Tag: Weight

¿Cuál es el mejor ejercicio para ti? La pista está en tu sangre

Unos investigadores estudian las proteínas de la sangre para saber por qué algunos de nosotros respondemos a ciertas formas de ejercicio mejor que otros.

Si todos empezamos mañana la misma rutina de ejercicios, algunos se pondrán mucho más en forma, otros se pondrán un poco más en forma, y unos pocos pueden llegar a perderla. Las respuestas individuales al ejercicio pueden variar de forma así de salvaje y, hasta ahora, imprevisible. Pero un nuevo y fascinante estudio de más de 650 hombres y mujeres sugiere que los niveles de ciertas proteínas en nuestro torrente sanguíneo podrían predecir si responderemos, y cómo, a diversos regímenes de ejercicio.

El estudio necesita ser replicado y ampliado, pero representa un comienzo significativo hacia un análisis de sangre que indique los mejores tipos de ejercicio para cada uno de nosotros, y si podemos esperar obtener más o menos beneficios del mismo entrenamiento que nuestro cónyuge, descendientes u otros compañeros de entrenamiento o rivales.

La respuesta al ejercicio es un tema que probablemente debería discutirse más a menudo y abiertamente de lo que se hace. Sabemos que el ejercicio es maravilloso para nuestra salud. Innumerables estudios demuestran que las personas que hacen ejercicio tienden a vivir más tiempo, con más felicidad y con menos riesgo de padecer muchas enfermedades que las personas sedentarias.

Pero esos resultados se refieren a promedios generales. Si se analizan los datos de los estudios con detenimiento, se puede encontrar una vertiginosa gama de reacciones, que van desde el enorme aumento de la salud y la forma física en algunas personas hasta la ausencia de ellas en otras. (Lo mismo ocurre con las respuestas a los programas de pérdida de peso).

Desgraciadamente, poco sobre nuestros cuerpos y vidas predice actualmente cómo responderemos al ejercicio, incluyendo nuestra genética. Los estudios demuestran que gemelos idénticos, con idéntico ADN, pueden reaccionar de forma muy diferente a los entrenamientos, y lo mismo sucede con personas igualmente delgadas, obesas o con una buena condición física al comienzo de un nuevo programa de ejercicios. Algunos, por razones misteriosas, acaban más en forma y más sanos que otros.

Estos enigmas intrigaron a investigadores de la Universidad de Harvard, el Centro Médico Beth Israel Deaconess de Boston y otras instituciones. Los científicos llevaban mucho tiempo interesados en comprender cómo el ejercicio altera el entorno molecular dentro del cuerpo, así como la forma en que esos cambios influyen en la salud, y en lo diversas que pueden ser las alteraciones.

Ahora, para el nuevo estudio, que se publicó en mayo en Nature Metabolism, decidieron ver si ciertas moléculas de la sangre de las personas podrían estar relacionadas con la forma en que sus fisiologías reaccionan a los entrenamientos. Para averiguarlo, recurrieron en primer lugar al valioso conjunto de datos producidos durante el estudio a gran escala Heritage, que había profundizado en el ejercicio y la salud de los padres y su descendencia adulta. El estudio Heritage incluía pruebas precisas de laboratorio sobre la aptitud aeróbica de las personas, así como extracciones de sangre, seguidas de 20 semanas de ejercicio aeróbico moderado y más pruebas.

Los investigadores ahora extrajeron los registros de 654 hombres y mujeres que habían participado en el Heritage, abarcando un abanico de edades y etnias, y comenzaron a examinar a fondo su sangre. Se centraron en la variedad de moléculas proteicas grandes y complejas que se crean en los tejidos de todo el cuerpo y que, cuando se liberan en el torrente sanguíneo, fluyen y ponen en marcha procesos biológicos en otros lugares, afectando al funcionamiento de nuestros cuerpos.

Utilizando herramientas moleculares de última generación, los científicos empezaron a enumerar el número y los tipos de miles de proteínas en el torrente sanguíneo de cada una de las 654 personas. A continuación, tabularon esas cifras con los datos sobre la aptitud aeróbica de cada uno antes y después de sus cinco meses de ejercicio.

