Researchers discover how a high-fat diet causes type 2 diabetes










In addition, variations in susceptibility to type 2 diabetes may result from inherited differences in the gene for GnT-4a that may ultimately affect its level or activity. These findings could have important clinical implications because reduced GnT-4a expression has been observed by other researchers in tissue samples from humans with diabetes. “If you could somehow stimulate production of this enzyme, you might be able to render animals, and perhaps humans, resistant to high-fat diet-induced diabetes,” said Marth.


“If our findings can be applied to humans, they should give us important insights into how type 2 diabetes may be prevented and treated,” he said.

While a deficiency of insulin can cause diabetes, too much insulin can also be harmful, and has been found to contribute to the pathogenesis of cancer, cardiovascular disease, ovarian diseases, and Alzheimer’s disease. “It may be that suppressing insulin production to some degree could be beneficial in such disorders, and that could theoretically be achieved by inhibiting the GnT-4a glycosyltransferase,” Marth said.

Source: Howard Hughes Medical Institute


17 thoughts on “Researchers discover how a high-fat diet causes type 2 diabetes

  1. gary taubes

    At the risk of sounding faddist, if, as the last paragraph says, ” too much insulin can also be harmful, and has been found to contribute to the pathogenesis of cancer, cardiovascular disease, ovarian diseases, and Alzheimer’s disease,” and if as Marth says, “It may be that suppressing insulin production to some degree could be beneficial in such disorders,” than why don’t they just tell people to eat less carbohydrates? That suppresses insulin. It doesn’t enrich the pharmaceutical industry, but it certainly shuts down insulin. It does it even better than simply eating less calories. See, for instance, the classic paper on the subject: Grey N, Kipnis DM. Effect of diet composition on the hyperinsulinemia of obesity.
    N Engl J Med. 1971 Oct 7;285(15):827-31.

  2. anonymous

    Incredible considering that there is a higher rate of diabetes type 2 in asian people who do not eat a western style diet. They do however indulge in sugars (which incidentally is also abundant in western diets)

  3. I think they contradict themselves somewhat: in Para 4 they say that the insulin producing cells fail, then later in the same sentence say that later those same cells pump out too much insulin (the latter is true)… the point is, if the cells had failed, they would not be pumping out too much insulin and in fact would be more likely to produce T1 diabetes instead. As a T2 diabetic, I know my insulin producing cells are doing just fine at the moment (with the help of medication to keep them controlled) but that in future if I dont control my diet and weight, they will fail…

    IMO Type2 diabetes is more about *being* fat than consuming fat and sugars, and I wish I had listened to my GP who knew this, over 30 years ago.

  4. Alex

    AFAIK this doesn’t really make sense. Type 2 Diabetes is not caused by a lack of insulin. Type 2 Diabetes patients usually have relatively high insulin levels. The high blood sugar levels result from a insulin insensitivity of cells. The insensitivity is a result of chronically elevated insulin levels.

    If this chronic insulin elevation (e.g. through overeating foods with a high glycemic load or just “being fat” as fat cells seem to stimulate the pancreas to produce insulin) persists for a long time, it might cause the pancreatic cells to “burn out” which will “turn” a type 2 diabetic into a type 1.

    Simply the fact of eating something causes the organism to produce insulin (some studies show, that the insulin response a defined amount of sugar is higher, if the sugar solution is eaten compared to an IV injection). Sure the insulin response is usually lower for high fat and/or protein foods than for high carbohydrate foods. But it is not like that eating a high fat diet “causes failure of insulin-secreting”.

    It is correct, that it “inhibits insulin-secretion” (this is AFAIK known since the “early nineties”). The problem is, that the “western diet” is not just high in saturated fatty acids, but basically high in everything. So you have high insulin levels (but not high enough due to the inhibition) and high blood sugar. So you might get the “benefits” of a type 2 diabetic before actually being one.

    “too much insulin can also be harmful” might be the understatement of the year. AFAIK excessive insulin levels are currently considered as “Teh Cause” ™ for (western) health problems.

    Additionally chronically high insulin levels inhibit some positive effects of exercise (e.g. increased HGH production and utilization of “storage fat”) and promote the build up of fat cells (which in turn again increase insulin levels).


    p.s. sorry english is not my first language

  5. Diabetes, myth and medicine..Western medicine just doesn’t get it. The type 2 disease is not clinically diagnosed in ‘civiilized’ Western societies until serious sequelae or complications are underway… IGT, its major precursor, is most often not diagnosed nor treated at all, and the lag period (between IGT and type 2 DM ) of about 15-20 years progressively damages the major organ systems till signs and symptoms develope. .

    If the above were corrected, hospitals, especially the acute care type, would be in trouble, since a significant portion of their medical and surgical admissions relate to the type 2 disease and its multi system manifestations.

    In addition (this is quite true but unpopular) an astonishly high percentage of exogenously (self) administered insulin is not only unnecessary but detrimental to the diabetic individual who still has beta cell function but is highly resistant, and it gets worse since the additional insulin just makes them hungrier and more resistant, augmenting system pathology and an earlier demise, especially via cardiovascular disease.

    The above should be obvious but it isn’t. Keeping biguanides out of this country till the 80’s was very foolish, but made (economic?) sense, and the sulfonylureas are still way overused, often dangerously. Even Lilly and Pfizer (probably) know and remember phenformin…DBI . . meaning don’t buy insulin.

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  7. David Morgan

    I think the article does not explain itself well. What it is saying is that initially the fat (and I wonder which type) inhibits insulin production causing a glucose high. The high glucose then causes overproduction of insulin. The pancreas does produce insulin in two phases. The first phase is usually stored rerady for a carb meal, the second phase responds to high blood glucose. But the interesting thing is why do the cells produce a response in the second phase if they cannot produce one in the first? I have certainly read that many people believe that T2 onset starts with the inabilty to respond at phase 1.

  8. jim

    So, we go forward studying abnormal diets. Does it not make sense to study those who eat what would be considered a proper, holistically therapeutic diet. Ok. We know that elevated insulin levels are bad, and it appears that an elevated fatty diet is bad. Am I missing something, or have too many physicians and researchers failed to get the kind of dietary and nutritional training necessary to guide their patients toward good dietary habits. Should we spend some of our time finding out what works, in conjunction with the study of the abnormal? A little physicianal CSM, (Common Sense Medicine), can go along way toward reviving some not long dead habits and disciplines of past generations….When was the last time you heard the phrase, “don’t eat too much of that; it is very rich”? So, Where is Grandma, we need her most?……jim

  9. bernard

    the key is to keep insulin sensitivity high at the glut-4 receptors.
    that can be achieved with metformin,lipoic acid (the r form) and with omega-3 fatty acids.

  10. d.rosart

    Disrupts or downregulates? It seems to me that people on a high fat lower carbohydrate diet would need less insulin. No?
    This reminds me of the protein kidney thing. High protein may be bad for people with kidney disease, but has not been shown to cause kidney disease. Perhaps high fat disrupts insulin production in people who don’t make enough insulin (only perhaps), but is harmless to the rest of us? These were normal mice, not normal humans.

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