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.

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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.  

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Original publish date  Sept. 2, 2010

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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.

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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.