The LoBAG Diets for treatment of Type II Diabetes and IGF-I: Updated & Expanded

Bump ...

Does dietary protein raise blood glucose?  Not in normal or Type 2 diabetics it doesn't.  This will be the topic of a post today or tomorrow.  There is a disturbing, in my opinion, trend in the low carb community to now demonize protein.  Your usual Atkins style diet is no longer "good enough" or "well formulated" enough for most.  This keto kraze has gotten really krazy!

As far as I'm concerned, the danger of people like Jimmy Moore is no better epitomized than by this trend.  You have lots of people regurgitating his claims that his liver makes too much glucose out of protein and this is implicated in his weight issues.  Nevermind all of the evidence to the contrary.  Leaving weight loss aside, yes, this is anecdotal, but we have no other "evidence" to go by!  Long term low carbers seem to have worsening glucose tolerance over time.  Almost to a one, and these are people who were not diabetic or in some cases even IR (by HOMA) at baseline.  

The LoBAG acronym stands for Low BioAvailable Glucose and were developed by Nuttall and Gannon.  These are some of the earliest studies I blogged on here at the Asylum.  As they were not weight loss diets, they are the closest thing we have to seeing what happens in the maintaining state, though they are unfortunately too short in duration to draw any long term conclusions.

In T2's with twice the protein consumption and equicaloric carbohydrate consumption (30% protein, 30% carb, 40% fat) the 24-hour glucose exposure decreased as the insulin exposure increased with specific mention of increasing IGF-1 inhibiting endogenous glucose production.  EGP, per my last blog post, is the ultimate cause of the hyperglycemia in diabetes.  If higher protein ingestion aggravated this, we would not see the promising results we do with the LoBAG diets.

Previous bump 11/4/11

Another Bumpity Bump Bump from yesteryear when my blog had one tenth the readership it has today.  Why am I bumping this one?  Well, for one, Paul Jaminet cited one of these studies in his rebuttal to Rosedale in the whole safe starch debate.  It is worth noting that Dr. Mary Gannon is also a darling of Feinman's Nutrition & Metabolism society, see, for example, here.  I'm going to add some comments on that paper at the end of this post.  So Gannon & Nuttal have been advocating for some carbs for some time.  They are for lowering carbs, but not to levels that the strident low carbers advocate.  These researchers also unabashedly identify their diets as high protein.  

Original publish date  Sept. 2, 2010

Metabolic effect of a LoBAG30 diet in men with type 2 diabetes 
This diet consists of 30% Carb / 30% Protein / 40% Fat   (About 15g carb for every 200 calories intake)

Although neither is ketogenic or strictly low carb, a 2000 calorie diet would contain 100g or 150g carbs for LoBAG-20 and LoBAG-30 respectively.  This would put both diets in at least the carb restrictive range and in range of Paleo/Primal diets.

These same researchers first tested a LoBAG-40 diet.  At 200g carbs for a 2000 calorie diet, this is probably not Low BAG, but it is LoWER.  The 30% diet was the last one tested, so this post will rely heavily on the discussion in that study as it incorporates comparisons to the other diets.  

These three studies are done in Type 2 diabetics, are intended to be weight maintenance diets, and are based on increased protein and reducing carbohydrates.  LoBAG-40 basically reduces carbs in the common diet by 15% (55% to 40%) and replaces them with protein at 30% (15% to 30%).   LoBAG-20 cut the carbs in half from the LoBAG-40, this time replacing the carbs with fat at constant protein.  LoBAG-30 splits the carb baby.  Therefore, although these studies all involved diabetic men (there were some normal controls), they provide a good comparison of lipids and other health markers across a range of carbohydrate consumptions with protein content held constant.  In other words, in the context of a high protein diet (30%) they examine the effect of the other 70% from fats and carbs from 20/50 to 40/30 split -- not quite, but almost from a one-third/two-thirds carb/fat split for energy to the "flipside" of the coin, a two-thirds/one-third carb/fat split.

