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Feature

Surgeons at work

For obese patients with type 2 diabetes, surgery is an option.

All our trials

U offers clinical trials and surgical options to treat, prevent, or cure diabetes.

By Deane Morrison

From M, summer 2006

Diabetes is wreaking havoc on about 1 in 17 Americans, leading to accompanying chronic illness and early deaths. Prominent among its victims are the poor; people of American Indian, Asian, black and Hispanic descent; and, increasingly, children. The World Health Organization estimates that more than 175 million worldwide have diabetes, with 300 million cases projected by 2025. Along with first-class diabetes management care and research into the cause and prevention of the disease (see Defeating diabetes), the University is conducting numerous clinical trials and pioneering surgical options for people with diabetes. In 1983 the National Institutes of Health launched a major clinical study to investigate the power of intensive blood glucose control measures to prevent or minimize complications in type 1diabetes patients. The Diabetes Control and Complications (DCCT) Trial, now in its follow-up phase at the University and 26 other centers nationwide, showed such clear benefits for strict glucose management that patients in the control group were switched to intensive treatment. Even so, their rate of complications continued to climb in comparison to the participants who received that treatment from the start. "[The study] shows that intensive therapy must begin as soon as possible," says John Bantle of the Division of Endocrinology and Diabetes, the University's principal investigator in the study. "It also came out in the study that intensive treatment protected against heart attack, angina, and stroke." In second national trial, BARI 2D (Bypass Angioplasty Revascularization 2 Diabetes), Bantle, principal investigator Carl White, a University cardiologist, and their colleagues are studying which surgical or medical (mainly drug) therapies will best protect the cardiac health of people with type 2 diabetes. In a third trial, Look AHEAD (Action for Health in Diabetes), Bantle and University principal investigator Robert Jeffery, of the epidemiology department, are part of a national team investigating weight loss as a primary therapy for type 2. "Type 2 may have multiple causes, probably from multiple genes," says Elizabeth Seaquist, director of the University's Center for Diabetes Research. Whatever the cause, type 2 diabetes means a two- to four-fold higher risk of death from cardiovascular disease. As the University's principal investigator for the national ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, Seaquist is helping determine if lowering blood sugar into the normal range will cut those patients' death rate from heart attack and stroke. Results from BARI 2D and Look AHEAD are not known yet. The trials are monitored by a committee set up by the National Institutes of Health, which examines the data and decides if and when a treatment has proven itself one way or the other. In the best case, as in DCCT, all patients are switched to the treatment group because the benefits are indisputable. In another project, Seaquist and Gulin Oz, of the radiology faculty, are spearheading a study of the role that glycogen-animal starch, the storage form of glucose-in the brain may play in type 1 diabetes patients, particularly those who fail to notice when their blood sugar drops too low and black out suddenly. Working at the University's Center for Magnetic Resonance Research, they head the only team in the world that can measure glycogen in the brains of living people.

Surgeons and stem cells

The University has been at the forefront of surgical diabetes treatment since 1966, when University surgeons William Kelly and Richard Lillehei performed the world's first pancreas transplant. About 1,900, or 10 percent of all such transplants in the United States, have since been performed at the University, many by David Sutherland. Three other surgeons-Raja Kandaswamy, Abhinav Humar, and Rainer Gruessner-also perform the transplants. But transplanting a whole pancreas isn't the only way to supply fresh beta cells. Another is to extract islets from a donor pancreas and inject them into the patient's portal vein. The vein carries the islets into the liver, where some take up residence and start producing insulin. The University's Bernhard Hering is a world expert in the procedure, which is much less rigorous than a pancreas transplant for the recipient. But it's difficult to harvest usable islets in large numbers. In most transplant centers, 70 percent of patients require more than one donor. "We've improved islet procedures so that only 30 percent of patients need more than one donor," says Sutherland. Pancreas and islet donors are scarce, so Sutherland, Hering and their colleagues at the University's Diabetes Institute for Transplantation and Immunology have turned to other species as possible donors. This year, Hering headed a team that found a drug regimen that allowed islets taken from pigs to escape rejection for up to six months after being transplanted into monkeys. The research marked the first step in bringing this type of therapy to people. Beta cells are also under study in the University's Stem Cell Institute. A team led by Meri Firpo has coaxed human embryonic stem cells to produce small amounts of insulin, and the researchers are applying for support from the Juvenile Diabetes Research Foundation to continue their work. People with type 2 diabetes benefit from gastric bypass, a surgical procedure that shunts food past part of the stomach and small intestine to help obese people lose weight. "All such patients show improvement, and up to 80 percent are cured of diabetes," says University surgeon Sayeed Ikramuddin, who has performed 1,300 gastric bypasses in the last four years. One factor may be that the procedure raises levels of a hormone that stimulates beta cells. A new treatment on the horizon is an "analog" drug similar to the natural hormone. Ikramuddin is also working with Swedish colleagues to find ways of performing less invasive gastric bypasses by entering the body through the mouth.

To learn more about the trials underway at the University, click here or here.