Endocrine system

Insulin resistance (diabetes and nonalcoholic fatty liver disease)

Mechanisms by which obesity influences the disease state

In individuals with overweight or obesity, adipose tissue is overwhelmed with free fatty acids, and this can lead to the deposition of fatty acid into tissues that normally take up glucose, including muscle, liver, and pancreatic beta cells. This results in reduced insulin sensitivity to glucose, and insulin resistance. Not all individuals with obesity who develop insulin resistance will go on to develop diabetes as their pancreatic beta cells can manage to release adequate levels of insulin to compensate for the decreased insulin sensitivity. However, insulin resistance is a risk factor for the development of diabetes, and in cases where the pancreatic beta cells are unable to produce enough insulin to compensate for the decreased insulin sensitivity, diabetes and the potential for hyperglycemia occur⁷.

Insulin resistance can also result in other problems as well as diabetes. Insulin regulates the synthesis of the lipoprotein lipase, which ordinarily breaks down triglycerides (fats). For this reason, insulin resistance can cause increased levels of triglycerides, which causes more fatty acid to be transported to the liver, and this can in turn lead to nonalcoholic fatty liver disease⁸.

Benefits of weight loss

• Whilst weight gain causes a reduction in insulin sensitivity, evidence shows us that weight loss which is maintained results in enhanced insulin sensitivity⁹, therefore reducing the risk of diabetes and fatty liver disease.
• A major multicenter clinical trial showed that weight loss of 5-7% of body weight reduced the risk of developing type 2 diabetes by 58% in adults.¹⁰