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Does a High-Fat Diet Cause Type 2 Diabetes?
Posted By Guest On August 24, 2011 @ 8:11 am In Diet,Fat,Guest Posts,Worker Bees' Weekly Bites | 185 Comments
This is a special guest post from Denise Minger  (thank you, Denise!). When fear-inducing news headlines hit the papers (and airwaves and iPads…) - High-Fat Diet Linked to Breast Cancer , Eating Whole Grains Will Help You Live Longer , Fish Oil Linked to Prostate Cancer  – she’s the person to go to for an honest and entertaining critique of the research. In the last week I’ve received an untold number of emails from inquiring Mark’s Daily Apple readers about this latest health news “bombshell”. So, naturally, Denise…
It’s that time again. Your inbox is filling up with emails from your low-fat friends. Your mom left four voicemails ordering you to throw away your bacon now (and clean your room while you’re at it). Your diet-savvy coworker left a Yahoo! News article on your desk, weighted in place with a muffin. This just in: High-fat diets cause diabetes—and researchers have proof, doggonit!
At least, that’s what you’d assume from reading headlines like “How Fatty Food Triggers Diabetes ” and “Study Reveals How High-Fat Diet Causes Type-2 Diabetes .” It might come as a surprise, then, that this study isn’t really about food at all – it’s about the effect of obesity on gene expression. In mice, no less. This is a classic example of the media spinning an article to help it grab attention, because most people wouldn’t give a flying Fudgsicle if they knew what it was really about.
If you haven’t browsed it already, you can check out the study’s abstract here , officially titled “Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport.” (The full text is securely tucked behind a $32 pay-wall.) Between the jargony bits and focus on mice, it might be tempting to slide this study into the Slush Pile of Unworthiness – but it’s actually pretty interesting. Here’s the lowdown.
Basically, the researchers fed a bunch of mice a high-fat diet designed to make them obese, which consequently raised the levels of free fatty acids (FFAs) in their blood. Although we’ve known for a while that FFAs interfere with glucose metabolism , this study uncovered a new piece of the obesity-diabetes puzzle.
In order to gauge your blood sugar and decide how much insulin to secrete, the beta cells in your pancreas have little glucose-sensors hanging out on their surface. Those sensors are maintained by an enzyme called GnT-4a glycosyltransferase (can we call it George for short?). As this study discovered, high levels of FFAs interfere with two of the proteins necessary for producing GnT-4a (er, George), leaving beta cells unable to figure out how much glucose is in your blood. When that happens, those cells can’t release the right amount of insulin to keep your blood sugar in check. Wham, bam, diabetes.
That’s how it works in mice, at least. To clarify the pathway in non-mice, the researchers grabbed some cell samples from humans and cultured them with palmitic acid, a fat sometimes used to simulate the effect of free fatty acids. Lo and behold, the fat interfered with the same two proteins that got goofed up in obese, FFA-ridden mice.
So what does this mean for you and me? Are high-fat diets going to make us obese, fill our blood with free fatty acids, and push us to the brink of diabetes? Should you listen to your mother and feed the bacon to the trashcan?
Before we talk diet, let’s talk rodents. In this study, researchers used a popular, inbred mouse strain affectionately referred to as C57BL/6J. Despite their cuteness, the only one who can get away with that kind of name is R2-D2 , so let’s use some lab slang and call these mice “black sixes.”
Black-six mice are beloved among researchers, and for good reason. Along with being easy to breed, they’re uber-susceptible to obesity, high blood sugar, insulin resistance, leptin resistance, and all that other fun stuff plaguing modern humans. They’re also genetically predisposed to getting type 2 diabetes , making them particularly useful for the study at hand. And perhaps most importantly, all it takes to send them into a downward spiral of disease is some extra dietary fat. It’s like their kryptonite. Which brings us to…
Although this paper doesn’t give us a detailed description of what the mice were eating, it does reference the product numbers for their formula diets – so we can sleuth out the scoop straight from the manufacturer. Here’s a PDF  of what the high-fat diet contained.
Ouch! Where to start?
It’s hard to say which part of this diet sucks the most. The 175 grams of pure sugar? The splash of high omega-6 soybean oil? The suspiciously disease-promoting casein? The main calorie source as hydrogenated coconut oil? The fact that a quarter of the “high fat” diet consists of refined carbohydrates? The complete absence of anything resembling food?
Indeed, even if you believe high-fat diets can be healthy, it’s hard to find any redeeming qualities in this one. For starters, the primary fat is a hydrogenated oil, which doesn’t belong in the body of any living organism, whether two-legged or four. As far as obesity goes, rodents have dramatically different responses to the types of fat  they eat—with rats, for instance, getting tubby from lard but slimming down with marine oils. And hydrogenation aside, some mice strains gain different amounts of weight when their high-fat diet consists of unsaturated fats rather than saturated fat . So can we extrapolate the effects of this diet to high-fat diets in general? No way. Not for mice, and certainly not for humans.
