Obesity is a problem because it increases insulin resistance, limiting the body’s ability to use insulin. Insulin resistance is believed to be the first sign of what can become diabetes. As it turns out, fat is not just an inactive tissue that sits there in the body. It produces, especially when inflamed, cytokines (a type of protein) that affect the liver, which in turn produces substances that interfere with insulin usage.
Another potentially negative impact of excess fat is that people who are obese have high levels of free fatty acids (FFAs) in their blood. Various tissues take up the FFAs and use them instead of glucose as fuel. The result is insulin resistance and increased blood glucose levels.
Obesity is not a guarantee of diabetes, however. In fact, only 20% to 25% of people at risk for diabetes (whether obese or not) will develop abnormal beta-cell function and ultimately diabetes. The reason goes back to Dr. Cumming’s reference to the “health” of the individual’s beta cells, and is thought to be tied to the cells’ genetic programming.
An increase in insulin resistance causes the beta cells to compensate by increasing secretion of insulin. In fact, people who are obese and have insulin resistance actually increase the number of beta cells and their output of insulin. This compensation keeps blood glucose levels normal. The compensation can go on for many years, or for a lifetime. People can be obese and even insulin resistant their entire lives and never develop diabetes. In diabetes, however, the compensation either fails to occur at all, or cannot keep up with the insulin resistance. Essentially, the beta cells are either genetically programmed to compensate, or they aren’t.
Taken as a whole, the most common contemporary view is that a genetic predisposition to diabetes is necessary — but not sufficient — to develop the disease. The trigger is environmental: obesity (which itself has a genetic basis), aging, and/or lifestyle. Once the process starts, a cascade of dysfunctions occurs: The beta cells begin to fail, there is an increase in glucose secretion by the liver, and insulin resistance increases. The beta cells cannot compensate, and they continue to deteriorate, raising blood glucose levels — a vicious cycle.
There is another view, however. Dr. Daniel Porte, Jr., Professor of Medicine at the University of California, San Diego, School of Medicine, and his collaborators have suggested that a “primary defect” in the beta cell reduces insulin secretion. This affects the complex central nervous system regulatory mechanism that controls energy homeostasis, or a state of equilibrium in the body. Specifically, in this theory, reduced insulin availability to the brain causes signals to increase food intake, leading to obesity and subsequent obesity-induced insulin resistance. Ultimately, the same vicious cycle is created. The difference is that the “neurocentric” model places the beginning of the process in the beta cells rather than in excess body fat.
The neurocentric model would place more emphasis on environmental factors such as abundant, high-calorie foods and lack of physical activity. Both of these factors enhance the response to the brain’s hunger signals.
“Fetal origins” hypothesis
Another interesting hypothesis that may ultimately support either of the others is the “fetal origins” hypothesis. It has long been observed that there is a relationship between birth weight and the risk of developing diabetes later in life. Some researchers have described the relationship as “linearly inverse”—that is, low birth weight is a predictor of diabetes—while others have described it as “u-shaped,” meaning that there are consequences to both low and high birth weight. Various causal factors that have been suggested include either maternal undernutrition or overnutrition.