Attacking an Epidemic: Type 2 Diabetes
“An ounce of prevention is worth a pound of cure” referred to the benefits of preventing fires, not disease. But Ben Franklin’s aphorism also applies to people at risk for type 2 diabetes. Some 26 million Americans already have type 2 diabetes, incurring healthcare bills totaling $250 billion a year. Millions more are at risk for developing the disease. If current trends continue, one in three Americans will have diabetes by 2050.
The major cause of the type 2 diabetes epidemic is obesity. Excess body fat not only swells the waistline but also alters the blood, filling it with inflammation-causing chemicals that make various tissues more resistant to insulin, the hormone that directs cells to absorb glucose from the bloodstream to use as an energy source.
“The body compensates for insulin resistance by telling beta cells in the pancreas to make more insulin,” says Jeffrey E. Pessin, Ph.D., professor of medicine (endocrinology) and of molecular pharmacology, the Judy R. and Alfred A. Rosenberg Professorial Chair in Diabetes Research and director of the Diabetes Research Center at Einstein. “But this works only for so long. Over time, beta cells have an increasingly hard time secreting insulin, and they eventually begin to fail.” Insulin’s absence allows sugar levels in the blood to rise, setting the stage for serious health complications such as heart disease, hypertension, kidney failure, foot amputations and blindness.
Could type 2 diabetes and its complications be prevented? To find out, Einstein and 26 other sites nationwide collaborated on a landmark clinical trial—the Diabetes Prevention Program (DPP)—that began in 1995. The DPP studied whether a lifestyle intervention (modest weight loss and exercise) or treatment with metformin (an oral diabetes drug that suppresses glucose production in the liver) could prevent or delay the onset of type 2 diabetes in people at high risk for the disease.The results of the DPP, published in the New England Journal of Medicine in 2002, showed clearly that these measures could help prevent type 2 diabetes and that lifestyle changes were especially effective.
For overweight adults with prediabetes (blood glucose levels higher than normal but not high enough to warrant a diabetes diagnosis), their incidence of diabetes was reduced by 58 percent with lifestyle changes and by 31 percent with metformin, compared with those who received a placebo. People 60 and over especially benefited from lifestyle intervention, which reduced their diabetes risk by a remarkable 71 percent. And lifestyle changes worked equally well in men and women and across all major ethnic groups.
Allen M. Spiegel, M.D., then director of the National Institute of Diabetes and Digestive and Kidney Diseases (the trial’s primary sponsor) and now the Marilyn and Stanley M. Katz Dean at Einstein, called the DPP findings “a major step toward the goal of containing and ultimately reversing the epidemic of type 2 diabetes in this country” and noted that “every year a person can live free of diabetes means an added year of life free of the pain, disability and medical costs incurred by this disease.”
The DPP showed that overweight or obese people can avoid or delay developing type 2 diabetes simply by losing weight—ideally through regular physical activity and a low-fat, low-calorie diet. Millions of people urgently need to adopt those measures, as the following statistics show:
- More than one-third of American adults (35 percent) were classified as obese in 2011–2012 (as noted in an October 2013 report from the National Center for Health Statistics). This translates to more than 78 million people at high risk for developing type 2 diabetes.
- In New York City, 58 percent of adults and nearly 40 percent of children are overweight or obese. As a result, one in three adult New Yorkers now has type 2 diabetes or prediabetes.
- The obesity epidemic is especially acute in the Bronx, with one of the highest obesity incidences of any county in the United States. Nearly 70 percent of Bronx adults—about 630,000 people—are overweight or obese.
- $4 billion is spent annually in New York City on healthcare costs related to obesity.
Do DPP Benefits Last?
The DPP followed patients at risk for diabetes for an average of only three years and so couldn’t answer some key questions, such as: Can people ward off diabetes indefinitely if they stick with their medications and a healthy lifestyle? Will at-risk people who change their behaviors but still develop diabetes experience less frequent or less severe complications? Such questions are being addressed in the Diabetes Prevention Program Outcomes Study, or DPPOS, which is following the original DPP participants for an additional 15 years.
