Insulin Resistant, Pre Diabetes
Conditions
Keywords
insulin resistant
Brief summary
The possibility that obesity-associated inflammatory changes may play a role in the pathogenesis of type 2 diabetes (2DM) has led to increased interest in the possibility that salicylates might represent a useful treatment to improve glucose tolerance. Several studies, performed in patients with 2DM, as well as in nondiabetic, obese individuals, have demonstrated that salicylates have beneficial effects on glucose and insulin metabolism, but have not led to a coherent view as to the mechanism(s) involved. In this research proposal we will use specific methods to quantify insulin mediated glucose uptake (IMGU), glucose-stimulated insulin secretion rate (GS-ISR), and insulin clearance (I-Cl) in overweight/obese, nondiabetic, insulin resistant individuals. We will use the insulin suppression test (IST) to quantify IMGU in nondiabetic, overweight/obese volunteers to identify those individuals who are sufficiently insulin resistant to be enrolled in this study. We will then use the graded glucose infusion technique in these insulin resistant subjects to generate specific measures of both GS-IS and I-Cl. Following these baseline measurements, salsalate or placebo will be administered for one month to the participants, after which time the IST and the graded glucose infusion will be repeated to quantify and compare the changes in IMGU, GS-ISR, and I-Cl that have resulted from salsalate versus placebo. These results will provide for the first time quantitative data of the effect of salicylates on IMGU, GS-ISR, and I-Cl in overweight/obese, insulin resistant, nondiabetic individuals.
Interventions
DRUGsalsalate
Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner
DRUGPlacebo
Participants will take 3 tablets with breakfast and 4 tablets with dinner
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers, * BMI 25-35kg/m2, * Without severe anemia, kidney, liver disease or any current GI ulcers or bleeding * Or on any medication contraindicated with salsalate
Exclusion criteria
* Recent history of GI bleed or ulcers, * CVD or on anticoagulants * Severe kidney or liver disease * Allergies to aspirin * Taking aspirin or anti inflammatory medication on a regular basis and cannot be taken off for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of Insulin Action With the Insulin Suppression Test (IST) | after treatment for one month | Compare changes in insulin sensitivity as assesses by the IST before and after treatment between salsalate and placebo group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of Insulin Clearance With the Graded Glucose Infusion Test (GGIT) | one month on treatment | compare changes in insulin clearance as assessed by the GGIT before and after treatment with salsalate to placebo |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Salsalate 3500mg in 2 Divided Doses a Day Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner
salsalate: Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner | 26 |
| Placebo Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner
Placebo: Participants will take 3 tablets with breakfast and 4 tablets with dinner | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Salsalate 3500mg in 2 Divided Doses a Day | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 10 | 54 years STANDARD_DEVIATION 10 | 54 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 12 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 9 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 27 | 0 / 14 |
| serious Total, serious adverse events | 0 / 27 | 0 / 14 |
Outcome results
Primary
Quantification of Insulin Action With the Insulin Suppression Test (IST)
Compare changes in insulin sensitivity as assesses by the IST before and after treatment between salsalate and placebo group
Time frame: after treatment for one month
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Salsalate 3500mg in 2 Divided Doses a Day | Quantification of Insulin Action With the Insulin Suppression Test (IST) | -3 mmol/L |
| Placebo | Quantification of Insulin Action With the Insulin Suppression Test (IST) | 2 mmol/L |
Secondary
Quantification of Insulin Clearance With the Graded Glucose Infusion Test (GGIT)
compare changes in insulin clearance as assessed by the GGIT before and after treatment with salsalate to placebo
Time frame: one month on treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Salsalate 3500mg in 2 Divided Doses a Day | Quantification of Insulin Clearance With the Graded Glucose Infusion Test (GGIT) | -6 pmol/min x 4h |
| Placebo | Quantification of Insulin Clearance With the Graded Glucose Infusion Test (GGIT) | 0 pmol/min x 4h |