The evidence is convergent. Multiple independent sources reach the same conclusion, the underlying mechanism is well-characterized, and even the field's most cautious voices treat it as worth doing.
there are conditions in which you can have elevated LDL and this may be an indication of insulin resistance so the overarching idea here and I think many people will say in the lipids field now is that the main driver of atherosclerosis is probably insulin resistance and pre-diabetes metabolic syndrome
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the part of it that's so interesting to me is that there's a large body of literature suggesting that the LDL particles become stickier and the sub endothelial space becomes stickier in insulin resistance states and this is where I think we get back to that idea I love what you said the Rosetta Stone of so many chronic diseases seems to be insulin resistance and I would posit my hypothesis would be that the initiator of atherosclerosis for many people is insulin resistance
however you know reverse causation is also possible which is that if you have insulin resistance all these other things happen that make your LDL particles reside longer and then those are the things that end up being that there are actually causative and atherosclerosis and then the LDL particle residence time is just kind of I along for the ride
what Tommy just said I hope we'll go down in history as a game-changing idea because you guys should like rewind the podcast and just listen to that because that is a fantastic explanation of the alternative hypothesis
if you are studying lipid ology in a sick population then LDL pasco all of a sudden looks super important because everybody's endothelium is already screwed
that probably what we're seeing what the disordered lipid panel is insulin resistance and that is probably the main issue that we need to be going after
it's not about how much LDL is in your blood it's about how much LDL gets stuck in your arterial law and that relationship is not linear
But it's the insulin resistance that provide that is the total overarching context. And I believe it's the insulin resistance that is the spark that burns the the wood. You know, you can store a bunch of wood in your garage. It's not going to spontaneously combust unless lightning hits it. And that lightning strike is the insulin resistance.
what we know about ldl as i mentioned a little bit earlier is that essentially no matter what your level of ldl is either at 70 milligrams per deciliter or 150 milligrams per deciliter you can develop atherosclerosis if you are insulin resistant
the thesis that i will advance in the remainder of this podcast is that i will try to prove to you that ldl does not directly injure the endothelium of the blood vessels and the context is everything the metabolic dysfunction also known as insulin resistance is the proximate event the first event of atherosclerosis
the thesis that i will advance in the remainder of this podcast is that i will try to prove to you that ldl does not directly injure the endothelium of the blood vessels and that context is everything that metabolic dysfunction also known as insulin resistance is the proximate event the first event of atherosclerosis
atherosclerosis is not related to ldl number it's related to insulin sensitivity
i believe that in diabetics and those who are insulin resistance and we know that these individuals have impaired immunity have impaired wound healing isn't it likely they also have impaired wound healing in their arterial vascular tree and that the damage to the endothelium which probably is connected with insulin resistance directly is the beginning event of atherosclerosis and then ldl gets wrapped into that
the true drivers of atherosclerosis which I believe are insulin resistance impaired repair of endothelial cells which is always going to be happening because we're always going to be denuding the endothelium of our inside blood vessels because we're always going to be damaging our blood vessels which means that we're all going to have some process of fatty streaks and repair
these medical students are not being challenged during their Cardiology rotations when they see Cardiology patients who have had heart attacks to think about the root cause of their atherosclerosis they're not taught that insulin resistance that metabolic dysfunction lie at the root of atherosclerosis
LDL is involved in that and potentially necessary for that but doesn't initiate it this is the necessary but not sufficient idea
I think we should be focusing on insulin resistance and other things that are clearly or more clearly indicted as causal in atherosclerosis