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I've never noticed any long term effect of niacin with elevation of blood glucose, but I've always taken it with a reasonably strict low-carb diet.

Short-term, niacin gives a decrease in lipolysis, with a rebound in free fatty acids a few hours later. Long term, there's a certain degree of tolerance that builds up. So basal free fatty acids can increase--this might be a big part of what causes niacin's effect on fasting and postprandial blood glucose, physiological insulin resistance from the elevation in free fatty acids. Niacin was actually involved in sorting out physiological insulin resistance from free fatty acids in the first place. Researchers wanted to see if the free fatty acids were responsible for the insulin resistance/glucose intolerance that happens in most animals during an extended fast. Starve a rat, and time the dose of niacin just right, and when the animal is refed carbohydrate, the glucose intolerance is gone. Pair this with an infusion of free fatty acids, so that the decrease in lipolysis doesn't affect blood levels of free fatty acids, and the glucose intolerance returns. Since a ketogenic diet or starvation itself are already high free fatty acid states, the long term increase in free fatty acids that comes with niacin tolerance should have less of an effect on blood glucose in those states. All I have to back this up is plausibility and personal experience, so I don't really know if this is generally true or not.

http://en.wikipedia.org/wiki/Niacin_receptor_1

Quote:

GPR109A is believed to be an important biomolecular target of niacin which is a widely prescribed drug for the treatment of dyslipidemia and to increase HDL cholesterol but whose therapeutic use is limited by flushing.[5] In GPR109A knockout mice, the effects of niacin on both lipids[6] and flushing[7] is eliminated. Furthermore, in arrestin beta 1 knockout mice, niacin's effect on flushing is greatly reduced while the lipid modifying effects are maintained.[8]

The precise mechanism of action of niacin therapeutic effects has not been fully elucidated, but appears to work in part through activation of GPR109A which reduces the levels of intracellular cAMP thereby inhibiting lipolysis in adipocytes.[9] In contrast, the flushing effect is due to GPR109A activation of ERK 1/2 MAP kinase[10] mediated by arrestin beta 1.[8] Activation of MAP kinase in turn causes release of prostaglandin D2 from Langerhans cells in the skin

The blue is interesting. I tend to build up tolerance to the flushing effect of niacin fairly quickly. I've seen it suggested that schizophrenics and family members of schizophrenics are more tolerant of the flushing. Maybe for the blood lipid effects, I don't have to be chasing the flush so much.

I found the Hyperlipid blog when Peter left a comment on Dr. Davis's blog years ago about how ketones are ligands for some nicotinic acid receptor or other--I'm not sure if it's the one above. But ketones, like niacin, are also insulin mimetics in certain respects, promoting sparing of protein and also regulate lipolysis--which makes sense, if ketones are high enough, probably lipolysis is already sufficient to provide ketones where they're needed.