A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors

Figure 2

Progression from obesity through metabolic syndrome to diabetes and to increased cancer risk. As an individual’s weight increases, they progress from having a normal weight to being overweight and with time become obese. There is a concomitant increase in high levels of circulating nonesterified fatty acids accompanied by high fasting serum glucose concentrations or hyperglycaemia. Many of these obese individuals exhibit a sufficient number of the defining symptoms to be classified as having metabolic syndrome. The high fasting serum glucose and development of insulin resistance induce chronic secretion of insulin from the pancreas, and the individual manifests hyperinsulinaemia. Eventually, the excessive demands on the pancreas lead to failure of insulin secretion, and diabetes is established. Diabetic therapies stimulate insulin secretion or administer exogenous insulin. Insulin concentrations must reach supraphysiological levels to be effective because of the chronic insulin resistance caused by the continued high concentrations of nonesterified fatty acids released from adipocytes. The combination of hyperinsulinaemia and endocrine or paracrine stimuli from adipose tissue increases the risk that these individuals will develop certain types of cancers.