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Chronic Disease, Obesity, Research, Stanford News

Faulty fat cells may help explain how Type 2 diabetes begins

Faulty fat cells may help explain how Type 2 diabetes begins

heavywaterWhy do some obese people develop Type 2 diabetes while others don’t? New evidence suggests the answer may lie just beneath the skin. A study published this month in the Journal of Lipid Research found metabolic anomalies in the subcutaneous fat of a group of people at risk for diabetes. Basically, fat cells under their skin weren’t very good at storing fat.

That’s a problem because fat that doesn’t get stored in these cells must go somewhere, and it often ends up in other organs, such as the liver, muscle, pancreas and heart. In those locations, there is evidence that too much fat causes “lipotoxicity,” in part by interfering with the messages of the sugar-handling hormone insulin.

The new research, a collaboration between Stanford’s Tracey McLaughlin, MD, and her colleagues here and at UC Berkeley and the National Institutes of Health, used a state-of-the-art technique developed by Berkeley’s Marc Hellerstein, MD, PhD, to monitor fat synthesis and storage in the subcutaneous fat cells of 15 people. All of the subjects were overweight or obese. Half were insulin resistant: Although their blood-sugar levels were normal, their bodies responded poorly to their own insulin, a state that precedes full-blown Type 2 diabetes. (Many scientists think that understanding insulin resistance could lead to preventive strategies for Type 2 diabetes.) The other subjects had normal insulin sensitivity.

Each day for four weeks, the subjects drank a few sips of heavy water, a non-radioactive substance labeled with “heavy” hydrogen atoms that have an extra neutron. After four weeks, the scientists took small samples of the subjects’ subcutaneous belly fat and measured how much heavy hydrogen had been incorporated into the cells’ stored fat molecules and their DNA.

The insulin-resistant subjects had less heavy hydrogen in their fat molecules than the insulin-sensitive subjects, suggesting that their subcutaneous fat cells made and stored less fat during the study. The amount of heavy hydrogen in the DNA of the two groups’ fat cells was the same. This means that the insulin-resistant people were making new subcutaneous fat cells at the same rate as the insulin-sensitive people. The bodies of the insulin-resistant people could generate new fat cells under the skin, but the cells didn’t work quite right.

“This is an important extension of limited static and nonhuman data supporting the hypothesis that dysfunctional fat storage in subcutaneous adipose tissue contributes to obesity-associated insulin resistance,” the scientists wrote, adding that future identification of the molecules that cause this problem may help researchers develop drugs that could treat insulin resistance and prevent Type 2 diabetes.

Previously: The role of nutrition in diabetes prevention and management, Preventing pre-diabetes from turning into diabetes and The importance of regular exercise in delaying and treating diabetes
Photo by Kim P

Big data, Events, Pediatrics, Pregnancy, Research, Stanford News

Stanford hosts inaugural Childx conference this spring

Stanford hosts inaugural Childx conference this spring

Chandler's 15 Month CheckupRegistration is now open for the first ever Childx conference, a TED-style conference focused on inspiring innovation in pediatric and maternal health. The conference will bring thought leaders from several disciplines to the Stanford campus April 2 and 3 for two days of conversation about how to harness many branches of medicine to solve the health problems of pregnancy, infancy and childhood.

“Pediatric medicine faces unique challenges,” said systems biology researcher Dennis Wall, PhD, who leads the conference’s scientific advisory board. “Most children are quite healthy, which can make it difficult to attract adequate research attention to severe pediatric diseases that affect relatively few children. At the same time, every child’s health status is influenced by a complex array of factors, which cause decades-long ripple effects as today’s children mature into tomorrow’s adults.”