“The average age of our study participants is now in the mid-60s, so this phase should show whether people can maintain an active lifestyle with advancing age,” says Jill P. Crandall, M.D., professor of clinical medicine (endocrinology), a DPP investigator and now one of the DPPOS’s principal investigators. “Perhaps most important, we’ll find out whether the DPP interventions help reduce diabetic complications.”
“Perhaps most important, we’ll find out whether the DPP interventions help reduce diabetic complications.”
The findings from the current phase of DPPOS are expected in 2015. “We assume and hope that the program will produce long-term benefits, but we don’t know for sure,” says Dr. Crandall, who is also an attending physician in endocrinology at Montefiore Medical Center.
Walking the Walk
The DPP finally gave clinicians a highly effective remedy for preventing diabetes or slowing its onset. The next and arguably more formidable challenge is motivating patients to take the “medicine” prescribed by the DPP—no easy task. Studies assessing patient compliance have found that as few as 60 percent of type 2 diabetes patients adhere to the medication regimen prescribed for them.
As few as 60 percent of type 2 diabetes patients adhere to their medication regimen
Patients are even less likely to follow healthy eating and exercise recommendations than to do something relatively simple such as taking a pill, notes Elizabeth A. Walker, Ph.D., R.N., professor of medicine (endocrinology) and of epidemiology & population health and co-leader of the DPP’s medication adherence group.
“Eating in particular is highly complex,” Dr. Walker notes. “It’s fraught with emotions. It’s about comfort food, family, memories of Mom’s home cooking. Plus, you have to decide what to eat several times a day. The challenge of eating well is never ending.”
Dr. Crandall says that the realities of everyday life can also interfere with healthful habits. “For example,” she asks, “how do you inspire adults to exercise when they are working two jobs and must take two buses to get to the local YMCA? How do you encourage children to eat fresh fruits and vegetables when fast foods are available on every corner?”
The task of translating the DPP findings into workable remedies falls to behavioral scientists such as Dr. Walker. Below are descriptions of her work and that of other like-minded faculty at Einstein and its primary teaching hospital, Montefiore Medical Center.
What Do Men Want?
A few years after the DPP issued its findings, the Centers for Disease Control and Prevention teamed with the YMCA to bring the DPP’s lifestyle intervention to communities nationwide. Now known as the National Diabetes Prevention Program (NDPP), this yearlong effort consists of 16 weekly group sessions on diet and exercise, followed by periodic “booster” classes. The NDPP is now offered in some 250 locations in 26 states.
The NDPP reportedly is working well, yet it can’t begin to reach all those who need it. This is especially true in the Bronx, with its single YMCA site for a population of 1.4 million and a high incidence of obesity.
The clear need for more resources prompted Dr. Walker to apply for and win a grant from the Leon Lowenstein Foundation, Inc., of New York to study whether modifying the Bronx NDPP could pave the way for more such programs in the borough.
One of the most compelling findings to arise from her study was that men make up just one in ten Bronx NDPP enrollees. “This is a significant problem,” says Dr. Walker. “Men have a somewhat higher risk of developing type 2 diabetes than women, and black and Latino men have a higher risk than Caucasian men.”
It’s too early for a definitive explanation for the gender disparity found in the Bronx NDPP classes, but Dr. Walker suspects a major reason is that the men simply aren’t as interested as women in “lifestyle” programs. “If that’s true,” she says, “we think that we can get more men in the door by emphasizing physical activity and making the group activities a bit more competitive.”
Dr. Walker and her colleagues (who include officials at the Bronx NDPP and healthcare providers and administrators at Montefiore) are also looking at ways to improve overall enrollment, increase retention rates, lower economic barriers to participation and find additional sites for hosting the program. Montefiore has now begun offering the NDPP program at some of its own clinics, including classes taught in Spanish. And the medical center has updated its electronic medical record system, allowing clinicians to refer patients to a diabetes prevention program more easily.
“At Montefiore we’ve made diabetes prevention a top priority,” says Peter A. Selwyn, M.D., M.P.H., professor and chair of family and social medicine at Einstein and Montefiore, professor of epidemiology & population health, of medicine and of psychiatry and behavioral sciences at Einstein and director of the Office of Community Health and Wellness at Montefiore. “We’re working to find new ways of promoting healthy behaviors and healthy environments. In public health, we often talk about making the healthy choice the easy choice. That tactic is critical in preventing diabetes.”
