Diabetes: Two Centuries of Scientific Advances Tempered by Two Decades of Societal Setbacks

Dean Kenneth Polonsky Kenneth S. Polonsky, MD

The year 1812 was full of historic events: French Emperor Napoleon Bonaparte invaded Russia, the United States declared war on the United Kingdom, and English author Charles Dickens was born. It was also the year when a humble Boston-based publication got its start, only to become the most widely read and respected medical journal in the world, with more than 600,000 readers in 177 countries.

As part of a celebration to mark its bicentennial, the New England Journal of Medicine has invited top experts in various fields to contribute to a series of 26 articles and essays to illustrate how far medicine has come along in those two centuries. Among articles in the Oct. 4 issue is one chronicling "The Past 200 Years in Diabetes," written by Kenneth S. Polonsky, MD, who is identified simply as being "from the Department of Medicine, University of Chicago."

Although diabetes had been recognized for more than 3,000 years by 1812, "essentially nothing was known about the mechanisms responsible for the disease," writes Polonsky, executive vice president for medical affairs at the University of Chicago and dean of the Biological Sciences Division and Pritzker School of Medicine. "No effective treatment was available and diabetes was uniformly fatal within weeks to months."

Since then, researchers have made enormous progress. Ten scientists received the Nobel Prize for work related to the disease. Insulin was hypothesized in 1910, discovered in 1921, and successfully tested in humans in 1922 -- a series of events that "may be the most dramatic example of the rapid translation of discovery in basic science into a benefit for patients," he writes.

Insulin serves as a flagship for the entire biological revolution. It was one of the first proteins for which the amino acid sequence was determined, the first hormone to have its three-dimensional crystal structure determined, the first hormone cloned and the first to be produced by recombinant DNA technology, the foundation for the biotech industry.

Unfortunately, while "there is much good news to report regarding diabetes" from the scientific viewpoint, Polonsky writes, "from a public health standpoint little progress has been made … and we are arguably worse off now than we were in 1812."

Diabetes now affects 21 million people in the United States, nearly 27 percent of those over 65 years of age, at an estimated annual cost of $174 billion in 2007.

As physicians learned how to treat severe insulin deficiency, the common form of the disease in 1812, changes in diet and lifestyle, and the massive surge in obesity, have led to a worldwide epidemic of type 2 diabetes, which involves insulin resistance and impaired insulin secretion. As a result, diabetes has become "one of the most common and most serious medical conditions humankind has had to face," he says.

Despite this epidemic, thanks to advances in immunology, the discovery of diabetes susceptibility genes and the identification of relevant molecular pathways and new gene targets, Polonsky remains optimistic that another breakthrough as dramatic as the discovery of insulin will occur.

"Timely prevention of this disease at the population level is essential," Polonsky concludes. "Lifestyle modification will undoubtedly play a key role," he adds, but "more definitive solutions will depend on the ability of basic science to point prevention and treatment in new directions."

October 2012