Thursday, March 13, 2008

Glucose as a cure for hypertriglyceridaemia?

This is a very interesting paper, cited in one of Bruce's comments. It's interesting enough that it really had me thinking, so here are the thoughts. Eating 80% carbs continuously through the day cranks up your triglycerides, but they only go up overnight when you stop eating the carbs. Inhibiting overnight lipolysis with either a B3 infusion or by maintaining insulin levels at 30-50microIU/ml, by drinking 60g of sugar solution every two hours (gulp), sorts the rise in trigs out. Sort of. No, it does sort it out.

This is a cracker.

We know that B3 and insulin both inhibit hormone senstitive lipase in adipose tissue, so they limit FFA delivery to the plasma and so to the liver. The presumption, in this fascinating 1973 paper, is that this is what drops the triglycerides. But is this what is happening? In addition to inhibiting hormone sensitive lipase does insulin have a roll in inhibiting VLDL secretion? Can't be bothered chasing this at the moment, but I'll bet it does. After all, failure of the liver to listen to insulin is "associated" with massive elevations of triglycerides in some unlucky people. Niacin acts through the beta hydroxy butyrate receptor. Does activation of this receptor do anything in the liver? Like drop tryglycerides maybe?

There's a bit about B3 and trigs here.

"A second mechanism has been postulated. The second mechanism by which it’s postulated that there’s a decrease in triglyceride synthesis involves a pathway of triglyceride synthesis in which the last step in triglyceride synthesis is catalyzed by an enzyme called DGAT2. It is postulated that niacin may also act through inhibiting DGAT2".

If we look at the dutch study, comparing a group of type 2 diabetics who were crossed over between 89% carbohydrate calories and 89% fat calories we see that there was essentially no difference in fasting free fatty acids, yet the fasting triglycerides in the high fat period were half those of the high carb period. Not only that but the ability of insulin to suppress free fatty acids during a clamp (elevate plasma insulin and then give a glucose infusion to maintain a constant non fatal blood glucose level) was markedly reduced in the high fat group, yet still trigs were low during this phase. See table 2.

The whole premise of the 1973 paper, that FFAs induce hypertriglyceridaemia looks wrong to me, or at least simplistic. Insulin and B3 (which is a pharmacological mimic of beta hydroxybutyrate) suppress VLDL production (fasting trigs) from the liver. Never mind what they do to FFAs.

That all night oral glucose drinking dropped the morning trigs at the cost of an all night combined hyperglycaemia and hyperinsulinaemia. This isn't treating a problem, this is correcting a lab number at the cost of glucose poisoning. Fatty liver anyone?

Aside: The type IV hyperlipoproteinaemia patients spent 24 hours with blood glucose levels between 130 and 150mg/dl in the study, and insulin levels at over 100microIU/ml for most of that 24 hour period. And their cardiovascular problems will get blamed on the triglycerides!!!!!!

Enthralling paper, but I don't think I'd take it as an endorsement of drinking 60g of glucose every 2h through the night to lower my "fasting" triglycerides. If I had elevated triglycerides, which I don't!

Peter

5 comments:

donny said...

Even if you did want to lower free fatty acids by eating glucose, there's a better way.
David Jenkins did a study where he had people either sip glucose water every fifteen minutes for three and a half hours or take it all at a gulp. With the gulp, the free fatty acids went down but bounced up beyond baseline in four hours. (The bottom of the bounce was at the two hour mark pretty much) Sipping brought a similar reduction, but without the rebound. (I found it remarkable, since each sip was only 3 and a half grams of glucose, that it had as strong an effect on free fatty acids as it did.
http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN77_01%2FS000711459700010Xa.pdf&code=73b0b96089c50c18454f2789ffa4ab4d

Peter said...

Hi donny,

That exactly fits in with this paper form back in 1964. The function of basal insulin is to inhibit lipolysis. I keep trying to work this in to a world view. Certainly the acute phase insulin response looks like an emergency add on to deal with a situation the body doesn't like (rapidly rising blood glucose) but meets often enough to have the crash box in place for.

Peter

PS link doesn't work, be interested to get the paper and read the discussion.

donny said...

Maybe this'll work. looks a bit longer, anyways.

http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN77_01%2FS000711459700010Xa.pdf&code=240b031d5df17af5968140bc4db80943

Eugene Goh said...

This is interesting. I did not know that glucose could be a cure for hypertriglyceridaemia as I only know that triglycerides and high cholesterol
levels are contributing risks to cardiovascular diseases.

Peter said...

Hi Eugene,

I don't really think that glucose is a cure for hypertriglyceridaemia. What appears to be happening is that, on VERY high carbohydrate diets, triglycerides are formed in the liver from carbohydrate and exported as VLDL particles, lots of them. The exportation is suppressed by insulin, so if you drink glucose all night you will maintain elevated insulin all night, make even more triglycerides in your liver but fail to release them. This is a classic recipe for fatty liver and cardiovascular disease. That's what I mean by treating a "number". Elevated triglycerides are a risk for heart disease because they represent elevated carbohydrate levels in the diet and insulin resistance in the liver. I'm unaware that there is any good evidence relating elevated cholesterol to heart disease, hence (in part) this blog.

Peter