Y surgieron patrones claros. Los investigadores descubrieron que los niveles de 147 proteínas estaban fuertemente asociados a la condición física inicial de las personas. Si algunos de esos números de proteínas eran altos y otros bajos, los perfiles moleculares resultantes indicaban el estado de forma de la persona.

Y lo que es más interesante: otro conjunto de 102 proteínas tendía a predecir la respuesta física de las personas al ejercicio. Los niveles más altos y más bajos de estas moléculas —pocas de las cuales coincidían con las proteínas relacionadas con la aptitud física básica de las personas— profetizaban el grado en que la capacidad aeróbica de alguien aumentaría, si es que lo hacía, con el ejercicio.

Por último, dado que la capacidad aeróbica está tan estrechamente vinculada a la longevidad, los científicos cotejaron los niveles de las distintas proteínas relacionadas con la capacidad aeróbica en la sangre de las personas inscritas en otro estudio de salud que incluía registros de mortalidad, y descubrieron que las firmas protéicas que implicaban una respuesta de menor o mayor capacidad aeróbica también significaban vidas más cortas o más largas.

En conjunto, los resultados del nuevo estudio sugieren que “las herramientas de perfiles moleculares podrían ayudar a adaptar” los planes de ejercicio, afirmó Robert Gerszten, profesor de medicina de la Facultad de Medicina de Harvard y jefe de medicina cardiovascular del Centro Médico Beth Israel Deaconess, que dirigió el nuevo estudio con su autor principal, Jeremy Robbins, y otros.

Una persona cuya firma protéica en el torrente sanguíneo sugiera que podría ganar poca forma física con una rutina estándar y moderada de caminata, ciclismo o natación, por ejemplo, podría ser guiada para realizar entrenamientos de mayor intensidad o de resistencia, dijo Gerszten.

Sin embargo, tanto él como Robbins señalaron que este campo de investigación está todavía en sus inicios. Los científicos tendrán que estudiar a muchas más personas, con disparidades mucho más amplias en cuanto a su salud, su estado físico, su edad y su estilo de vida, para determinar qué proteínas son las más importantes para predecir la respuesta de un individuo al ejercicio. Los investigadores esperan, además, poder volver atrás y encontrar el origen de esas moléculas para comprender mejor cómo el ejercicio rehace nuestro cuerpo y moldea nuestra salud. Gerszten afirma que es de esperar que dentro de unos años se obtengan resultados más precisos.


The Best Type of Exercise? A Blood Test Holds Clues

Researchers are studying the proteins in blood to learn why some of us respond to certain forms of exercise better than others.

If we all begin the same exercise routine tomorrow, some of us will become much fitter, others will get a little more in shape, and a few of us may actually lose fitness. Individual responses to exercise can vary that wildly and, until now, unpredictably. But a fascinating new study of more than 650 men and women suggests that the levels of certain proteins in our bloodstreams might foretell whether and how we will respond to various exercise regimens.

The study needs replication and expansion, but represents a meaningful start toward a blood test to indicate the best types of exercise for each of us, and if we can expect to gain more or less benefit from the same workout as our spouse, offspring or other training partners or rivals.

Exercise response is a topic that probably should be discussed more often and openly than it is. We know exercise is wonderful for our health. Countless studies show that people who exercise tend to live longer, more happily and with less risk of many diseases than sedentary people.

But those findings refer to broad averages. Parse the study data closely and you can find a dizzying gamut of reactions, from outsized health and fitness gains in some people to none in others. (The same is true of responses to weight-loss programs.)

Disobligingly, little about our bodies and lives currently predicts how we will respond to exercise, including our genetics. Identical twins, with identical DNA, can react quite differently to workouts, studies show, as can people who are equally lean, obese or aerobically fit at the start of a new exercise program. Some, for mysterious reasons, wind up fitter and healthier afterward than others.

