Fasting hyperinsulinemia is associated with an increased risk of atherosclerotic complications of heart attack and stroke. This has resulted in the concept that insulin may promote atherosclerosis in spite of the absence of any evidence that insulin is atherogenic either in the human or in experimental models. Recent evidence shows that insulin exerts vasodilatory, anti-platelet and anti-inflammatory effects at the cellular level in vitro and in the human in vivo. Since atherosclerosis is a chronic inflammatory process of the arterial wall, insulin may be potentially anti-atherosclerotic in the long term. More recent data on experimental atherosclerosis in the mouse shows that (1) insulin administration reduces the number and the size of atherosclerotic lesions in apo E null mice and (2) in IRS-2 null mice, the interruption in insulin signal transduction results in enhanced atherogenicity. Finally, the use of a low dose of insulin infusion in patients with acute myocardial infarction has been shown to markedly improve clinical outcomes, both in diabetic and nondiabetic patients. Our own most recent data show that a low dose infusion of insulin in patients with acute myocardial infarction induces a reduction in nflammation (C-reactive protein and serum amyloid A) and oxidative stress, and promotes fibrinolysis. We conclude that insulin is anti-inflammatory and potentially antiatherogenic and may be of use in the treatment of cardiovascular inflammatory conditions.
It seems that the demonization of insulin has followed much the same path as the correlation = causality logic of LDL and atherosclerosis. Elevated LDL correlates with CVD, but there is not a whole lot of actual evidence demonstrating that the LDL itself directly causing atherosclerosis. LDL remains a fairly reliable marker for determining risk (though it must be considered along with other factors), and whatever the flaws (and there are many) in cholesterol theories, this shouldn't be ignored out of hand. If A causes B, and A causes C, then someone with B likely has C.
So with the insulin, we have hyperinsulinemia correlating with CVD, but as stated in the abstract above, there's little evidence that it causes it directly. The "A" in this scenario seems to be elevated free fatty acids (NEFA/FFA) leading to "B" = hyperinsulinemia and "C" = atherosclerosis. But in this case the correlation/causation connection may be even more convoluted. Because there's an intermediate factor in all this -- the ever-increasingly apparent root of all evil: insulin resistance. The way I see it is this: Fat stores exceeding an individual's storage capacity lead to IR of the fat cells and/or excessive release of NEFA. Elevated NEFA induces IR in peripheral tissues. It is cellular resistance to insulin's inhibitory roles in these cells that ultimately lead to metabolic dysfunction and/or cell damage/death. In this regard, the relationship is not so much one of insulin not being the cause of atherosclerosis, etc., but the resistance masks the fact that it would appear that insulin is actually protective against it!
Inflammation, shmimflamation! :
Atherosclerosis is an inflammatory process.7 All the major classical risk factors for atherosclerosis, hypercholesterolemia, diabetes, hypertension, smoking, and menopause are associated with (and probably cause) inflammation. If high insulin levels are atherogenic, one would expect it also to exert part of its negative effect on the vessel wall through inflammatory processes. Recent evidence which we shall now review shows that just the opposite is the case, i.e., that insulin is anti-inflammatory.The article goes on to summarize such research. I'll let the more science minded read that for themselves (heck, I'm just too lazy at the moment to do a decent summary), but this section concludes with:
In view of the anti-inflammatory and vasodilatory effect of insulin, insulin resistance may be expected to be pro-inflammatory and a proconstrictor state. This indeed is the case. Obesity,31 type 2 diabetes,32 and other insulin resistant states, such as polycystic ovary syndrome (PCOS),33 are pro-inflammatory and are associated with abnormal vascular reactivity and platelet hyperaggregability. (clumping & clotting)
........... Insulin sensitizers have been shown to exert anti-inflammatory43–46 and anti-atherosclerotic effects.47,48 Thiazolidinediones (TZD) exert anti-inflammatory effects at the molecular and cellular levels.The article goes on to conclude as follows:
These facts, should encourage us to increase our understanding of these novel effects of insulin so that
(1) we have an improved conceptualization of inflammation in states of insulin resistance and the relationship of these states to atherogenesis;
(2) we explore the potential therapeutic role of insulin in inflammatory conditions, such as acute myocardial infarction; and
(3) we investigate novel potential therapeutic application of insulin sensitizers such as thiazolidinediones as anti-inflammatory agents.I broke these out in more bullet form to address them.
(1) I take this to mean the lipid hypothesizers need to rethink as much as the carbohydrate hypothesizers do. Both need to re-think the role of dietary composition (and total intake) in terms of its impact on insulin SENSITIVITY, not insulin per se.
(2) Insulin is, as Martha Stewart would say, a GOOD thing. There's much promise in using it. Insulin therapies have evolved from slow acting secretagogues (substances that enhance insulin secretion), to pumps delivering a more consistent, physiological basal level in T1's etc.
(3) OK, I'm probably in agreement with many who disdain the whole "this gives us more reason to look into more drugs" angle, but we have to be pragmatic about it. A Type 1 does not make insulin. In that regard, whatever technology allows them to mimic insulin levels in a normal person, I would be grateful for it. Type 2 is a far more varied diagnosis as the degree of irreversible damage (as opposed to suppressed function) cannot be assessed with mere fasting glucose levels or tolerance tests. If you're hyperinsulinemic, you still have functional beta cells. Temporarily giving them a rest with LC while you lose weight and reverse the IR that is causing the elevated insulin is a great strategy. But if you cannot adhere to this, or if LC doesn't result in the desired weight loss, then it may well be worthwhile to at least temporarily look into pharmaceutical intervention that allows for insulin to "do its thing". I wonder, even, if insulin might be helpful to the hyperinsulinemic T2 -- enough exogenous insulin may keep the pancreas from having to work overtime to produce the elevated levels that your body is telling it to anyway. There's nothing about the hormone that is deleterious!!!!!!!!
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