Barry Groves -has he missed something?

borofergie

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Type of diabetes
Type 2
Treatment type
Diet only
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Racism, Sexism, Homophobia
+1 to all pianomans questions.

I know that it's dangerous to extrapolate from anecdotal evidence, but speaking as an overweight T2 diabetic, I spent most of last 20 years following a "low fat diet", in a vain attempt to control my weight. I wonder how many of us were really exposed to "too much" dietry fat pre-diagnosis? For me, and lots of others, if you were overweight and cared about losing it, then you tried to avoid fatty foods wherever possible (but stayed fat anyway).

With the proliferation of "low-fat" products in the shops and the "low-fat" indocrination that I've suffered all my adult life, I find it difficult to get enough fat in my low-carb diet, and I'm eating a lot more now than I ever did before I was diagnosed.
 

RussG

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401
Thanks Phoenix.

It is accurate to point out that the plural of anecdote is not data and thus it is dangerous to extrapolate. As for Pianoman's questions - these don't appear to be the basis of the trial. They were attempting to establish a biological pathway for T2 from obesity, at this stage irrespective of how obesity was achieved. AFAIK they were not looking at how one becomes fat, but suffice to say that a high fat diet did make the mice obese. No doubt there are other ways of achieving the same end point but they used a high fat diet here. Ergo it is accurate to say that a high fat diet in this experiment caused mice to become diabetic (as well as the other conclusions about the glucose sensing mechansim). That doesn't say that it is the only way to become diabetic.

FYI: here are the dietary breakdowns:

Mice were provided either a standard diet (16.4% protein, 73.1% carbohydrates and 10.5% fat with 4.07 kcal g−1; D12329, Research Diets) or a high-fat diet (16.4% protein, 25.5% carbohydrates and 58.0% fat with 5.56 kcal g−1; D12331, Research Diets).
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2414.html#/methods

Unless I've read it wrong, the point seems to be that becoming obese interrupts the mechansim for glucose / insulin homeostasis, i.e. the counter regulatory effect of glucose and insulin production / reception.

Given that not everyone who is obese becomes diabetic, and not everyone with (T2) diabetes is obese, this sounds like important research. I think your problem, guys, is with the newspaper report, not the science. It's not all about bashing low carb or promoting low fat, people.
 

pianoman

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332
RussG said:
... the point seems to be that becoming obese interrupts the mechanism for glucose / insulin homeostasis, i.e. the counter regulatory effect of glucose and insulin production / reception ...
And there could also be a chicken/egg situation where this same disrupted homeostasis leads to excess fat storage... a vicious cycle.

The breakdown by macronutrients does not answer my question about the types of fats.

Science is supposed to be about generating questions.
 

RussG

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401
pianoman said:
RussG said:
... the point seems to be that becoming obese interrupts the mechanism for glucose / insulin homeostasis, i.e. the counter regulatory effect of glucose and insulin production / reception ...
And there could also be a chicken/egg situation where this same disrupted homeostasis leads to excess fat storage... a vicious cycle.

The breakdown by macronutrients does not answer my question about the types of fats.

Science is supposed to be about generating questions.

[I'm not a scientist, and as Phoenix says the article is hard to follow but...]

Yes, I could well see a destabilising vicious circle here, but that's not what has been tested. They made mice fat. These mice had an impaired glucose sensing mechanism. It would appear that the mice on a 73% carb diet didn't have this impairment, or certainly not as strongly.

I'm afraid you'd have to email the authors to ask what type of fat was given. The paper doesn't seem to specify. Someone else asked what the carb intake was, hence I provided the breakdown from the article.

As for generating questions, well yes that's a fundamental of the scientific method and is certainly what has come out of the research. The point I was making was that some of you seemed to me to be jumping to the conclusion that the science was saying *only* dietary fat intake causes diabetes. The report doesn't say that, even if the newspaper reports perhaps allow people to (erroneously) make that assumption.

Clearly high levels of FFA are correlated with high fat intakes in this experiment as that's how the scientists achieved them. That doesn't mean they are not also correlated with other things. That's the problem with correlation, there can be multiple causal routes with the same end point. I think the report is fairly clear that this improves our understanding of how and why obesity can trigger diabetes but also raises lots of questions. I'm not quite sure what your issue is here?

If you want to prove that 'pro-inflammatory vegetable oils' are worse for you than 'naturally occurring fats' you'll have to pitch something to the Medical Research Council. This research doesn't address that point. That doesn't weaken the conclusions for me.
 

pianoman

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332
As you say I may simply be reacting to the implication of the headline that "eating fat will cause Type 2"... that is perhaps not what the researchers are saying but that does seem to be the way it is being interpreted especially by those who already believe this to be an established fact.

---
Edited to add...

Mice were provided either a standard diet (16.4% protein, 73.1% carbohydrates and 10.5% fat with 4.07 kcal g−1; D12329, Research Diets) or a high-fat diet (16.4% protein, 25.5% carbohydrates and 58.0% fat with 5.56 kcal g−1; D12331, Research Diets).
Regarding the dietary breakdowns I think it important to be clear when referring to the percentage of energy from each macronutrient, that these diets were not isocaloric: with the standard diet at 4.07 kcal/gm and the high-fat at 5.56 kcal/gm... surely they deliberately overfed the high-fat mice? Which would mean changing multiple variables at the same time.

