Introduction: Overcoming Insulin Resistance with T1D

This is the Insulin Resistance in Type 1 Diabetes guide. It’s a practical, mechanism-first framework for understanding why insulin stops working as well over time in T1D — and what you can realistically do about it.

This is written for well-informed people living with T1D and clinicians. It’s deliberately more technical and conceptual than the exercise system, because insulin resistance is a systems problem: liver, muscle, fat, kidney, brain, gut hormones, glucagon — all pulling on the same rope.

Finish this page to understand the T1D challenge, or jump ahead if already familiar.

• Part 1: Defining Insulin Resistance in T1D
• Part 2: Eight Reasons for Insulin Resistance
• Part 3: Seven Solutions to Improve Insulin Sensitivity

Why insulin resistance matters in type 1 diabetes

Insulin resistance is often framed as a “type 2 diabetes issue”. That framing is too narrow. In type 1 diabetes, insulin resistance really matters because when insulin becomes less effective, glucose control becomes harder, insulin requirements creep up, and the whole system becomes noisier and more volatile.

More importantly, evidence suggests that as insulin resistance increases, the risk of cardiovascular events (heart attacks and strokes) and all-cause mortality rises in a dose–response manner in people living with T1D.

Why type 1 is uniquely exposed to insulin resistance

People with T1D do not produce insulin from the pancreas — but that does not make them immune to insulin resistance. In fact, the route of insulin delivery creates unique challenges.

In people without diabetes, insulin is released directly into the portal vein (the blood supply that goes straight to the liver). The liver gets first access to insulin, which helps shut down unnecessary glucose output quickly and store incoming meal glucose efficiently. Peripheral insulin exposure (muscle and fat) remains relatively low.

In T1D, insulin is delivered into subcutaneous tissue (under the skin), not the portal vein. That reverses the natural gradient:

• The liver can be under-insulinised, so it keeps producing glucose when it shouldn’t, contributing to glucotoxicity (high glucose itself drives insulin resistance).
• Peripheral tissues can be over-insulinised (muscle and fat see more insulin than nature intended), which can promote fat storage and metabolic dysfunction.

This liver–periphery mismatch is one reason insulin resistance can become a bigger practical problem in T1D than most people appreciate.

This diagram is worth including here because it explains a common mechanism (sometimes described as a DAG-driven effect in muscle), but it only covers one of the major drivers.

The framework: the Ominous Octet

This guide uses the Ominous Octet framework originally developed by Dr Ralph DeFronzo — eight dysfunctions that collectively drive insulin resistance and glucose dysregulation.

Although the Octet is typically taught in the context of type 2 diabetes, most of its principles also apply in T1D. The point here is not to relabel T1D as T2D. The point is to understand which biological levers are actually moving your insulin requirement.

This guide is an application of insights drawn from deep, mechanistic teaching resources. If you want to go all-in, these three long-form episodes are the backbone:

• Ralph DeFronzo — “Insulin resistance masterclass…”

What this guide covers (and what it doesn’t)

This three-part guide will cover:

• How insulin resistance works mechanistically in eight different ways (the Octet).
• Why those mechanisms matter in T1D specifically (portal–peripheral mismatch, glucagon behaviour, glucotoxicity, etc.).
• What can realistically improve insulin sensitivity, using both lifestyle and pharmacology as “tools”.

This is informational education, not individual medical advice. Several interventions here can require immediate insulin adjustment. Without pre-planned dose changes, hypoglycaemia risk can rise sharply.

Two examples that matter up front:

• GLP-1 receptor agonists are not officially indicated for T1D in most guidelines. In practice, insulin requirements can drop quickly (often materially). If insulin is not reduced deliberately, the risk of hypos rises.
• SGLT-2 inhibitors can raise DKA risk if not used carefully and with appropriate ketone awareness.

Defining insulin resistance in type 1 diabetes

The gold standard research method for measuring insulin resistance is the hyperinsulinaemic–euglycaemic clamp: insulin is infused at a fixed high rate and glucose is infused to maintain normal glucose levels. The more glucose required to hold euglycaemia, the more insulin sensitive the person is. It is highly accurate — and not practical for everyday clinical use.