The conference, developed and sponsored by Stanford’s Child Health Research Institute, has five themes:

  • Definitive stem cell and gene therapy for child health
  • The arc of fetal, developmental/cognitive, and adult health
  • Accelerating child and maternal health innovation
  • Precision medicine for rare and historically untreatable childhood disease
  • The health ecosystem and the impact of social, economic, political, environmental, and cultural issues on children’s health and well-being

Featured guests include Martin Andrews, who leads Glaxo Smith Kline‘s rare diseases team; Nadia Rosenthal, PhD, founding director of the Australian Regenerative Medicine Institute; Harvard’s Matthew Gillman, MD, an expert on early-life prevention of chronic disease; Sheena Josselyn, PhD, a neuroscientist at the University of Toronto and the Hospital for Sick Children who studies molecular processes behind learning and memory; and Donald Schwarz, MD, the director of the Robert Wood Johnson Foundation, as well as a large cast of Stanford stars from several areas of pediatric medicine.

“Pediatric medicine needs to turn its focus more to creating advanced, technology-enabled solutions that will increase our ability to detect, monitor and treat child health,” Wall said. “No pediatric conference to-date has combined these key themes of precision healthcare with the most pressing challenges and opportunities in child and maternal health. The inaugural Childx will be the first conference to do so.”

The conference will welcome maternal and child health researchers, clinicians, investors, industry experts and interested community members. Early bird registration is open through February 28.

Addiction, Health Policy, In the News, Pediatrics

To protect teens’ health, marijuana should not be legalized, says American Academy of Pediatrics

To protect teens' health, marijuana should not be legalized, says American Academy of Pediatrics

teen smoking Today, the country’s most prominent group of pediatricians issued a policy statement that opposes marijuana legalization and advocates for policies to help minimize the drug’s harmful effects on children and adolescents. The new statement, from the American Academy of Pediatrics, was written in response to recent research on adolescent brain development and the biology of addiction, as well as a changing national climate on marijuana laws.

I spoke with Stanford’s Seth Ammerman, MD, an adolescent medicine specialist and the lead author of the new statement and accompanying technical report. Ammerman studies substance-use issues in youth and also has extensive experience working with at-risk young people, in part through his role as medical director of the Adolescent Health Van run by Lucile Packard Children’s Hospital Stanford.

“The national trend is definitely toward more medical marijuana, and also toward legalization for adults,” he said. “This trend can definitely affect kids, so it was really important for the Academy to have a voice, to be working on a national conversation about this.”

During our conversation, Ammerman explained some of the latest research that has motivated the AAP’s stance against marijuana legalization:

In the past decade, we’ve learned that brain development doesn’t finish until one’s early to mid-20s, and substance use can alter the developing brain. There are a few ways we know this: One, there’s clear evidence that the younger you start using drugs regularly, the more likely you are to become addicted. This is true for alcohol, tobacco, and marijuana, among others. For those who put off substance use until their late teens or early 20s, addiction rates are significantly lower.

We also know that the developing brain is very vulnerable to substance use. One in 10 adolescents who use marijuana become addicted. That means that 90 percent won’t — which is the good news — but the problem is we can’t predict which 10 percent will develop addiction.

We also have a lot of research about the adverse effects of marijuana use. Heavy users fare worse in many ways: their cognitive levels fall, they are less likely to finish high school or attend college, and they tend to suffer more from depression. Most users are not heavy users, but again, we can’t predict who will fall into this category.

The AAP is also in favor of decriminalizing marijuana, replacing current criminal penalties with lesser criminal or civil penalties and drug treatment. This is an especially important step to reduce the long-term damage to educational and job opportunities that currently comes with marijuana arrests, Ammerman said, adding: “There is a significant problem of racial inequity associated with marijuana arrests: minorities are way over-arrested and their lives are messed up because of marijuana arrests. It’s a very important step to say we need to help kids, not punish them.”

Previously: Medical marijuana not safe for kids, Packard Children’s doc says, Pediatrics group calls for stricter limits on tobacco advertising and To reduce use, educate teens on the risks of marijuana and prescription drugs

Photo by mexico rosel

Patient Care, Pediatrics, Public Health, Research, Stanford News

Study finds gaps in referring California’s tiniest babies to follow-up care

Study finds gaps in referring California's tiniest babies to follow-up care

preemie feet2When very fragile babies go home from the hospital after birth, they often require special follow-up care. But a new Stanford study has found that some high-risk infants aren’t receiving referrals to the follow-up care they need.

