Aspirin for Insulin Resistance ~ Revisited

I've previously blogged on the effects of high doses of salicylates, aka aspirin, and insulin resistance.  In summary from that paper/post:

... high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling.

So I was poking around in my Downloads folder the other day and happened across this paper:


Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes  (I've cleaned up the excerpts from the citation #'s as I find them distracting)

Insulin resistance is a primary factor in the development of type 2 diabetes, and recent studies have implicated fatty acid activation of a serine/threonine kinase cascade in the pathogenesis of insulin resistance.   Recently Yuan et al. hypothesized that IKKβ is a key downstream mediator in this process and demonstrated that high doses of salicylates, which inhibit IKKβ activity, reversed hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling .

In short,  IKKβ is an enzyme involved in immune pathways, blocking its action has beneficial effects on sensitivity to insulin.

Herein lies the quintissential chicken-egg debate.  Which comes first?  Inflammation or IR?  In any case ...

This study involved 9 adult (avg age = 48), obese (avg BMI = 37), Type II diabetics (6M/3F).  They were tested before and after 2 weeks high dose aspirin treatment (avg dose almost 7g/day).  Baseline values served as control in this study (as opposed to a placebo group).  The results for various parameters are shown below:

In words:

Two weeks of aspirin treatment resulted in a drop of about 40 mg/dl in fasting plasma glucose concentration, and this drop was not associated with any episodes of hypoglycemia. There was a small but significant decrease in creatinine clearance rate (12%) that normalized following discontinuation of aspirin. There were also significant decreases in concentrations of plasma cholesterol (15%), HDL cholesterol (10%), triglycerides (48%), and C-reactive protein (17%).

In the discussion they add:

We found that a 2-week trial of high-dose aspirin treatment was accompanied by significant decreases in hepatic glucose production (22%), fasting plasma glucose (24%), fatty acids (50%), and triglycerides (48%) and a 19% increase in peripheral glucose disposal. 

Hmmmm.... 

Wanna cheat on your next cholesterol test?  Lots of aspirin and alcohol* just may do the trick!

* Raise that HDL, further lower the FBG