Most of us know insulin resistance means your body doesn’t respond well to insulin. But did you know that some people develop high insulin levels not because of resistance, but because their bodies don’t clear insulin properly? 

I am going to explain the difference between insulin resistance and insulin clearance. 

Both conditions can lead to type 2 diabetes, obesity, and fatty liver, but through very different mechanisms. 

Insulin resistance happens when your body’s cells, especially in the muscle, liver, and fat tissues, stop responding effectively to insulin. 

In healthy individuals, insulin helps glucose move from your bloodstream into your cells for energy. But when resistance develops, your body needs more insulin to achieve the same effect. Over time, this leads to hyperinsulinemia, or high insulin levels. 

Insulin clearance is the process by which insulin is removed from the circulation, mainly by the liver. The process is called hepatic insulin clearance. And to a lesser extent, by the kidney and peripheral tissues.

If your liver doesn’t clear insulin efficiently, insulin builds up in your blood. Even if your cells aren’t resistant, you may still have elevated insulin levels, called reduced insulin clearance. 

Reduced insulin clearance leads to metabolic syndrome:

When insulin clearance is reduced, your body stays in a high-insulin state for longer periods. Chronic high insulin, even in the absence of resistance, can:

• Promote fat storage in the liver and the abdominal region.   
• Suppress breakdown lipids and increase burn fat. 
• It causes downregulation of insulin receptors, creating insulin resistance. 

So, reduced clearance can actually cause insulin resistance later and create a cycle. 

The liver is central to both insulin action and insulin clearance. When the liver accumulates fat it leads to Non-alcoholic fatty liver disease, and it loses its ability to metabolise insulin efficiently. 

This leads to less clearance, more circulating insulin, and further accumulation of fat. In clinical practice, we check fasting insulin or HOMA-IR to assess resistance, but we rarely look at insulin clearance. Understanding clearance could help explain why some lean individuals have high insulin and metabolic issues, while some obese individuals maintain normal insulin sensitivity. 

Metabolic assessment might include C-peptide to insulin ratios, a marker for insulin clearance, to personalise metabolic treatment and detect early dysfunction. 

Both insulin resistance and reduced clearance can be improved by:

• Exercise enhances insulin sensitivity and promotes hepatic insulin metabolism. 
• Calorie control and weight loss reduce liver fat and restore insulin clearance. 
• Higher-fibre, low-refined-carbohydrate diets stabilise insulin secretion. 
• Sleep and stress management also regulate insulin pathways.

Kripa, is a Specialist Dietitian at The London Obesity & Endocrine Clinic. She has helped many patients overcome weight management barriers. ©Simplyweight


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