Hyperinsulinemia, Hyperglycemia and Insulin Resistance

Over in the comments on the Taubes Toothpick post, starting around here, Nostril Damus (funny!) challenged my contention that the only carb implicated in IR is fructose, a carb that doesn't elicit an insulin response.  ND posited that other carbs cause hyperinsulinemia cause self-downregulation of insulin receptors leading to IR.  Then Melchior posted about a study where hyperinsulinemia and hyperglycemia/insulinemia induced insulin resistance which provided more food for thought.  

I thought on this a bit and think it is worthwhile to repeat in a post of its own and add a few more comments.

So a direct quotation of ND's premise:  "Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration."

Unfortunately only the abstract is available free online, but it does contain some interesting information.  Here's the study:

Effect of sustained physiologic hyperinsulinaemia and hyperglycaemia on insulin secretion and insulin sensitivity in man.

Insulin: Understanding its Action in Health and Disease

Another bookmarking post.  I may or may not have linked directly to this article in a primary blog post before, but I'm doing it now.  Hat-tip to LynMarie Daye in this post at her Adipo-Insights blog.

Insulin: understanding its action in health and diseasel

The Physiologic Effects of Insulin

Mostly a bookmarking post here.  I wanted to share this link:  http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html

I think it's a pretty good summary of insulin's actions vis a vis glucose transport, metabolism and fat tissue.

Coconut allergies anyone?

This isn't so much a science post but an open question to my readers.  Although I did adopt a different skin care regime about the time I started low carbing in 2007, I'm pretty confident in attributing a goodly portion of my cleared skin to my diet.   I had suffered from mild (relative to some images I see) adult acne for years, mostly on chin, hairline and back/bra-line.  This all pretty much cleared up to where I hadn't had a breakout worth mentioning in two years.  And one would think that somewhere in those longer cheats at least I would have consumed enough wheat or other culprit to set off a breakout, but nada.  Then summer 2009 I did an IF experiment.  I consistently followed a 5 hour eating window for 3 months.  I lost 10 lbs in the first couple of weeks but gained several pimples!  OK, so perhaps something about the fasting was killing off toxins and they were coming out my pores??  Thinking back, however, something else changed in my diet.   I was making this peanut butter/coconut oil ball dessert.  PB had been a part of my diet here and there and I have no issues with it, but CO was new.   So anyway, I gradually just phased out CO as it didn't produce any more losses and that was that.  The breakouts had gone away but thought nothing really of it.  

Fast forward to the end of this past summer.  I had been relaxing things a bit for a while consuming quite a bit of sushi.  All of a sudden I was getting rather large pimples all over my back and eventually several on my chin.  I figured maybe the sushi, but there was a spell when I didn't eat it at all and the breakouts continued.  Although I was eating a few more carbs as I've shared, I wasn't eating any more wheat or grains than I might have consumed on a prolonged cheat ... probably less.  Well, then I started thinking, this was when I was eating a lot of coconut shreds, fresh coconut, and using coconut milk in my coffee.

It would be a real bummer to discover it being so, but I fear I have a coconut intolerance.  I did notice a slight weight loss/change in body size eating all the coconut so would hate to have to avoid that possible strategy to lose a bit more.  I regularly use a mix of MCT/olive oil for salad dressing so it's not those FA's in the fat to blame.

Anyone ever experience something like this, or am I just weird?  I keep seeing stuff on contact dermatitis for coconut in skincare products, but nothing really for allergies, intolerance or acne.  Thanks in advance!

Must See "TV" for those suffering from CDS

CDS = Calorie Denial Syndrome

Thanks to Wolfstriked for linking to this in comments.

BBC Story about Low Carb Dieting - Part 1

BBC Story about Low Carb Dieting - Part 2

BBC Story about Low Carb Dieting - Part 3

BBC Story about Low Carb Dieting - Part 4

BBC Story about Low Carb Dieting - Part 5

Just a few thoughts on this aside from the content so that my opinions will not cloud your listening of the presentation:

I found it interesting that they showed both Westman and Foster exercising (running and playing basketball) in their intros in the piece.  Indeed they are interviewed in their gym clothes!  Then there's Dr. Mary Vernon horseback riding.  Did we need so many closeup chewing scenes?  And, lastly, was the full rear (albeit blurred) Sipowitz moment in the shower, actually that rather lengthy soaping/showering scene, really necessary as a backdrop to the discussion of ketosis?

