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. 


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

* Raise that HDL, further lower the FBG


Anonymous said…
Salicylates can be crazy-making, though! My son is on the Feingold Diet (low salicylate) because we learned that high doses (through fruit) made him just about jump out of his skin.

If you're salicylate sensitive, you can have all sorts of neurological reactions, from hyperactivity to OCD to bedwetting and migraines. Powerful stuff!
This is good to know. I will avoid taking asprin today because I'm getting blood work tomorrow.

Maybe I'll get hopped up afterward by snorting BC Powder and drinking Budweiser.

Wait a that's how to look like a rock star!
Unknown said…
What do we know of the other effects of taking 7g of aspirin a day? Are they tolerable given the desired results? Is this being considered for longterm treatment of blood glucose and lipid abnormalities? Have to wonder if the other effects aren't worse than the condition being treated.

Dr put me on multaq for my a-fib. Not happy reading stuff on the nets about it--trashing the liver and double mortality. Hope it's short term.
CarbSane said…
I've seen no short term issues in the various studies but one longer term study (sorry I lost the link) where it protected women from colon cancer it caused bleeding in a significant percent. I'm thinking this is probably why it's not used, although it could just be those evil pharmaceutical companies and that aspirin is cheap and off patent ;)
Unknown said…
Forgot about the $$$ aspect of it. Much better to develop a new drug with all the $$ that involves, but maybe better secondary effects. Innovation in the medical industry!
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