What Causes Insulin Resistance? Understanding Why It Develops

Insulin resistance doesn’t develop overnight. It is the result of a combination of metabolic, hormonal, genetic, and lifestyle factors that gradually change how the body responds to insulin. Understanding these causes helps explain why some people progress to prediabetes or type 2 diabetes, while others do not.

In this article

• Weight Gain and Visceral Fat
• Physical Inactivity
• Diet and Inflammation
• Hormonal Conditions
• Medications That Reduce Insulin Sensitivity
• Genetics and Family History
• Other Medical Conditions

1. Weight Gain and Visceral Fat

One of the strongest contributors to insulin resistance is excess weight — especially fat stored around the abdomen. Visceral fat produces inflammatory chemicals that alter how insulin receptors work.

As fat cells enlarge, they change the shape of the insulin receptor (“the lock”), making it harder for insulin (“the key”) to open the channel that lets glucose enter the cell.

Over time, this drives higher insulin levels and eventually higher glucose levels. This process is the foundation of insulin resistance.

2. Physical Inactivity

Muscles are the largest site of glucose disposal in the body. When muscles are not regularly used, they become less responsive to insulin. Even a modest increase in activity improves how efficiently muscles take up glucose.

3. Diet Patterns and Inflammation

Diets high in ultra-processed foods, refined carbohydrates, added sugars, and saturated fats can worsen insulin resistance. These foods contribute to inflammation, weight gain, and impaired cellular insulin signalling.

In contrast, dietary patterns rich in fibre, vegetables, legumes, and minimally processed foods can improve insulin sensitivity over time.

For more on reversing insulin resistance, see our upcoming guide: How to Improve Your Insulin Sensitivity.

4. Hormonal Conditions That Cause Insulin Resistance

Several endocrine disorders can reduce insulin sensitivity, independent of weight or lifestyle. These include:

• PCOS (Polycystic Ovary Syndrome) – strongly linked with insulin resistance.
• Cushing’s Syndrome – excess cortisol counteracts insulin’s effect.
• Acromegaly – high growth hormone reduces insulin sensitivity.
• Hypothyroidism – slows metabolism and worsens glucose handling.

Insulin resistance plays a major role in the development of metabolic syndrome and fatty liver disease as well.

5. Medications That Can Cause Insulin Resistance

Some commonly used medicines interfere with how the body responds to insulin. These include:

• Glucocorticoids (steroids)
• Certain blood pressure medicines
• Antipsychotic medications
• Some HIV treatments

6. Genetics and Family History

Some people are genetically more prone to insulin resistance. A family history of type 2 diabetes, gestational diabetes, or PCOS significantly increases the likelihood of developing it.

Ethnic groups with higher risk include Asian, South Asian, African, Middle Eastern, Hispanic, and Pacific Islander backgrounds.

7. Other Medical Conditions Associated With Insulin Resistance

Certain rare genetic or metabolic conditions can also impair insulin signalling, including lipodystrophy, myotonic dystrophy, and Werner syndrome. While uncommon, they highlight the diverse biological pathways that affect insulin sensitivity.

Trusted External Sources

• NIDDK – Insulin Resistance & Prediabetes
• CDC – Insulin Resistance Basics
• PubMed – Research on insulin resistance mechanisms

These links provide additional evidence-based information without directing users to commercial competitor sites.