An Eastern Intervention
A borough away from the Bronx but a world apart, other Einstein researchers are studying diabetes prevention among Chinese immigrants in Lower Manhattan—another community that could benefit from a customized approach to diabetes prevention.
“The NDPP is a good idea—it brings people to a place to both learn and exercise—but it’s not ideal for this particular community,” explains Judith Wylie-Rosett, Ed.D., professor of epidemiology & population health (health promotion and nutrition research) and of medicine (endocrinology) and the Atran Foundation Chair in Social Medicine. “Chinese immigrants prefer getting their healthcare advice from Chinese physicians. So if you want to reach this population, you have to go through the local practices rather than the YMCA.”
Dr. Wylie-Rosett gained her insights from working with several organizations serving New York City’s Chinese-American community. That collaboration has yielded recommendations for tailoring the NDPP intervention to this group. “We’ve learned, for example, that many Chinese aren’t comfortable talking about personal issues in a group setting, so we’ve added telephone counseling for certain topics,” she says.
Other adaptations include adding karaoke—a favorite Asian pastime—to the stress-management session; distributing healthy Chinese recipes; and tailoring discussions on how body fat relates to diabetes (reflecting that Asians tend to develop the disease at a lower body mass index [or BMI, an indicator of body fat] than other groups do).
Dr. Wylie-Rosett and her colleagues are currently finishing a pilot study to test whether the revamped program is acceptable and effective.
Empowering Bangladeshi Women
Just a mile from the Einstein campus, the Bronx Bangladeshi community is the fastest-growing immigrant group in New York City. Until recently, its health needs were largely unknown. A 2012 survey by Alison Karasz, Ph.D., associate professor of family and social medicine, found that an astonishing 74 percent of local Bangladeshi women were either overweight or obese and that more than 15 percent had type 2 diabetes—the highest rates in the city.
Offering these women a program such as the NDPP lifestyle intervention might have seemed a logical response. But Dr. Karasz, a clinical psychologist who has been practicing in the Bronx South Asian community for years, had a different idea.
74 percent of local Bangladeshi women were either overweight or obese and more than 15 percent had type 2 diabetes—the highest rates in New York city
“Intensive lifestyle programs such as the NDPP are highly effective in the general population,” she says. “But they’re based on Western theories of ‘empowering the individual’ that tend to ignore the extent to which learning and behavior change are embedded in social networks and communities.” When recruiting women from such a traditional hierarchical society into treatment, she adds, “it’s important to make sure that their families are on board with the program.”
Such considerations prompted Dr. Karasz and her colleagues to develop two lifestyle interventions aimed at improving women’s nutrition and exercise habits: SAATHI (South Asians Acting Together for Health Improvement) and APPLE (Activating People to Pursue Lifestyle Change through Empowerment). Both programs build social networks that offer support for women as they change their behaviors in ways acceptable to family members. For example, each participant is partnered with a bondhu (“friend” in Bengali) who helps her set goals and maintain her lifestyle changes.
The approximately 50 women recruited so far into SAATHI and APPLE lost an average of 5.8 percent of their weight after completing the programs. And, says Dr. Karasz, about 75 percent of enrollees complete the programs—a much better retention rate than other lifestyle programs designed for immigrants have achieved. She believes these programs could serve as a model for diabetes prevention and treatment programs in other traditional immigrant communities.
Focus on Children
Readers of a certain age may remember when type 2 diabetes was called “adult-onset” diabetes, since it didn’t usually appear until middle age. But diabetes has been trending younger and younger in recent years—a direct consequence of the rise in childhood obesity. Einstein and Montefiore have launched several initiatives to help children avoid the disease. One example is B’N Fit (the Bronx Nutrition and Fitness Initiative for Teens), founded and directed by Jessica Rieder, M.D., M.S., associate clinical professor of pediatrics (adolescent medicine) at Einstein and an attending physician in adolescent medicine at The Children’s Hospital at Montefiore.
B’N Fit is a nine-month weight-management program that helps obese inner-city adolescents adopt healthy lifelong nutritional and physical activity skills; develop coping skills and personal responsibility; and use family, social and community resources to achieve personal goals. Begun in 2005, B’N Fit is a collaborative effort of The Children’s Hospital at Montefiore and the Mosholu Montefiore Community Center.
