Body and Brain
Diabetes is no longer a problem primarily of overweight, insulin-resistant Americans.
In just two decades, the number of people in the world with diabetes has rocketed from 30 million to 285 million, with the latter number projected to increase another 60 percent by 2030.
China has the highest number of diabetics over the age of 20, approximately 39 million, followed by India with 30 million and the United States with 26 million diabetes patients. Seven of the 10 countries with the highest number of known diabetics are in the developing world.
We asked Dr. Jerrold Olefsky, a professor of medicine and longtime diabetes researcher at the University of California San Diego, to talk about why the disease has gone global and what can be done.
Q: What are the factors driving the growth of diabetes worldwide?
A: It’s important to understand that Type 2 diabetes (the most common form of the disease) is characterized by a condition called “insulin resistance,” in which the body does not effectively use the insulin secreted from the pancreas. The Type 2 diabetes epidemic is paralleled by an obesity epidemic. And since obesity is the most common cause of insulin resistance, it is the obesity epidemic that is driving the rising incidence of Type 2 diabetes.
Not all obese people are diabetic, but the great majority of people with Type 2 diabetes are obese. As dismaying as this is, the situation is made worse by the fact that the obesity epidemic in the U.S. is affecting younger and younger people. This is a particularly bad scenario because, in general, the longer you have diabetes, the greater the complications.
If you want to identify the major factors causing the diabetes epidemic, you need to look no further than our collective waistlines. We are an increasingly sedentary society, constantly bombarded with the easy availability of convenient, calorically dense, relatively cheap foods that are easy to prepare. In fact, preparation is not even necessary. Fast food restaurants are everywhere. From a global perspective, urbanization and Westernization are the key underlying causes of obesity and Type 2 diabetes.
Q: How well is diabetes understood? How much remains a mystery?
A: In recent years, there have been tremendous advances in our understanding of the cellular and molecular causes of Type 2 diabetes, and while many questions still remain, a reasonable understanding of this disease has emerged.
There are two main factors to consider: insulin resistance and decreased insulin secretion. Insulin resistance is a condition in which the insulin that the body secretes from the pancreas in response to rising blood glucose levels does not work efficiently to stimulate removal of glucose from the blood stream. We know that obesity sets up a situation of chronic, low-grade tissue inflammation, and this inflammatory response causes liver, muscle and fat cells to become insulin resistant. There is also a buildup of excess lipids (fats) and lipid metabolites in cells, which can make insulin resistance worse.
As if this weren’t enough, diabetic patients also have a problem with respect to insulin secretion. When a normal person eats carbohydrate- and protein-containing foods, the pancreatic response is to increase the rate of insulin secretion which then stimulates tissues to efficiently metabolize these foodstuffs. In patients with Type 2 diabetes, the pancreatic islets do not respond properly to increased glucose levels and insulin secretion is subnormal. When you have inadequate insulin secretion coupled with insulin resistance, it’s not hard to see why hyperglycemia (high glucose levels) occurs.
Q: Lifestyle and diet are central to both preventing and treating diabetes, but changing behaviors seems more problematic and challenging than, say, developing a pharmacological solution. Is diabetes a disease that could, theoretically, be solved with a pill?
A: As attractive as a single pill might sound, such a magic bullet is not around the corner. The hard work of diet and exercise remain the cornerstones of anti-diabetic therapy.
Given the major role of obesity in causing Type 2 diabetes, an anti-obesity pill would have major clinical benefit as an anti-diabetic therapeutic, but this has been a difficult challenge with many more failures than successes. Humans are wired to eat. It’s in our DNA as a survival mechanism. This hard-wiring has proved maladaptive in a society where there is an overabundance of readily available food.
Since such a pill would have to be taken chronically, it would need to be extremely safe with sustained long-term efficacy. No such medicine has been identified.
There are, however, pharmacologic treatments for aspects of diabetes, such as boosting insulin secretion, correcting insulin resistance or lowering blood sugar levels. Current combination therapies are generally effective for most patients. Of course, newer and better anti-diabetic medications are always needed. The good news is that there are several new therapeutics currently in different stages of clinical testing.