I did find more detail on these diets on-line:

Standard...
http://www.researchdiets.com/pdf/Data Sheets/D12329.pdf

and

High-Fat...
http://www.researchdiets.com/pdf/Data Sheets/D12331.pdf

To answer my own question: the fats in both cases are some Soybean Oil but mostly Hydrogenated Coconut Oil. Hydrogenation I understand, converts what is otherwise an healthy natural Fat into a Trans Fatty Acid -- in which case giving even more of this fat is a questionable practise... small wonder it led to ill-effects at the metabolic level?
 

RussG

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401
Fair enough pianoman. I think there is a major problem with scientific literacy amongst journalists. The scientists are usually fairly precise in what they say and what the conclude. Journalists, less so.
As regards the diet – I still don’t think they were in any way comparing the propensity of any diet to provoke diabetes. I guess the scientists would adhere to the excess calorie intake = obesity model and the easiest way to get excess calories is via fat, which is more calorific per gram. Hence, yes they deliberately overfed the mice to make fat mice.

I don’t think that the lack of comparable calorie content is thus an issue for this experiment. [It’s mildly interesting to note that the mice on the high carb, lower calorie diet didn’t appear to have the same results, but that’s another day].

As for the type of fat, well both diets included the same fat types, but in differing quantities but only the high intake diet mice had strong responses. I suppose to be accurate all you can say is that obesity caused by high fat intake of hydrogenated coconut oil and soybean oil interrupts the glucose / insulin homeostatic mechanism. You’d have to do further tests to see whether just eating ‘natural’ fat makes any difference.
 

pianoman

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332
You might reread the articles above... I see they mention obesity in the opening discussion and in their conclusions but the body of the article, where they discuss the actual trial, only talks about the metabolic effects of increased FFAs which they conclude is due to the diet. I'm concerned that there is some guilt by association going on here... it is not at all clear to me that they are saying obesity leads to this disordered condition, but rather they are saying the diet leads to it... and of course everyone already knows an high-fat diet causes obesity -- except that we don't already know that.

Yes both diets used the same man-made trans-fats which have been recognised as deleterious and humans are advised to minimize or eliminate their use, but the standard diet had only 40g per serving while the high-fat had over 300g per serving -- not an insignificant difference, I'd hope you agree?

I think if the headline were re-written to state that mice over-fed on a diet high in trans fats had deleterious metabolic effects we might be left with a different impression.

As above: I'd say this study raises more questions than it answers and it is premature to be drawing conclusions from it.

A particular red-flag for me is where they quote the Lead researcher Dr Jamey Marth as saying
"The identification of the molecular players in this pathway to diabetes suggests new therapeutic targets and approaches towards developing an effective preventative or perhaps curative treatment. This may be accomplished by beta cell gene therapy or by drugs that interfere with this pathway in order to maintain normal beta cell function."
Surely if the cause is diet, then why reach for a patent-able and profitable solution rather than a simple dietary intervention?
 

RussG

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401
Hi Pianoman - on a basic level, it's not premature to be drawing conclusions, provided the conclusions are justified by the data. It's a bit early for the papers to be saying that high fat diets cause diabetes, without a shadow of a doubt, but that's a journalistic problem, not a scientific one.

As far as I can tell they did also supplement some mice with directly added (i.e. not dietary) palmitic acid, an FFA, and saw a similar response but not as pronounced. The mice on the high (trans)fat diet had higher FFA levels than the mice on the high carb diet or the added FFA ones.

I'm not sure about not knowing that a high fat, hypercaloric diet causes obesity (or at least in mice) - they fed mice a high fat diet that was hypercaloric and the mice became obese. Other mice were fed a lower calorie, higher carb diet and didn't. I go back to my earlier point that there are other ways of becoming obese, but excess calories and high fat intake do seem to do it.

I agree that the intake levels differed significantly - all that suggests though is that trans fats are not directly harmful in themselves, but they are in high quantities. I don't think that's particularly novel.

A connection between diet, obesity and diabetes exists in multiple species and is the basis of an escalating human health problem. The factors responsible provoke both insulin resistance and pancreatic beta cell dysfunction but remain to be fully identified. We report a combination of molecular events in human and mouse pancreatic beta cells, induced by elevated levels of free fatty acids or by administration of a high-fat diet with associated obesity, that comprise a pathogenic pathway to diabetes. Elevated concentrations of free fatty acids caused nuclear exclusion and reduced expression of the transcription factors FOXA2 and HNF1A in beta cells. This resulted in a deficit of GnT-4a glycosyltransferase expression in beta cells that produced signs of metabolic disease, including hyperglycemia, impaired glucose tolerance, hyperinsulinemia, hepatic steatosis and diminished insulin action in muscle and adipose tissues. Protection from disease was conferred by enforced beta cell–specific GnT-4a protein glycosylation and involved the maintenance of glucose transporter expression and the preservation of glucose transport. We observed that this pathogenic process was active in human islet cells obtained from donors with type 2 diabetes; thus, illuminating a pathway to disease implicated in the diet- and obesity-associated component of type 2 diabetes mellitus.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2414.html

