← The Peter Attia Drive

#140 - Gerald Shulman, M.D., Ph.D.: A masterclass on insulin resistance—molecular mechanisms and clinical implications

Dec 7, 2020 2h 8m 12 insights
<div><span> Gerald Shulman is a Professor of Medicine, Cellular & Molecular Physiology, and the Director of the Diabetes Research Center at Yale. His pioneering work on the use of advanced technologies to analyze metabolic flux within cells has greatly contributed to the understanding of insulin resistance and type 2 diabetes. In this episode, Gerald clarifies what insulin resistance means as it relates to the muscle and the liver, and the evolutionary reason for its existence. He goes into depth on mechanisms that lead to and resolve insulin resistance, like the role of diet, exercise, and pharmacological agents. As a bonus, Gerald concludes with insights into Metformin's mechanism of action and its suitability as a longevity agent.</span></div> <div> <p>We discuss:</p> <ul type="disc"> <li>Gerald's background and interest in metabolism and insulin resistance (4:30);</li> <li>Insulin resistance as a root cause of chronic disease (8:30);</li> <li>How Gerald uses NMR to see inside cells (12:00);</li> <li>Defining and diagnosing insulin resistance and type 2 diabetes (19:15);</li> <li>The role of lipids in insulin resistance (31:15);</li> <li>Confirmation of glucose transport as the root problem in lipid-induced insulin resistance (40:15);</li> <li>The role of exercise in protecting against insulin resistance and fatty liver (50:00);</li> <li>Insulin resistance in the liver (1:07:00);</li> <li>The evolutionary explanation for insulin resistance—an important tool for surviving starvation (1:17:15);</li> <li>The critical role of gluconeogenesis, and how it's regulated by insulin (1:22:30);</li> <li>Inflammation and body fat as contributing factors to insulin resistance (1:32:15);</li> <li>Treatment approaches for fatty liver and insulin resistance, and an exciting new pharmacological approach (1:41:15);</li> <li>Metformin's mechanism of action and its suitability as a longevity agent (1:58:15);</li> <li>More.</li> </ul> <p>Learn more: <a href="https://peterattiamd.com/">https://peterattiamd.com/</a><br /> <br /> Show notes page for this episode:  <a href="https://peterattiamd.com/geraldshulman">https://peterattiamd.com/geraldshulman</a> <br /> <br /> Subscribe to receive exclusive subscriber-only content: <a href="https://peterattiamd.com/subscribe/">https://peterattiamd.com/subscribe/</a><br /> <br /> Sign up to receive Peter's email newsletter: <a href="https://peterattiamd.com/newsletter/">https://peterattiamd.com/newsletter/</a><br /> <br /> Connect with Peter on <a href="http://facebook.com/PeterAttiaMD"><u>Faceboo</u></a><u>k</u> | <a href="http://twitter.com/PeterAttiaMD"><u>Twitter</u></a> | <a href="http://instagram.com/PeterAttiaMD"><u>Instagram</u></a>.</p> </div>
Actionable Insights

1. Prioritize Metabolic Health

To delay the onset of death and chronic disease, it is essential to prioritize and fix one’s metabolism.

2. Embrace Diet and Exercise

Diet and exercise are the most effective strategies to address and reverse metabolic issues and improve overall health.

3. Find Sustainable Weight Loss

Identify a weight loss strategy that works for you and that you can adhere to long-term, as sustained adherence is crucial for lasting results beyond initial weight loss.

4. Reverse Muscle Insulin Resistance with Exercise

Engage in regular exercise, such as three 15-minute bouts on a StairMaster at 65% MVO2 max for six weeks, to normalize insulin-stimulated muscle glycogen synthesis and reverse insulin resistance.

5. Acute Exercise Reduces Liver Fat

A single 45-minute bout of exercise can lead to increased glucose deposition as muscle glycogen, significant reductions in de novo lipogenesis, and lower liver triglycerides.

6. Exercise for Type 1 Diabetes

Patients with Type 1 diabetes engaging in modest intensity aerobic exercise (e.g., brisk walking for 1-2 hours daily) can achieve reasonable glycemic control with significantly reduced insulin requirements, especially when restricting carbohydrates.

7. Understand Insulin Resistance

To truly understand longevity, it is crucial to comprehend the meaning and implications of insulin resistance.

8. Prioritize Subcutaneous Fat Storage

If fat must be stored, it is metabolically healthier to store it subcutaneously rather than inside liver and muscle cells.

9. Monitor Triglyceride Levels

Consider triglyceride levels above 100 mg/dL as abnormal and a red flag, especially if they are more than twice your HDL cholesterol.

10. Assess Insulin Sensitivity

To understand your metabolic health, consider getting tested for insulin sensitivity, which can reveal insulin resistance even in lean, young individuals.

11. Re-listen to Complex Content

When encountering technical or complex information, re-listening to the content can significantly aid in retention and deeper understanding.

12. Explore Membership Program

To deepen your knowledge in health and wellness, consider joining the podcast’s membership program for in-depth content and benefits at peteratiyahmd.com/subscribe.