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

Not Applicable

Completed

Conditions: Pre Diabetes
Insulin Resistant

Interventions: Drug: Placebo
Drug: salsalate

Registration Number: NCT02007577

Lead Sponsor: Stanford University

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner
salsalate 3500mg in 2 divided doses a day	salsalate	Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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