New paradigm of insulin resistance

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Insulin resistance is much different than conventionally taught, said Jason Fung, MD, during the virtual 2020 Institute for Functional Medicine Annual International Conference.

There are two phases or disease processes of type 2 diabetes, beta cell dysfunction and insulin resistance. Fung said. Increasing fasting insulin compensates for insulin resistance keeping blood glucose normal, or hyperinsulinemia. However, after prolonged periods of hyperinsulinemia, beta cells burn out, insulin production falls, and blood glucose rises.  

The standard paradigm of insulin resistance is the “lock and key,” in which glucose enters the body, which produces insulin, and insulin acts as a key to insulin receptors, unlocking and receptor and allowing glucose to enter the cell and generate energy. In insulin resistance, the lock and key mechanism doesn’t work; though the insulin and receptor are structurally intact, something blocks the lock and prevents glucose from entering the cell, leading to a high level of glucose in the bloodstream and a low level of glucose inside the cell. This phenomenon is thought of as “internal starvation.”

In type 1 diabetes, where there’s not enough insulin, the intracellular internal starvation makes sense. However, this is not the typical phenotype of type 2 diabetes. Patients with type 2 diabetes are often overweight or obese with fatty livers and fat around the organs, which Fung said is not internal starvation.

“If the cells are not getting any glucose, why are they so full of fat?” said Fung. “That’s the real question.”

There is no current answer to what causes insulin resistance, Fung said. Considering resistance in other scenarios, Fung said resistance to antibiotics is caused by exposure to the antibiotics themselves, as is resistance to viruses, which are caused by exposure leading to the body developing antibodies and eventually the body becomes resistant. The systems in the body are always adapting in a process known as homeostasis, Fung said. It’s exposure that leads to resistance.

This leads to the new paradigm, known as the overflow paradigm, in which the cell is with even though insulin and the insulin receptor may be normal. This explains why type 2 diabetes patients don’t experience internal starvation but rather symptoms of excess glucose. If internal starvation is true, more insulin is necessary. However, giving more insulin on top of an existing overflow may make the disease worse.

The problem is not only blood glucose, but rather whole-body glucose, Fung said. That’s why giving more insulin is not the answer. While insulin exposure may target the symptoms and improve blood glucose, it does not address the underlying causes of insulin resistance and hyperinsulinemia. Insulin resistance is an overflow phenomenon, he said. Like fixing an overflowing suitcase, the solution is not packing in more insulin, but removing insulin. Thus, the focus should be on reinforcing cycles of resistance—exposure causes resistance, and therefore preventing resistance should start by reducing exposure.

For example, resistance requires high hormonal levels and constant stimulus. In today’s modern world, people are eating more often, eating late at night, as well as eating throughout the day for longer windows of time. The high levels of insulin from what one eats combined with the persistence of high levels from when one eats results in insulin resistance. Both obesity and type 2 diabetes are diseases of hyperinsulinemia, said Fung.

There are several factors contributing to hyperinsulinemia and insulin resistance, said Fung. Simply, the problem is too much glucose and insulin. The solution is not to type 2 diabetic patients more insulin. Insulin causes weight gain and, though it may improve blood glucose, it makes the underlying disease worse.

To reverse type 2 diabetes, which is essentially too much sugar in the body, Fung suggests a low carbohydrate diet to lessen sugar intake and intermittent fasting to burn through glucose.

“The way we approach diabetes depends on the paradigm,” said Fung. “Don’t want to treat a probvme of insulin with more insulin.

“We don’t want to treat a problem of insulin with more insulin,” Fung said. “These dietary solutions have the potential to completely get rid of type 2 diabetes with no drugs, no surgeries, and no costs. All we need to do is give people the knowledge to take control of their own disease.”

Editor’s note: Click here to explore our 2020 Institute for Functional Medicine Annual International Conference live coverage.