There's a lot here, so I'll likely put up more summary/comparison posts in the future based on this series.  For now I would like to focus on one result:
We obtained evidence in previous studies (14, 15) that increasing the protein content of the diet resulted in an increase in IGF-I concentration. The current data provide additional support. Increasing the protein content of the diet from 15 to 30% resulted in an 35% increase in IGF-I regardless of whether the carbohydrate content was 40% (14), 20% (Nuttall and Gannon 2005), or 30% as in the present study. Thus the dietary protein-induced increase in IGF-I is independent of the amount of dietary carbohydrate and fat.
What is IGF-I?  IGF-I stands for Insulin-like Growth Factor I.    This paper (that I will blog separately on at some point) offers up a good descriptive summary of it's purpose and studies on its actions.  The reference links remained intact when I C&P'd them so I've left them in despite the "clutter".
INSULIN-LIKE GROWTH FACTOR I (IGF-I) is a growth-promoting peptide that shares many structural and functional similarities with insulin. In the circulation, IGF-I is highly protein bound, and only free IGF-I is biologically active. In vitro, physiological concentrations of IGF-I stimulate glucose transport and metabolism in muscle, and these effects are mediated via a specific IGF-Ireceptor (28), although some effects of IGF-I may be mediated by insulin/IGF-I hybrid receptors (44). The IGF-I receptor is highly homologous to the insulin receptor (17, 36). Both ligands, IGF-I and insulin, activate receptor tyrosine kinase activity, leading to a cascade of intracellular events resulting in the stimulation of glucose utilization.

The effects of IGF-I on whole body and muscle glucose metabolism have been studied extensively in animals (21, 35, 37, 50) and in humans (2, 12, 19,27, 38, 46). IGF-I augments glucose uptake, glucose oxidation, and nonoxidative glucose disposal in a dose-dependent fashion, similar to insulin (2, 12,27, 38). IGF-I also suppresses endogenous (primarily hepatic) glucose production (EGP) (2, 12, 38), although it appears to be less effective than insulin in both animals (21, 22, 35) and humans (27). In animal models of type 2 diabetes mellitus (4, 23), the ability of IGF-I to augment glucose disposal is impaired. The acute effects of IGF-I on peripheral and hepatic glucose metabolism in type 2 diabetic humans have been less well characterized. Laagerand and Keller (26) demonstrated that the decline in plasma glucose concentration in response to intravenous IGF-I was impaired in type 2 diabetic individuals,but this study did not examine whether the IGF-I resistance was present in skeletal muscle, in liver, or in both. In a previous study (7), we demonstrated that chronic subcutaneous IGF-I administration in type 2 diabetic patients inhibited EGP, reduced the fasting glucose concentration, and produced a small increase in insulin-mediated glucose disposal. In the present study, we have compared the effects of IGF-I and insulin on peripheral (muscle) and hepatic glucose metabolism by using doses of IGF-I and insulin that elicit a similar stimulation of whole body glucose disposal in healthy control subjects.
Translation:  Insulin is not the only hormone involved in glycemic control through it's action.  IGF-I does so in an "insulin like" fashion, and may even substitute for insulin on some hybrid receptors.  IGF-I seems less potent at controlling (via suppression) glucose production in the liver, but does have some effect nonetheless.  

Various diabetic meds target this glucose production (EGP) to control FBG and HbA1c and T2's have low IGF-I levels.

What all of these studies demonstrate is that the advice to limit protein for glycemic control is misguided for T2 diabetics.  Increasing protein alone resulted in marked improvement in glycemic control for each diet.  

So the outcome of the LoBAG diets increasing IGF-I is a promising one.  This increase corresponded to the doubling of protein consumption irregardless of carbohydrate and fat content of the diet.  Therefore, at least for T2's, there may be reason to reconsider the restriction of protein in their dietary treatments.  These results suggest just the opposite.