Dr. Rieder and her colleagues recently evaluated 349 adolescents (two-thirds of them severely obese) who enrolled in B’N Fit. The 91 participants who completed the program showed significant improvement in their BMIs, consumed significantly more servings of fruit and vegetables daily and participated significantly more often in vigorous physical activities—all in spite of school obligations, family emergencies and transportation issues. But nine months after the teens completed the program, their BMIs had increased significantly.
The participants showed significant improvement in their body mass index (BMI) and ate significantly more fruits and vegetables daily
“Our findings indicate that a nine-month program isn’t long enough to have a sustained impact on obese inner-city teens,” says Dr. Rieder. “These kids need long-term support for sticking with the healthy lifestyles that are so crucial for losing weight and keeping it off.”
Dr. Wylie-Rosett is developing a program similar to B’N Fit for preteens at risk for diabetes, but adding parents to the mix. “Our goal is to make a healthy lifestyle a family agenda,” she says. The program features recreational and educational activities for kids plus workshops for parents that include advice on healthy eating and effective parenting strategies.
Ideally, the program will change the family dynamic when it comes to eating—making the dinner table the focal point of meals, for example. “In many households, the TV is on all the time, and everyone eats in front it,” says Dr. Wylie-Rosett. “There’s no regular meal time. We think it’s important for family members to eat together, to talk to each other and to pay attention to what they’re eating.”
Dr. Wylie-Rosett is planning to test the intervention on several hundred Bronx families.
Resveratrol to the Rescue?
If lifestyles changes aren’t enough to prevent diabetes, perhaps a glass of red wine can do the trick.
As many oenophiles know, red grapes contain a chemical called resveratrol that can normalize glucose metabolism, prevent cancer and heart disease and prolong life spans—at least in animals. In a 2010 pilot study of 10 older patients with prediabetes, Dr. Crandall and her Einstein colleagues found that resveratrol supplements improved the subjects’ insulin sensitivity and postmeal glucose tolerance—the first study to link resveratrol to a benefit in humans.
Dr. Crandall was later awarded a $600,000 grant from the American Diabetes Association to expand her inquiry into resveratrol. She will study 30 people ages 50 to 80 who have impaired glucose tolerance to see how resveratrol supplements affect postmeal metabolism of blood glucose. Preliminary studies will explore how resveratrol works by examining cellular function (in muscle samples obtained from study participants) and by testing resveratrol’s effect on blood vessel function.
Resveratrol supplements must be used because diet alone can’t supply what is believed to be a therapeutic concentration of the compound: Researchers estimate that you’d need to drink hundreds bottles of wine per day to obtain the resveratrol levels found therapeutic in mice.
“Our earlier work has given us reason to be hopeful,” says Dr. Crandall. “Given the easy availability, low cost and apparent safety of resveratrol supplements, a positive finding could have an enormous impact on human health.”
The Diabetes Outlook
Even if resveratrol proves useful in preventing diabetes, much more must be done to put a dent in the diabetes epidemic.
“All the things that drive the epidemic are societal—the limited availability of healthy foods in many neighborhoods, the relentless junk-food advertising aimed at children, the lack of recreational opportunities in urban areas,” says Dr. Crandall. “We need a major national public health campaign aimed at diabetes prevention, similar to campaigns used to curb smoking or mandating seatbelt use.”
That effort, she says, may involve requiring people to change their behavior, not just suggesting they do so. “We banned smoking from public spaces, making it harder to light up,” she notes. “The bottom line is that people are much safer.
“It’s an enormous challenge,” Dr. Crandall acknowledges, “but the potential benefits are huge. If we can prevent diabetes, we would also reduce the incidence of heart disease, high blood pressure, cancer, and many other complications.” Ben Franklin would certainly have approved.
Preventing Type 1 Diabetes
People at risk for type 2 diabetes can prevent or slow the onset of the disease through diet, exercise or drugs. But the search continues for a way to stave off type 1 diabetes, which affects about 5 percent of all people who have the disease.