R.I.P. Jack Lallane

An icon if there ever was one.  I remember watching his show as a kid.  Ninety Six and looking pretty darned healthy up to the end!!  That's a good long life.  

http://www.bestweightlossmealplans.com/low-fat-diet-plan/jack-lalanne-sample-meal-plan/

Looking at that diet it is actually one that is fairly low in carbs.  But it contained a fair amount of fructose by LC standards, and notice something else?  It was also relatively low fat, and certainly low in added fats.  Just food for thought.

You will  be missed Jack! 

Stick a Toothpick in It? Taubes' 4-pronged Carb/Insulin "Fork" Loses its Tines

In the comments at Jimmy's blog on my interview podcast, several comments either directly or by inference say I failed to make my case against Taubes.  Well, I think I did pretty much get to what I consider the four prongs of Taubes carb/insulin hypothesis, but I've decided to try and summarize this in a blog post.  Another common comment is that I'm somehow nit-picking at minutia, basically if folks lose weight on low carb, it doesn't matter the details of why.  To those, if they are reading this, I would say that any objective view of my arguments would lead to the conclusion that these are NOT minor details, they are the sum total of Taubes' evidence in support of his hypothesis.  Not only has he NEVER debunked the calorie-based theories on obesity, but almost all evidence in support of his "alternate" theory HAS been.  

I will not be referencing this post, it's all been done before here, and I don't have the time to trace down every link etc.  

So, what do the four prongs of the fork stuck in the potato above represent?  

The Glucose Fatty Acid Cycle

LOTS of info in this summary by my favorite sci-crush Keith Frayn.  This is mostly a bookmarking post as reader Margaret mentioned this article in the comments elsewhere.  It's a good, if not lengthy read.  Perhaps someday I'll get around to summarizing it, but for now, just a link & the abstract.

The glucose–fatty acid cycle: a physiological perspective 

Glucose and fatty acids are the major fuels for mammalian metabolism and it is clearly essential that mechanisms exist for mutual co-ordination of their utilization. The glucose–fatty acid cycle, as it was proposed in 1963, describes one set of mechanisms by which carbohydrate and fat metabolism interact. Since that time, the importance of the glucose–fatty acid cycle has been confirmed repeatedly, in particular by elevation of plasma non-esterified fatty acid concentrations and demonstration of an impairment of glucose utilization. Since 1963 further means have been elucidated by which glucose and fatty acids interact. These include stimulation of hepatic glucose output by fatty acids, potentiation of glucose-stimulated insulin secretion by fatty acids, and the cellular mechanism whereby high glucose and insulin concentrations inhibit fatty acid oxidation via malonyl-CoA regulation of carnitine palmitoyltransferase-1. The last of these mechanisms, discovered by Denis McGarry and Daniel Foster in 1977, provides an almost exact complement to the mechanism described in the glucose–fatty acid cycle whereby high concentrations of fatty acids inhibit glucose utilization. These additional discoveries have not detracted from the important of the glucose–fatty acid cycle: rather, they have reinforced the importance of mechanisms whereby glucose and fat can interact.

Deleterious Effects of NEFA II: Panceatic beta cell impairment

Non-esterified fatty acids are deleterious for human pancreatic islet function at physiological glucose concentration

Progression from normal glucose tolerance to Type 2 diabetes results from a gradual deterioration in beta-cell function, in the presence of insulin resistance [1]. Over the past 10 years, the role of excess glucose in the alteration of beta-cell function has become increasingly clear and has led to the concept of glucotoxicity [2, 3].  At the same time, the deleterious effect of increased NEFA was suggested by studies on Zucker diabetic fatty (ZDF) rats, an animal model of Type 2 diabetes combined with obesity. The authors showed that altered beta-cell function was preceded by an important increase in the plasma concentration of NEFA and subsequent triglyceride (TG) accumulation in pancreatic islets [4, 5]. This hypothesis, also referred to as lipotoxicity, was confirmed by in vitro exposure of isolated islets to NEFA [6, 7, 8]. However, whether glucose and NEFA alter beta-cell function synergistically or separately, remains controversial.

