Milkshakes and insulin resistance: the perfect storm

Insulin resistance is the foundation^[1] for many of the diseases that afflict the developed world, including metabolic syndrome, cardiovascular disease^[2], and type 2 diabetes. Accordingly, it should come as no surprise that a lot of research has investigated how and why insulin resistance develops.

One avenue of this research is among people with obesity, as dysfunctions^[3] in fat tissue metabolism are a central player in the development of insulin resistance, and having more fat increases the chance of something going wrong with it. However, people with obesity have a lot going on, which makes isolating the effect of any single variable on insulin resistance difficult. Similarly, while some^[4] researchers^[5] have overfed normal-weight people to mimic how obesity develops, these studies do not allow for the determination of any potential mechanisms underlying insulin resistance that occur before changes in body composition and fat mass.

More recently, researchers have^[6] experimentally^[7] induced^[8] insulin resistance in a matter of hours by infusing people with free fatty acids. Some of the potential mechanisms at play are shown in Figure 1. It has been known since at least the 1990s^[9] that elevated levels of circulating free fatty acids cause insulin resistance, but infusing free fatty acids is hardly representative of the real world. For instance, infused concentrations of free fatty acids far exceed^[10] what even the most insulin resistant people experience.

References: Castro, AV, et al. Arq Bras Endocrinol Metabol. 2014 Aug.
Chaurasia, B, Summers, SA. Trends Endocrinol Metab. 2015 Oct.

Accordingly, there has been a growing interest in causing insulin resistance in a short amount of time via dietary changes. Some studies have^[11] shown^[12] that overfeeding with a high-fat diet causes insulin resistance in a couple days, but this observation is not^[13] consistent^[14]. Being able to reliably and quickly induce insulin resistance in healthy participants without corresponding changes in body weight and composition would be a valuable tool for studying mechanisms of insulin resistance, such as the earliest signaling events and body tissue changes that occur as insulin resistance develops. The current study reports on a model of rapid diet-induced insulin resistance in healthy adults.

Studying insulin resistance and its development in humans can be tricky because of the numerous confounding variables present in people who are insulin resistant, including diet and lifestyle factors. The current study sought to develop a diet that rapidly induced insulin resistance among healthy people to avoid much of the “noise” that often accompanies insulin resistance development.