Scientists led by Teresa P. DiLorenzo, Ph.D., professor of microbiology & immunology and of medicine (endocrinology) and the Diane Belfer, Cypres & Endelson Families Faculty Scholar in Diabetes Research at Einstein, believe the answer may lie with immune-system cells called dendritic cells. They patrol the body looking for foreign invaders such as bacteria, viruses or toxins.
After capturing the invaders, dendritic cells break them into fragments and present them to T cells—thereby priming T cells to attack anything in the body that displays those fragments. Type 1 diabetes occurs when T cells mistakenly view the pancreas’s beta cells (the body’s source of insulin) as potential threats and then launch an autoimmune attack that destroys them.“Suppressing all of the body’s T cells could prevent or even reverse type 1 diabetes,” says Dr. DiLorenzo. “However, this would lead to serious side effects, such as an increased susceptibility to infections and cancer. Our approach seeks to suppress only those T cells responsible for destroying the beta cells.”
Here’s where dendritic cells come in. New research has revealed that dendritic cells can influence T cells in two diametrically opposite ways: provoking T cell attacks in some circumstances and suppressing attacks in others. Dr. DiLorenzo is trying to bolster the suppressive side of dendritic cells—essentially enlisting them to “teach” T cells not to attack beta cells of the pancreas.
Type 1 diabetes occurs when T cells mistakenly view the pancreas’s beta cells—the body’s source of insulin—as potential threats and then launch an autoimmune attack
The autoimmune attack on beta cells targets specific antigens, including a peptide (small protein) within proinsulin, the precursor to insulin. In studies of diabetic mice, Dr. DiLorenzo and her colleagues deliver this antigen to a dendritic cell-surface receptor called DEC-205. After the dendritic cells ingest the antigen, they present it to T cells.
When the antigen was later introduced into the mice, no immune response occurred—evidence that T cells of the mouse immune system now tolerate this peptide. If the same strategy works in humans, says Dr. DiLorenzo, it might be possible to protect people at high risk for type 1 diabetes from developing the disease.
Pathway to Prevention
Einstein researchers are also participating in a study called Pathway to Prevention, which recruits people at increased risk for type 1 diabetes to learn more about how it develops. Study subjects are selected by screening the blood relatives of those with type 1 diabetes and testing them for antibodies associated with the disease.
People with those so-called autoantibodies have a 10- to 15-fold greater risk of developing type 1 diabetes compared with people with no family history, says Rubina A. Heptulla, M.B.B.S., professor of pediatrics (endocrinology) and of medicine at Einstein and chief of pediatric endocrinology and diabetes at The Children’s Hospital at Montefiore, one of the screening sites. Pathway to Prevention is part of TrialNet, an international network of researchers and institutions dedicated to the study, prevention and early treatment of type 1 diabetes.
The BODY Garden
Four years ago, it was a vacant lot. Today the Bronx, Obesity, Diabetes and You (BODY for short) garden features six raised vegetable beds, fruit bushes, a lettuce table, a gravel path, flower beds, picnic tables, compost bins and herb plantings. Students in Einstein’s BODY club are using this space just south of Montefiore’s Weiler Hospital to introduce Bronx residents to the joys of planting, harvesting and (most important) eating healthy food and making exercise a daily routine—two big ways to prevent or control type 2 diabetes.Last May, BODY garden volunteers hosted their first school group: 150 fourth graders from P.S. 89.
“When I started BODY, I thought I’d have to pull teeth to get busy Einstein students involved, but the reality was the opposite—my peers led and participated in many BODY activities over the last three years,” says Ross Kristal, Class of 2015, who has type 1 diabetes. “They brought a steady stream of creative ideas to the table, and the Einstein faculty and administration helped us implement them.”
Ross is now digging into population health research focusing on diabetes and obesity and has passed his BODY trowel to graduate students Tony Bowen and Julie Nadel.
Simple Test, Sensational Impact
More than 40 years ago, research conducted at Einstein helped connect a type of hemoglobin called HbA1c to diabetes—a discovery that has transformed the way diabetes is diagnosed, treated and prevented.
The story begins in 1968 when Samuel Rahbar, M.D., Ph.D., a Jewish-Iranian scientist, was examining blood samples in his lab at the University of Tehran. Nearly 20 years earlier, Linus Pauling had found that an aberrant type of hemoglobin was responsible for sickle cell anemia. Dr. Rahbar was looking for other hemoglobin variants that might be linked to human disease. After screening thousands of blood samples, he saw something interesting in the blood of a 67-year-old woman.
