Professor Gerald I. Shulman has reshaped our understanding of the root causes of insulin resistance and type 2 diabetes. The Yale University scientist is the 2025 recipient of the Diabetes Prize for Excellence, awarded by the European Association for the Study of Diabetes (EASD) and the Novo Nordisk Foundation.
For more than 30 years, Shulman has revealed how fat stored in the wrong places — inside muscle and liver cells — disrupts insulin signalling. His work also showed that lifestyle changes and new drugs that are in the pipeline can reverse the damage.
Shulman is George R. Cowgill Professor of Internal Medicine and Cellular & Molecular Physiology at Yale School of Medicine where also serves as Co-Director of the Yale Diabetes Research Center, and Investigator Emeritus at the Howard Hughes Medical Institute. His work combines clinical insight, advanced imaging, and biochemical analysis to map the molecular pathways of insulin resistance, helping to guide scientific thinking and shape new treatments.
“Professor Shulman’s research has transformed how we think about the origins of type 2 diabetes,” said Chantal Mathieu, President of EASD. “By pinpointing the role of ectopic fat in muscle and liver, and showing how these changes can be reversed, he has provided a foundation for new preventive and therapeutic strategies. His contributions have changed the field, from basic science to patient care.”
The prize honours outstanding diabetes research or technological contributions and is accompanied by DKK 6 million, with DKK 5 million for research and the remainder as a personal award. Shulman will deliver his prize lecture at the 61st EASD Annual Meeting in Vienna, 15-19 September 2025.
Childhood summers sparked a lifelong diabetes question
Shulman’s fascination with metabolism began long before medical school. His father, a physician, ran a summer camp for children with type 1 diabetes in northern Michigan.
“As a nine-year-old, I watched my fellow cabinmates having their urine checked daily for glucose and ketones, standing in line for their daily insulin injections, and adjusting their diet just to stay healthy,” Shulman recalls.
“Sometimes they’d get it wrong — their blood glucose would crash, and we’d rush to get them orange juice before they lost consciousness. I saw what could happen if you didn’t get it under control fast. It made me wonder — why does the body lose its ability to handle glucose in the first place? That question stayed with me.”
After completing his residency training in internal medicine and clinical fellowship in endocrinology, Shulman realised that to truly help patients, he needed to understand the “why” of their disease. He moved into research to uncover the biochemical roots of insulin action and insulin resistance.
Turning metabolism snapshots into real-time movies
Early in his career, Shulman pioneered the use of magnetic resonance spectroscopy (MRS) to study human metabolism in real time.
“Before MRS, we were taking snapshots — single blood tests or biopsies,” he says. “With MRS, it’s like making a movie. We could watch glucose and lipids moving through the body’s organs without invasive procedures.”
Shulman’s group showed that these misplaced fats — especially diacylglycerols — act like “molecular vandals” and disrupt the insulin signaling system. In muscle, diacylglycerols block glucose uptake; in liver, they trigger excess glucose production even when the body has enough.
“We realised it wasn’t obesity itself that caused insulin resistance,” he explains. “It was where the fat was stored. Fat under the skin is relatively harmless — but in muscle or liver cells, it’s like oil spilled on the street. That’s why even some lean people, or those with very little body fat [lipodystrophy], can develop insulin resistance and diabetes.”
Reversing the damage: removing harmful fat in liver and muscle
Shulman’s work didn’t stop at mechanism. His team showed that losing even a small amount of ectopic liver and muscle fat — through diet, exercise, or targeted drugs — could restore insulin sensitivity and normalise blood glucose concentrations.
“One of the most encouraging things we’ve found is how quickly this can change,” he says. “Within several weeks, the right intervention can drop hepatic fat content and improve hepatic insulin action even without normalization of body weight.”
This explains why caloric restriction or GLP-1 agonist treatments can reverse insulin resistance even before major weight loss. His group also showed that exercise can bypass ectopic lipid-induced defects in insulin signalling and reverse muscle insulin resistance.
Shulman explains: “Based on this molecular mechanism, we have developed several new drugs that increase the ability of the liver and muscle cells to burn more fat and reduce harmful lipids inside these cells. This lowers the activity of key enzymes that block insulin action and reverse insulin resistance — targets we’ve been chasing for three decades.”
“In early human trials, we’re seeing marked reductions in hepatic fat content and hyperlipidemia with improved insulin sensitivity, and no safety concerns so far. Combined with GLP-1 analogues, especially the new oral GLP-1 agonists, these drugs should boost effect, lower costs, and make treatment accessible to more people.”
A survival trick that now fuels disease
Shulman also explored the evolutionary basis for ectopic lipid-induced insulin resistance. He discovered that this mechanism once protected humans during starvation: when food was scarce, the body shifted fat into muscle and liver cells triggering this same mechanism of lipid-induced insulin resistance to spare glucose for the brain.
“That survival adaptation was great when food was scarce,” he says. “In today’s world of chronic overnutrition, the same process promotes insulin resistance, type 2 diabetes and other diseases,” he says. “In today’s toxic environment of highly palatable, ultra-processed foods, ectopic lipid-induced insulin resistance has become harmful, leading not only to type 2 diabetes but also fatty liver disease, heart disease, Alzheimer’s disease and obesity-associated cancers.”
Shulman is now combining MRS with genetics, metabolomics, and clinical trials to identify people at risk before disease develops.
“My long-term goal is early detection and reversal of insulin resistance — fixing the plumbing before the flood — in this case, restoring insulin sensitivity before diabetes starts,” he says. “Now that we have identified this molecular basis for insulin resistance and have new drugs in the pipeline that safely reverse this process. I think we should be looking ahead to treating ectopic lipid-induced insulin resistance in young individuals just like we do hypertension and hypercholesterolemia. In this way we can prevent type 2 diabetes, along with MASLD/MASH, hyperlipidemia, Alzheimer’s disease and obesity-associated cancers – long before blood sugars rise.”
From curiosity to breakthroughs that change lives
From summers at his father’s diabetes camp to global recognition, Shulman’s career has been driven by a simple question: why does the body lose control of its own energy balance? His answers have changed how the world understands — and treats — diabetes.
“I’m honoured to receive this prize,” says Shulman. “The most precious funding is the unrestricted dollar — it lets you take chances and explore ideas no one else would support. That’s when breakthroughs happen. What excites me most is turning those discoveries into strategies that improve people’s lives. That’s why we do the science.”
About EASD
The European Association for the Study of Diabetes (EASD) e.V. is a membership-based non-profit organisation with the mission to promote excellence in diabetes care through research, networking, and education. Its Annual Meeting is one of the largest diabetes conferences in the world, attracting thousands of delegates each year.
EASD is a leader in education for healthcare professionals and develops statements and guidelines that translate the latest research into best practices in diabetes management. It publishes Diabetologia, a major monthly international journal with an impact factor of 10.2 (2024).
In 2000, EASD reinforced its commitment to diabetes research by creating the European Foundation for the Study of Diabetes (EFSD), which has since committed over €130 million to research.
For more information, please visit: www.easd.org
