Gerald Reaven, scientist who coined ‘Syndrome X,’ dies at 89

Gerald Reaven’s decades of research at Stanford helped show that insulin resistance could lead to Type 2 diabetes and multiple other diseases.

- By Tracie White

Gerald Reaven

Gerald “Jerry” Reaven, MD, who gained international recognition for coining the term Syndrome X — now known as metabolic syndrome — died Feb. 12 at his home on the Stanford University campus. He was 89.

An endocrinologist and professor emeritus of medicine at the Stanford School of Medicine, Reaven was one of the first researchers to argue for the existence of insulin resistance, a diminished response to the hormone insulin. It was a controversial concept that met with huge opposition. But Reaven proved the naysayers wrong. In 1988, he also introduced the novel idea of a link between insulin resistance and a cluster of other metabolic abnormalities that together greatly increased the risk for cardiovascular disease, which he called Syndrome X.

“Jerry Reaven was a true Stanford pioneer,” said Lloyd Minor, MD, dean of the School of Medicine. “He was the consummate scientist whose rigorous scholarship was a model for researchers at Stanford and around the world. He will be missed.”

Never one to back down from a fight, Reaven broke ground when he argued for the existence of insulin resistance as an early and critical link in the development of Type 2 diabetes and conducted numerous studies over many decades proving the existence of insulin resistance and its many implications for metabolic diseases and cardiovascular diseases.

“Jerry Reaven was a giant in the Department of Medicine,” said Robert Harrington, MD, professor and chair of medicine at Stanford. “His scientific contribution in describing and then further defining insulin resistance is one of the great achievements in metabolic disease over the last 50 years.” 

Insulin resistance controversy

In the 1950s, when Reaven started out as a researcher, it was believed that there was only one type of diabetes and that it was caused by a lack of insulin.

“In the late ’70s early ’80s, there was a lot of controversy about insulin resistance, and Jerry was not shy about standing up and sharing his opinions,” said Frederic Kraemer, MD, professor and chief of endocrinology, gerontology and metabolism at Stanford. “He was tenacious when it came to defending his scientific observations. He didn’t like to accept opinions; he liked to accept facts — facts generated from well-controlled scientific investigations.”

In 1988, during the American Diabetes Association Banting award lecture, he introduced the concept of the link between insulin resistance and other metabolic abnormalities, calling it Syndrome X. This constellation of conditions — increased blood pressure, high blood sugar and abnormal HDL cholesterol and triglyceride levels — later became known as metabolic syndrome and has become a useful indicator of increased risk for heart disease, stroke and diabetes.

Reaven continued to actively conduct research until October, when bad health finally kept him at home. He co-authored more than 800 papers in scientific journals and currently has at least two more in the pipeline. He was also the author of several books, including a popular book on Syndrome X and its repercussions on cardiovascular health. He was a mentor to many scientists both at Stanford and around the world.

‘Science was his life’

“I visited him at his house just before the Super Bowl in February, when I knew he was sick,” said Joshua Knowles, MD, an assistant professor of cardiovascular medicine. “He was very sad he couldn’t be at work. I brought a paper on the effects of insulin resistance on different race and ethnicities. He wanted to see the data. Science was his life.”

Reaven was a Midwesterner and a baseball fan. He was born in Gary, Indiana, on July 28, 1928, but grew up in Cleveland, which accounts for his lifelong “affection and frustration” with the Cleveland Indians baseball team, said his son, Peter Reaven, MD, an endocrinologist and director of the diabetes research program at the Phoenix Veterans Affairs Health Care System in Arizona.

“Both my dad and my mom were academics,” he said. His mother, Eve Reaven, PhD, is a retired electron microscopist who lives in the Stanford home where she and Jerry raised their three children. “Often dinner conversations were about academics and science. Somehow that became comfortable.”

But Peter said his father also made time for outside interests. Gerald Reaven loved sports, Broadway plays, jazz singers and literature. He traveled to Cuba when he was young to search for Hemingway. He always made the time to play sports with his children and continued to play on softball teams for many years. He was known for throwing birthday parties for faculty and staff, many of whom knew his favorite dessert was chocolate pie.

“He was a huge Cleveland Indians fan,” said Knowles, who often heard broadcasts of the games coming from Reaven’s computer at work. Knowles, who studies the genetic basis of insulin resistance, spoke of the many lessons he learned from Reaven over the years as both his trainee and colleague. Among them: “The fortitude to stick with an idea if you really believe in it, against external pressure” and “the need to find a scientific passion that keeps you coming to the lab on the weekend.”

“Jerry was often the only faculty member here on Saturday and Sunday,” Knowles said. “On many weekend mornings I would arrive after playing basketball and shoot the breeze with Jerry in his office. That dedication is infectious.”

Reaven earned his undergraduate and medical school degrees at the University of Chicago and completed his residency training at the University of Michigan. He joined the Stanford faculty in 1960. He worked at the School of Medicine first in the endocrinology division and then, after semi-retirement, in the cardiovascular division. “He was an amazing thinker,” said Sun Kim, MD, an associate professor of medicine who studies insulin resistance and diabetes. “He was a deep thinker who wanted the truth to be told. He loved work. He literally worked till the end.”

Reaven won numerous awards, including the William S. Middleton Award for outstanding achievement in medical research from the Veterans Affairs Administration, the Banting Medal for Scientific Achievement from the American Diabetes Association, the Banting Memorial Lecture from the British Diabetes Association, the Fred Conrad Koch Award from the Endocrine Society, the Distinction in Clinical Endocrinology Award from the American Association of Clinical Endocrinologists, and the National Lipid Association Honorary Lifetime Member Award.

In addition to his wife and son, he is survived by daughters Marci Reaven of New York and Nancy Reaven of Los Angeles and their families.

In lieu of flowers, the family asks for consideration of a memorial donation to support the Gerald M. Reaven Memorial Research Fund either online or by making a check payable to “Stanford University” and sending it to Stanford University Development Services, P.O. Box 20466, Stanford, CA 94309-0466. Please note “In Memory of Dr. Gerald Reaven” online or on the memo line of the check.

A memorial service is being planned. 

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