How Much Carbohydrates Can You Eat Before a High Fat Diet Becomes Unhealthy? Increasing Carbohydrate Intake Turns Physiological Into Pathological Insulin Resistance

High carb + high fat, that's one "high" too much for your health.
As a SuppVersity reader you should be aware that the average "high fat diet" that's fed in rodent (and human) studies to prove how bad dietary fat is for us contains almost as much carbohydrate as it contains fat sources.

Against that background a study like the one a group of scientists from the Gillings School of Global Public Health at The University of North Carolina at Chapel Hill have conducted recently has actually been long overdue: A study to clarify how much carbs are too much carbs when they're consumed on top of a high fat diet.

The conflicting results of previous studies, some of which "have shown that carb-rich diets promote development of insulin resistance and T2DM, while others have shown that high-carb diet is protective against insulin resistance and T2DM compared to HFD" and the fact that there's plent of evidence that shows that "low-carb diet is not necessarily protective against insulin resistance and diabetes" (Mei. 2014), were occasion enough for Shuang Mei and colleagues to readdress the roles of dietary fat and carbs in insulin resistance and T2DM.
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The scientist goal was to answer several key questions: (1) First, are dietary carbs necessary for the HFD-induced insulin resistance? (2) Second, how much carb is too much or sufficient to promote the HFD-induced insulin resistance? (3) Third, is fat essential for insulin resistance?

To find the corresponding answers to these questions, the scientists conducted a combined in vitro and in vivo study, in the course of which they kept a group of C57BL/6 mice on chow (ad libitum diet) that contained 0.1, 5%, 10%, and 25.5% carbs on top of 58% fat but dissimilar amounts of protein, i.e. 41%, 37%, 32% and 16.5% of the chow (vs. 23.1%), for 5 weeks. They tracked the calorie consumption, body weight and fat gains, insulin sensitivity, intra-tissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle of the muscle and determined the role of hepatic gluconeogenesis in the HFD-induced insulin resistance.
Figure 1: White body fat (x10) and energy intake (kcal) relative to body weight (left); body weight at the end of the study, expressed relative to the body weight of the standard chow control group (Mei. 2014)
In addition, Mei et al. examined the effects of fatty acid exposure in cultured cells (not shown) and confirmed that the presence of  fatty acids "is essential for the development of insulin resistance induced by chronic exposure to insulin." (Mei. 2014)
Figure 2: Fasting glucose (left) and fasting insulin (right) values - carbs exacerbate the effects of HFD (Mei. 2014)
Against that background it's not surprising that data in Figure 1 and Figure 2 shows that the rodents became insulin resistant even at 0.1% of carbohydrates in the diet. The degree of insulin resistance, on the other hand, was "dramatically elevated", when the carbohydrate intake was increased to 5% and 10% - with the 10% carb + high fat diet being "sufficient to induce a maximal level of insulin resistance." (Mei. 2014)
Physiological insulin resistance: Insulin resistance is not always bad. When you're low on glucose, as it would be the case when you're dieting (=being in a caloric deficit) and consuming only a relatively low amount of carbs, the downregulation of your bodies insulin sensitivity can stabilize your blood sugar levels by helping to maintain adequate hepatic gluconeogenesis (the production of glucose mostly from amino acids) and avoiding an "uncontrolled" uptake of the scarce glucose from your blood. In the absence of exuberant amounts of carbohydrates, this physiological form of insulin resistance is thus a way to cope with the energy- and macronutrient availability and not generally bad.
A very similar effect was observed for the accumulation of ectopic fat and oxidative stress in liver and skeletal muscle, which was present and significant on the low carbohydrate + high fat diet, but became "dramatically enhanced", only when the amount of carbs in the diet was increased.

In this context it's interesting to mention that the insulin resistance was mediated primarily by an increase of the hepatic expression of key gluconeogenic genes - an increase that was most dramatic by HFD with little carbs. This, as well as the previously cited fact that the occurrence of muscular and hepatic insulin resistance in a cell study depended on the the presence of fatty acid lead Mei et al. to conclude that (a) "dietary carbs are not necessary for HFD to induce insulin resistance but can aggravate insulin resistance in a dose-dependent manner"; and (b) "HFD [in this case really high fat, low carb] alone causes insulin resistance in liver and skeletal muscle with or without dietary carb." (Mei. 2014)
Study says: If you go high carb, you better go really high carb (learn more) - and the study at hand may actually prove why.
Bottom Line: Despite the fact that I have no doubt that the aggravating effects of high(er) carbohydrate intakes on the metabolic damage due to high fat dieting is relevant to human beings, as well, it remains to be seen, if these will occur at the same relatively low amounts of carbohydrate intakes in humans, as they did in the mice in the study at hand (I assume esp. athletes can tolerate more).

If we assume this was the case, many people who are currently jumping aboard the low carb craze, would be ruining their health unless they this form of dieting only while being in a caloric deficit - a state that precludes the accumulation of ectopic (visceral) and liver fat and benefits from an increase in insulin resistance and gluconeogenesis, since both processes contribute to higher and more stable blood sugar levels - and yes, this is what we call physiological insulin resistance!
  • Mei, Shuang, et al. "A Small Amount of Dietary Carbohydrate Can Promote the HFD-Induced Insulin Resistance to a Maximal Level." PloS one 9.7 (2014): e100875.
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