14: Overcoming Insulin Resistance in Type 1 Diabetes

In this deep-dive episode, John Pemberton explores the misunderstood world of insulin resistance in people with type 1 diabetes. Drawing on years of personal experience, clinical expertise, and the latest research, he breaks down why insulin resistance matters—even in a condition defined by insulin deficiency.

Click here for the detailed 3-part write up

The episode walks through the 'Ominous Octet', eight mechanisms that drive insulin resistance, and explains how they impact blood glucose control, weight management, and long-term health. More importantly, it offers practical strategies to reduce total daily insulin dose through lifestyle changes, activity, nutrition, and pharmacological options.

Whether you're living with T1D, supporting someone who is, or simply want to better understand the complex interplay between insulin and the body, this episode provides clarity and direction.

Takeaways:

• People with T1D often require more insulin due to lack of portal delivery and higher peripheral levels
• Insulin resistance occurs in the liver, muscle, brain, kidneys, gut, and fat tissue
• Measuring units per kilogram is a useful proxy for insulin sensitivity
• Activity is the most powerful modifiable factor for improving insulin sensitivity
• Weight loss, high-protein diets, and reduced saturated fat intake all help reduce resistance
• GLP-1 and dual agonists (e.g., tirzepatide) show promise for T1D, but are not yet widely approved
• SGLT2 inhibitors and pioglitazone offer targeted benefits but must be used with care
• A multifaceted approach is often needed to lower insulin needs and support health

Chapters:

00:00 - 02:10 | Introduction

• John Pemberton welcomes listeners to Episode 14.
• Shares his background: living with T1D, creating the Glucose Never Lies Education Programme, and motivation from personal and family experiences.
• Introduces co-host Louise (not present in this episode).
• Outlines the episode focus: insulin resistance in type 1 diabetes.

02:10 - 04:35 | Why Insulin Resistance Matters in T1D

• T1D often leads to higher insulin doses.
• High insulin doses are linked to increased risk of cardiovascular disease and mortality.
• Importance of understanding and managing insulin resistance to reduce long-term health risks.

04:35 - 06:50 | The Metabolic Disadvantage in T1D

• Describes differences in insulin delivery: endogenous (via portal vein in non-diabetics) vs. exogenous (subcutaneous in T1D).
• Explains how peripheral insulin levels are 4–8x higher in T1D, contributing to insulin resistance.

06:50 - 09:15 | The Ominous Octet

• Introduces eight mechanisms of insulin resistance (based on Dr. Ralph DeFronzo’s work): 
  1. Liver insulin resistance
  2. Muscle insulin resistance
  3. Beta-cell dysfunction
  4. Hyperglucagonemia
  5. Brain insulin resistance
  6. Gut hormone dysfunction
  7. Fat cell dysfunction
  8. Kidney (renal) insulin resistance

09:15 - 11:30 | Measuring Insulin Resistance

• Euglycemic clamp = gold standard (not used in T1D).
• Use total daily insulin (TDI) per kilogram as a practical metric.
• Defines ranges:
  • <0.4 units/kg = insulin sensitive
  • 0.5–0.7 = mild insulin resistance
  • 0.7–1.0 = moderate
  • 1.0 = high insuli