Beneficial Effect of Salicylates: Insulin Action, Secretion or Clearance?

Study Overview
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Brief Summary
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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.

Official Title
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Beneficial Effect of Salicylates: Insulin Action, Secretion or Clearance?

Conditions
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Pre Diabetes, Insulin Resistant

Intervention / Treatment
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* Drug: salsalate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: salsalate 3500mg in 2 divided doses a day<br>Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner | Drug: salsalate<br>* Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner<br>|
| Placebo Comparator: placebo<br>Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner | Drug: Placebo<br>* Participants will take 3 tablets with breakfast and 4 tablets with dinner<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | after treatment for one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | one month on treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin resistant