Episode 14: Overcoming Insulin Resistance in Type 1 Diabetes

Click here for Episode 14: Overcoming Insulin Resistance in Type 1 Diabetes

Click here for the detailed 3-part write up

Show notes

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 insulin resistance
• Notes the influence of residual C-peptide production.

11:30 – 22:35 | Deep Dive Into the 8 Causes

1. Beta Cell Dysfunction – No suppression of glucagon after meals.
2. Muscle Insulin Resistance – Fat accumulation blocks insulin signalling.
3. Liver Insulin Resistance – Continued glucose output after meals.
4. Fat Cell Dysfunction – Insulin locks fat in cells, making weight loss harder.
5. Kidney Insulin Resistance – Increased glucose reabsorption via SGLT2.
6. Brain Insulin Resistance – Alters hunger signalling, increases appetite.
7. Gut Hormone Dysfunction – Reduced GLP-1 and GIP response.
8. Hyperglucagonemia – Excess glucagon drives glucose release from liver.

22:35 – 31:40 | Lifestyle Solutions

• Activity:
  • Most powerful tool. Reduces TDI, improves insulin sensitivity.
  • Activity “snacking” helps (e.g., a walk after meals).
• Weight Loss:
  • 5–20% weight loss improves insulin resistance.
  • Strategy: High protein (1.5–2g/kg), strength training, 500–1000 kcal deficit.
• Nutrition:
  • Limit saturated fat and liquid sugars (especially fructose).
  • Moderate carb (25–40% daily intake).
  • Use glucose-only hypo treatments.
  • Emphasize fibre and pre-bolusing.

31:40 – 43:10 | Pharmacological Solutions

1. GLP-1 Receptor Agonists (e.g. Semaglutide):
   • Benefits: Weight loss, lower insulin needs, reduced glucagon.
   • RCT shows 10% weight loss, 10% TIR improvement.
2. Dual GLP-1/GIP Agonists (e.g. Tirzepatide):
   • Greater effect in T2D (22% weight loss).
   • Small observational study in T1D shows 30% insulin dose reduction.
   • Not yet funded or licensed for T1D.
3. SGLT2 Inhibitors:
   • Block glucose reabsorption.
   • Increase glucose excretion.
   • Caution: DKA risk.
4. Pioglitazone:
   • Redistributes fat from liver/muscle to subcutaneous tissue.
   • Effective but misunderstood due to minor weight gain.
5. Metformin:
   • Works in liver to reduce glucose output.
   • Less potent than other agents (~5% insulin dose reduction).

43:10 – 45:30 | Final Thoughts

• Multiple drivers = need for multifaceted approach.
• Summary:
  1. Maximize physical activity.
  2. Target weight loss if needed.
  3. Reduce saturated fat and liquid sugar.
  4. Consider pharmacology if needed, in discussion with your team.
• John reflects on his own insulin needs increasing due to injury and how he’s adjusting accordingly.

45:30 – End | Teaser & Close

• Upcoming episodes: Partying with T1D, under-5s management, and skincare for tech users.
• Encouragement to share, comment, and revisit the content.
• John thanks listeners and acknowledges how long it took to learn this—compressed into 40 minutes.

Resources

• The GNL Insulin Resistance Guide
• C-Peptide article