In type 2 diabetes, insulin resistance is often inferred using fasting insulin or HOMA-IR. In T1D that approach breaks, because endogenous insulin production is absent or very low. In practice, insulin resistance in T1D is commonly approximated using total daily insulin (TDI) per kilogram (U/kg) — imperfect, but useful as a “signal”, especially across time.

What insulin-sensitive “looks like” in numbers

In a healthy adult without diabetes, the body produces roughly ~35 units of insulin per day. That is a rough reference point for high insulin sensitivity and low metabolic risk.

For adults living with T1D, typical total daily insulin requirements range from about 0.4 to 1.0 U/kg, but can be higher (sometimes up to 2.0 U/kg in more insulin resistant states).

Illustrative adult examples:

• 75 kg male: typically ~30–75 units/day, but at the higher end could be ~150 units/day.
• 60 kg female: typically ~24–60 units/day, but at the higher end could be ~120 units/day.

One way of framing insulin sensitivity in adults with T1D (estimated from DCCT data) is:

• <0.4 U/kg → very insulin sensitive (≈14%).
• 0.4–0.5 U/kg → insulin sensitive (≈11%).
• 0.5–0.7 U/kg → insulin resistance emerging (≈30%).
• 0.7–1.0 U/kg → significant insulin resistance (≈35%).
• >1.0 U/kg → high insulin resistance (≈9%).

For children aged 1–12, broadly similar ranges are often used (≈0.4–1.0 U/kg). For ages 12–18, insulin needs often rise due to puberty and hormones. One way of framing this (imputed from German DPV data) is:

• <0.4 U/kg → very insulin sensitive (≈2%).
• 0.4–0.6 U/kg → insulin sensitive (≈11%).
• 0.6–0.8 U/kg → insulin resistance begins (≈29%).
• 0.8–1.2 U/kg → significant insulin resistance (≈53%).
• >1.2 U/kg → high insulin resistance (≈5%).

Major in the majors: how to use these numbers without losing your mind

These categories are not a moral scoreboard. They are a signal. They help you see direction of travel and choose sensible interventions.

An important reality check: aiming for 0.4–0.6 U/kg can be aspirational for many adults with T1D — similar to aiming for very high time-in-range. The better question is: what is the next winnable step from where you are now?

Two practical examples of “winnable steps”:

• If you are currently >1.0 U/kg, getting below 1.0 is a meaningful physiological shift.
• If you are around 0.7 U/kg, moving to 0.6 can be a major improvement — but only if glucose control is maintained or improved.

Essential point: don’t sacrifice glucose control just to reduce insulin use. Lowering insulin at the expense of higher glucose levels is rarely a worthwhile trade-off. Don’t rob Peter to pay Paul.

Also: total daily insulin is influenced by many factors — age, puberty, sleep, illness, medications, weight distribution (visceral vs subcutaneous), ethnicity, gender, residual C-peptide (if present), and more. This guide reports common patterns; you still have to interpret them for your circumstances.

Why fat loss can feel like a trap in type 1 (the “doors” problem)

In T1D, higher peripheral insulin exposure can make fat storage easier and fat release harder. A useful mental model is two “doors” on the fat cell:

• The storage door (often described via lipoprotein lipase activity) can be pushed open by insulin.
• The exit door (often described via hormone-sensitive lipase activity) can be held shut by insulin.

When circulating insulin is high, fat can be stored readily while being difficult to mobilise. People can end up feeling like they are “starving from the outside and the inside”: reduced intake, but poor access to stored fuel. It’s not a character flaw. It’s an energetic access problem.

What happens next

This page is the frame. The real work is the next two parts:

• Part 2: Eight Reasons for Insulin Resistance — the Octet, explained in T1D terms.
• Part 3: Seven Solutions to Improve Insulin Sensitivity — lifestyle and pharmacology as complementary tools, with realistic trade-offs.

Navigation

• Part 1: What is Insulin Resistance with T1D
• Part 2: Eight causes for insulin resistance
• Part 3: Seven solutions to improve insulin sensitivity

GNL References

• Episode 14: Overcoming Insulin Resistance.
• Epiddose 17: GLP-1 Podcast
• Episode 8: Activity Snacking podcast
• Activity Guide
• Exercise Guide
• GLP-1 FAQ

Peter Attia “The Drive” Must Listens

• Attia #337 — Ralph DeFronzo masterclass
• Attia #87 — Rick Johnson on fructose
• Attia #140 — Gerald Shulman masterclass