These enigmas intrigued researchers from Harvard University, the Beth Israel Deaconess Medical Center in Boston, and other institutions. The scientists had long been interested in how exercise alters the molecular environment inside the body, as well as how those changes influence health, and how diverse the alterations can be.

Now, for the new study, which was published in May in Nature Metabolism, they decided to see if certain molecules in people’s blood might be related to how their physiologies react to workouts. To find out, they turned first to the valuable trove of data produced during the large-scale Heritage study, which had delved into exercise and health in parents and their adult offspring. The Heritage study included precise, laboratory testing of people’s aerobic fitness, as well as blood draws, followed by 20 weeks of moderate aerobic exercise, and more testing.

The researchers now pulled records for 654 of the men and women who had participated in Heritage, covering a range of ages and ethnicities, and began looking deeply into their blood. They focused on the varieties of large, complex protein molecules created in tissues throughout the body that, when released into the bloodstream, flow to and jump-start biological processes elsewhere, affecting how well our bodies work.

Using state-of-the-art molecular tools, the scientists began enumerating the numbers and types of thousands of proteins in each of the 654 people’s bloodstreams. Then they tabulated those figures with data about everyone’s aerobic fitness before and after their five months of exercise.

And clear patterns emerged. The levels of 147 proteins were strongly associated with people’s baseline fitness, the researchers found. If some of those protein numbers were high and others low, the resulting molecular profiles indicated how fit someone was.

More intriguing, a separate set of 102 proteins tended to predict people’s physical responses to exercise. Higher and lower levels of these molecules — few of which overlapped with the proteins related to people’s baseline fitness — prophesied the extent to which someone’s aerobic capacity would increase, if at all, with exercise.

Finally, because aerobic fitness is so strongly linked to longevity, the scientists crosschecked levels of the various fitness-related proteins in the blood of people enrolled in a separate health study that included mortality records, and found that protein signatures implying lower or greater fitness response likewise signified shorter or longer lives.

Taken as a whole, the new study’s results suggest that “molecular profiling tools might help to tailor” exercise plans, said Dr. Robert Gerszten, a professor of medicine at Harvard Medical School and chief of cardiovascular medicine at Beth Israel Deaconess Medical Center, who conducted the new study with its lead author, Dr. Jeremy Robbins, and others.

Someone whose bloodstream protein signature suggests he or she might gain little fitness from a standard, moderate walking, cycling or swimming routine, for instance, might be nudged toward higher-intensity workouts or resistance training, Dr. Gerszten said.

This area of research is still in its infancy, though, he and Dr. Robbins said. Scientists will need to study far more people, with far broader disparities in their health, fitness, age and lifestyle, to zero in on which proteins matter most for predicting an individual’s exercise response. The researchers hope, too, to backtrack and find where those molecules originated, to better understand how exercise remakes our bodies and molds our health. Expect further and more-refined results within a few years, Dr. Gerszten said.

The Best Time of Day to Exercise for Metabolic Health

Late-day exercise had unique benefits for cholesterol levels and blood sugar control, a study of overweight men eating a high-fat diet found.

Evening exercise may be more potent than morning workouts for improving metabolic health, according to a helpful new study of exercise timing. The study, which looked at high-fat diets and overweight men, found that late-day workouts moderated the undesirable health effects of a greasy diet, while morning exercise did not.

The study involved only men who were eating a fatty diet, but adds to growing evidence that exercise timing matters and, for many of us, working out later might have particular advantages.

Although we may be only dimly aware of this, operations inside our bodies follow busy, intricate and mutable circadian schedules. All of our tissues contain molecular clocks that coordinate biological systems, prompting our blood sugar to rise and dip throughout the day, along with our hunger, heart rates, body temperature, sleepiness, gene expression, muscle strength, cell division, energy expenditure and other processes.

The full workings of these internal clocks remain mysterious. But scientists know they recalibrate themselves, based on complex cues from inside and outside of our bodies. Most obviously, they synchronize to light and sleep. But they also set themselves by meals, meaning that when we eat, as well as what we eat, may influence our health and metabolism.

