Insulin resistance comes first. Hyperinsulinaemia follows. Obesity emerges downstream.

A recent review paper suggests that insulin, rather than insulin resistance, is a key driver of obesity. This thinking places a significant burden upon #suger as a key driver for insulin induced obesity. The authors state the following -

• Reducing refined carbohydrates

• Managing glycaemic load

The “hyperinsulinaemia causes obesity” model is compelling, but it risks oversimplifying a tightly coupled system. An alternative interpretation is:

Insulin resistance comes first. Hyperinsulinaemia follows. Obesity emerges downstream.

1. The Compensation Model: Why Insulin Rises

In early metabolic dysfunction, tissues—especially muscle and liver—become less responsive to insulin.

Key Point

Elevated insulin may not be pathological at first—it is homeostatic compensation to maintain normal glucose levels.

This is well documented in prediabetes, where:

• Blood glucose can remain normal

• Insulin levels are already significantly elevated

2. What Causes Insulin Resistance in the First Place?

The critique gains strength when examining upstream drivers. Insulin resistance is strongly linked to:

Ectopic Fat Accumulation

Fat stored in non-adipose tissues (liver, muscle) interferes with insulin signaling.

Inflammation

Low-grade chronic inflammation disrupts intracellular pathways like IRS–PI3K–Akt.

Mitochondrial Dysfunction

Reduced oxidative capacity impairs energy handling, promoting lipid buildup.

Genetic Susceptibility

Some individuals develop insulin resistance independent of insulin exposure levels.

3. Mechanistic Conflict: Cause vs Consequence

The hyperinsulinaemia model assumes:

High Insulin → Fat Gain → Insulin Resistance.

But the alternative model suggests: Insulin Resistance → High Insulin → Fat Redistribution & Gain.

Why This Matters

If insulin resistance is primary:

• Lowering insulin alone may not address root dysfunction

• The real issue is cellular energy handling, not just hormonal signaling

4. Evidence from Human Studies

Several lines of evidence challenge insulin-first causality:

A. Lean Insulin-Resistant Individuals

Some people develop insulin resistance without obesity, suggesting:

• Resistance is not merely a consequence of fat gain

• It can precede and potentially drive later weight gain

B. Overfeeding Studies

In controlled overfeeding:

• Insulin rises after metabolic stress begins

• Lipid accumulation and reduced insulin sensitivity often appear early

C. Pharmacological Evidence

Drugs that increase insulin levels do not universally cause obesity in all contexts, and:

• Some insulin-sensitizing drugs improve weight/metabolic outcomes without lowering insulin directly

5. The Role of Adipose Tissue Expandability

A more nuanced model centers on fat storage capacity:

• If subcutaneous fat can expand safely → metabolic health preserved

• If capacity is exceeded → fat spills into liver/muscle → insulin resistance

In this view:

• Insulin is attempting to protect against lipotoxicity

• Failure of storage systems—not insulin itself—is the core issue

6. Reconciling Both Views (Most Likely Reality)

The most defensible position is not binary, but bidirectional: Insulin Resistance ↔

Hyperinsulinaemia

↓

Positive Feedback Loop

↓

Progressive Weight Gain

• Insulin resistance can initiate the process

• Hyperinsulinaemia can amplify and sustain it

7. Implications for Treatment

If insulin resistance is primary

Focus Areas Shift

• Improve insulin sensitivity (exercise, weight training, sleep)

• Reduce ectopic fat (especially liver fat)

• Address inflammation and metabolic flexibility

Dietary Interpretation Changes

It’s not just about lowering insulin spikes:

• Total energy balance still matters

• Nutrient partitioning depends on tissue health

Bottom Line

The insulin-centric model is valuable—but incomplete on its own.

Hyperinsulinaemia may be a powerful accelerator of obesity—but insulin resistance is likely the spark.

Ignoring insulin resistance risks treating a downstream signal rather than the upstream dysfunction.