The study, which appears in the February issue of The Journal of Pediatrics, analyzed statewide data on more than 10,000 California babies born in 2010 and 2011 who were considered high risk because they had very low birth weights. Of those who survived to hospital discharge, 20 percent did not receive referrals to the state’s high-risk follow-up program.

From our press release on the research:

Babies who weigh less than 3.3 pounds at birth, nearly all of whom are born prematurely, are at risk for a variety of neurologic and developmental problems in childhood. In California, all babies with a very low birth weight who received care in a California Children’s Services-approved neonatal intensive care unit qualify for a state-supported, follow-up program that provides diagnostic assessments and services until they turn 3.

“If we cannot succeed in that first step of getting these babies referred to follow-up, we’re at a critical disconnect for what we can offer them as they grow and develop,” said Susan Hintz, MD, professor of neonatal and developmental medicine and lead author of the study.

The study analyzed which very-low-birth-weight babies were receiving referrals. Neonatal intensive care units that treated more of these babies referred a higher proportion of such patients to follow-up care, and babies with several types of medical problems were more likely than others to receive referrals. Babies whose birth weights were on the higher end of the low-weight category were less likely to get referrals, as were those of African-American and Hispanic descent.

The good news, however, is that the data was collected just after California revamped its high-risk follow-up program. Hospitals with low referral rates are already receiving feedback to help them improve, and those with high referral rates are being studied to see how their successes can be transferred to other settings. More from our release:

“We’ve already made substantial improvements in site-specific online tools and resources available to hospitals for nearly real-time feedback, and referral rates now appear to be higher than they were during 2010 and 2011,” Hintz said.

California is ahead of other states in having a comprehensive, statewide program to help high-risk infants, [she] added. “The expectation that all our high-risk infants will be referred is enormously innovative in this country,” she said.

Previously: Preemies face increased risk of death in early adulthood, Stanford study finds, NICU trauma intervention shown to benefit mothers of preemies and How Stanford researchers are working to understand the complexities of preterm birth
Photo by Jenny

Pediatrics, Research, Stanford News

Silicon Valley entrepreneur Sean Parker establishes allergy center at Stanford

Silicon Valley entrepreneur Sean Parker establishes allergy center at Stanford

DrKariNadeau-Dec2014Here at Scope, we’ve often written about the life-threatening nature of allergic reactions and the work that Stanford scientists are doing to understand dangerous allergies. For instance, Stanford immunologist Kari Nadeau, MD, PhD, (pictured at right) leads research to combat children’s food allergies with oral immunotherapy, a treatment in which patients consume tiny but gradually increasing doses of their allergy triggers under a doctor’s supervision.

Today, the efforts of Nadeau and other Stanford allergy researchers are receiving a big boost. Silicon Valley entrepreneur and philanthropist Sean Parker has announced that he’s donating $24 million to establish an allergy research center at Stanford, which Nadeau will lead. Parker has a personal interest in the topic because of his own experience with severe food allergies. Scientists at the Sean N. Parker Center for Allergy Research at Stanford University will study the underlying mechanisms of all types of allergies in children and adults and will aim to develop lasting allergy cures.

From the press release about the center’s launch:

“We are excited about the center because there is enormous clinical need for better understanding of and treatment for allergies,” said Lloyd Minor, MD, dean of Stanford University School of Medicine. “For instance, the recent profound increase in the incidence of serious food allergy is fascinating and deeply concerning at the same time. Sean Parker’s generous gift will enable Stanford Medicine experts, under Dr. Nadeau’s leadership, to collaborate and innovate across academic disciplines for the benefit of millions of people with allergies.”

“I am thrilled and honored to direct the Sean N. Parker Center for Allergy Research at Stanford University,” said Dr. Nadeau, associate professor of pediatrics at the medical school and an immunologist at Lucile Packard Children’s Hospital Stanford and Stanford Health Care. “Sean is well-versed in immunology, and has been a fantastic partner to work with. He’s an entrepreneur and visionary, and we look forward to using this gift and center as the springboard to improve the lives of those adults with allergies through immunotherapy that goes beyond oral therapy.”