And let’s remember that we’re dealing with a particularly fat-sensitive creature here. Although most mice turn into metabolically deranged messes when they eat too much fat (which makes sense, considering their natural diet is mostly grains), not all of them succumb to the same fate. Black sixes are one of the unlucky types that get rapidly obese on high-fat diets, but some other strains remain lean on the same cuisine  and are far more resistant to diabetes.
This brings us to a major problem with rodent studies in general. As this paper explains , there’s literally no standard for what “high fat” means, and rodent researchers have thrown everything from 20%-fat diets to 60%-fat diets under the same “high fat” umbrella. Usually those diets contain a hefty portion of sugar, too. Not only does this make the rodent literature hard to navigate, but it also gives an incomplete picture of the effect of diet on obesity – because something special happens when mice get a truly high-fat menu.
Case in point: this study  on ketogenic diets in rodents. As we might expect, researchers found that mice eating a moderately high-fat diet became obese, leptin resistant, and insulin resistant – but when they dropped the sugar and increased fat to around 78% of calories, the mice “lost all excess body weight, improved glucose tolerance, and increased energy expenditure” without even reducing calorie intake. In other words, a high-fat diet undid the damage of a moderately high-fat diet.
So what can we learn from all this? Does this study – or rodent research in general – have much relevance for those of us who lack tails, fuzzy ears, and adorable pink noses?
The answer is an equivocal “yes and no.” One reason mice are a favored lab animal is that they share so many genes with humans – 15,187 of them , to be exact. Heck, it was only 90 million years ago that we split from a common ancestor. I’ve met Okinawans older than that!
But that doesn’t mean gene expression always works the same, or that the causes and progression of disease are identical across species. Even when high-fat diets catapult mice towards diabetes, for instance, their markers for disease don’t always resemble ours. Unlike metabolically damaged humans, who tend to have rock-bottom HDL cholesterol and rising triglycerides, some mice experience higher HDL and unchanged (or reduced!) triglycerides when eating the diets that make them diseased  (PDF). This points to some clear differences between how humans and mice experience diet-induced metabolic problems.
And that includes the diabetes pathway in this study. We have enough high-fat, low-carb research at this point to know that such a diet won’t cause an unstoppable snowball towards obesity in humans like it does in some mice. If anything, its impact on diabetes is beneficial . So even if weight gain (and the associated increase in free fatty acids) sets us down Diabetes Avenue, a high-fat diet isn’t necessarily the instigator in humans. Especially not a high-fat diet that’s based on real food instead of hydrogenated coconut oil.
Bottom line: Mice are actually useful little suckers when it comes to studying genes and biochemical processes – but only when we clearly understand the limitations. Disney-themed costume parties aside, you are not, and never will be, a mouse. Nor will a mouse ever be you. So when it comes to studies like this one, white out the headline, read with an open but critical mind, and then invite Mother Dearest over for a bacon brunch.
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 High-Fat Diet Linked to Breast Cancer: http://www.marksdailyapple.com/high-fat-diet-linked-to-breast-cancer/
 Eating Whole Grains Will Help You Live Longer: http://www.marksdailyapple.com/will-eating-whole-grain-fiber-help-you-live-longer/
 Fish Oil Linked to Prostate Cancer: http://www.marksdailyapple.com/fish-oil-prostate-cancer/
 How Fatty Food Triggers Diabetes: http://www.dailymail.co.uk/health/article-2025953/Fatty-food-triggers-diabetes-Scientists-believe-discovery-paves-way-Type-2-cure.html
 Study Reveals How High-Fat Diet Causes Type-2 Diabetes: http://www.netdoctor.co.uk/interactive/news/theme_news_detail.php?id=800699576&tab_id=116
 the study’s abstract here: http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2414.html
 interfere with glucose metabolism: http://www.ncbi.nlm.nih.gov/pubmed/12784183
 R2-D2: http://www.starwars.com/databank/droid/r2d2/
 genetically predisposed to getting type 2 diabetes: http://diabetes.diabetesjournals.org/content/37/9/1163
 Here’s a PDF: http://www.researchdiets.com/pdf/Data%20Sheets/D12331.pdf
 dramatically different responses to the types of fat: http://www.nature.com/oby/journal/v15/n4/fig_tab/oby2007608f1.html#figure-title
 unsaturated fats rather than saturated fat: http://www.nature.com/oby/journal/v15/n8/full/oby2007238a.html
 remain lean on the same cuisine: http://www.ncbi.nlm.nih.gov/pubmed/1621856
 As this paper explains: http://www.nature.com/oby/journal/v15/n4/full/oby2007608a.html
 this study: http://ajpendo.physiology.org/content/292/6/E1724.full
 15,187 of them: http://www.miller-mccune.com/blogs/today-in-mice/the-tangled-tale-of-black-6-unraveled-3669/
 when eating the diets that make them diseased: http://www.ajcn.org/content/62/2/458S.full.pdf
 its impact on diabetes is beneficial: http://www.annals.org/content/142/6/403.short
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