This was a helpful reminder that body weight isn't just about energy in versus energy out, it's also about the hormonal signals that determine what the body does with that energy. The biology is clearly more nuanced than calories alone.
I may be missing something as I only have access to the abstract. But, to build the insulin hypothesis and the thrust of the article based upon 14 patients and no control group seems like a bridge too far from an evidentiary standpoint. The theory of insulin is the problem makes cool mechanistic sense. I don't see the human RCTs to support that calories don't matter in this story....I have various posts about how and why we get excited about cool theories but w/o rigorous clinical evidence, I will remain an "open-minded" skeptic on this topic.
Thank you very much, Dr. Fung. I genuinely enjoyed reading all nine parts of this series.
A few questions, however, still remain unresolved in my mind, and I have rarely found clear, integrated answers to them:
What is the metabolic difference between a food that causes a sharp, short-lived insulin peak and one that causes a lower but more prolonged insulin response?
What primarily drives post-meal insulin secretion: the rise in circulating glucose itself, or the combined effects of gastric signals, gastric emptying, intestinal nutrient sensing, and incretin hormones such as GLP-1 and GIP?
If blood glucose were the main driver, would an equivalent amount of intravenous glucose produce the same insulin response as oral glucose, or does the difference between oral and intravenous administration reveal the importance of the gut and the incretin effect?
How should we distinguish true pancreatic insulin secretion from the insulin eventually measured in the peripheral circulation, given that a substantial and variable proportion may be cleared during the first pass through the liver?
Does peripheral insulin accurately reflect the insulin exposure of the liver through the portal circulation?
Could alterations in the gut microbiome, intestinal permeability, low-grade inflammation, and the gut–portal vein–liver axis directly affect hepatic insulin resistance, substrate handling, and energy metabolism?
I am not asking you to answer these questions here. However, should you continue the series, I would be very interested to read your perspective on them.
Thank you again for an engaging and thought-provoking series.
This framing of insulin vs glucose seems reductionist to me. The body tends toward triples in hormones; there is a dance between insulin and cortisol and glucose, evidenced by ‘stress’ making us fatter. Cortisol acts on insulin, giving another input to maintaining homeostasis…think set point in weight. I suspect weight changes are more than just pulling on two levers, insulin and glucose.
Were the people on the insulin cold? I imagine the extra fat didn’t come from nowhere. The fat stored was not fat burned, and I imagine the caloric deficit drew from the metabolism since it couldn’t draw from the fat stores.
This was a helpful reminder that body weight isn't just about energy in versus energy out, it's also about the hormonal signals that determine what the body does with that energy. The biology is clearly more nuanced than calories alone.
I may be missing something as I only have access to the abstract. But, to build the insulin hypothesis and the thrust of the article based upon 14 patients and no control group seems like a bridge too far from an evidentiary standpoint. The theory of insulin is the problem makes cool mechanistic sense. I don't see the human RCTs to support that calories don't matter in this story....I have various posts about how and why we get excited about cool theories but w/o rigorous clinical evidence, I will remain an "open-minded" skeptic on this topic.
Thank you very much, Dr. Fung. I genuinely enjoyed reading all nine parts of this series.
A few questions, however, still remain unresolved in my mind, and I have rarely found clear, integrated answers to them:
What is the metabolic difference between a food that causes a sharp, short-lived insulin peak and one that causes a lower but more prolonged insulin response?
What primarily drives post-meal insulin secretion: the rise in circulating glucose itself, or the combined effects of gastric signals, gastric emptying, intestinal nutrient sensing, and incretin hormones such as GLP-1 and GIP?
If blood glucose were the main driver, would an equivalent amount of intravenous glucose produce the same insulin response as oral glucose, or does the difference between oral and intravenous administration reveal the importance of the gut and the incretin effect?
How should we distinguish true pancreatic insulin secretion from the insulin eventually measured in the peripheral circulation, given that a substantial and variable proportion may be cleared during the first pass through the liver?
Does peripheral insulin accurately reflect the insulin exposure of the liver through the portal circulation?
Could alterations in the gut microbiome, intestinal permeability, low-grade inflammation, and the gut–portal vein–liver axis directly affect hepatic insulin resistance, substrate handling, and energy metabolism?
I am not asking you to answer these questions here. However, should you continue the series, I would be very interested to read your perspective on them.
Thank you again for an engaging and thought-provoking series.
Who knew? Everybody except the doctors.😂🤣😂
I really enjoy reading what Dr. Fung has to say AND the way he says it. He enlightens all of us and I’m grateful that he takes our education on!
This framing of insulin vs glucose seems reductionist to me. The body tends toward triples in hormones; there is a dance between insulin and cortisol and glucose, evidenced by ‘stress’ making us fatter. Cortisol acts on insulin, giving another input to maintaining homeostasis…think set point in weight. I suspect weight changes are more than just pulling on two levers, insulin and glucose.
Awesome. 👏
What you eat… matters.
Were the people on the insulin cold? I imagine the extra fat didn’t come from nowhere. The fat stored was not fat burned, and I imagine the caloric deficit drew from the metabolism since it couldn’t draw from the fat stores.