Most researchers believe exercise timing likewise tunes internal clocks. But the results of relevant past studies have been inconsistent. Some suggest morning workouts, before breakfast, incinerate more fat than evening exercise. Others find the opposite. And some recent experiments indicate that early exercise, if it is intense, actually impairs blood-sugar control, while the same workouts, performed later, smooth blood-sugar spikes and improve metabolic health, which may have particular benefits for heart health and controlling Type 2 diabetes.

Most of those studies, though, focused on one type of exercise and rarely controlled people’s meals during the experiments, making it difficult to tease apart the effects of exercise timing from those of what and when people eat.

So, for the new study, which was published in May in Diabetologia, scientists affiliated with the Mary MacKillop Institute for Health Research at Australian Catholic University in Fitzroy, Australia, and other institutions, set out to control people’s diets while tinkering with their workout timing.

They began by recruiting 24 sedentary, overweight Australian men (not including women to avoid issues related to women’s menstrual cycles). The scientists invited these volunteers to the lab, checked their aerobic fitness, cholesterol, blood-sugar control and other aspects of health, asked about current eating habits, and then set them up with meal deliveries.

The meals consisted of about 65 percent fat, since the researchers wished to learn how exercise timing might affect fat metabolism, as well as blood-sugar control. The volunteers ate the unctuous foods, and nothing else, for five days and visited the lab for more tests. Then the scientists divided them into three groups. One would start exercising every day at 6:30 a.m., another at 6:30 p.m., and the last would remain sedentary, as a control.

The exercise routines were identical, intermingling brief, intense intervals on stationary bicycles one day with easier, longer workouts the next. The exercisers worked out for five consecutive days, while continuing the high-fat diet. Afterward, the researchers repeated the original tests.

The results were somewhat disturbing. After the first five days of fatty eating, the men’s cholesterol had climbed, especially their LDL, the unhealthiest type. Their blood also contained altered levels of certain molecules related to metabolic and cardiovascular problems, with the changes suggesting greater risks for heart disease.

Early-morning exercise, meanwhile, did little to mitigate those effects. The a.m. exercisers showed the same heightened cholesterol and worrisome molecular patterns in their blood as the control group.

Evening exercise, on the other hand, lessened the worst impacts of the poor diet. The late-day exercisers showed lower cholesterol levels after the five workouts, as well as improved patterns of molecules related to cardiovascular health in their bloodstreams. They also, somewhat surprisingly, developed better blood-sugar control during the nights after their workouts, while they slept, than either of the other groups.

The upshot of these findings is that “the evening exercise reversed or lowered some of the changes” that accompanied the high-fat diet, says Trine Moholdt, an exercise scientist at the Norwegian University of Science and Technology, who led the study in Australia as a visiting researcher. “Morning exercise did not.”

This study does not tell us how or why the later workouts were more effective in improving metabolic health, but Dr. Moholdt suspects they have greater impacts on molecular clocks and gene expression than morning exertions. She and her colleagues hope to investigate those issues in future studies, and also look at the effects of exercise timing among women and older people, as well as the interplay of exercise timing and sleep.

For now, though, she cautions that this study does not in any way suggest that morning workouts aren’t good for us. The men who exercised became more aerobically fit, she says, whatever the timing of their exercise. “I know people know this,” she says, “but any exercise is better than not exercising.” Working out later in the day, however, may have unique benefits for improving fat metabolism and blood-sugar control, particularly if you are eating a diet high in fat.

I Feel Great About My Neck

It took me to my mid-40s to learn not to depend on anyone else’s approval of my appearance.

Like many of you, I have spent the last 14 months staring at my neck. In all of human history, perhaps no necks (or eyes, or foreheads) have been inspected so relentlessly, and with such attention to detail, as ours collectively have since last March, while working and socializing from home. If Narcissus had been required to look into a high-definition camera, with or without a ring light, for hours each day, would he have been so enamored with his own appearance?

Based on the surge in people currently seeking cosmetic procedures, what some are calling the “Zoom boom,” it seems unlikely.

