Type Two Diabetes Mellitus
Conditions
Keywords
diabetes, obesity
Brief summary
Leptin therapy improves insulin sensitivity in people with leptin-deficiency but it is not known whether it improves insulin action in persons who are not leptin deficient. The purpose of the present study was to determine whether leptin therapy has effects on insulin action in obese subjects with type 2 diabetes mellitus (T2DM). A randomized, placebo controlled trial was conducted in obese subjects with newly-diagnosed T2DM. Subjects were randomized to treatment with placebo, low-dose, or high-dose leptin. Insulin sensitivity was measured.
Detailed description
Leptin therapy improves insulin sensitivity in people with leptin-deficiency but it is not known whether it improves insulin action in persons who are not leptin deficient. The purpose of the present study was to determine whether leptin therapy has weight loss-independent effects on insulin action in obese subjects with type 2 diabetes mellitus (T2DM). A randomized, placebo controlled trial was conducted in obese subjects with newly-diagnosed T2DM. Subjects were randomized to treatment with placebo (saline), low-dose (30 mg/d), or high-dose (80 mg/d) recombinant methionyl human (r-met hu) leptin for 14 days. Multi-organ insulin sensitivity before and after treatment was evaluated by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labelled tracer infusions to measure glucose, glycerol and fatty acid kinetics.
Interventions
DIETARY_SUPPLEMENTplacebo
saline placebo
DRUGlow-dose leptin
30mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days
DRUGhigh-dose leptin
80mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days
Sponsors
Amgen
National Institutes of Health (NIH)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* diagnosed with type 2 diabetes for less than ten years * Body mass index 25 - 40 * hemoglobin A1C 7.5% - 12.0% * fasting blood glucose between 90 and 240mg/dL
Exclusion criteria
* smoking * pregnancy * diabetes medications * regular exercise (more than 3 hours per week) * uncontrolled hypertension: systolic blood pressure greater than 160 or diastolic blood pressure greater than 95
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Glucose Disposal - a Measure of the Body's Ability to Process Sugars. | baseline | pre-treatment glucose disposal. In general, a high glucose disposal rate is a marker of healthy metabolic function. Glucose disposal is measured by tracking the amount of tagged glucose in the bloodstream over time. It is adjusted to subject body weight. |
| Post-treatment Glucose Disposal. I.e. Glucose Disposal After Treatment With Leptin or Placebo. | fourteen days | This is a measure of the body's ability to metabolize sugar after treatment with either leptin or a placebo. We compare the effect of leptin therapy on insulin-mediated stimulation of glucose disposal with that of placebo. In general, a high glucose disposal rate is a marker of healthy metabolic function. Glucose disposal is measured by tracking the amount of tagged glucose in the bloodstream over time. It is adjusted to subject body weight. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Plasma Leptin Concentrations | baseline | Leptin is an endogenous hormone. Here we measure the pre-treatment concentration of naturally-occurring leptin in the blood. |
| Post-treatment Plasma Leptin Levels | fourteen days | plasma leptin levels after fourteen days ingestion of either leptin or placebo. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from August 1998 to August 1999. All subjects were recruited via the Volunteer for Health system at Washington University School of Medicine.
Participants by arm
| Arm | Count |
|---|---|
| Placebo saline placebo for fourteen days | 6 |
| Low-dose Leptin 30mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days | 6 |
| High-dose Leptin 80mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Low-dose Leptin | High-dose Leptin | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Age, Continuous | 53 years STANDARD_DEVIATION 2.9 | 54 years STANDARD_DEVIATION 1.6 | 60 years STANDARD_DEVIATION 1.2 | 56 years STANDARD_DEVIATION 1.9 |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Baseline Glucose Disposal - a Measure of the Body's Ability to Process Sugars.
pre-treatment glucose disposal. In general, a high glucose disposal rate is a marker of healthy metabolic function. Glucose disposal is measured by tracking the amount of tagged glucose in the bloodstream over time. It is adjusted to subject body weight.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline Glucose Disposal - a Measure of the Body's Ability to Process Sugars. | 14.3 mmol/kg body weight/minute | Standard Error 3.1 |
| Low Dose Leptin | Baseline Glucose Disposal - a Measure of the Body's Ability to Process Sugars. | 18.4 mmol/kg body weight/minute | Standard Error 3.6 |
| High Dose Leptin | Baseline Glucose Disposal - a Measure of the Body's Ability to Process Sugars. | 16.7 mmol/kg body weight/minute | Standard Error 2.4 |
Primary
Post-treatment Glucose Disposal. I.e. Glucose Disposal After Treatment With Leptin or Placebo.
This is a measure of the body's ability to metabolize sugar after treatment with either leptin or a placebo. We compare the effect of leptin therapy on insulin-mediated stimulation of glucose disposal with that of placebo. In general, a high glucose disposal rate is a marker of healthy metabolic function. Glucose disposal is measured by tracking the amount of tagged glucose in the bloodstream over time. It is adjusted to subject body weight.
Time frame: fourteen days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-treatment Glucose Disposal. I.e. Glucose Disposal After Treatment With Leptin or Placebo. | 17.5 mmol/kg body weight/minute | Standard Error 2.5 |
| Low Dose Leptin | Post-treatment Glucose Disposal. I.e. Glucose Disposal After Treatment With Leptin or Placebo. | 20.7 mmol/kg body weight/minute | Standard Error 3 |
| High Dose Leptin | Post-treatment Glucose Disposal. I.e. Glucose Disposal After Treatment With Leptin or Placebo. | 19.1 mmol/kg body weight/minute | Standard Error 3.3 |
Comparison: The null hypothesis was that there would be no change in glucose disposal between the three groups (placebo, low dose leptin, and high dose leptin). Power calculations were done showing that 6 subjects in each arm was enough to detect a 35% between group difference in glucose disposal at the 0.05 level with 80% power.p-value: >0.05ANOVA
Secondary
Baseline Plasma Leptin Concentrations
Leptin is an endogenous hormone. Here we measure the pre-treatment concentration of naturally-occurring leptin in the blood.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline Plasma Leptin Concentrations | 27 Micrograms/Liter | Standard Error 7 |
| Low Dose Leptin | Baseline Plasma Leptin Concentrations | 24 Micrograms/Liter | Standard Error 8 |
| High Dose Leptin | Baseline Plasma Leptin Concentrations | 35 Micrograms/Liter | Standard Error 10 |
Secondary
Post-treatment Plasma Leptin Levels
plasma leptin levels after fourteen days ingestion of either leptin or placebo.
Time frame: fourteen days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-treatment Plasma Leptin Levels | 25 Micrograms/Liter | Standard Error 5 |
| Low Dose Leptin | Post-treatment Plasma Leptin Levels | 76 Micrograms/Liter | Standard Error 19 |
| High Dose Leptin | Post-treatment Plasma Leptin Levels | 5024 Micrograms/Liter | Standard Error 500 |
Comparison: The null hypothesis is that treatment would not effect plasma leptin levels.p-value: <0.01t-test, 2 sided
Comparison: null hypothesis was that plasma leptin levels would be equal after treatment in the placebo and high-dose leptin groups.p-value: <0.01t-test, 2 sided