Previously: Taking a bite out of food allergies: Stanford doctors exploring new ways to help sufferers, Ask Stanford Med: Pediatric immunologist answers your questions about food allergy research and Researchers show how DNA-based test could keep peanut allergy at bay

Chronic Disease, Neuroscience, Parenting, Pediatrics, Research

High blood sugar linked to reduced brain growth in children with Type 1 diabetes

High blood sugar linked to reduced brain growth in children with Type 1 diabetes

Some areas of the brain grow more slowly in children with Type 1 diabetes than those without, according to findings published this week in Diabetes. Researchers also found that children with the highest and most variable blood sugar levels had the slowest brain growth.

Glucose, the main form of sugar in our blood, is the brain’s primary fuel, and in Type 1 diabetes, the body loses the ability to produce a key hormone needed to regulate blood sugar levels. Type 1 diabetes treatment for children has often focused on making sure their glucose levels don’t get too low, since very low glucose can quickly put someone into a coma. But it’s emerging that chronically-high sugar is also bad for the brain.

The better the glucose control, the more likely that a child’s brain development will be unimpeded.

The new study, conducted at Stanford and four other universities, tracked brain structure and cognitive function in 144 young children with Type 1 diabetes and a comparison group of 72 children without diabetes over 18 months. MRI scans showed that the brains of both groups of kids were growing, but gray- and white-matter growth was slower in several areas of the brain in the diabetic children.

“These studies provide strong evidence that the developing brain is a vulnerable target for diabetes complications,” the researchers wrote. The affected brain areas have a variety of roles, including visual-spatial processing; auditory, language and object processing; executive function; spatial and working memory; and integration of information from sensory systems.

I asked two of the paper’s Stanford authors for more thoughts about what they found.

“The magnitude of the group differences in brain growth over time was surprising,” said Allan Reiss, MD, the study’s senior author. “I actually thought these differences would be more subtle — they were not.”

Past studies have found cognitive and brain-structure changes associated with diabetes in older patients, but this research stands out because the kids included were so young — at the start of the study, their ages ranged from 4 to just under 10, with an average age of 7 — and because the study had a prospective design, following children forward in time. In addition to examining brain structure, the researchers also tested the kids’ cognitive function with standard tests of IQ, learning and memory, and mood and behavior, among others. They saw no significant differences in cognitive function between the two groups, a finding Reiss said did not surprise him.

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Imaging, Neuroscience, Patient Care, Pediatrics, Research

Stanford-led study suggests changes to brain scanning guidelines for preemies

Stanford-led study suggests changes to brain scanning guidelines for preemies

preemieOne big challenge of having a premature baby: the uncertainty. With good medical care, a great many preemies do very well, but some face long-term disabilities, medical complications and developmental delays, and others, sadly, die in infancy. Unfortunately, doctors can’t always tell how a baby will fare in the long term.

A new study, led by a Stanford team and conducted at 16 sites around the country, is part of the ongoing effort to change that. The researchers examined what type and timing of brain scans give doctors the greatest ability to predict preemies’ neurodevelopmental outcomes in toddlerhood. The research, published online today in Pediatrics, found that for babies born more than 12 weeks early who survive to near their original due dates, brain scans performed near their due date are better predictors than scans done near birth.

Most preemies already get at least one brain scan. That’s because national guidelines recommend that preemies’ doctors perform a cranial ultrasound seven to 14 days after birth to look for immediate problems such as bleeding into the brain. (Ultrasound is a good fit for the needs of fragile infants: Babies’ fontanelles provide “acoustic windows” to the brain, and ultrasound is non-invasive, uses no radiation, requires no sedation, and can be performed with a portable scanner brought to the bedside.) Some prior research has shown that these early scans can also give information about an infant’s risk of cognitive, motor and behavioral deficits or delays in childhood, but the predictive value of these early scans can be fairly low.