...In this study, we examined the influence of NEFA on human islet function with or without concomitant increased glucose concentrations. Because lipid metabolism seems to have a crucial role in lipotoxicity [8], we also studied the expression of genes involved in this metabolism. 

NOTE:  GSIS = glucose stimulated insulin secretion  aka your acute or Phase I insulin response to carbs that is lacking in T2's.

With our model of in-vitro human islets, we showed that beta-cell alterations characteristic of clinical Type 2 diabetes, including loss of GSIS and decrease in insulin content, can be reproduced with either increased glucose or NEFA concentrations. The deleterious effect of high glucose is well established [2, 3], but increased NEFA at physiological glucose concentrations were also able to significantly alter GSIS and insulin content. These results are in accordance with previous studies [6, 10, 33], but argue against the hypothesis that increased glucose is a prerequisite for the deleterious effect of NEFA on betacell function [11, 12, 13, 14]. 

Bottom line:  NEFA alone can alter beta cell function.

Insulin Wars IV.1: Todd Becker of Getting Stronger blog responds

I received an email from Todd Becker of Getting Stronger blog who tried to add his comments/responses to my review of his contribution on Jimmy's blog regarding James Kreiger's Insulin Series.

Here is a link to that installment:  Insulin Wars IV: Todd Becker of Getting Stronger blog

I did my best to retain the emphasis/formatting from Todd's email.  So, with apologies in advance if any of my responses are repetitious of my initial post, without further adieu:

Todd writes:

Hi CarbSane,

Congratulations on your articulate, informative and passionate podcast interview on Jimmy Moore’s site. Small world: I’ll be a guest on his podcast in a few weeks. Your interview inspired me to look at your blog, where lo and behold I found your critical review of my analysis of James Krieger’s views about insulin, which I wrote for Jimmy’s blog. I appreciate the time and thought that went into your analysis, and I’ve learned several interesting things from your site. But if you would permit me, I’d like to respond to what you wrote about my analysis. To do full justice to both of us would take many pages, and would bore most readers, so I’d like to just make a few basic points here to set the record straight, and to raise some additional questions:

I'm more than happy to do this.  The comments feature here at blogger is limited.  For one thing, if you use even one HTML tag for emphasis, a length limit kicks in.  For another, detailed responses would not be done justice for discussion purposes due to the flat form non-threaded nature of the response system here.  I do however have a response to many of Todd's points, so I think it is best to do that within the context of a single blog post.  So ... Todd's remarks will be (indented) in a quotation in default font.  My responses will be in purple, not-indented, and I'll try to be consistent to use a "CS:" so there won't be any confusion.

My Interview with Jimmy Moore

CLICK HERE

WOW, thanks (not) Jimmy for your characterization of me as a low carb skeptic.  I'm not.  I'm a skeptic of the so-called science.

{Stuff in these parentheses were updated ~2:40 pm 1/21/11 ...  Seems I'm being taken to task a bit over at Jimmy's blog for "trashing" him when apparently I should be thanking him profusely.  I did thank him in an email, at the end of my interview, and previously on this blog, but I did neglect to do so once again here.  Probably because at the time of this post I was a bit miffed by Jimmy's lead ins in the podcast and what I consider mis-characterizations of me.  Kevin over in the comments who actually writes the show notes has claimed authorship for part of this so I won't blame Jimmy for that.  Thanks Kevin for correcting that.  I have since been labeled a "taunter" and essentially had words put into my mouth by Jimmy himself such as fraud though I'm not sure I ever used those words.  Anywho, there's no need to waste good cyberink on minor quibbles.  I do thank Jimmy for the opportunity and commend him for bringing voices counter to low carb dogma to the wider audience.   So, I'll leave the rest of this intact.}

I don't really appreciate how Jimmy characterized me as anti-low carb on his blog either:

Coming up Monday, we’ll hear from an enthusiastic anti-low-carb blogger who calls herself CarbSaneto talk about why she thinks bestselling author Gary Taubesis a fraud and that the low-carb diet is not the whole story. Take a listen for yourself and decide whether she has a point or not. 