Some additional comments:

  • As relates to the whole "safe starches" thing, although the LoBAG20 diet is 20% carb, this was for diabetic men.  It is quite reasonable to presume that even the 20% group exceeded PHD 150g starch, yet still had impressive results.  Certainly the 30% group exceeded the 150g maximum and they did comparably well to the 20%ers.
  • These studies were done on weight maintaining level.  I believe if combined with mild calorie restriction and weight loss, these diets would be highly effective in managing diabetes.
The paper on N&M's site has some interesting content:
Rationale for increasing the protein content of the diet
Amino acids derived from protein are converted to glucose through gluconeogenesis. In 1915, Janney reported that 3.5 g of glucose were produced from 6.25 g of ingested meat protein [11]. Thus, theoretically and actually, for every 100 g protein ingested, 56 g of glucose can be produced. For other proteins the range of glucose produced was 50–84 g.
However, in 1924, Dr. MacLean in England gave 250 g meat, which contains ~50 g protein to a subject with type 2 diabetes whose fasting glucose concentration was ~280 mg/dl [12]. Following ingestion of the beef, the glucose concentration remained stable for the 5 hours of the study. When the subject was given 25 g glucose on a separate occasion, the amount of glucose that theoretically could have been produced from the 50 g protein in the 250 g meat, the glucose concentration increased to nearly 600 mg/dl.
With this [12] and other information [13-18], several years ago, we determined the glucose and insulin responses to 50 g of protein given in the form of lean beef to 8 normal subjects [19] and 7 subjects with type 2 diabetes [20]. When normal subjects ingested the 50 g protein, the plasma glucose concentration remained stable during the 4 hours of the study. When subjects with type 2 diabetes ingested 50 g protein, not only was the glucose stable, it actually decreased (Figure 2).
I've seen, too many times to count, something about how LC'ers should keep protein low because excesses get turned to glucose and mess with your carb/insulin metabolism.  The above is counter to that, as are the results of G&N (or N&G depending on the paper) with their LoBAG diets.  I think the graphic below speaks volumes:
Net 24-hour integrated glucose (left) and insulin area responses (right) to ingestion of a 15% protein (red bar) or 30% protein (black bar) diet in 12 subjects with type 2 diabetes.

That's pretty impressive, the 18% increase in insulin resulted in a 38% decrease in 24-hour total glucose exposure.  I believe the attempts to lower insulin through diet in diabetics because they're hyperinsulinemic in the basal state are woefully misguided.  You WANT that postprandial insulin spike that you're probably lacking.  

Is IGF-1 becoming the latest peptide to demonize?  Seems so.


Unknown said…
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Galina L. said…
As I understand the standard LC advice, it is not a protein restriction, but just eating your norm, while limiting carbs and not restricting fats. I am afraid different sources may see the norm differently. Since I am not somebody who are capable of keeping diligent record of my food, I didn't try to find out the perfect number. However, it feels like my body knows it already. From my experiences , I can tell it can be difficult to overeat or seriously increase protein consumption without practicing some grazing. Contrary to a popular LC opinion, increasing fat for me is a piece of cake. Carbohydrates even easier. There is some build-in brake in protein consumption, that can be override by culinary tricks, but it feels like it is better to obey. May be not everybody is the same in that regard. Sorry, I know it sounds very unscientific.
There is also some information on Wiki, according to which it is better to practice moderation in things that promote IGF-1. For example "IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death." There is also something about accelerated aging.
Sue said…
Protein restriction is recommended by a lot of posters on different LC/paleo forums when someone is diabetic or having issues with high blood sugar.
CarbSane said…
@Galina: As Sue says, PR is very commonly recommended for LC'ers who are not in ketosis, not losing weight or still having BG issues despite going LC. For the latter I tend to think those are the folks who would do better on HCHPLF diets.