And yet I find myself, midway through my 40s, freed from agonizing over my best angle, feeling just fine about my neck. Great, actually. This is no small feat, as anyone who’s read Nora Ephron call tell you.

Fifteen years ago, Ephron, who would have turned 80 this month, published the essay collection “I Feel Bad About My Neck: And Other Thoughts on Being a Woman” — and people have been referencing it ever since. I was 31 that summer, just entering the decade that fashion magazines l set up as though it were a creature-of-the-deep horror movie: While things might appear to be fine, terrors were lurking under the surface waiting to take me down if I didn’t take the necessary precautions.

I recall reading Ephron’s title essay in my bathtub, emerging from the hot water to inspect my neck in the mirror and promptly resolving to pay close attention to its care. And I did. Along with the rest of my face, it was washed and moisturized daily without fail. I did this for years with the quiet superiority of someone who’s been shown the answer to the exam before taking it. Ephron provided guidance.

Her words — funny and blunt and smacking of honesty — felt like a blast of fresh air. To those of us not yet feeling bad about our necks, there was still time! Not just to take preventive measures, but to enjoy ourselves. You should not feel bad about how you looked in a bikini until you were 34, Ephron said, at which point, goodbye to all that. Our necks would not go wrong until age 43, at which point nothing could be done. Before these sell-by dates, however, failing to enjoy ourselves was foolish.

This was the radical gift Ephron gave us: Permission to enjoy ourselves even if it came with a deadline. There was nothing that suggested this was possible in any women’s magazine I had ever come across, which were (and largely remain) compendiums of all the things that were wrong with us and needed to be fixed if we wanted to find love or happiness or worth in the world, let alone have fun.

I didn’t need to look far to see the cruelty of adhering to this system. My mother was a woman who could quote Shakespeare, tell you the Latin root of any word and routinely did crossword puzzles in pen. And yet, one of my most abiding memories of her was her endless battle to lose 20 pounds and her inability to recognize her own beauty. It wasn’t until a year or so before her death, when her body and her mind had been ravaged by her illness, taking with it those stubborn pounds, that she finally took joy in her own appearance. “Isn’t it amazing how thin I am?” she said one afternoon, acknowledging her skeletal frame, an unmistakable note of triumph in her voice. I’ve heard similar stories from so many friends, and it feels like a gut punch every time.

The fourth essay in “I Feel Bad About My Neck” is titled “On Maintenance.” In it, Ephron describes every single beauty routine she subscribed to. This was nearly a decade before the advent of self-care beauty sites; in some ways, Ephron was ahead of her time. “Maintenance,” she says, “is what you do just so you can walk out the door knowing that if you go to the market and bump into the guy who once rejected you, you won’t have to hide behind a stack of canned food.”

When I reread the collection midway through last year, looking for some joy, this line, and not all the deadlines and ruminations on death, is the one that remained lodged in my head. It turns out I have reached my mid-40s unable to conceive of a life in which the idea of running into an ex-boyfriend, or any man really, factors into my thinking over my appearance. I do think quite a bit about what I wear, and like Ephron enjoy an excess of bath oil, and own many creams. Where I’ve learned to stop short is considering the thoughts of others, let alone ex-boyfriends, regarding the results.

No doubt, this is a result of timing. The years since I entered my 40s included the #MeToo movement and Covid-19. After witnessing so many women publicly reveal their traumatic experiences at the hands of men, and then watch as they drowned under the responsibilities that come with getting all the things you are supposed to be after with all this maintenance, I found myself asking: What is this maintenance for exactly? Who am I hoping will give me permission to feel great, or expect me to feel bad? I feel great. I can’t be convinced otherwise.

Which is not to say I have been able to live Ephron’s advice successfully. One of the skills I’ve acquired since turning 40 is the ability to recognize there will likely always be a gap between seeing a photo of myself and appreciating it. That gap, I’ve realized, is the time it takes me to overcome all the ways I’ve been taught to value myself in the world. The older I get, the more I understand that delay as evidence of a sort of theft. One that I’m only now understanding has occurred, and it is my anger over that which has helped shorten it.

