High saturated fatty acid intake induces insulin secretion by elevating gastric inhibitory polypeptide levels in healthy individuals


Insulin resistance is central to the etiology of the metabolic syndrome cluster of diseases. Evidence suggests that a high-fat diet is associated with insulin resistance, which may be modulated by dietary fatty acid composition. We hypothesized that high saturated fatty acid intake increases insulin and gastric inhibitory polypeptide (GIP) secretion. To clarify the effect of ingested fatty acid composition on glucose levels, we conducted an intervention study to investigate the insulin and plasma GIP responses in 11 healthy women, including a dietary control. Subjects were provided daily control meals (F-20; saturated fatty acids: monounsaturated fatty acids: polyunsaturated fatty acids [S:M:P] ratio, 3:4:3) with 20 energy (E) % fat, and followed by two isoenergetic experimental meals for seven days each. These meals comprised 60E% carbohydrate, 15E% protein, and 30E% fat (FB-30; high saturated fatty acid meal; S:M:P, 5:4:1; and F-30: reduced saturated fatty acid meal; S:M:P, 3:4:3). On the second day of the F-20 and the last day of F-30 and FB-30, blood samples were taken before and 30, 60, and 120 min after a meal tolerance test. The plasma glucose responses did not differ between F-20 and FB-30 or F-30. However, insulin levels were higher after the FB-30 than after the F-20 (p < 0.01). The GIP response after the FB-30 was higher than that after the F-30 (p < 0.05). In addition, the difference in the incremental GIP between FB-30 and F-30 correlated significantly and positively with that of the insulin. These results suggest that a high saturated fatty acid content stimulates postprandial insulin release via increased GIP secretion.


Alex’s Notes: This study comes at a convenient time. Just the other day I had a discussion of Facebook regarding carbohydrate back-loading and its relationship to circadian-determined insulin sensitivity. Long story short, insulin is higher with standardized meals in the morning and glucose is not lower, confirming a basic principle of biochemistry – higher blood fatty acid and cortisol levels after overnight fast lowers insulin sensitivity in the morning. So here is another reason breakfast is overrated. But I digress.

The above establishes that fatty acids impair insulin sensitivity, but this conclusion may be premature. There are numerous types of fatty acids that are utilized differently within the body, and it would be naïve to think they all impacted insulin sensitivity identically – at least without some evidence. Previous research in rats has demonstrated that insulin resistance is promoted by unsaturated fat, omega-6 fatty acids, and saturated fat, but it is improved by omega-3 fatty acids. It has also been demonstrated in men that greater intramuscular unsaturation and total percentage of long-chained polyunsaturated fatty acids are associated with greater insulin sensitivity.

Thus, it does seem prudent to judge the type of fatty acid with great importance. This brings us to the study at hand, which performed a week-long dietary intervention in 11 healthy and young Japanese women (average age of 23.6 years; BMI of 22). The subject consumed one of two test meals (see below) for seven days in a randomized crossover with a 21-day washout period. Before embarking on the week of test meals, the subjects for one day consumed control meals, and the researchers did their measurement stuff after both time periods so as to have comparative data not only between the two test meals, but also how they fared against the control meal. The composition of the three meals is shown below.


Control (F-20)

Low saturated fat (F-30)

High saturated fat (FB-30)

Energy (kcal)




Protein (g)




Fat (g)




S : M : P




n-6 / n-3




Carbohydrates (g)




Starch (g)




Simple sugar (g)




Dietary Fiber (g)




**S:M:P is the ratio of saturated : monounsaturated : polyunsaturated fatty acids

What should be apparent is that the test meals are completely identical except for the relative amounts of saturated and polyunsaturated fatty acids. Another interesting note is that the sugar content is very low, with 93% of the carbohydrates coming from starch. In terms of the fats used, the FB-30 group used butter, while the F-30 group used soybean oil.

No significant differences were found between the three meals for blood glucose levels. Similarly,no significant differences were noted in insulin concentrations between the control and F-30 meals, but insulin concentration was significantly higher following the FB-30 compared to the control. Thus, it appears that saturated fat leads creates and insulin resistant environment, which now begs the question, why?

The researchers also measured gastric inhibitory polypeptide (GIP), which is secreted within the small intestine and stimulates insulin secretion from the pancreas. The GIP levels following the FB-30 meals were significantly higher than that following the F-30 meals, and C-peptide (a measure of insulin production) was also greater in the FB-30 group. Thus, it appears that saturated fat elevates levels of GIP, which leads to greater insulin secretion. What is unfortunate is that the researchers don’t provide the GIP response to the control meal, and thus we cannot see how the meal compared relative to a slightly lower total fat intake.

To put these results bluntly, saturated fat (at least in the form of butter) increases the amount of insulin needed to dispose of co-ingested carbohydrates and thus causes insulin resistance. Interestingly, a similar study to this was performed to compare butter to olive oil. It was found that although olive oil leads to greater GIP production than butter; it did not lead to greater levels of insulin or glucose. Compared to the current study that utilized a constant 40% monounsaturated fatty acid content, olive oil is 74% monounsaturated fat, suggesting that all fat in general elevated GIP, but only saturated fat leads to insulin resistance.

So what does this all mean? It means that all the anti-carbohydrate, glycemic index loving people need to get their facts straight. Adding butter to your baked potato may lower the GI, but it doesn’t lower the insulin response. In fact, it elevates the response and leads to insulin resistance. But you don’t need me to tell you that. All we have to do is use common sense and look to nature. Name one food that is high in both fats and starches or sugars. It can't be done. Nature knows best and it makes sense that buttered potatoes are harder to deal with physiologically.

An addendum: I wanted to add this in case anything were to ever happen to the Facebook comments on this article. A reader asked, "what does this study mean in simple words (for simple minded People like me)? Does it mean that combining saturated fat and starchy carbs increases Insuline resistance? And if yes, what exactly does that mean for diabetic people's dietry? And is there evidence that high intake of saturated fat per se increases Insuline resistance?"

My answer was as follows. In simple terms this study shows that consuming saturated fat with carbohydrates causes your body to work harder to lower blood glucose into normal range. It makes your body need to secrete more insulin to get the job done, which is by definition insulin resistance. One key problem diabetics have is elevated blood lipids that perpetuate the insulin resistance they suffer from. So for a diabetic, it would be best to keep fats and carbs in separate meals. Now you don't need to be zero fat/carb when you eat one or the other, just try to keep starches and added fats separate. In other words, don't butter your potato.

It should also be noted, as I mentioned in the article, that unsaturated fats don't cause this problem. Thus, roasting your potatoes in olive oil should be fine, as would consuming your potato with salmon or other fatty fish. Finally, yes, there is a proven association of high saturated fat content within muscle tissue and muscular insulin resistance. So how do you elevate the saturated fat content of muscle tissue? Simple, it has been shown to be directly related to dietary intake.

I want to add that I am not bashing saturated fat, but these studies definitely show that a high intake is not as great as so many butter-balls and bullet-proof coffee folk believe, especially if you are a diabetic or an athlete (both need greater insulin sensitivity). 


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