I guess your headlines might generate more hits which is fine with me.  Hopefully more will see the truth.

I heard this for the first time today too which made me nervous as I typed this post out.  Just listened.  I'm OK with it except for the nervous laughter at times.  Better than getting a case of the Ummms I suppose.

Some links {fixed them, thanks flo!} to things I discussed with Jimmy with regards to GCBC that were the impetus for the interview:

GCBC Reference Check ~ Part I of ? ~ Metabolic Adaptability & Energy Balance

GCBC Reference Check ~ Part II of ? ~ Insulin Resistance (again)

GCBC Reference Check ~ Part III of ? ~ Is glycerol phosphate rate-limiting?

Insulin Resistance ~ Taubes v. Frayn

Fat Accumulation: Taubes v. Frayn ~ ASP in vivo in humans

A summary of my differences with GT's premises:  The 11 Critical Conclusions of Taubes

{Edited to add}  This is the post that got this ball rolling:  Glyceroneogenesis v. Taubes.  The question on that Reshef paper remains unanswered by Taubes.

Have at me gang!

Countering Anti-Energy Balance, CI=CO Arguments ~ Part I The 3500 Cal = 1 Pound Fat

Calories In - Calories Out = Change in Energy Stored

I continue to be amazed by the number of people who argue against this basic physical law.  This series will discuss the various versions by which folks seek to argue against this.  

This installment will consider the argument that 1 pound of fat = 3500 calories is incorrect.

= 3500 Cals??

More on Water Weight & Insulin

There's an interesting related conversation on this topic going on over at Paul Jaminet's site:

Water Weight: Does It Change When Changing Diets? Does It Matter?

For those not familiar with the Perfect Health diet, one component is to get ~400 cal in "safe starches" -- around 100g.  For those transitioning to their diet from a low carb diet, some have experienced a not-unexpected weight gain.  I've added some thoughts to the comments there and -- can't be sure and some is just a hunch -- but I think any weight bounce is probably more carb associated, predominantly glycogen repletion.  It may well be due to replenishing other "carb" molecules with their associated water as well.  My guess is that for the most part these changes show up on the scale more than in dimensions.  That was my experience during the almost 3 years of my "low carb cheating" plan.  I can't know for sure for the first year and a half or so of that, because I never weighed, but I didn't gain size during my cheats (pants still fit fine) and later after I weighed I sometimes saw a few pound gain, but again this didn't effect the fit of the skinny-jeans much if at all.  

However my current interest/focus is building on this recent post of mine:

Insulin, Weight Loss & Water Weight

In that post I referenced two studies that I'll repeat link to here:

Changes in abdominal subcutaneous fat water content with rapid weight loss and long-term weight maintenance in abdominally obese men and women - This one discusses how following rapid weight loss and improvement in insulin sensitivity of the fat tissue, fat mass increases due to increased associated water resulting from improved blood flow.

Disparate Hydration  in Adipose and Lean Tissue Require a New Model for Body Water Distribution in Man.  This one discusses various models of determining total body water content, and the contribution of adipose tissue often ignored for lean populations.  It also discusses the extra and intracellular distribution of water in adipose tissue and lean tissue.

Insulin, Weight Loss & Water Weight

Reader kds posted a link to this Peter of Hyperlipid's blog post about the following study:  .Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults

Basically, diazoxide is a compound that has been used to treat hypoglycemia and reduces insulin secretion.   Two groups of 12 obese hyperinsulinemic adults were treated with diazoxide or placebo for 8 weeks while each consuming the same Optifast diet.  Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P < 0.001), greater decrease in body fat (P < 0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and greater attenuation of acute insulin response to glucose (P < 0.01).   This is pretty phenomenal and difficult to fathom -- almost twice the weight loss.  It was also reported that there was no significant change in resting energy expenditure (REE, RMR, BMR), and substrate use, as derived from indirect calorimetry, did not reveal any significant change in carbohydrate or fat metabolism in either group.  IOW, there was no stimulation of fatty acid oxidation accompanying the proposed decreased lipogenesis (presumably they're referring to esterification not de novo lipogenesis) and/or increased lipolysis (as evidenced by increases in FFA/NEFA levels).