I’m struck, now, too, by the whiteness of Ephron’s concept of beauty. In the section about hair care, Ephron notes that she went to Africa in 1972 and will never return because “there were no hairdressers out in the bush, and as far as I was concerned, that was the end of that place.” She goes on to express her envy for all Asian women: “I mean, have you ever seen an Asian woman whose hair looks bad?” In her book, “Thick: And Other Essays,” Tressie McMillan Cottom, an associate professor of sociology at the University of North Carolina, Chapel Hill, writes: “Beauty is for white women. If not all white women.” Ephron’s adherence to white beauty standards undergird most of the book.

Ephron, like my mother, was also a complicated woman from a generation that demanded that its women hew to a different idea of womanhood every 10 years and then punished them for it. I am not. These days when I look back at photos of my younger self, acutely aware that I’ve always possessed the things I was taught to believe I was lacking, I can think of my old subscriptions to fashion magazines only as a sort of violence I was enacting upon myself.

Ephron wrote about all the time and money it required to maintain, but I wish she’d also reflected on the brain space. When I think about beauty standards these days — the ones my mother followed, the ones I have — what I mostly consider is all the space the not feeling good took up. It took up most of my mother’s life, and a large portion of my own. I consider all the things that weren’t done, and all the rooms that weren’t walked into because so much of the language of beauty is simply about forcing you to itemize for yourself, over and over, all the ways in which you don’t deserve to be where you are.

Here’s the thing. I feel fine about my neck. And not because all those years of massage and moisturizing rescued me from the dreaded age 43 deadline; about this particular date I must tell you Ephron was correct. I have on occasion tried to feel bad about this, but I can’t. I do not, it turns out, feel bad about my neck, because I do not need to.

Glynnis MacNicol is the author of the memoir “No One Tells You This.”

New Drugs Could Help Treat Obesity. Could They End the Stigma, Too?

Obesity has stalked Marleen Greenleaf, 58, all of her life. Like most people with obesity, she tried diet after diet. But the weight always came back.

With that, she has suffered a lifetime of scorn and stigma. Jeering comments from strangers when she walked down the street. Family members who told her, when she trained for a half-marathon, “I don’t think it’s good for you.”

Then, in 2018, Ms. Greenleaf, an administrator at a charter school in Washington, D.C., participated in a clinical trial for semaglutide, which is a new type of obesity drug, known as incretins.

Over the course of the 68-week study, Ms. Greenleaf slowly lost 40 pounds.

Until then, she had always believed that she could control her weight if she really tried.

“I thought I just needed more motivation,” she said. But when she took semaglutide, she said that “immediately, the urge to eat just dissipated.”

Incretins appear to elicit significant weight loss in most patients, enough to make a real medical and aesthetic difference. But experts hope that the drugs also do something else: change how society feels about people with obesity, and how people with obesity feel about themselves.

If these new drugs allow obesity to be treated like a chronic disease — with medications that must be taken for a lifetime — the thought is that doctors, patients and the public might understand that obesity is truly a medical condition.

“We all believe this drug will change the way we see obesity being treated,” said Dr. Caroline Apovian, an obesity specialist at Brigham and Women’s Hospital. (Dr. Apovian, like most leading obesity researchers, consults for several drug companies. She is on the advisory board of Novo Nordisk, the maker of semaglutide, and is paid for attending advisory board meetings.)

Decades of studies have repeatedly showed that there are powerful biological controls over individual body weights. Identical twins reared apart had nearly identical body weights. Adopted children ended up with body mass indexes like those of their biological parents, not those of their adoptive parents. Metabolism slows as people lose weight, forcing them to regain it.

And yet, obesity “is like having a mark on your forehead,” said Dr. Scott Kahan, chair of the clinical committee for The Obesity Society, a scientific membership organization.

People with obesity are more likely to be passed over for jobs, be paid less than others with the same abilities and training, and be treated poorly by doctors, who spend less time with them and offer fewer preventive services.

