This year's focus on diabetes comes as the nation grapples with a dramatic upsurge of cases. Diabetes is a condition in which the body does not make enough of the hormone insulin or manage it properly. Sugar builds up in the blood, damaging nerves and blood vessels and driving up the risk for blindness, kidney failure, heart failure, heart attacks, and nerve damage. A distinction is made between type-1 diabetes, in which children cannot produce the insulin they need, and type-2 diabetes, in which the body cannot produce enough insulin, usually because of excessive weight gain. The 18 million diabetes cases now reported in the United States - with the vast majority type 2 - are posing a challenge to the medical community. And the disease is claiming more and more children. It's a health-care burden with a litany of complications (blindness, amputation and cardiovascular disease), and the estimated growth in type-2 diabetes will double at a faster rate than the population as a whole. Posters displaying students' diabetes research were entered in a competition on the day of the symposium. Jonathan Zippin, '08, an MD-PhD student in the Department of Pharmacology, and Ola Karylowski-Martin, '05, a graduate student in the Department of Biochemistry, won honorable mentions. Alex Banks, a student at Columbia University College of Physicians and Surgeons, took first prize for his studies on insulin action.
Nadine Wertheim, a postdoctoral associate, discusses her research on intracellular retention of glucose at a poster competition as part of the Irving Weinstein Visiting Lectureship.
Dr. Nathan is director of the General Clinical Research Center and Diabetes Center at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School. He was one of the architects of the Diabetes Control and Complications Trial (DCCT), serving as editor for all DCCT publications. Dr. Nathan co-chairs the national Epidemiology of Diabetes Interventions and Complications Study, and is the chairman of the Diabetes Prevention Program, an NIH-sponsored multicenter trial to prevent type-2 diabetes. With more than 200 articles in the medical literature, Dr. Nathan is an internationally recognized expert on diabetes and its complications.
"The prevalence of type-2 diabetes is rising in epidemic proportions worldwide," he said. "It's a dire problem."
Weill Cornell graduate students Ola Karylowski-Martin and Jonathan Zippin, with Columbia graduate student Alex Banks, won prizes for their posters on diabetes research.
Dr. Nathan stressed the importance of preventing diabetes with lifestyle changes - since the disease grows increasingly difficult to manage after its onset.
"Once the horse has left the barn, it's difficult to control," he said.
Diabetes has a genetic basis - Native Americans are highly susceptible - and does vary with age, but it does not express itself without the proper environmental factors. Studies have shown a close link between weight gain and diabetes onset; diabetes and obesity are "co-epidemics," Dr. Nathan said, often arriving on each other's heels. In general, the more overweight a person is, the more insulin his or her body needs. Some overweight people develop type-2 diabetes when their bodies cannot produce enough extra insulin. As more Americans become obese, the rate of diabetes rises sharply.
A key component of preventing diabetes is preventing weight gain, Dr. Nathan said. As the country has shifted from an agrarian society to a corporate one, our society is marked by a glut of food, a decrease of activity, and a highly sedentary way of life.
Farmers used to expend at least a calorie of energy to produce a calorie of food. "Now, there's a vast disconnect between the food we eat and the labor we expend to get it," Dr. Nathan said.
Pinpointing causes of type-2 diabetes, Dr. Nathan cited obesity, especially central obesity (around the waist and hips), and a sedentary lifestyle. He also mentioned metabolic syndrome, a cluster of symptoms including large waist circumference, hypertension, elevated glucose levels, high triglycerides and blood pressure, that affects 25% of American adults today. Dr. Nathan advocates a strategy of treating individual symptoms to tackle the disease as a whole.
Lowering glycemic levels in a patient dramatically reduces the risk of long-term complications, especially before diabetes has begun. This state of "normoglycemia" is best achieved through diet and exercise, with even modest weight loss effective (five or ten pounds).
Dr. Nathan led a study on interventions for pre-diabetes patients, comparing groups who underwent behavioral modifications, took the drug metformin, and took a placebo drug. The goals were modest (7% body weight loss, and 150 minutes a week of moderate physical activity) but the gains were marked. The lifestyle group lost weight both during the study and long term, with the best record of weight loss after four years. The risk of developing diabetes was reduced 58% with lifestyle modification, 31% with metformin, and each therapy was projected to delay its development by 11 and 3 years, respectively. The results remained constant across the range of ethnic groups that were included in the study.
He looked at our major obsession with diet - especially the Atkins and South Beach diets, on the best-seller list - and inveighed against the risks inherent in both "low-fat/high-carb" diets and "low-carb/high-fat" diets. A low-fat diet might promote insulin resistance, while a low-carb diet might lead to heart disease, increased cholesterol and calcium loss in the bones. A behavioral approach, weaving changes into one's life, best combats weight gain and curbs diabetes in the long term.
Dr. Convit is an associate professor of psychiatry and the medical director of the Center for Brain Health at the New York University School of Medicine. His NIH-sponsored research utilizes imaging techniques to study activity in the brains of diabetes and metabolic syndrome patients.
Dr. Convit spoke of diabetes' toll on the mind, seldom mentioned in studies of the disease.
"The old axiom that the brain sits in a privileged position, and gets all the glucose supply it needs, no longer holds true," Dr. Convit said.
The brain depends on glucose for its metabolic needs, he explained. Diabetics in every age group have more cognitive impairment than non-diabetics, even controlling for other complications.
Cognitive tests show that individuals with poor glucose regulation score poorly on memory performance tests. Those tests centered on "descriptive" short-term memory (regulated by the hippocampus) showed the most starkly different results between diabetics and non-diabetics.
Interaction between increased cortisol and insulin resistance may restrict transport of glucose across the blood brain barrier, depriving hippocampal cells of nourishment and causing hippocampal atrophy, in effect starving the brain.
Diabetics are also twice as prone to depression, decreased cognition and brain pathology, according to Dr. Convit's research.
"We have high hopes for cross-institutional collaboration to link institutions, to get at issues and to complement each others' expertise," Dr. Convit said.
Dr. Convit's work has recently expanded to include obese adolescents with type-2 diabetes, a group whose cognitive impairments during formative years will inhibit them from reaching their potential. This group will likely suffer from the complications of the illness during young adulthood.
Photos by Melissa Hantman.