Now, some may accuse me of rationalizing, but for all the claims I may disagree with, I have yet to see any of the "experts" -- even Taubes and Eades and the MA crowd -- imply that fatty acids can magically be "flushed" from the body without being "burnt" off (beta oxidation).  The only way out is for the LCFA to be broken down ultimately to CO2.  Therefore, there HAS to be an explanation here because insulin is not a magic molecule capable of creating or destroying matter.  If the diazoxide (DZ) didn't lead to increased fatty acid oxidation, and REE was unchanged, then likely futile cycling and uncoupling were not involved either -- these would cause increases in both FA oxidation and REE as they "blow off" or "waste" fatty acids.

So ... where did the fatty acid mass go?

Comments on Tom Naughton's Interview with Taubes on Why We Get Fat

Why We Get Fat: Interview With Gary Taubes - Tom Naughton

This is a pretty long interview, so I'm not going to address all of the points, but just a few of the exchanges.

GT:  I’m always asking myself, “How can I explain this to a general audience? How can I simplify the science to the point that it is barely noticeable?” In fact, often the best science writing has no noticeable science at all.

OK ;-)

Fat Head: I found those critiques rather odd, considering that Good Calories, Bad Calories includes an entire chapter titled Conservation of Energy, in which you wrote at length about the laws of thermodynamics and how nutritionists misinterpret them. How do you deal with criticisms of your books coming from people who clearly haven’t read them?

Another Why We Get Fat review (again, not mine)

http://www.weightymatters.ca/2011/01/book-review-gary-taubes-why-we-get-fat.html

Found this one because I was getting some hits from this unbeknownst to me website.  Towards the end of the review one of my Taube$ posts is linked to.  I've since refrained from addressing Taubes' personal motivations.  My exposing of his omissions and outright misrepresentations should speak for themselves at this point.  

Zoe Harcombe ~ Walking Advertisement for Low Carb Eating?

Zoe Harcombe made a bit of a splash in the LC community thanks in part to the following article in the Daily Mail:  Everything you thought you knew about food is WRONG

The subtitle:  Fibre's bad for you. Fat's healthy. And five-a-day is a gimmick to make fruit and veg firms rich. Or so claims a remarkable new book...


Just say no to fruit and starchy carbs that the government is pushing on you ... right?

Harcombe sings the praises of butter and eggs, and meat and *real food*.  She shuns the idea of dieting and restricting foods.   Clearly she's drunk the Taubes Kool Aid on calories and insulin.

So her diet is fairly low carb and extolls the virtues of animal foods -- meat, fish, eggs, butter, dairy.

Random thoughts on Why We Get Fat

Why We Get Fat:  So I’m on a cruise ship in parts unknown of the Carribean which has given me the opportunity for people watching in their natural habitat.  Folks, we don’t need a book, or this blog, or any scholarly thesis.  And there are a lot of Europeans on this cruise in addition to the Americans for my observation of the modern human in the wild.  We EAT TOO MUCH. 

OK so you’re on vacation.  Great.  All the food is included in the cost.  Great.  Does that mean you have to shovel as much food as humanly possible down the pie hole three meals a day and midnight buffet?  Apparently for some people!  Do you not get your money’s worth if you don’t eat something from every station or something?  Over at GT’s blog they’re again debating the stupid 20 cal/day balance.  It’s not that folks!  It’s if you spend 10 days on a cruise ship and eat 2000 cal/day more than you burn lying around the deck drinking another 1000 cal/day in cocktails, you will disembark weighing several pounds more than when you came aboard.  If you don’t do anything to compensate upon arriving home, then you’re going to be a little fatter until the next time you let your hair down on vacation or a party, etc.    Thinking back, this WAS me.  Perhaps not stuffing myself silly, but definitely overeating.  So looking around at other’s plates its really a no-brainer why some of the passengers are heavier than others.  Are there thin folks with lots of food?  Sure.  But they apparently have the metabolisms to eat this way.  I also note that it’s not the ones walking laps around or putting in some miles on the elipticals that I later see trying to satisfy that exercise induced hunger I keep hearing about. 

