Diabetes Mellitus, Insulin-Dependent
Conditions
Keywords
type 1 diabetes, diabetes, new onset, CSII, insulin sensitivity, beta cell function, beta cell preservation
Brief summary
Within 4 weeks after diagnosis of type 1 diabetes, 10 subjects (pubertal males, 12-17 years old) will be randomized to either receive multiple daily injection (MDI) using Lantus insulin, or continuous subcutaneous insulin infusion (CSII; pump therapy). The study evaluates how these modes of therapy affect insulin sensitivity (measured by the euglycemic-hyperinsulinemic clamp studies and adiponectin concentration changes) and beta cell function (measured by mixed meal tolerance testing).
Detailed description
Within 4 weeks after diagnosis of type 1 diabetes, 10 subjects (pubertal males, 12-17 years old) will be randomized to either receive multiple daily injection (MDI) using Lantus insulin, or continuous subcutaneous insulin infusion (CSII; pump therapy). The proposed protocol compares the changes in diabetes control between pump therapy and MDI treatment groups. More importantly, however, the study evaluates how these modes of therapy may affect the honeymoon period and glycemic control, specifically focusing on changes in insulin sensitivity (measured by the euglycemic-hyperinsulinemic clamp studies and adiponectin concentration changes) and beta cell function (measured by mixed meal tolerance testing). Demonstrating that pump therapy at the time of diagnosis of type 1 diabetes prolongs the honeymoon phase by improving insulin sensitivity and beta cell function may have important therapeutic implications that could influence the standard of care in pediatric diabetes.
Interventions
DEVICEInsulin pump therapy
CSII initiated within 1 month of diagnosis
DRUGMultiple daily injections using insulin glargine + rapid acting analog
MDI as control
Sponsors
Nemours Children's Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patient between the age of 12 and 17 years inclusive at time of entry into study (i.e., after their 12th but before their 18th birthday) * Type 1 diabetes mellitus for no more than 10 days * pubertal (Tanner stage 2 or above) * The patient and parents or guardians should be able to do simple math calculations (necessary for pump management) * Parent or legal guardian must give signed informed consent
Exclusion criteria
* No other chronic medical conditions (well-controlled thyroid disease is OK, and mild asthma is OK if the patient is not on chronic inhaled or oral daily corticosteroids) * Exceptional psychological stress, more than expected for circumstances of having the new diagnosis of diabetes * Inability or unwillingness to comply with requirements of the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 24 months | Insulin sensitivity - glucose infusion rate (GIR) obtained from hyperinsulinemic-euglycemic clamp. Higher GIR reflects higher insulin sensitivity, lower GIR reflects lower insulin sensitivity. |
| Beta Cell Function | 24 months | Beta cell function as assessed by peak c-peptide using mixed meal tolerance testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1c | 24 months | Hemoglobin A1c (HbA1c) (%) |
| Percent Body Fat | 24 months | Percent body fat based on DEXA scan (%BF) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pump Therapy (CSII) Use of pump therapy
Insulin pump therapy: CSII initiated within 1 month of diagnosis | 6 |
| Multiple Daily Injections (MDI) Use of MDI (basal bolus therapy with glargine)
Multiple daily injections using insulin glargine + rapid acting analog: MDI as control | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Pump Therapy (CSII) | Multiple Daily Injections (MDI) | Total |
|---|---|---|---|
| Age, Continuous | 14.1 years STANDARD_DEVIATION 1.1 | 13.7 years STANDARD_DEVIATION 1.4 | 13.9 years STANDARD_DEVIATION 1.2 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Beta Cell Function
Beta cell function as assessed by peak c-peptide using mixed meal tolerance testing
Time frame: 24 months
Population: 12 adolescents were randomized, 6 per treatment group, well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pump Therapy (CSII) | Beta Cell Function | Baseline | 2.1 ng/mL | Standard Error 0.4 |
| Pump Therapy (CSII) | Beta Cell Function | 24 months | 1.1 ng/mL | Standard Error 0.4 |
| Multiple Daily Injections (MDI) | Beta Cell Function | 24 months | 1.6 ng/mL | Standard Error 0.9 |
| Multiple Daily Injections (MDI) | Beta Cell Function | Baseline | 1.7 ng/mL | Standard Error 0.3 |
Primary
Insulin Sensitivity
Insulin sensitivity - glucose infusion rate (GIR) obtained from hyperinsulinemic-euglycemic clamp. Higher GIR reflects higher insulin sensitivity, lower GIR reflects lower insulin sensitivity.
Time frame: 24 months
Population: 12 adolescents were randomized, 6 per treatment group, well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pump Therapy (CSII) | Insulin Sensitivity | Baseline | 8.6 mg/kg/min | Standard Error 1.6 |
| Pump Therapy (CSII) | Insulin Sensitivity | 24 month | 5.8 mg/kg/min | Standard Error 1 |
| Multiple Daily Injections (MDI) | Insulin Sensitivity | Baseline | 6.2 mg/kg/min | Standard Error 1.3 |
| Multiple Daily Injections (MDI) | Insulin Sensitivity | 24 month | 4.8 mg/kg/min | Standard Error 0.9 |
Secondary
Hemoglobin A1c
Hemoglobin A1c (HbA1c) (%)
Time frame: 24 months
Population: 12 adolescents were randomized, 6 per treatment group, well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pump Therapy (CSII) | Hemoglobin A1c | Baseline | 10 percentage of glycosylated hemoglobin | Standard Error 0.4 |
| Pump Therapy (CSII) | Hemoglobin A1c | 12 months | 6.1 percentage of glycosylated hemoglobin | Standard Error 0.3 |
| Pump Therapy (CSII) | Hemoglobin A1c | 24 months | 6.8 percentage of glycosylated hemoglobin | Standard Error 0.4 |
| Multiple Daily Injections (MDI) | Hemoglobin A1c | Baseline | 10.2 percentage of glycosylated hemoglobin | Standard Error 0.3 |
| Multiple Daily Injections (MDI) | Hemoglobin A1c | 12 months | 7.0 percentage of glycosylated hemoglobin | Standard Error 0.6 |
| Multiple Daily Injections (MDI) | Hemoglobin A1c | 24 months | 7.5 percentage of glycosylated hemoglobin | Standard Error 0.5 |
Secondary
Percent Body Fat
Percent body fat based on DEXA scan (%BF)
Time frame: 24 months
Population: 12 adolescents were randomized, 6 per treatment group, well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pump Therapy (CSII) | Percent Body Fat | Baseline | 20 percentage of body fat | Standard Error 2.6 |
| Pump Therapy (CSII) | Percent Body Fat | 12 months | 18.5 percentage of body fat | Standard Error 3.6 |
| Pump Therapy (CSII) | Percent Body Fat | 24 months | 17.4 percentage of body fat | Standard Error 2.5 |
| Multiple Daily Injections (MDI) | Percent Body Fat | Baseline | 21.6 percentage of body fat | Standard Error 4 |
| Multiple Daily Injections (MDI) | Percent Body Fat | 12 months | 20.3 percentage of body fat | Standard Error 3.8 |
| Multiple Daily Injections (MDI) | Percent Body Fat | 24 months | 20.5 percentage of body fat | Standard Error 2.3 |