Episode 14: Overcoming Insulin Resistance in Type 1 Diabetes

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

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

Beta Cell Dysfunction – No suppression of glucagon after meals.
Muscle Insulin Resistance – Fat accumulation blocks insulin signalling.
Liver Insulin Resistance – Continued glucose output after meals.
Fat Cell Dysfunction – Insulin locks fat in cells, making weight loss harder.
Kidney Insulin Resistance – Increased glucose reabsorption via SGLT2.
Brain Insulin Resistance – Alters hunger signalling, increases appetite.
Gut Hormone Dysfunction – Reduced GLP-1 and GIP response.
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., 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

GLP-1 Receptor Agonists (e.g. Semaglutide):
- Benefits: Weight loss, lower insulin needs, reduced glucagon.
- RCT shows 10% weight loss, 10% TIR improvement.
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.
SGLT2 Inhibitors:
- Block glucose reabsorption.
- Increase glucose excretion.
- Caution: DKA risk.
Pioglitazone:
- Redistributes fat from liver/muscle to subcutaneous tissue.
- Effective but misunderstood due to minor weight gain.
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: alcohol and T1D, under-5s management, and skincare for tech users.
Encouragement to share, comment, and revisit the content.
Thanks listeners and acknowledges how long it took to learn this—compressed into 40 minutes.

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