Gerald “Jerry” M Reaven: the “father of insulin resistance”BMJ 2018; 360 doi: https://doi.org/10.1136/bmj.k1174 (Published 13 March 2018) Cite this as: BMJ 2018;360:k1174
Gerald “Jerry” M Reaven was a pioneer in insulin research, whose discoveries formed the basis of the concept of metabolic syndrome. He is credited with developing the first quantitative method to measure insulin mediated glucose uptake in humans (1970). He used this tool to establish the importance of insulin resistance in human disease, most notably type 2 diabetes. He also showed how insulin had a role in cardiovascular disease in people who do not have diabetes.
Reaven first laid out his framework for syndrome X, the role of insulin resistance in human disease, in a lecture in 1988, when he received the Banting medal for scientific achievement, the highest honour awarded by the American Diabetes Association.1 The condition would later become more commonly known as metabolic syndrome.
“There’s not one shred of evidence that insulin resistance causes obesity,” Reaven combatively wrote. “Insulin resistance means that insulin isn’t acting correctly. So if you don’t have enough insulin or if your cells aren’t responding to insulin, you can’t deposit glucose into cells. If anything, you would lose weight.” Furthermore, excessive insulin could damage the lining of coronary arteries and increase the risk of heart disease.
His studies showed that total calories consumed affected body weight. But for people with insulin resistance, the composition of those calories, the mix of fats and carbohydrates in the diet, could have profoundly different effects on cardiovascular risk. The best diet for them was one of 45% carbohydrates, 40% fats (particularly “good” monounsaturated and polyunsaturated fats), and 15% protein. The findings ran counter to the then current recommendations by the American Diabetes Association.
Reaven’s arguments were controversial at the time; the prevailing view was that there was only a single form of diabetes, now known as type 1 diabetes. “Jerry was not shy about standing up and sharing his opinions. He was tenacious when it came to defending his scientific observations,” said Stanford colleague Frederic Kraemer. “He didn’t like to accept opinions; he liked to accept facts—facts generated from well controlled scientific investigations.”
“Today, insulin resistance is recognised as pathognomonic of type 2 diabetes. In large part, this is thanks to Reaven’s pioneering work. It led to an explosion of investigations into insulin action and diabetes, an enormous body of research that continues to this day,” said Lester Salans. He was an early postdoc in Reaven’s laboratory and went on to become director of the National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, then dean of the Mount Sinai Medical School.
Reaven wrote a book for the general public in 2000, Syndrome X: The Silent Killer. In it he summarised his findings and offered general guidance for lifestyle and dietary changes that could improve the health of people with, or at risk of developing, metabolic syndrome. It “is a classic book written by a giant in the subject of physiology, and I think it has stood the test of time relatively well,” wrote neuroscientist and diet guru Stephan Guyenet in 2017. “Although some of Reaven’s views were controversial at the time he first articulated them, at this point many of them have been incorporated into mainstream thinking.”
Reaven received his undergraduate degree in 1949 and qualified in medicine in 1953, both at the University of Chicago. Additional training took place at Stanford University Medical School and the University of Michigan. That was broken up by two years in the US Army Medical Corps, as was common for many of his generation. The silver lining was a posting to Europe and regular hours that allowed time for adventures and starting a family, which the intensity of an immediate research career might not have allowed.
Reaven returned to Stanford to complete his training and in 1960 joined the teaching faculty there, stepping back to active emeritus status in 1995. His research continued until late in 2017, when his health started to fail. He was coauthor of more than 800 papers, with two more in press.
His numerous recognitions include the Veterans Administration’s William S Middleton award for outstanding achievement in medical research (1987), the distinction in clinical endocrinology award from the American Association of Clinical Endocrinologists (2003), and the Fred Conrad Koch award from the Endocrine Society (2006).
“Jerry has always been a truly independent thinker and one who never accepted dogma or consensus views. He had the ability to gather a varied research team, consider input from everyone, produce high quality studies exploring the physiology and pathophysiology of carbohydrates and lipid metabolism in humans, and see the bigger picture among the details,” his colleagues wrote in a 2014 tribute to Reaven in Diabetes Care.2
“His mentorship style encouraged creativity, independent thinking, and self reliance . . . a key lesson was the concept of scholarship,” added one time postdoc Jerrold Olefsky. That particularly played out in his “meticulous and painstaking” drafting of scientific papers. It “forced you to think through every detail of every figure, all the possible implications, and how every relevant prior literature reference fits into the picture.”
“Jerry Reaven was a true pioneer,” added Lloyd Minor, dean of Stanford’s 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.”
Gerald Reaven died in Palo Alto, California. He leaves Eve Reaven, a microbiologist and his wife of six decades; and three children.
Gerald “Jerry” M Reaven (b 1928; q Chicago 1953), died from undisclosed causes on 12 February 2018