“I said to myself, ‘What is this? This isn’t fitting with any of the known hemoglobins,’” Dr. Rahbar recalled years later in an interview. The woman’s medical records indicated that she had diabetes—prompting Dr. Rahbar to examine the blood of 47 more people with diabetes, all of whom had the same unusual type of hemoglobin. He published his findings later that year in a paper, “An Abnormal Hemoglobin in Red Cells of Diabetics.”
Dr. Rahbar was eager to confirm his findings in a different laboratory, so later that year, he came to Einstein as a visiting scientist working under Helen M. Ranney, M.D., a professor of medicine and pioneer in studying hemoglobin and sickle cell anemia.Drs. Rahbar and Ranney analyzed blood samples from people in the neighborhoods around Einstein and found the same unusual hemoglobin in 140 diabetic patients. In describing their findings in 1969 in Biochemical and Biophysical Research Communications, the researchers noted that their novel “diabetic component” appeared identical to HbA1c—one of five recently identified hemoglobin subtypes.
Drs. Rahbar and Ranney analyzed blood samples from people in the neighborhoods around Einstein and found the same unusual hemoglobin in 140 diabetic patients
Uniquely, HbA1c involved a specific fraction of hemoglobin that had been “glycated,” or chemically combined with glucose. And the higher a person’s blood glucose level, the larger the percentage of total hemoglobin that was converted to HbA1c. Drs. Rahbar and Ranney reported that HbA1c made up 4 to 6 percent of normal subjects’ total hemoglobin compared with 7.5 to 10.6 percent of the total hemoglobin of diabetic patients.
In the late 1970s, investigators in Einstein’s new Diabetes Research and Training Center were among the first to put HbA1c to practical use: they tested HbA1c levels of Bronx diabetes patients enrolled in long-term studies as a way to monitor patients’ blood glucose control. But not until 1984 did the test get its big break, with the launch of the landmark Diabetes Control and Complications Trial.
The DCCT—a nationwide study funded by the National Institutes of Health—compared different treatments for type 1 diabetes head to head. It used the HbA1c test to assess each treatment’s effectiveness in controlling blood sugar levels over the
In 1993, the DCCT reported that intensive blood sugar control, as measured by HbA1c level, dramatically reduced the long-term complications of type 1 diabetes. (Einstein’s role in the DCCT is described in “”.)
The HbA1c test soon became a game changer. Glucose tests such as finger-prick testing report blood glucose levels at a particular moment, which helps patients adjust daily insulin doses. But such tests offer no information about the long-term blood glucose levels that so crucially influence whether com-plications will develop in someone with diabetes.
By contrast, the HbA1c test measures a patient’s average blood glucose level over the previous two or three months (the lifespan of a red blood cell). Clinicians now routinely test their diabetes patients’ HbA1c levels several times a year. They adjust patients’ therapies accordingly, to optimize blood glucose control and minimize the risk of life-threatening complications.
The HbA1c test has now been validated for diagnosing types 1 and 2 diabetes and for monitoring prediabetic patients to prevent full-blown diabetes from developing. (The American Diabetes Association now regards a diabetes diagnosis as being warranted when someone’s HbA1c level is greater than or equal to 6.5 percent.) In addition, measuring HbA1c has become the FDA’s gold standard for evaluating the effectiveness of new diabetes treatments. It’s no surprise that HbA1c was recently called “one of the most important biological molecules in modern medicine.”
Dr. Rahbar returned to Iran after his stint at Einstein. During the Iranian revolution he was accused of being cozy with the Shah’s family, lost his professorship at the University of Tehran and fled to the United States in 1979 with his wife and three daughters. He reunited with Dr. Ranney, who by then was at the University of California–San Diego, and studied diabetes for the next 33 years at the City of Hope National Medical Center in Duarte, CA.
In June 2012 the American Diabetes Association bestowed a special, one-time National Scientific Achievement Award—the Samuel Rahbar Outstanding Discovery Award—on Dr. Rahbar himself, to honor him for his discovery of HbA1c as a marker for diabetes. He died the following November at age 83.