The new study examined both cranial ultrasound and MRI performed close to the baby’s due date, which is also when most preemies are ready to go home from the hospital. A lot changes in the brain during those first few weeks, perhaps explaining why later scans did a significantly better job of predicting which children would have persistent neurodevelopmental problems when the doctors checked in with them at 18 to 22 months of age.

“Neuroimaging may help us understand what a child’s outcome may look like, and ultimately help us focus our attention in terms of the type of follow-up and specific interventions that could best support a child after discharge from the hospital,” said Susan Hintz, MD, the study’s lead author and a neonatologist at Lucile Packard Children’s Hospital Stanford.

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Autism, Behavioral Science, Events, Stanford News

Thinking in pictures: Stanford hosts Temple Grandin

Thinking in pictures: Stanford hosts Temple Grandin

Grandin Temple - smallEarlier this week, I got to hear a presentation by Colorado State University animal behavior expert Temple Grandin, PhD, who is widely known not just for her extensive work to enhance animal welfare, but also because she is one of the world’s most prominent individuals with autism. Like many others, I first became familiar with Grandin’s work through Oliver Sacks’ 1995 book, An Anthropologist on Mars. (The title came from Grandin’s description of how she feels when trying to decode the subtleties of social interactions.) Since I first read Sacks’ book, I’ve written frequently about autism research and treatment, and I’ve gotten some sense of how phenomenally important Grandin is to the autism community. So it was quite a thrill to be sitting just a few feet from her as she spoke to an overflow crowd at the School of Medicine.

Grandin’s talk focused on understanding animal behavior and reducing animals’ stress, but she interwove descriptions of her research with comments on how living with autism has influenced her work – and, indeed, how it influences the world around us. “A little bit of autism gives you Silicon Valley,” she quipped in the introduction to her talk. Although her subject was animals’ stress, at the heart, she was explaining different ways of thinking: in words or in pictures.

Animals think in pictures, especially when it comes to determining which elements of their environment are stressful or frightening, Grandin said: “Animals are all about sensory detail, little bits of detail we tend not to notice.” At one point in the talk, she showed a photo of a cow bending forward to investigate a spot of sunlight on the floor of the room where it was about to have a veterinary exam. To a human, this spot would likely seem insignificant, but to the cow, it is a foreign object that needs to be approached with caution.

“Novelty is a strong stressor for animals,” Grandin said, adding that if something visually new is forced in an animal’s face, it’s scary. The cow in the photo needs a few minutes to sniff the sun spot and figure out that it’s harmless; a human trying to force the situation will soon have a frightened, resistant animal to handle. Humans also have to keep in mind that our word-oriented brains may not categorize “novelty” in the same way that an animal does. For instance, an animal that has become accustomed to the sight of a blue-and-white umbrella may still be frightened by an orange tarp, Grandin said. To people, they’re both rain protection, but to a horse or cow, “It’s a different picture!”

Like many children with autism, Grandin began speaking later than most kids, and she still thinks in images more intuitively than words. “I see movies in my imagination, and this helped me understand animals,” she said. She likened her memory to Google Images, explaining that for her, a particular word will pull up many associated images, categorized by type. Her designs for meat-processing plants, now in use in half of the meat-processing facilities in North America, rely on her ability to mentally take a “cattle’s-eye view” of each step in the animal’s journey before slaughter, playing out a movie in her head that shows her where animals could be forced to encounter new things that might frighten them.

As well as describing her own work, Grandin advocated for broader acceptance of different kinds of thinkers, both with and without autism. People may think predominantly in pictures, or in patterns (that’s the math whizzes among us), or in words, she said, and we need educational and employment systems that can nurture and benefit from each of these ways of thinking. “There is too much emphasis on deficits [of children with autism], and not enough on building their strengths,” she said.

Grandin’s complete talk, which was hosted by the Department of Comparative Medicine, will soon be available on the department’s news website.

