The readership in this blog continues to grow and it is not lost on me that a vast majority of current readers are unfamiliar with the bulk of my work here on this blog. I think I'm closing in on 1000 posts which would make me one of the more prolific bloggers around ... for better or worse! As such, I more than understand that it would be darned near impossible to catch up, etc. So a few comments in that vein.
- I do try to link to older relevant content in my posts and I do use a "related posts" widget. The latter is imperfect as it randomly selects using the labels function, but it's worth more than just glossing over if you're a newer reader.
- Speaking of labels, while I do have a lot, I do try to only use the labels when there is relevant information in a post. Not perfect on that account, but I try, so for those looking for more information, there are the labels.
- There is a search function for this blog. It works pretty well, but at times I find using plain Google.com with the site:carbsanity.blogspot.com search easier to navigate for relevant hits.
- I also employ a Chronological Posts widget on the right sidebar. While there are a lot of posts, my post titles are usually pretty descriptive so scanning through that may be helpful. I used to have that widget on a page here, that was much easier to read, but when Blogger upgraded, it stopped working. Sorry about that!
- You can always ask! I am in the process of working on some summary pages for most often discussed topics. It's just not a priority so I can't make any promises. Since this blog started as merely sharing my research and thoughts, it was never organized around some central mission statement, etc. Constructive criticism and input on rectifying that is always welcome.
So that of the way, I thought that one more way to highlight older content might be to bump posts. I have been doing this from time to time, especially when on vacation, but I plan to do this on a more formal basis from here on -- every Thursday. And since Wednesday is "Hump Day", this will be the Over the Hump Bump. Feel free to groan.
Today's Bump was inspired by comments here. One thing I brought up there is that some of the current issues with obesity and diabetes may be attributable to the increase in low birth weight babies here in the US. While LBW and premie status are not one and the same, the numbers overlap substantially. So a few source citations for those interested on this and the link to developing obesity:
- Born a Bit Too Early: Recent Trends in Late Preterm Births: The preterm (less than 37 weeks of gestation) birth rate rose by more than 20 percent in the United States between 1990 and 2006 (1). Most of this increase was among infants born toward the end of the preterm period, at 34 to 36 full weeks of pregnancy, or during the period known as “late preterm” (1,2). Although babies born before the 34th week of pregnancy are at the greatest risk of early death and life-long morbidity (3), it is becoming increasingly recognized that infants born late preterm are less healthy than infants born later in pregnancy (4–9).
- March of Dimes: Summary: about 8% of babies are born prematurely in the US, and about 10% are "growth restricted": "a baby doesn’t gain the weight she should before birth. You may hear the terms “growth-restricted,” “small-for-gestational age” or “small-for-date” to describe these babies. They may have low birthweight simply because their parents are small. Others may have low birthweight because something slowed or stopped their growth in the womb."
- Why Low Birth Weight Is Linked to Obesity Later in Life: Study Provides Explanation: Paraphrase, LBW babies develop fewer neurons in appetite control centers.
- The Effect of Birth Weight on Childhood Obesity: The Barker Hypothesis (1990) posits that “compromised” growth in utero may be associated with differential organ development (the severity and effects depending upon the timing of the insult) with increased allocation of nutrients to adipose tissue during development. This may then result in an accelerated weight gain during childhood, which could contribute to a relatively greater risk of various illnesses (including cardiovascular diseases) later in life. Our result that the “compromised” subpopulation has a faster postnatal growth rate during childhood (Figure 1(a)) supports the Barker Hypothesis (1990) and tends to resolve the paradox among birth weight, obesity, and cardiovascular diseases.
As you can see, it is not enough to explain the full epidemic, but it MAY be part of it ... especially since we have seen an increase in the so-called medically obese normal people or whatever you want to call those with glucose intolerance that are not obese.
My reason for bumping this is that in looking back I saw something that once again caught my eye, but now moreso than before. It is becoming increasingly clear that the concept of IR as we know it in the progression of Type 2 diabetes is likely wrong. This is not something I discovered or came up with, but it has been an ongoing point of contention amongst researchers in the realm. This was the main point of the article I wrote recently for Alan Aragon's Research Review. I'm sorry that I cannot share that with you as it is premium content for AARR, (you can always subscribe and have access to the archives). Still, while not all in one place, most of the research referenced in that article has been discussed here over the past several months, and it is a topic I will continue to blog on here.
The current general knowledge about diabetes is that the muscle cells become insulin resistant causing a backup of glucose in the blood stream. The low carb line is that the adipose tissue acts as a last-chance glucose "sink" and when the adipose tissue finally becomes insulin resistant, hyperglycemia ensues. Many have looked into the cause-effect "chicken-and-egg" relationship between hyperinsulinemia and IR, but both general ideas still put the defect in the periphery first. There is little if any evidence to support this, however. Meanwhile there is much evidence, such as the paper discussed in the original article below, that the defect may not even involve insulin per se, but further initiates in the adipose tissue. You see, in the LBW babies, we see a decrease in adipose glucose transporters (GLUT4) and increased adipose tissue. The GLUT4 in muscle is not reduced. And, importantly (yet unfortunately), this defect persists even with weight loss.