The experimental conclusions that I read from this are that a) they fed some mice a high (trans)fat diet and the mice became obese. b) These obese mice had high levels of FFA. c) these levels interfered with the mice's ability to regulate glucose and insulin. d) mice fed a high carb, lower calorie diet didn't have either the increased FFA or inmpaired response. e) mice with induced levels of FFA not via diet also had a similar response, but not as strongly. I think the phrase 'illuminating a pathway to disease' is clear that they are not suggesting that this is a direct causal link or the only link.

the only real claims they are making are:

Elevated concentrations of free fatty acids caused nuclear exclusion and reduced expression of the transcription factors FOXA2 and HNF1A in beta cells. This resulted in a deficit of GnT-4a glycosyltransferase expression in beta cells that produced signs of metabolic disease, including hyperglycemia, impaired glucose tolerance, hyperinsulinemia, hepatic steatosis and diminished insulin action in muscle and adipose tissues. Protection from disease was conferred by enforced beta cell–specific GnT-4a protein glycosylation and involved the maintenance of glucose transporter expression and the preservation of glucose transport

Pianoman: Surely if the cause is diet, then why reach for a patent-able and profitable solution rather than a simple dietary intervention?

I don't think they are saying the (only) cause is diet. I think the paper is fairly clear that diet plays a part, genetics play a part but other factors unknown are involved. The actual genesis of the test seems to be that they noticed mice with a defect in the GnT-4a glycosyltransferase encoded by the Mgat4a gene had a version of T2. They assumed that GnT-4a plays an important role in glucose regulation and wanted to test that.
 

pianoman

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332
Again I am seeing guilt by association -- maybe it is so insidious that others miss it, but if you re-read both your own post and the article you quoted, you can see that "high fat" diet" and "high calorie" diet appear to be one and the same... they are used interchangeably but they are not equivalent.

Yes in this trial the high-fat diet was also hypercaloric but a diet with a higher percentage of energy from fat does not have to be hypercaloric.

My diet would be described as high fat and yet I am steadily losing excess fat mass... having lost a considerable amount already.

It is still not clear to me that they are saying obesity caused these changes, rather that increased FFAs did.

Perhaps you have access to the full article? I'm not willing to pay US $32

How long did this study run for? Are we looking at a short term effect of overeating on a diet high in trans fats? How does this compare to what mice usually eat? Are they adapted to eat this much fat, of any kind? How does this compare to overfeeding humans... because not all obese humans are overfeeding otherwise they would just keep getting bigger and bigger and bigger.

I agree totally that the media have misrepresented the basic findings of this study. Which is why I first posted in this thread as others seemed to be running with the headlines.

RussG said:
I agree that the intake levels differed significantly - all that suggests though is that trans fats are not directly harmful in themselves, but they are in high quantities. I don't think that's particularly novel.
Not novel at all, so why do they continue to use trans fats in these trials knowing that they are harmful?. Not novel but not insignificant either... especially as this trial seems to pivot on FFAs which they suggest are due to a diet high in a type of fats for which many Doctors have called for an outright ban on human consumption. And although the detail breakdown of these diets was freely available for those of us savvy enough to dig down and use the internet, there is no mention of trans fats anywhere in the other papers or articles. That for me places a huge question mark over the integrity of this research.
 

LesleyMac

Newbie
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2
I agree with borofergie....we should all read Jenny Ruhl, who is herself diabetic. SHE KNOWS WHAT WE ARE GOING THROUGH!
She also lets us know very early in the book....
WE DON'T HAVE DIABETES BECAUSE WE ARE FAT...WE ARE FAT BECAUSE WE HAVE DIABETES..YEA!!!!
Low Carb is great for me, with a sluggish metabolism, after 8 weeks, I have lost 7 lbs without any effort apart from not eating potatoes, rice, pasta, bread and cakes. You just can't help but loose weight! AND...I don't feel awful hunger pangs.
Low carbs.....Worth a try? Definitely!
borofergie said: Jenny Ruhl has some interesting things to say about this study (and the legions of other rodent based revelations on diabetes). Picking up on the title of a paper that you haven't read, because you think you agree with its conclusions (which you haven't read), is the worst kind of confirmation bias.
borofergie
 

WhitbyJet

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1,597
LesleyMac, I agree, totally. I found Jenny Ruhl enlightening, however I didnt get into low carbing until just a few years ago and even then I did in very gradually unlike others I know who were brave enough to go cold turkey on the carbs.
I really do enjoy the low carb lifestyle now, I always find myself something suitable to eat when dining out, at home I cook and bake and am constantly trying out new recipes. I just had to think differently thats all, I still eat cakes and muffins, just that they are low carb and home made without any of the artificial ingredients.
I dont miss the carby stuff any more, especially since I have discovered some excellent low carb bread recipes.
Fried bread, fried eggs, bacon, mushrooms, tomato and a mug of tea with cream for breakfast YAY :D