What is the Carbohydrate Insulin Model?

Defining the CIM Model

The "carbohydrate-insulin model" (CIM) contrasts with the calorie focused standard model of obesity, in which an imbalance between calorie intake and output leads to weight gain. In the CIM, proposed by Professor  David Ludwig MD PhD ( Ludwig et al, 2018), excessive intake of high glycemic carbohydrates alters metabolic and hormonal environment in the human body to drive overeating and fat gain.

Both the CIM and the energy balance model recognize a relationship — based on the energy conservation low of physics — linking energy intake, energy expenditure and weight gain. However, in the CIM, causality is reversed. The CIM proposes that, over the long term, the process of getting fat leads to a positive energy balance, not the other way around.

In other words, the CIM focuses on the metabolic and hormonal changes associated with excessive carbohydrate consumption that alter hunger drive, metabolic rate, and fuel partitioning, leading to fat gain over the long-term. The CIM makes several predictions.

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Hunger and Overeating

First, the CIM observes that high-glycemic carbohydrates, by increasing the insulin-to-glucagon ratio, lowers circulating metabolic fuels in late post-prandial period, around 3 - 5 hours after a meal, potentially leading to increased hunger and overeating.

A randomized controlled feeding trial demonstrated that a high-carbohydrate diet increased early post-prandial insulin and decreased late post-prandial total energy availability in the bloodstream, including glucose, fatty acids, and ketone bodies, as compared to a low-carbohydrate diet ( Shimy et al, 2020). This makes sense biologically as insulin drives glucose uptake, inhibits lipolysis, and inhibits hepatic ketogenesis.

The practical implication of this late-postprandial low energy availability phenomenon is that high-carbohydrate diets could challenge a person’s ability to maintain weight loss through caloric restriction over long-term. In support of this possibility, data show that, after weight loss, high-carbohydrate weight maintenance diets are associated with a 43-51% increased blood flow to the brain’s reward center as compared to higher fat low-carbohydrate diets ( Holsen 2021).

Other data also show that, even when carbohydrates are controlled, glycemic index predicts brain reward center activation late post-prandial feelings of hunger ( Lennerz et al, 2013), implying that not all sources of carbohydrates are equal in the CIM because higher glycemic carbohydrates spike insulin to a greater extent.

Total Energy Expenditure

Second, the CIM predicts that high-carbohydrate diets may decrease energy expenditure as a means to defend a higher weight set point. This prediction was examined in the Framingham State Food Study, a 20-week randomized controlled trial in which individuals who had lost weight were randomly assigned to 20% fat 60% carb (low fat), 40% fat 40% carb, or 60% fat 20% carb (low carb) weight maintenance diets that were controlled for protein and in which calories were adjusted to maintain weight. The study found that, among 120 persons on average, the low carb group required 278 more Calories per day to maintain weight as compared to the low fat group ( Ebbeling et al, 2018,  Ebbeling et al, 2020).

Fuel Mispartitioning

Third, the CIM predicts that high insulin levels can bias fuel partitioning towards fat, as opposed to lean mass, even when calories are controlled. This has been demonstrated in rats in which administration of insulin leads to fat gain even when caloric intake and activity are controlled to prevent excessive weight gain ( Torbay et al, 1985) and in rodents with high vs low-carbohydrate, calorie-controlled diets ( Pawlak et al, 2004).

While the concept of insulin-driven fuel mispartitioning is difficult to test experimentally in humans (beyond the natural experiment of exogenous insulin treatment), is consistent with other data showing that hypothalamic insulin resistance is associated with weight regain at nine months and two years after lifestyle intervention, as well as the preferential partitioning of excess fuel into inflammatory abdominal visceral fat, even when body mass index is controlled ( Kullmann et al, 2020).

Criticisms of the CIM Model

There are, admittedly, criticisms of the CIM. For example, the doubly labeled water method used in the Framingham State Food study was criticized on “theoretical possibility that … [differential] fluxes through biosynthetic pathways” could limit the accuracy of the methodology used in that trial ( Hall et al, 2019). However, this challenge was met in a secondary analysis that confirmed that individuals eating a low-carb diet required 200 – 300 more Calories per day to maintain their weight ( Ebbeling et al, 2020).

Additionally, some researchers note that low-carbohydrate diets don’t appear to increase energy expenditure as compared to low-fat diets in short-term trials. However, this might not be an entirely fair assessment, given that biological adaptation to a low carbohydrate diets takes several weeks ( Vazquez 1992). Indeed, a 2021 meta-analysis of 29 controlled feeding studies found that studies shorter than 2.5 weeks duration showed a small disadvantage of low-carbohydrate diets for total energy expenditure, whereas those longer than 2.5 weeks showed a larger advantage for low-carbohydrate diets ( Ludwig 2021). Therefore, it is important that all trials designed to properly test the CIM be of sufficient duration, ideally at least one month for energy expenditure and at least 6 months for body composition.

Short-term studies show CICO works best. Long-term studies show low-carb diets have an advantage. Life is a marathon.

Most recently, an opinion piece was published in Science that tried, again, to debunk the CIM. Being an opinion piece, it didn’t provide any new data but tried to summarize the counterpoints against the CIM.

It was interesting to see how the senior author, who has historically been responsible for most of the attacks on the CIM, structured his argument. He focused on the results of short-term trials and mouse data, while attempting to invalidate the results of long-term human randomized controlled trials performed by Professor Ludwig by claiming that “these results were likely due to a miscalculation of energy expenditure,” a statement that was previously refuted in the peer-reviewed literature. ( Ebbelinget al, 2020)

Additionally, he explains that long-term randomized controlled trials have not been conducted to refute the CIM because such long-term low-carb diets “raise ethical concerns due to potential harm to health.” I find this interesting because well-formulated ketogenic diets are safe for most people and, more importantly, long-term randomized controlled trials and other years-long controlled trials have been conducted in people living on ketogenic diets safely. For further insight into the counterpoints to this most recent Science article, you can click here.

Final Words

That said, the CIM is not a proven model by any means nor is it the entire picture. A more comprehensive view of the CIM model would include the long-term effects of the vicious cycle of insulin spikes and overeating — namely, the development of insulin resistance and metabolic dysfunction.

In truth, the impact of insulin resistance on many organs throughout the body, include muscle cells and the brain, is probably the core of the obesity epidemic. However, in our modern food environment, the CIM provides a gateway to the development of insulin resistance, as high-glycemic carbohydrates establish the vicious cycle that precipitates insulin resistance in the first place.

In a nutshell, the CIM provides a novel foundation for innovating solutions to tackle the obesity crisis. It’s something different. And we need different because business as usual hasn’t worked.

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