The exact cause of insulin resistance remains unknown. However, there are several factors whose presence increases the likelihood that insulin resistance will be found. They include:

• Overweight and obesity, particularly abdominal obesity. Extra fat tissue makes the body more resistant to insulin’s effects.
  
  
• Lack of physical activity.
  
  
• Low HDL (“good”) cholesterol and high LDL (“bad”) cholesterol.
  

• 

• High blood pressure.
  
  
• Acanthosis nigricans. A condition that manifests as dark patches of skin.
  
  
• Genetics. A history of type 2 diabetes in immediate family.
  
  
• Polycystic ovarian syndrome.
  
  
• Age older than 45.
  
  
• Smoking.
  
  
• Race and ethnicity. People who belong to certain ethnic groups, including Latinos, African-Americans, Native Americans and some Asian-Americans, are more prone to insulin resistance and type 2 diabetes.
  
  
• Gestational diabetes.
  
  
• History of heart disease.
  
  
• Certain medications. For example, certain steroids are inhibitory to the islet cells of the pancreas and can cause insulin resistance, according to the American Diabetes Association. Other drugs that may lead to insulin resistance include antiretrovirals (HIV drugs), estrogens and some antihypertensives.
  
  
• Low levels of testosterone (male hypogonadism). Recent studies link declining levels of testosterone in men (occurring naturally with age or as the result of testosterone-blocking drugs used to treat some prostate cancers) to insulin resistance, sexual dysfunction and other health problems.
  
  
• Certain chemicals. Some research has linked insulin resistance to Agent Orange, a dioxin-containing herbicide used during the Vietnam War. In 2005, the U.S. Department of Defense finished analysis of its 20-year Air Force Health Study by concluding that type 2 diabetes was the most important health problem found in the crewmen who sprayed Agent Orange. Some studies have found a possible link between other chemicals, such as bisphenol A (found in many consumer plastics), and insulin resistance.

Many researchers believe that abnormalities in chemical reactions within the cells prevent the cells from properly reacting to insulin. There is some evidence that patients with insulin resistance lack a glucose transporter called GLUT4. Glucose transporters are the molecules that move glucose (blood sugar) into the cells.

Research also indicates that substances in the blood including RBP4 (retinol binding protein) and PAI-1 (plasminogen inactivator) may be involved in insulin resistance. Scientists have found that some people have extreme insulin resistance because of autoantibodies (self antibodies) to the insulin receptor or mutations in the insulin receptor.