#59–Jason Fung, M.D: Fasting as an antidote to obesity, insulin resistance, T2D, & metabolic illness

KEYPOINTS

• 01

  Fung reframes insulin resistance as an overflow problem, not a locked door.

  The standard 'lock and key' model says glucose can't get into a cell because the cell has stopped responding to insulin. Fung argues it may instead be unable to enter because the cell, especially the liver cell, is already overfilled with glucose and fat. He says this explains the paradox of an 'insulin-resistant' liver that is still busily turning glucose into new fat. In his view the underlying problem is hyperinsulinemia, too much insulin over time, rather than insulin resistance itself.

• 02

  Pushing in more insulin covers up type 2 diabetes rather than treating it.

  Fung's view is that sulfonylureas, insulin and DPP-4 inhibitors all raise insulin and push more glucose into tissues that are already full. Blood sugar improves while total-body glucose gets worse. He says this is why the disease looks 'chronic and progressive': patients go from one drug to large insulin doses over ten years and the disease never gets better.

• 03

  Lowering blood glucose with more insulin protected small blood vessels but not the heart or brain.

  Attia notes that intensive glucose-control trials improved some small-vessel (microvascular) outcomes, such as in the kidneys, but not large-vessel (macrovascular) outcomes in the heart and brain. If insulin doses have to double to get glucose from 200 to 150, those outcomes may even get worse. Fung connects this to the failures of ACCORD, ADVANCE and VADT. Attia says seeing this pattern about three years earlier was the 'aha moment' that made him see hyperinsulinemia itself as harmful.

• 04

  SGLT2 inhibitors fit Fung's model because they remove glucose from the body.

  These drugs make the kidneys excrete glucose, which lowers total-body glucose and insulin rather than moving sugar into the liver. Fung credits them with organ protection not seen with older drugs, and notes that people lose weight on them. As a nephrologist, he points out that they were the first new drugs to slow diabetic kidney disease since ACE inhibitors in the 1980s.

• 05

  Fung sees insulin resistance and fatty organs as the body protecting itself.

  In his analogy, insulin delivers glucose to houses on a street. Once a house is full it stops answering the door, which is insulin resistance, so insulin bangs harder. He cites lipodystrophy, where people with almost no body fat have some of the worst insulin resistance ever measured, as evidence that storing fat protects against excess glucose. Without places to store it, fat ends up in the liver.

• 06

  Fung thinks causation runs mostly from insulin to obesity.

  Whenever insulin rises, with insulin injections or sulfonylureas, people gain weight. When it falls, with SGLT2 inhibitors or untreated type 1 diabetes, they lose weight. Attia adds a counterpoint: in Samuel Klein's New England Journal of Medicine study, liposuction removed about 20 pounds of fat with no metabolic benefit, although critics note liposuction only removes fat under the skin, not visceral fat. Attia says the direction of causation may not change what you do clinically.

• 07

  Many chronic diseases may be 'diseases of too much growth'.

  Fung links hyperinsulinemia to breast cancer and to proliferative disease through shared nutrient-sensing pathways: insulin, mTOR and AMPK. Attia describes meeting a researcher whose 2006 theoretical paper, rejected by nearly every journal, predicted rapamycin would be the top longevity drug. The first study showing rapamycin extends lifespan came in 2009. Attia calls it the most promising longevity agent as of 2019.

• 08

  Hormones send growth signals to muscle and fat in different directions.

  Attia explains that insulin builds both muscle and fat, which is why some bodybuilders use it. Testosterone builds muscle but breaks down fat. Cortisol is the worst of both, breaking down muscle while building fat. He sketches this on a whiteboard for patients to show that nutrition, exercise and hormone therapy are all ways of steering these signals.

• 09

  Fung believes the effect of bariatric surgery on diabetes is mostly due to fasting.

  Attia notes that after a Roux-en-Y gastric bypass, patients often stop needing insulin within about 10 days, before they've lost much weight, and that insurers have treated surgery as the only recognized way to reverse type 2 diabetes. Attia once worked on designing a trial to separate the surgical, dietary and calorie-restriction effects. Fung's view is that 'the fasting does everything', and that 7- to 14-day fasts can produce the same resolution.