All arrows are pointing these days towards glucose uptake and de novo lipogenesis in the adipocyte as being intricately linked to lipolysis from adipose tissue. So, SO, much to share with you on this! It is the inappropriate lipolysis from adipose tissue, and thus inappropriate release of NEFA that sets the cascade in motion.
Lastly, I would note that the original post was made not even a year into my blogging here. I have left it pretty much "as is" (fixed formatting a bit and may have altered a sentence or two but I have no desire to waste time reversing irrelevant changes) as I think it is important to realize that all of us change and evolve in our thinking and understanding as we learn new information. I am not sure if "insulin resistance" is as much the proper term any more as it may even be that there are simply fewer GLUT4's in the adipose tissue to "hear" the insulin signal. This too, may change as more is discovered. Whatever we call it, however, this much is pretty clear at this point: Impaired glucose uptake in adipose tissue, not excessive glucose uptake in adipose tissue is seen in the early stages, and may even be genetic/determined at birth, and this is linked in some manner to the inability of the adipocyte to properly regulate NEFA release through lipolysis (and glyceroneogenesis ... shhhhhhhh).
Original Publication: 12/8/2010
Viewpoints on the Way to the Consensus Session: Where does insulin resistance start? The adipose tissue
This is a rather current (2009) fairly long review article that pretty much summarizes what I've come to understand through my research. The "concensus" in the title kinda caught my eye for reasons my regular readers would probably find obvious.
Anyway, I thought I would share this find without extensive excerpts. I'd otherwise probably be quoting half of the piece. But I'll share the summary graphic of fat being our largest endocrine organ.
One thing that did catch my interest was the summary paragraph:
PRIMACY: INSULIN RESISTANCE STARTS IN ADIPOSE TISSUE—
Studies in twins, who have been raised apart and together (54), have documented that body fat distribution and metabolic abnormalities are a clustering genetic trait. Heritability in the Framingham study, including genetic and early environment contributions, was 57% for subcutaneous and 36% for visceral fat mass (51). As reviewed by Fernandez-Twinn and Ozanne (55), because of intrauterine nutritional and hormonal factors, low–birth weight newborns have more fat and are at higher risk of metabolic and cardiovascular diseases in adulthood. It is noteworthy that fat accretion occurs during the last trimester and maternal under-nutrition in animals during late pregnancy leads to glucose intolerance in adult offspring, in association with reduced adipose, but not muscle GLUT4, content and increased adipose tissue mass.
I don't know that I had ever read this about low-birth weight babies before. It seems so counter-intuitive. Also the influence of maternal nutrition in animals is of interest. One wonders if in true poverty this is at least in part the cause of those obese moms Taubes so often refers to.
The embryonic origin of adipose tissue, i.e., the paraxial mesoderm, gives rise to truncal fat, whereas the lateral plate mesoderm gives rise to fat in the limbs (35), which also reﬂects the relationship between fat distribution and adult metabolic risk.
Never heard this before either. Makes me wonder even more about my change in fat distribution now well into adulthood since I've low carbed. (Things that make me go hmmmmm?)
Recent human studies from our lab (16) have documented that whereas systemic inﬂammation, whole-body/skeletal muscle/hepatic insulin resistance, hypertension, dyslipidemia, and hyperglycemia all are reversed by weight loss, adipose tissue insulin resistance and hypoperfusion are not. This is consistent with the notion that GLUT4 translocation defects are inducible and reversible in myocytes but not in adipocytes (27). Like fat speciﬁc insulin resistance in obesity prone individuals, catecholamine resistance of adipose tissue does not regress with weight loss (56), partly explaining a tendency to regain the lost weight.
Now THIS is depressing! But li'l old CarbSane is very perplexed by this!! One would think that adipose tissue insulin resistance would mimic insulin deficiency (e.g. Type 1 diabetes) in terms of making one LESS prone to obesity, both through Taubes' insulinocentric theory and observations in T1's. At the very least, when adipose IR manifests itself fully we seem to get excessive release of NEFA. Maybe it's that the IR exists all along and it just exascerbates NEFA release from fat cells the fuller they get? Perhaps researchers are misinterpreting the excessive NEFA release as insulin not being able to do it's thing when it's more that it needs to do it on so many triglycerides? Head spinning on this one. Still, if it's the case, and carbs had anything to do with inducing fat accumulation through movement of glucose into the cell, this would again be inconsistent with that theory.
In conclusion, fat-speciﬁc insulin resistance appears to be an early and irreversible defect that can explain the causal relationship between adipocyte dysfunction, extra-adipose tissue (i.e.,muscle and liver), and insulin resistance. The origin of this association can be traced to genetic and embryonic programming, long before the development of metabolic disease in adulthood.
Depressed now. About the permanency thing, although my n=1 personal experience would indicate otherwise, though perhaps not in a good way. Seems I've increased my IR prone fat while reducing my IS prone fat. WTF does that mean????