What mechanisms lead to insulin resistance in cells in the presence of long-term high blood sugar levels?

THE insulin resistance of cells The development of diabetes is caused by several interrelated mechanisms, including long-term high blood sugar levels:

• Continuous insulin loading: 

Due to persistently high blood sugar levels, the pancreas continuously produces large amounts of insulin to transport sugar into the cells.

This continuous high insulin level (hyperinsulinemia) over time reduces the insulin sensitivity of cells, meaning that the cells become less and less responsive to insulin 2 3 .

• Obesity, especially belly fat: 

Visceral adipose tissue releases hormonally active, pro-inflammatory substances (e.g. cytokines) that impair insulin effectiveness. This increases inflammation, which further impairs cellular insulin sensitivity 1 4 6 .

• Sedentary lifestyle: 

Lack of physical activity reduces the insulin sensitivity of muscle cells, making the body less able to use the glucose in the blood 1 4 .

• Diet high in sugar and refined carbohydrates: 

Regular consumption of these results in consistently high insulin levels, which in the long term reduces the cells' response to insulin 1 5 .

• Chronic inflammation: 

Persistent inflammation in the body—often caused by obesity, especially abdominal fat—further impairs the effectiveness of insulin in cells 1 6 .

• Hormonal imbalance: 

Certain hormonal disorders (e.g., hypothyroidism, PCOS) can also reduce insulin sensitivity 1 5 .

• Receptor problems: 

In the long term, the function of insulin receptors on the surface of cells deteriorates or they are formed incorrectly, so insulin is less able to affect the cells 7 .

• Genetic factors: 

In some people, hereditary predisposition also plays a role in the development of insulin resistance 2 7 .

• Stress and cortisol: 

Chronic stress causes high cortisol levels, which also worsens insulin sensitivity 1 .

• Sleep disorders: 

Poor quality or insufficient sleep causes hormonal imbalances, which reduce insulin sensitivity 5 .

In summary:

Due to persistently high blood sugar levels, the body constantly produces too much insulin, and the cells "adapt" to it, becoming less and less responsive to it.

This process is further exacerbated by obesity, lack of exercise, poor diet, inflammation and hormonal imbalances, which together lead to insulin resistance for the development of 1 2 3 5 .