So how am I faring now?  I’m doing quite well!  I’m still comfortably fitting my size 8 pants for casual dinner and karaoke last night.  I had breakfast the first couple of days but have skipped it since.   I just can’t eat 3 meals in a day anymore.  I did feel a bit badly for the heavier lady behind me at the omelet station the first morning though.  All I had on my plate was a few lox and bacon and I ordered 2 eggs over easy.  She was ordering an egg white omelet and commented on how good my breakfast looked.  Felt like telling her to go for it but bit my tongue.   At lunch I make sure to get my veggies in and a protein.  But, had an ABSOLUTELY sinful brownie (it was more like warm melty fudge) with ice cream the other day … shared it with the hubby and both of us felt like we were on sugar highs!  Dinner I let my hair down a bit and have my starch and a few bites of dessert IF it’s worth it.  Two appetizers are not out of the question ;-)   Thing is, I really enjoy the food I eat.  I’m not sure I did back when I was eating so much.  I would probably lose weight if it weren’t for the increased EtOH consumption, because I’m very active on vacation.  On sea days I have been walking, taking (running up) the stairs, etc.  On shore days I get all the exercise I need trying to keep up with my brother-in-law (requires quite the power walking on these short legs o’ mine!) and snorkeling.  No gym required!

Ahhh well.  I’ll check in sometime soon with some comments.  Have a great day everyone!

2010 Rap Up

{cross posted on both blogs}

Like just about everyone, I thought I would jot down a few thoughts as a new year is upon us.   I can hardly believe it's 2011 already.  Wasn't that Y2K thing just like yesterday?

Without a doubt the biggest success for me is maintaining my weight loss.  I've seen some NSV's so I must be recomposing a bit despite not much movement on the scale.  When I return from vacation I do plan to give this another push.  But for someone who was never the same weight (except when ~300 lbs) for an entire month my entire adult life, I cannot express how monumental this is.  As I pack for warmer climates, I don't have to stress over finding out of season clothes b/c the summer stuff doesn't fit.  Wardrobe security is a wonderful thing! 

The best part is that this year maintaining was relatively easy and I've been able to eat more "normally" on a daily basis with a carb count ~75g avg.  I do find myself defaulting down to VLC some days and that's OK too.  Mindful eating and making sure I get my protein in is working.

Although I didn't accomplish much in the way of formal exercise, I went from being able to do like 8 "girlie" pushups to making the 100 and then onto real pushups I got up to quite a few.  I do need to revisit those, just being lazy.  But 2010 was a year of great physical accomplishments.  I don't feel my age, I feel younger than I did 10 years ago and I'm able to do so much w/o feeling overexerted or getting swollen ankles and such.   My wood pile workouts have been empowering.  I would love to try for something like a sprint tri (it would be 10 yrs since the last one), but not sure running is ever going to be for this post-obesity bod of mine.  We'll see.  I've got some thinking to do on that while I'm away.

So, how 'bout that low carb?  I consider myself semi-Paleo, semi-LC, semi-Perfect Health these days.  What I'm doing is working and I feel great.  I may tinker with things a bit, perhaps do IF for a stint to see if I can't lose some more weight.   Again, we'll see.   I'm in that strange place where there's weight to lose but no urgency to lose it.

EDIT!!  WOW, I can't believe I left out starting my blogs!  I thank all of you for reading and contributing to some great discussions here.  I know I've learned a lot and it's gratifying to have you great folks reading my work and making me think even more.  Even though there are far more popular blogs out there, never did I dream I would have so many readers so soon.  It's really nice not to just be talking to myself over here ;-) 

Looking forward to a great 2011!