In 1981, Jerry Summers learned by phone that his mother was likely to die in the next few days. He jumped in the car and drove from his Indiana home to Illinois. There he spent the next week in the hospital by her side, sleeping on couches and expecting any conversation with her to be their last.
He was wrong. She made it through the week and out of the hospital, against the odds, and lived for years longer. But Summers’s own health was changed. “I emerged from the week drinking water in huge amounts and going to the bathroom at every opportunity,” he recalled.
“By God,” he realized. “I’ve got diabetes.”
At the time, Summers was a lively 41-year-old. He ran five miles a day, even when that was not a thing people did. At 170 pounds, his body was not round or doughy, or any other descriptive term suggestive of metabolic disharmony—not someone a doctor would expect to develop diabetes. Summers accepted the diagnosis reluctantly.
“I remain convinced that genetics and the stress with my mother were the precipitating factors,” he recalled. His mother had been obese and had developed diabetes later in life, and his sister died at age three with a juvenile-onset version—but his own was not a prototypical “type 1” or “type 2” case. Summers has come to reject that duality altogether: “It was not obesity, poor diet, lack of exercise, or wrath of God.”
Despite running daily for decades, he now requires insulin. He counts grams of carbohydrates at every meal to estimate an effective dose, still sometimes overdosing and causing his blood sugar to plummet. It often feels much like a guessing game. During his decades living with the disease, medical science has seen progress in the treatment, but no cure. Lifestyle changes can go far, but cases like Summers’s illustrate their limitations.
Much of that comes down to gaps in understanding of what exactly is happening in the metabolic pathways of people with diabetes. This is especially vexing to Jerry’s son, Scott Summers, who was 14-years-old at the time of his father’s diagnosis. That day Scott vowed to find a cure.
Scott was not named for the Scott Summers of Marvel fame (more commonly known as Cyclops), but this was the analogous origin story of a scientist. His father’s diagnosis was Scott’s transformative moment—his spider bite, radiation blast, or, in the case of Cyclops, attack of his family’s spacecraft by the interstellar Shi’ar Empire. And unlike some children who promise to cure their parents but then go into finance or real estate, Summers actually went to graduate school and got a Ph.D. in physiology.
When Scott left the Midwest to work in a lab at the University of Pennsylvania, he got his first insight toward a hypothesis that he believes could revolutionize our understanding of human metabolism and disease—and could help explain why skinny people aren’t necessarily metabolically healthy, or vice versa.
“We now know that both lean and obese individuals are susceptible to diabetes,” Summers, now the chair of nutrition and integrative physiology at the University of Utah, explained to me. “We think it’s basically because of their lipid compositions, and the accumulation of one type in particular—called ceramides—that might be increasing susceptibility of people to diabetes.”
At the heart of this idea is the model that says obesity is associated with diabetes and heart disease because all three are due to an error in the way the body stores energy. We carry most fat as triglycerides in adipose (“fat”) cells, which contain tremendous amounts of energy.
“That’s a pretty safe way to store it,” Summers explains. At least, it’s not necessarily unhealthy to have this type of fat. “But some of that stored fat can actually spill out into another pathway and give rise to ceramides. We think those tend to be pretty toxic.”
Ceramides are a family of waxy lipids that have even been called “toxic fat,” as they were in the press release for Summers’s latest study in the journal Cell Metabolism. The researcher Bhagirath Chaurasia, who works with Summers, clarified that “toxic fat” is an accurate, non-sensational term, in that ceramides are involved in the process of lipotoxicity. That is, they cause dysfunction in other lipids. Because in addition to storing triglycerides, adipose cells also help the body sense its nutritional status by secreting compounds that communicate with other cells. Among those signals are ceramides, and alterations in this process seem to be at the root of much metabolic disease.
As with all substances deemed “toxins,” of course, the toxicity of ceramides is all about context. Ceramides are also part of sphingomyelin, the predominant lipid in many cell membranes. They account for about half of the fat in our skin, too— specifically the fat-rich matrix between mature skin cells that prevents water loss and impedes infectious agents. Ceramide-containing skin products have been shown to “hydrate and moisturize the epidermis” and aid in epidermal rebuilding. There’s no apparent danger in rubbing ceramides on your skin.
At the same time, Summers’s work suggests that ceramides play an influential role in the most common derangement of human metabolism today. In 2007, the Utah team found that mice who produced fewer ceramides were protected from diabetes and fatty liver disease. Since then, the researchers have been testing effects in human cells. There ceramides proved to decrease metabolic activity of fat tissue. As Chaurasia explains it, once ceramide synthesis is blocked, “Fat cells can burn more calories and become more sensitive to insulin. It also helps to increase the number of beige or brown adipose cells.”
Increasing brown adipose tissue (sometimes referred to as “good fat”) is a goal of many metabolism enthusiasts. While most adipose cells appear white, brown adipose is full of iron-rich mitochondria that are metabolically active. These cells burn energy instead of simply storing it. Having more brown fat is generally healthy, encouraging its formation hasn’t proven easy. As NIH director Francis Collins wrote in 2013, figuring out how to transform some of our white fat into brown fat “may be the first step toward developing game changing treatments for diabetes and obesity.”
Summers’ ceramide discoveries are a promising part of that step.
The potential commercial and scientific implications are serious. If some people simply have a genetic susceptibility to accumulate ceramides, blocking that pathway with a drug could be an effective approach to preventing diabetes. And for the millions of humans today with metabolic disease, this approach could moderate at least some impact of overeating and a sedentary life.
Summers’s team is now investigating practical ways to influence ceramide levels, with an eye to pharmaceuticals and specific lifestyle guidelines to mitigate risk (beyond broad platitudes about diet and exercise). For one, the ceramide-forming pathway seems to be blocked by, of all things, exposure to cold temperatures. While Summers is not an advocate of taking ice baths or wearing ice vests, as some cohorts of scientists are, his discovery could explain some of the metabolic benefits of being cold.
Even if none of this potential promise is realized, Summers believes his overarching message is critical: That type-two diabetes “is not simply a consequence of laziness or sloth.” It’s rather the result of complex orchestrations of processes that can’t always be dismissed as products of weak will or turpitude of character. Those dismissal stigmatize and stagnate research and treatment. And of course Scott’s father Jerry seems to be living proof of the complexity at play—both within his own cells and without.
“I was running seven miles a day until six months ago,” he told me last week. “Then I had to take a third job. Now I find it very difficult to work in running at all.”
At 77, Jerry is now driving for Uber. The last time he saw Scott, Jerry reminded him that he promised to find a cure. “I said, you better be hustlin’ up, because I’m running out of time.”
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