I hear a lot in LC circles about diets stimulating growth hormone, GH. IGF-1 is a similar. Context is needed. None of those things you listed are bad things. IGF-1 declines with aging. So if it accelerates aging I'm interested in a plausible mechanism.
I thinking about what you wrote in the glycemia post about how insulin locks fat into cells, which is exactly what NEFA "deranged" diabetics want - so it struck me when I was reading this post that protein would be fabulous for them b/c it doesn't send blood sugar thru the roof, but at the same time it induces a big postprandial insulin response. Talk about a great metabolic deal! Eating the protein doesn't spike blood sugar but it does bring on a surge in insulin & all the benefits that go with: locking fat away so harmful NEFAs are kept out of circulation + increase in satiety + it's hard to overeat protein that's not prepared in too "food reward'y" a way so it also functions as a built-in caloric restriction. Maybe protein is a diet "wonderfood" after all?
MM said…
Taubes had a section in GCBC about how high levels of IGF lead to cancer. Of course his mechanism was
high carb -> high insulin -> high IGF

This is probably way too simplistic. But I know cancer freaks people (including me) out so if someone says high IGF-1 leads to cancer, they're going to try to lower it. I thought he made a lot of assumptions and He didn't distinguish between different types of IGF, but lumped them all together.

"The role of IGF in cancer appears to be fundamental, albeit still controversial." -GCBC

What does that mean?? If it is fundamental how could it also be controversial? Whatever.
MM said…
Oops, didn't mean to capitalize "He" as if he were a god, although a lot of people might disagree with me on that. :)
OnePointFive said…
Two commonly given reasons for people with DM to avoid high protein diets.
First from the LC/HF believers who suggest that the protein will be converted to glucose, raise blood glucose levels and stop ketosis.
Second from conventional medicine. The waste products from a high protein diet are thought to place too much stress on already damaged kidneys.
Many people with T2 have CKD before they are diagnosed. (one US survey found that out of 8188 sujects, 299 had undiagnosed DM and 41% of these had CKD, 17% of those with prediabetes also had it)

Bernstein favours high protein

"Non-diabetics who eat a lot of protein don't get diabetic kidney disease. Diabetics with normalized blood sugars don't get diabetic kidney disease. High levels of dietary protein do not cause kidney disease in diabetics or anyone else. There is no higher incidence of kidney disease in the cattle-growing states of the United States, where many people eat steak more than once a day, than there is in the states where beef is more expensive and consumed to a much lesser degree."
Don't know how true this is, Texas has a high number of people with end stage CKD, but there are a lot of other social/economic factors that makes me think thatmany of those developing it may not be able to afford lots of prime steak.
Galina L. said…
Sure, content is everything.
I may not read all what is on LC blogs, I remember limiting protein advice for the purpose of a weight loss in the Bernstein's book, and the short fat fast in Atkins.
The chapter in the GCBC about cancer and other modern deceases left me with the impression that people on traditional diets have much slimmer chance to get it. I think traditional Russian diet doesn't provide a cancer protection. Most of people in my family from precious generations died of cancer, even though they never eat a fast food or had a diabetes or were obese. My father died at 51 of a heart attack. He was not even overweight. Grandfather who was thin all his life died at 72 of a liver cancer. They sure consumed a lot of bread and cereals, protein at every meal. That is why all that talk about super dangerous processed food lives we unconvinced. Home cooking is better but not an insurance of perfect health. I am doing what I can by following a paleo diet and practicing IF.
Lerner said…
When I began recently to again read weightlifting type discussions, I was struck at how signaling molecules that are considered very valuable, like mTOR, are the same as those considered very bad in oncology. E.g., temsorilimus is an mTOR inhibitor. The situation with AKT would be similar.

On a CRON group yaers ago, arachidonic acid was considered to be like satan. But I looked around and saw AA capsules being sold on a weightlifting site.

If some LCers demonize IGF-1, I don't think the weightlifters and Crossfitting LCers will take very kindly to that.

