peter attia paul grewal covid-19

Gerald Shulman, M.D., Ph.D.: A Masterclass On Insulin Resistance—Molecular Mechanisms And Clinical Implications | The Drive with Peter Attia #140

Key Takeaways

  • “If we are going to be serious about the business of delaying onset of death, we have to be serious about the business of delaying the onset of chronic disease.” – Peter Attia
  • Insulin resistance is the root cause of diabetes and downstream chronic disease
  • Diabetes amplifies atherosclerotic disease, Alzheimer’s disease, and cancer
  • About 50% of people with insulin resistance are asymptomatic
  • Young, lean adults are presenting with profound insulin resistance in muscle with no problems in the liver
  • Understanding insulin resistance will be critical for preventing and treating disease
  • Nuclear Magnetic Resonance (NMR) allows us to get biochemical information of metabolites (i.e., glucose) and key intermediates inside cells

Introduction

Gerald Shulman, M.D., Ph.D. is a Professor of Medicine, Cellular & Molecular Physiology, and the Director of the Diabetes Research Center at Yale. Dr. Shulman pioneered the use of magnetic resonance spectroscopy to non-invasively examine intracellular glucose and fat metabolism in humans. His work has led to significant paradigm shifts in our understanding of type 2 diabetes.

In this episode of The Drive, Dr. Gerald Shulman and Peter Attia discuss take a deep dive into the mechanisms of insulin resistance, what it really means, and the role of diet and lifestyle on insulin resistance.

Host: Peter Attia (@PeterAttiaMD)

Why Type 2 Diabetes Is So Harmful?

  • Diabetes is an abnormality of metabolism
  • Type 2 diabetes is the foundation upon which the major chronic diseases sit
  • Diabetes amplifies atherosclerotic disease, Alzheimer’s disease, and cancer
  • “If we are going to be serious about the business of delaying onset of death, we have to -e serious about the business of delaying the onset of chronic disease.” – Peter Attia
  • Metabolic associated fatty liver disease (MAFLD) is going to be the most common cause of liver disease, liver inflammation, end-stage liver disease, and liver cancer
  • Huge increase in cancers associated with obesity
  • In a healthy individual: carbohydrates are ingested and stored as mostly healthy liver and muscle glycogen
  • In a diabetic individual, two things happen: (1) the liver makes more glucose than it should be; (2) insulin is not causing glucose to be taken up by muscle

Using Nuclear Magnetic Resonance (NMR) To See Inside Cells

  • NMR: allows the molecular structure of a material to be analyzed by observing and measuring the interaction of nuclear spins when placed in a powerful magnetic field
  • NMR allows us to get biochemical information of measuring metabolite and track label as it’s metabolized inside the cell  
  • For the first time, you can measure intracellular pathway flux
  • Can measure key intermediates inside the cells and intracellular glucose
  • NMR allows you to target the cause of glucose abnormality:
    • If the block is synthase: glucose-6-phosphate and glucose should build-up
    • If the block is at hexokinase: lower glucose-6-phosphate and build-up of glucose  
    • If the block is at transport: reduction of both glucose-6-phosphate and glucose

Insulin Resistance & Its Causes

  • Insulin resistance: when you need more insulin than normal to cause the muscle to take up glucose, cause the liver to turn off glucose production, or cause the liver to take up glucose
  • Insulin in the fat cell: stops the breakdown of fat cells
  • Insulin resistance changes the fate of ingested carbohydrate from glycogen to fat
  • Insulin resistance is the root cause of diabetes, fatty liver disease, heart disease, and cancer
  • Almost everyone who is overweight or obese has insulin resistance
  • Understanding insulin resistance is going to be critical for preventing many chronic diseases
  • Fat inside the cell (different from fat outside the cell) is the best predictor for insulin resistance
  • You can be perfectly asymptomatic and have insulin resistance
  • About 50% of people with insulin resistance are asymptomatic
  • Young, lean adults are presenting with profound insulin resistance in muscle with no problems in the liver

Why Does Insulin Resistance Exist?

  • Theory: it’s protective against starvation
  • When animals and humans starve, fatty liver comes on
  • Insulin in the liver promotes glucose uptake and storage as glycogen
  • It’s only in recent years that we’ve been in environments of over-consumption and these same pathways are promoting disease by doing what was once protective  

Lifestyle And Insulin Resistance

  • Young, lean, non-smokers can reverse insulin resistance with exercise
  • Diet and exercise are really the best remedies for insulin resistance and diabetes
  • It’s easier to get people to lose weight in the short term – the key is finding what works for you and you can adhere to
  • Don’t get stuck on a diet dogma; instead, adopt what helps you
Drive with Dr. Peter Attia : , , , , , , ,
Notes By Maryann

More Notes on these topics

Top Insights and Tactics From

31 Best Podcasts of All Time

FREE when you join over 12,000 subscribers to the
Podcast Notes newsletter

No Thanks