I just wanted to put up a brief mention of this paper on acipimox.
Acipimox is an inhibitor of lipolysis. It's essentially useless as a therapy for anything, partly because it is derived from an incorrect paradigm but mostly because it's impossible to get it to work for any extended period of time. It's good for a week though.
So let's take a few diabetics, do some lab work on them, drop their FFAs using acipimox, then repeat their lab work a week later.
Fasting FFAs drop from 563 micromol/l (not actually very high) to 230 micromol/l (verging on pathologically low) and FBG drops from 8.5mmol/l to 7.0mmol/l. All highly significant, statistically.
Does this mean that they are fixed, i.e. they can go out and eat pizza all day and be normoglycaemic?
A diabetic person who drinks 75g of glucose in water will hit a 2h blood glucose of about 16mmol/l. With markedly reduced FFAs they will be graced with a 2h blood glucose of a mere 14mmol/l, which does not look like dropping. They're f*cked, metabolically. Last time I did this (2008ish??) my 2h BG was 3.4mmol/l.
It looks to me as if acipimox removes the normal physiological uncoupling associated with abnormally elevated FFAs and leaves the insulin resistance of a broken set of mitochondria there for all to see.
There is physiological insulin resistance associated with elevated FFAs. Then there is pathological insulin resistance from mitochondrial dysfunction.
Just wanted to say...