But people with obesity haven’t had many places to turn for help. The current obesity drugs lead to an average weight loss of only 5 percent to 10 percent. And because some of these drugs are approved only for limited time frames, the lost pounds almost always come back when the intervention ceases.

According to these studies, incretins seem to be different. Unlike other weight-loss drugs, they are naturally occurring hormones that affect systems central to obesity. The drugs slow stomach emptying, regulate insulin and decrease appetite, with mostly mild to moderate short-term gastrointestinal side effects.

The drugs will not banish obesity or make people truly thin. But people who take them can look and feel very different. For some, the medications lead to weight loss approaching that of bariatric surgery.

If incretins pass the approval process, they might help convince the most important constituency of all — doctors — that obesity is a chronic disease and that it can be treated, said Dr. Robert F. Kushner, an obesity researcher and clinician at Northwestern University. One reason many doctors don’t help patients with obesity is that they don’t know how, Dr. Kushner said. Diets and exercise, the usual nostrums, almost always provide short-term weight loss, at best.

Dr. Robert F. Kushner, an obesity researcher and clinician at Northwestern University. “I tell them this is a chronic ongoing medical problem, just like diabetes,” he said.
Dr. Robert F. Kushner, an obesity researcher and clinician at Northwestern University. “I tell them this is a chronic ongoing medical problem, just like diabetes,” he said.Taylor Glascock for The New York Times

The incretin taken by Ms. Greenleaf, semaglutide, made by Novo Nordisk, is before the Food and Drug Administration, with a decision expected in June. On average it elicited a 15 percent weight loss, but a third of those who took it lost 20 percent or more of their body weight in the study, similar to the amount lost with lap-band bariatric surgery.

Eli Lilly has a similar drug, tirzepatide, which combines two incretins. The company is testing it against semaglutide and hopes that it will be even more powerful.

Dr. Louis J. Aronne, an obesity specialist at Cornell Medical School, said that the combination of semaglutide and another experimental Novo Nordisk drug, cagrilintide, could produce as much as a 25 percent weight loss in a year, an amount like that achieved with sleeve gastrectomy, a popular form of bariatric surgery.

Although more than a half-dozen new hormonal drugs are being tested, Dr. Kushner said, only with long-term use can researchers learn if the new drugs control the many medical consequences of obesity, like diabetes and high blood pressure.

There is also the larger riddle of biological destiny: Are the body’s multiple and redundant systems to maintain body weight so powerful that they will exert control in the end, diminishing the effectiveness of the drugs?

Like other obesity specialists, Dr. Rudolph L. Leibel, a researcher at Columbia University who conducted many of the pivotal studies showing obesity is a disease, deplores society’s bias against his patients. But he has his doubts that perceptions will change with new treatments.

“My guess is that bias will persist and might even be exacerbated by the availability of ‘an easy way out,’” he said.

Dr. Kushner is more hopeful and points to the example of statins, which lower cholesterol and became available in the late 1980s. Until then, doctors could only suggest that patients with high cholesterol cut back on eggs and red meat.

Doctors “embraced statins,” Dr. Kushner said, because they could at last treat this condition. More powerful incretins, he added, could have the same effect on the medical profession.

He is unsure, though, whether patients will accept the disease label. They’ve been conditioned, he said, to believe that their weight is their own fault; all they have to do is eat healthier and exercise more.

When talking with patients, he doesn’t spend 20 minutes trying to convince them that they have a disease. In fact, he deliberately avoids using the word “disease” and instead says “condition” or “problem.”

“I tell them this is a chronic ongoing medical problem, just like diabetes,” he said.

Members of the general public pose a different challenge, Dr. Kushner said. With them, he said, “we may need to use a term like ‘disease.’”

He likens the situation to that of alcoholism or drug addiction, which was once thought to be indicative of a weak will or a moral failing. Researchers have successfully changed the conversation; many people now know that those who abuse alcohol or drugs have a disease and need treatment.

As for Ms. Greenleaf, she wants to take semaglutide again. The pounds crept back when the trial ended.

Obesity, she now realizes, “is not your fault.”

