Marks Daily Apple
Serving up health and fitness insights (daily, of course) with a side of irreverence.
24 Aug

Does a High-Fat Diet Cause Type 2 Diabetes?

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.

The Gist

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?

Mouse Tales

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…

The Diet of Doom

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.

When “High Fat” Isn’t High Fat

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.

Lessons For Non-Rodents

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.

You want comments? We got comments:

Imagine you’re George Clooney. Take a moment to admire your grooming and wit. Okay, now imagine someone walks up to you and asks, “What’s your name?” You say, “I’m George Clooney.” Or maybe you say, “I’m the Clooninator!” You don’t say “I’m George of George Clooney Sells Movies Blog” and you certainly don’t say, “I’m Clooney Weight Loss Plan”. So while spam is technically meat, it ain’t anywhere near Primal. Please nickname yourself something your friends would call you.

  1. I like cheese.

    Monte wrote on August 25th, 2011
    • So do mice :)

      Grok wrote on August 27th, 2011
  2. hey what does a vegetarian do, can cut out the dairy and the carbs but what do i replace it with. Meat and poultry in India is always of questionable variety, have been researching on this deist for over a week now and am completely confused. We in india have had lentils all kinds, kidney beans, whole grains and yes vegetables and fruits too, and now people are using unrefined vegetable oils, coconut, peanut, sesame seed, sunflower, mustard oil and organic oils are available easily now.I try to eat what is locally available, so peanut oil and sesame are what is used most at home. Paleo inspite its benefits is tough to follow here. So if anyones got a solution do reply.

    harman wrote on August 26th, 2011
  3. Fabulous, Mark and Denise. I emailed my query from the UK having read an article in the UK press. The above analysis is so accessible and comprehensive it has cleared up my concerns. Mark’s original post was also excellent and appreciated.

    Paul wrote on August 26th, 2011
  4. Just call me a black-six. After eight mths on Archevore, I am gaining weight. Went from 139 to 143.5 I’ve lost 5 inches at the waist and elsewhere doing 75% fat, 17% protein and 8% carb. I’ve played with different percentages. Getting very discouraged. I must be broken. Family now will not go Paleo as I am gaining fat with all that fat (grass fed whole cream, butter, bacon). 5 Primal workouts (beginner) has given me definition though. Could weight gain be all muscle gain? I’m in ketosis for part of the day most days. Very confused and can no longer suggest Paleo to anyone. Too embarassed it’s not working for me after 8 mths.

    Sandra Brigham wrote on August 26th, 2011
    • Sandra-Sounds frustrating! Have you had your body fat percentage tested? How are your clothes fitting? Weighing yourself on a scale only tells you how much your whole body weighs and some people can fluctuate anywhere from 5-7 lbs throughout the month (especially women who menstruate). If youre losing inches still and looking and feeling stronger and fitter you’re probably still making progress. Just food for thought–I know any extra lbs on the scale can be frustrating, so I’m not discounting how you’re feeling.

      Robinowitz wrote on August 26th, 2011
      • I agree with Robinowitz. if you’re losing inches and are in ketosis, you’re most likely losing fat. Maybe you should be keeping track of your fat % instead of your weight. But it also sounds like you’re eating too much fat–maybe you should increase your lean protein.

        Sue Minger wrote on August 26th, 2011
  5. Timely post. I was just reading an article by Drs Oz and Roisen where they claimed that any meat, processed or not, red or not, makes you gain weight. lol.
    CW strikes again.

    Lisa wrote on August 26th, 2011
  6. Your information has helped me understand and change my lifestyle. Thank you so much.

    Joshua Tenner wrote on August 26th, 2011
  7. If raw garlic is eaten everyday it not only increases efficiency of insulin but also regularizes the digestive system. In metabolic disorders like heart diseases, obesity, raw garlic can prove to be a boon. It is even helpful in obesity.

    soulmate wrote on August 27th, 2011
  8. Thank you for another well-written article demystifying nutrition research. You are the Rachel Carson of mouse studies.

    Another Halocene Human wrote on August 27th, 2011
  9. These comments bashing the study are making me cry. If you actually went to the abstract and read it you would see that the title is “Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport” and has to do with molecular mechanisms that prevent a body from regulating its blood glucose via insulin secretion because of a breakdown in blood glucose monitoring. The closest the authors get to attacking a high-fat diet is by saying “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.” So their claim is: obese mice + high fat diet or human cells with high levels of free fatty acids > interference with the glucose level sensing.

    And Denise seems mainly to be attacking the media reporting of this finding (maybe the university press release is also to blame, I haven’t seen it).

    Morten wrote on August 29th, 2011
  10. I had my sunday roast and must have eaten an A4 paper size of pork crackling! Not sure that would be great for me or the mice

    Stuart wrote on August 30th, 2011
  11. This really, really makes you think! Nice read thanks for the advice!

    Michael wrote on September 5th, 2011
  12. You are truly a excellent webmaster. The site loading pace is incredible. It sort of feels that you are doing any unique trick. Moreover, The contents are masterpiece. you’ve done a fantastic activity in this matter!

  13. Its relevant to remind about type II diabetes as it is one of the major lifestyle diseases worldwide. I like your writing style too.

    Sarinkumar wrote on January 28th, 2012
  14. LOL! :-)
    Only goes to show: not all studies are created the same…


    Mark wrote on February 5th, 2012
  15. I was wondering what the differences between “brown fat” and “white fat” are other than “one is good and the other bad”. Also, how does that relate to eating primally?


    David wrote on February 26th, 2012
  16. I was vegetarian most of my life but then realized the reason my parents have ill was because of our diet. I’ve changed my ways but they haven’t. I’m constantly trying to re-educate people about health, fat, meat etc. But it’s difficult to un-brain wash someone who’s been fed conventional nonsense for so many years.

    April wrote on May 31st, 2012
  17. Minger has chubby arms and a bloated face. At least in the one video I can find.

    Vitalis and Wolfe have man boobs. Only in america can diet “gurus” be flabby. Fallon is also rather overweight.

    Gyrate wrote on June 6th, 2012
  18. Didn’t Gary Taubes cover all this in his book back in 2011, and why is it conventional science is always having to play catch-up?

    Wenchypoo wrote on August 19th, 2012
    • Money talks, truth walks.

      Walter wrote on July 23rd, 2016

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