January 24, 2017 | by Samantha Bonar
City of Hope’s Diabetes & Metabolism Research Institute is committed to developing a cure for type 1 diabetes within six years, fueled by a $50 million funding program led by the Wanek family. Here, we take a closer look at the disease.
Type 1 diabetes is an autoimmune disorder in which the body’s immune system attacks and destroys the insulin-producing beta cells of the pancreas.
“Type 1 diabetes is very complicated,” said Defu Zeng, a professor in the Department of Diabetes Immunology at City of Hope who has been working on a cure for type 1 diabetes for the past 10 years. “It is caused by multiple genetic as well as environmental factors.”
It is a relatively rare disorder, affecting only about 1 million people in the United States. People with type 1 diabetes make up just 5 percent of the total diabetic population (which includes those with type 2 diabetes), according to the American Diabetes Association. It is usually diagnosed in children and young adults and was previously known as juvenile diabetes.
In type 1 diabetes, because of the destruction of the beta cells, the body does not produce sufficient insulin. Insulin is a hormone secreted by the pancreas that breaks down sugars and starches into a simple sugar called glucose, which cells use to perform essential functions. Insulin allows glucose to get from the bloodstream into the cells of the body. This process is essential for life.
While type 1 diabetes appears to have a strong genetic component, environmental factors such as viruses may trigger the disease.
Although type 1 diabetes was first documented more than 3,500 years ago, it was only in the last century with the discovery of insulin that some significant progress has been made against the disease.
The first known mention of diabetes symptoms was in 1552 B.C., when an Egyptian physician, Hesy-Ra, documented frequent urination as a symptom of a mysterious disease that also caused patients to waste away.
In 150 A.D., the Greek physician Arateus described the disorder as "the melting down of flesh and limbs into urine."
Centuries later, people known as "water tasters" diagnosed diabetes by tasting the urine of people suspected to have it. Those with sweet-tasting urine were diagnosed with diabetes.
In 1675, the word "mellitus," meaning honey, was added to the name "diabetes," meaning siphon. It wasn't until the 1800s that scientists developed chemical tests to detect the presence of sugar in urine, putting the “water tasters” out of business.
Early treatments for diabetes included exercise and a highly restricted diet. Early 19th-century diabetic diets included the "oat cure," "potato therapy" and the hugely popular "starvation diet."
Inevitably, diabetes led to premature death. In 1897, the average life expectancy for a 10-year-old child with diabetes was about a year. Those diagnosed at age 30 could expect to live about four years.
Doctors began to suspect the link between the pancreas and the disorder in the late 1800s, when researchers discovered that removal of a dog’s pancreas led to diabetes. In the early 1900s, Georg Zuelzer, a German scientist, found that injecting pancreatic extract into patients could help control symptoms. The unknown pancreatic extract was dubbed “insulin” in 1909.
A huge breakthrough came in the 1920s, when Frederick Banting, a physician in Ontario, Canada, had the idea to use insulin to treat diabetes. Banting and his team used insulin to successfully treat a diabetic patient in 1922 and were awarded the Nobel Prize in Medicine the next year. Also in 1922, Eli Lilly and the University of Toronto made a deal to begin mass-producing insulin.
“Before they identified insulin, the lifespan was so short. The patients would die within just a few years,” Zeng said. After they began “purifying insulin from pigs and cows, millions of lives were saved.” By 1945, a newly diagnosed 10-year-old had a life expectancy of 45 years; a 30-year-old had a life expectancy of 60.5.
“Human” insulin was not genetically engineered and made available until 1983 — thanks to work done in 1978 by City of Hope researchers Arthur Riggs, Ph.D. and Keiichi Itakura, M.D. Their research led to the development of the first biosynthetic human insulin. Since then, it has been the only treatment for type 1 diabetes.
“The invention of recombinant insulin has helped a lot,” Zeng said. “But life expectancy is still reduced. Hyperglycemia causes all kinds of complications, such as cardiovascular disease and loss of limbs and eyesight. Insulin supplementation cannot prevent these complications.”
In the last two decades, more than 300 insulin analogs have been identified, including 70 animal insulins, 80 chemically modified insulins and 150 biosynthetic insulins. These allow physicians the ability to customize treatment and reduce side effects while improving outcomes.
Even still, the life expectancy for people with type 1 diabetes is lower than that for the general population by about 15 years.
This is why for the last decade, City of Hope has been focused not on better treatments for type 1 diabetes, but finding a cure. Based on new understandings of the disease, leading-edge interdisciplinary research is underway, bringing together the fields of genetics, immunology and endocrinology. Current and soon-to-be-launched clinical trials range from a vaccine to bone marrow stem cell transplants.
City of Hope is confident that a cure — not just symptom control — will be achieved within the next few years.
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