time spent in the specified glycemic target range will be computed throughout study participation in 2-week increments.

Obtained at daily increasing to weekly intervals as effect modifier of beta-cell function.

Safety Measure - Height standard deviation score will be calculated from serial height measurements obtained during study visits using CDC age and sex specific references.

Safety Measure - Growth velocity will be calculated from serial height measurements obtained during study visits.

Safety Measure - Weight SDS and gain will be calculated from serial weight measures obtained during study visits with calibrated scale.

Safety Measure - Defined by elevated BOHB, blood pH <7.3 and serum bicarbonate <15. Rates will be computed as total number of events divided by total patient years of follow-up.

Safety Measure - Defined as blood glucose < 55 mg/dl and requiring glucagon or resulting in seizure or coma. Rates will be computed as total number of events divided by total patient years of follow-up.

Safety Measure - Rates will be computed as total number of events divided by total patient years of follow-up.

Safety Measure - Rates will be computed as total number of events divided by total patient years of follow-up.

Safety Measure - ChEDE-Q8 diagnostic score with clinical confirmation. Total number of events.

Safety Measure - Undesired weight loss or significant deceleration in longitudinal growth may warrant termination of study participation. Total number of events will be computed.

Safety Measure - LDL >200 mg/dl will trigger review of additional risk factors and may prompt diet modification to lower intake of saturated fats. If persistent, study participation may be terminated. Total number of events will be computed.