Btw, as an aside I'm surprised that the name Udo Erasmus doesn't seem to have ever been mentioned here. He was famous for his book, "Good Fats, Bad Fats". Sound somehow familiar? It's not like Gary what's-his-name came up with that from scratch :)
Galina L. said…
Lerner, I know, I mast start weight-lifting better sooner than later.
I am not afraid of eating protein, or raising IGF-1, or foods with arachidonic acid . I have in my possession the old Protein Power book, back then Dr. Eades was very hard on that particular substance. Nowadays it is not like a Satan for him anymore, probably others got more relax as well.
Jeff Consiglio said…
So higher IGF-1 doesn't increase cancer risk?
Jeff Consiglio said…
Also...I'm no shill for the vegan movement, but what do you make of the fact that some well known vegan doctors appear to flat-out cure type-2 diabetes with very high carb diets?

Like these folks...

Makes me think macro-ratios are kind of a red-herring for the most part. Two totally "opposite" diets seem to work well for diabetes...LC and well designed vegetarianism diets.

But the common denominator between both is real food and low intake of REFINED foods.

And a "plant based diet" is much more affordable for those poor folks in Texas (And elsewhere) than an LC diet.

Good gosh...did I just use the phrase "plant based diet" like all those militant vegans? I swear I'm not of them! I'm a recovering LC'er who is trying to figure out if high carb intake is ok for most people or not.
@ Galina & @Lerner - I lift weights regularly, 3x/week religiously (whole body) and when I tried the high-fat, low-protein route I felt awful. I actually de-conditioned, even though I was working out the same amount etc, and I actually got weaker. Now I don't go nuts on the protein, but my body (and signalling molecules apparently) seem to do better w/generous amounts of animal proteins. Also, I remember reading on a somewhat "fringe" site, this guy Brian Peskin, that AA might actually be beneficial (I wish I could remember why specifically). it caught my attention b/c it so went against the LC & Paleo dogma.
CarbSane said…
Hi Jeff,

More and more I keep thinking that LC does not cure diabetes unless someone loses a ton of weight, keeps it off, and is then able to transition to a higher carb diet so they actually use their pancreas. Long term low carbers, most who weren't diabetic to begin with, are constantly talking about how high their BG's spike if they have any carb. That can't be good!

Ya know, a lot of what I've been reading this past few weeks has me almost ready to try Fuhrman's diet (I have one of his books).

I have never bought into this notion that carbs are inherently harmful. Indeed I think that notion is utterly ridiculous and without basis.

When I first did LC I took Atkins' claim of peeing away massive amounts of calories through ketones on faith. How this has evolved into this demonization of insulin and starch and even natural frucose is beyond me. I just knew I could lose weight restricting carbs. I really feel -- especially this past year where other prominent voices are challenging this more publicly and loudly -- like I'm in some sort of bizarro world these days where some still believe that carbs are bad.

Indeed I disagree with the Jaminets on one basis of PHD, that being that fats burn cleanly and carbs don't. Seems more the other way around to me if anything.

Hyperglycemia seems to be a condition of nutritional excess in most cases.

As to IGF & cancer, well, I can't say either way, however I think we have to be very careful with this. Cancer cells are human tissue cells that have lost some of their signaling that tells them they are part of an organism. But they still retain many receptors and such of the cells they came from.

Here's a quick hit on IGF-1 deficiency and aging: IGF-1 & Brain Aging "Although research in this area is still evolving, our results
suggest that decreases in growth hormone and IGF-1 with age have both beneficial and deleterious effects."

A balancing act?
Galina L. said…
Evelin, do you see it as a some form of contradiction, that fasting, especially with exercise in a fasted state, raises both growth hormone level and a fasting BS? I didn't have higher than 100 FBS on VLC alone before practicing IF. I still continue IF because I think it has numerous health benefits and may be cancer-preventive. I am choosing higher growth hormone levels against lower FBS levels for now.
Jeff Consiglio said…
Fuhrman's diet approach does seem to be the most reasonable of the "plant based diet" advocates in that he isn't fat-phobic to the point of excluding nuts, avocados, etc.