Previously: A conversation with autism activist and animal behavior expert Temple Grandin, Growing up with an autistic sibling: “My sister has a little cup” and Finding of reduced brain flexibility adds to Stanford research on how the autistic brain is organized
Photo by Rosalie Winard

Patient Care, Pediatrics, Research, Stanford News

Better communication between caregivers reduces medical errors, study finds

Better communication between caregivers reduces medical errors, study finds

Miscommunication between caregivers is one of the largest causes of medical errors, but a new study published this week in the New England Journal of Medicine suggests that the problem is at least partly preventable.

The study at nine children’s hospitals, led by Boston Children’s Hospital and including our own Lucile Packard Children’s Hospital Stanford, tested the effects of a standardized method for medical residents to hand off information about their patients at shift changes. Shorter shifts for residents have increased the number of such hand-offs, putting the hand-offs themselves under more scrutiny in recent years.

At each participating hospital, medical residents were trained to use an acronym that reminded them what information to share about each patient, and in what order. The hand-off process included both oral and written communication, and ended with the person who was receiving the information repeating back a summary of what was shared with the person who gave it. The program also included other supports to ensure that the hand-off procedure was embedded in the hospital’s culture and did not have a negative effect on the doctors’ overall workflow.

The participating hospitals reduced their rate of medical errors by 23 percent, and preventable adverse events dropped by 30 percent. From a Boston Children’s press release about the research:

“Because we know that miscommunications so commonly lead to serious medical errors, and because the frequency of handoffs in the hospital is increasing, there is no question that high-quality handoff improvement programs need to be a top priority for hospitals,” says [lead study author Amy] Starmer. “It’s tremendously exciting to finally have a comprehensive and rigorously tested training program that has been proven to be associated with safer care and that meets this need for our patients.”

The program tested in the new research is available for free to any hospital that wants to implement it.

Previously: New study shows standardization makes hospital hand-offs safer, Less burnout, better safety culture in hospitals with hands-on executives, new study shows and Automated safety checklists prevent hospital-acquired infections, Stanford team finds

Pregnancy, Research, Stanford News, Women's Health

Stanford/VA study finds link between PTSD and premature birth

Stanford/VA study finds link between PTSD and premature birth

pregnant-silhouetteScientists have long suspected that post-traumatic stress disorder raises a pregnant woman’s risk of giving birth prematurely. Now, new research from Stanford and the U.S. Department of Veterans’ Affairs confirms these suspicions.

Women with “active” PTSD, diagnosed in the year before they gave birth, were 35 percent more likely than those without PTSD to spontaneously go into labor early and deliver a premature baby, the study found. Women whose PTSD had been diagnosed further in the past were not at increased risk, however.

The findings, published today in Obstetrics & Gynecology, are based on data from 16,344 births to female veterans. All of the women had been screened for PTSD. The researchers found that 3,049 babies were born to women diagnosed with the disorder at some point prior to delivery, and of these, 1,921 births were to women who had active PTSD.

“This study gives us a convincing epidemiological basis to say that, yes, PTSD is a risk factor for preterm delivery,” the study’s senior author, Ciaran Phibbs, PhD, associate professor of pediatrics and an investigator at the March of Dimes Prematurity Research Center at Stanford University, said in a press release. “Mothers with PTSD should be treated as having high-risk pregnancies.”

The VA has already adopted Phibbs’ recommendation for their patients and is now including a recent PTSD diagnosis among the factors that flag a woman’s pregnancy as high-risk. But the findings aren’t just for veterans, Phibbs told me. “The prevalence of PTSD is higher among veterans, but it’s still reasonably common in the general population,” he said. Nor was the PTSD-prematurity link limited to women with combat experience, he said. Half of the women in the study who had PTSD diagnoses had never been deployed.

Spontaneous premature labor, the focus of this study, accounts for about half of premature births. Phibbs’ team is now investigating the other half of preterm births: They are examining whether PTSD also influences a mother’s risk of developing medical conditions that could cause her physician to recommend an early delivery for the sake of the mother’s or baby’s health.

Previously: Maternal obesity linked to earliest premature births, says Stanford studyThe year in the life of a preemie – and his parents and How Stanford researchers are working to understand the complexities of preterm birth
Photo by Stefan Pasch

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