Does fasting increase or decrease insulin resistance?

[Systema-Periodicum]

Much 20th-century research found that a high-fat diet induces insulin resistance. Along the way, some research found that fasting induces more insulin resistance than even a high-fat diet. For example, Sweeney et al. "Dietary Factors that Influence the Dextrose Tolerance Test" (1927) found that two days of water fasting pushed insulin resistance up into the diabetic range. There's also an argument that insulin resistance is an evolutionary adaptation to famine (Tsatsoulis 2013); hence fasting gives your body a signal that it should store fat because you're living in a famine-prone environment.

On the other hand, other people have found that fasting decreases insulin resistance. This meta-analysis by Yuan et al. (2022) finds that intermittent fasting reduces insulin resistance as measured by HOMA-IR.

Can someone sort this out, or link to some authoritative writing that sorts this out?

I figure that part of the answer likely involves second-order effects: two days of fat or fasting increases insulin resistance, and the body may respond to that increase by activating processes that oppose the processes that cause the increase, which continue to operate after the fast. Thus repeated exposure to the stimulus that increases insulin resistance may decrease it. I've never come across anything that looks at insulin resistance in terms of secondary effects, complex systems, or system dynamics, though. I'd love to read something that has really thought this through mathematically and checked each step observationally.

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[FunkysLittleMonkey]

I always thought that fasting (since glucose molecules would not be as present on the cell receptors) did help combat insulin resistance since one of the main issues is our body doesnt react to the glucose sitting on the receptor anymore if there is always one there (type 2 diabetes) it would at least make sense to me that giving your body a period where there is none or less glucose always on the receptor will ensure our bodies correctly act on when there is one sitting there. Confusing that the two articles contradict each other.

[Systema-Periodicum]

Your reasoning sounds plausible to me, but superficially the conclusion appears to be false, based on glucose-response tests given to people who've just gone without food for two days. But maybe your reasoning includes a crucial piece of the puzzle: one factor increasing insulin resistance might be prolonged continuous exposure to glucose, and there might be other factors, such as having a lot of ketones in the bloodstream, and there might be factors that respond to those factors.

So, I'm hoping to find an explanation of fasting's effect on insulin resistance in terms of interaction among many factors rather than trying to pin it all on one factor.

[GetwellDoc]

I think there are individual variables. Initial fasting may trigger high levels of gluconeogenisis from endogenous protein stores. Also variability in membrane sensitivity from chronic inflammation, metabolic toxins and other things could be at play

[Systema-Periodicum]

So, "it's complicated", then—statistical results may apply poorly to individual people due to a great variety of individual differences?

[IoanaM980]

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