Seeing him and other vegan doctors reversing diabetes with HIGH carb diets was probably my first "ah-ha moment" that carbs in general are not pathogenic generators of diabetes.

That said, I still am wary of going real high in carbs. High triglycerides seems to be a very common outcome of high-carb diets....even those based upon whole plant foods.

For instance, in Denise Monger's review of the movie Forks over Knives, she points out that although Dr. Esselstyn "heart disease reversal" protocol did achieve good results in certain areas, but nonetheless resulted in real freakin high TRIGS.

Also, Scott Gardner of the "A to Z" Diet Trial says that the whole-foods based Ornish diet often resulted in bad trig-levels. I emailed him to ask if it was possible the women on the high-carb Ornish diet were eating a bunch of crap carbs which may have accounted for such results, but he was very adamant that the women had been instructed to get their carbs from "good carb" whole food sources.

So again, any diet which seems to result in high trigs seems less than ideal.

I must confess that at this time, based on my current understanding, I sort of straddle the fence between LC and higher carb paradigms. Sort of Zone diet-ish I guess.

I prefer a higher carb diet because I think it taste better and is much cheaper way to feed a family, but it seems that so many things need "to be just right" for real high carb diets to work.

- Vitamin D, magnesium, chromium, vanadium, etc all need to be ingested in optimum amounts

- Sleep status needs to be good (Sleep deprivation causes insulin resistance, and we are a chronically sleep deprived culture)

- Our culture's sedentary habits are not conducive to good insulin sensitivity in skeletal muscle

- Caffeine abuse may also screw with carbohydrate metabolism

- Aging decreases glucose handling ability, and we are an aging society as baby-boomers enter the "golden" years.

- etc, etc

Seems there is a conflagration of negative variables in our culture which makes it real hard for many (Or most?) to handle loads of carbs.

But I'm also no fan of keto-diets.

Seems the truth may lie in the middle somewhere.

Just some random thoughts this morning. Thanks for letting me rant a bit.
Galina L. said…
@ Jeff Consiglio,
Probably, the diet with 100 - 150 gram of carbs will fit your criteria better.Like that -
I found out that eliminating of snacks and bottled drinks makes feeding family much more affordable. Often people spend ridiculous amount of money by buying special snack food and drinks. Each time when my child (he grown up now) told me he was hungry, he got normal full meal, which kept him full longer.Also, we don't eat breakfast cereals.
CarbSane said…
@Jeff: Have you seen my triglyceride series? First of three parts (with links to progress) here.

Bottom line, I don't think that triglycerides are in their own right atherosclerotic -- rather high levels in certain contexts indicate IR and overnutrition that leads to lipo- gluco- and glucolipotoxicity.
CarbSane said…
@Galina: No I don't see an issue. I do caution that a lot of VLC'ers tend to rationalize the creeping up of FBG. Probably not an issue, but it does shine a light on interpreting any fasting biomarkers compared to the bulk "normal" population when consuming a radically different diet. Is it even relevant? I would say "seems not" in most cases ... at the very least one can't pick and choose and say "this is amazing" for result A while trying to explain away potentially unfavorable result B.
Sonnenschein said…
Thank you very much for providing the link to this post under your post from January 4, 2012! I am still searching for a conclusive answer for the IGF-1/cancer connection...It seems to be well established that taller women (over 5"5'; that is not too impressive) are more prone to cancer. Because of the increased height more IGF-1 seems to be circulating in tall womens`bodies (and they are more prone to multiple pregnancies as well for the same reason). On the other hand, as it is mentioned in one comment here, exercise (strength training) increases IGF-1, too, but it is said to be cancer-protective. Vegans seem to be less likely to develop cnacer because their diet is (relatively) low in protein. I am still trying to figure out what it means for cancer protection and in how much protein intake makes a difference! Is the IGF-1/protein/cancer connection really established or is this just a hypothesis?
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