Here is the "normal". Moon would describe this, correctly, as moderately arteriosclerotic. Lots of intimal hyperplasia and you can't tell much about the degree of damage to the elastic layer from this picture. I'm loathe to believe the authors' suggestion that the elastic layer is completely normal:
Next is the "non arteriosclerotic but dysplastic" artery from a sudden death victim. Burke et al ignore 100 years of pathology by describing it as non arteriosclerotic. You might forgive them as the lesions contain no cholesterol and they are lost in the idea that LDL cholesterol is the primary driver of arteriosclerosis which means, obviously, that they are not in a position to understand what they see. Or to investigate causes. They might want to start with copper status, ascorbate status, insulin levels at the time of death and familial problems with elastin structure; these might do for a start. Maybe clotting factors too. Also, given a retrospectoscope, the post prandial sympathetic response to a PowerBar would be very interesting. But LDL cholesterol? What can that have to do with the formative lesions of arteriosclerosis which contain no cholesterol?
Notice that the intimal thickening is present but there is also marked hypertrophy of the medial muscle cells. This is a classic resonse to severe elastosis, there's another post there; elastin as a regulator of vascular smooth muscle phenotype...
Peter
Afterthought: I wonder whether location of the artery matters. The left anterior descending coronary artery, where I have my seven point calcium score, is the least supported by cardiac muscle, so experiences the greatest trans-mural pressure gradient during systole. LAD is the classic site for calcification in non smokers. It would be interesting to see if sudden death victims have more superficial arteries supplying their AV node than non sudden death people........ Haven't checked the anatomy for this, hmmmmm.
Statins and adverse cardiovascular events in moderate-risk females: a statistical and legal ana lysis with implications for FDA preemption claims (Eisenberg & Wells) - www.beforeyoutakethatpill.com/2008/10/eisenberg_2008_atorvastatin.pdf
ReplyDeletePeter, may we continue our discussion from part I here? Not trying to be argumentative but I'd like to bring up a few observations 'cause this insulin stuff really matters to me.Trying hard not to be a fatty (5'9" 68 kg) while not being hungry.
ReplyDeleteThe 1st link you're right, it doesn't look like normal physiological conditions, I only wanted to bring up the rank order: palmitate > myristate > stearate approximately = oleate > linoleate approximately = linolenate. BTW I am not a palmitate hater, in fact life would be much simpler for me if palmitate is best, period. The scenario you gave to explain the GSIS makes sense, insulin resistance which occurs with a high-fat diet (for good reason) necessitates more insulin. A nice secondary possibility exists from reading Body by Science (McGuff), is that if we run our glycogen stores down thru resistance training, the resulting insulin sensitivity at muscle cells will reduce the GSIS. I probably would not load up on oleic acid (i.e. olive oil) since butter is only 25% palmitate at most and is nutritionally superior.
To continue on the insulinogenic potency of protein, at paleonu.com someone brought up the study PMID 20503441 " Protein causes a glycemic response." where " the [insulin] response was inversely related to the amount of meat consumed, over the range from 26 to 78 g of protein." Hmmm...any conjectures why?
Yeah I looked at the chicken graph, it barely moves from fasting basal insulin. What's the insulin AUC? I tried guesstimating it at 80 pmol/L * 120 min = 9600.
From beef protein study PMID 9356547, the calculated insulin AUC for 158g lean beef = 7910 pmol * min/L
Cornflakes and honeysmacks from the same study were around 9000, do these insulin AUCs make sense to you?
Great post.
Hi Peter,
ReplyDeleteapologies for interfering, I am an ignoramus, but is it not the hyperglycemia that is the problem? Is it not what dr. Harris said?
Hi lightcan,
ReplyDeleteYes, hyperglycaemia is very important, probably as a glycator of elastin (late in life, AGE formation in neonates seems a bit unlikely) and a damage agent for the endothelial cells. But I have a series of papers showing it controls cholesterol crystallisation and of course there is the infection hypothesis of unstable plaque to discuss. As we know hyperglycaemia markedly blunts your immune response to sepsis. You need to get the cholesterol in to the plaque for it to crystallise and the most plausible explanation I've seen so far s that it gets there through the adventitial blood supply to the media. But there's a bit more on IMT, GAG, insulin and physiology pushed to pathology to get through first.
Hi webster,
I notice this paper http://www.ncbi.nlm.nih.gov/pubmed/16627573 has gone free access since I downloaded the abstract. I think there is more to it that just IMTG stores (but these are very important, including what we do with the IMTGs), the ability to store glycogen appears to be blocked in hyperglycaemic models and glycogen storage ability is restored by enforced normoglycaemia too, without improving glucose oxidation, can't locate that later paper but it's around.
I think we do need an insulin response to protein, protein is used for anabolism so why not? Some components are more in need of insulin processing than others so why not have differentials. I also suspect that that there really is a cephalic response in insulin to eating and that controlling for this is a nightmare. Which then requires high quality duplicated research to establish what is normal, so it would be good to see more than one group producing data, not a luxury we have at the moment...
The link is fascinating. Obviously these people were fasting, had lipolysis ad physiological insulin resistance. As this breaks the metabolism returns to glucose based and insulin sensitivity increases, so glucose disposal per unit insulin gets "better". The dawn phenomenon beloved of Dr Bernstein. As you get in to type 2 diabetes this requires higher levels of carbohydrate (or protein in this case) to break it...
Peter
Thanks Peter,
ReplyDeleteYes, obviously, it's more complicated than that, and trying to find a bottom line is useless.
It's frustrating for me as a lay person that it is so complex and confusing sometimes. People who say 'make a decision about your health on your own' or 'read Taubes' or 'it's all on Pubmed' are a bit patronising. Not everybody can.
I'm looking forward to your future posts maybe I'm going to have an Aha moment.
Your explanations are appreciated as always Peter. What I'd like to know is how the insulin resistance of fat tissue changes in response to CHO restriction as in the link. Then which one is more sensitive, fat or muscle, or like you said is there more to it than IMTG?
ReplyDeleteStill don't know what the conclusion here on insulin and protein. The insulin response to protein makes sense, but as we saw in the chicken study sometimes it barely moves insulin from basal.
Would a high-protein diet be effectively as glucose-based as carbohydrate?
Hi Webster, sorry to be so long. Having looked around pubmed a bit on insulin response to protein I suspect that the chicken graph is a bit of a cheat!
ReplyDeleteThey chose one of the least insulogenic protein sources and used 60g wet weight. That is not a lot of protein! I think from looking round at insulin responses to protein they vary a fair bit but there is usually something, if you eat a meaningful amount.
Ultimately we do need some protein, we buy that with insulin and I have yet more respect for Kwasniewski and his target of 0.8g/kg/d ideal weight....
Peter