Earlier Diabetes Onset Could Raise Dementia Risk

The younger the age at diagnosis for Type 2 diabetes, the higher the risk for Alzheimer’s disease and other forms of dementia years later.

Type 2 diabetes is a chronic, progressive illness that can have devastating complications, including hearing loss, blindness, heart disease, stroke, kidney failure and vascular damage so severe as to require limb amputation. Now a new study underscores the toll that diabetes may take on the brain. It found that Type 2 diabetes is linked to an increased risk for Alzheimer’s disease and other forms of dementia later in life, and the younger the age at which diabetes is diagnosed, the greater the risk.

The findings are especially concerning given the prevalence of diabetes among American adults and rising rates of diabetes in younger people. Once referred to as “adult-onset diabetes” to distinguish it from the immune-related “juvenile-onset” Type 1 disease that begins in childhood, Type 2 diabetes is seen in younger and younger people, largely tied to rising rates of obesity. The Centers for Disease Control and Prevention estimates that more than 34 million American adults have Type 2 diabetes, including more than a quarter of those 65 and over. About 17.5 percent of those aged 45 to 64 have Type 2 disease, as do 4 percent of 18- to 44-year-olds.

“This is an important study from a public health perspective,” said the director of the Yale Diabetes Center, Dr. Silvio Inzucchi, who was not involved in the research. “The complications of diabetes are numerous, but the brain effects are not well studied. Type 2 diabetes is now being diagnosed in children, and at the same time there’s an aging population.”

For the new study, published in JAMA, British researchers tracked diabetes diagnoses among 10,095 men and women who were 35 to 55 at the start of the project, in 1985 to 1988, and free of the disease at the time.

They followed them with clinical examinations every four or five years through 2019. At each examination, the researchers took blood samples to evaluate fasting glucose levels, a measure used to detect diabetes, and recorded self-reported and doctor-diagnosed cases of Type 2 disease.

The researchers also determined dementia cases using British government databases. Over an average follow-up of 32 years, they recorded 1,710 cases of Type 2 diabetes and 639 of dementia.

The researchers calculated that each five-year earlier onset of diabetes was associated with a 24 percent increased risk of dementia. Compared with a person without diabetes, a 70-year-old diagnosed with Type 2 diabetes less than five years earlier had an 11 percent increased risk for dementia. But a diagnosis at age 65 was associated with a 53 percent increased risk of later dementia, and a diagnosis at 60 with a 77 percent increased risk. A person diagnosed with Type 2 at ages 55 to 59 had more than twice the risk of dementia in old age compared with a person in the same age group without diabetes.

The study was observational, so could not prove that diabetes causes dementia. But it was long-running, with a large study population. The researchers controlled for many factors that affect the risk for dementia, including race, education, heart conditions, stroke, smoking and physical activity, and the diabetes-dementia link persisted.

“These are exceptional data,” said Daniel Belsky, an assistant professor of epidemiology at Columbia Mailman School of Public Health who was not involved in the research. “These associations between the timing of onset of diabetes and development of dementia show the importance of a life-course approach to preventing degenerative disease.

“We are an aging population, and the things we fear most are degenerative diseases like dementia, for which we have no cures, no therapies, and very few modifiable pathways to target for prevention,” Dr. Belsky said. “We can’t wait until people are in their 70s.”

Why diabetes would be linked to dementia is unknown. “We can speculate on the mechanisms,” said the study’s senior author, Archana Singh-Manoux, a research professor at INSERM, the French national health institute. “Living a long time with diabetes and having hypoglycemic events is harmful, and there are neurotoxic effects of diabetes as well. The brain uses enormous amounts of glucose, so with insulin resistance, the way the brain uses glucose might be altered” in people with Type 2 diabetes.

Type 2 can be managed and its complications reduced by monitoring blood sugar and conscientiously following a well-designed, personalized program of medication, exercise and diet. Is it possible that such a routine could minimize the risk for dementia later in life?

“With better control, there was less cognitive decline than in those with poor control,” Dr. Singh-Manoux said. “So stick to your medication. Look after your glycemic markers. That’s the message for people who have diabetes.”