For him, research is personal

A half-dozen medical students crowd into a lab at Jefferson Medical College as Jeffrey Joseph points to a graph of a patient's blood sugar. While healthy levels stay within a narrow range, this man's pattern is wildly erratic, peaking at four times the normal amount after a meal and plunging dangerously low during sleep.

The graphs are from a diabetic named Brian who had his blood sugar, or glucose, continuously monitored over three days for a study, says Joseph, head of Jefferson's Artificial Pancreas Center.

"You know, Brian? From the lab."

He is referring to Brian Hipszer: assistant professor at the center, type 1 diabetic, and sometime guinea pig.

"He has modeled his own body for research purposes," says anesthesiologist Joseph.

Hipszer, who graduated from Drexel University with a doctorate in biomedical engineering, describes his relationship with Joseph, 54, as "yin and yang; he's clinical, I'm technical."

Their research aims to create the "holy grail" for type 1 diabetics - a "closed-loop" artificial pancreas that mimics the natural organ. They test different types of continuous glucose monitors and develop computer programs to automate insulin delivery. Such a system would require no input from the patient, thus "closing the loop."Hipszer believes that such an artifical pancreas will be available within 5 to 10 years.


A balancing act

Life for type 1 diabetics is a never-ending balancing act. Blood sugar levels outside the narrow healthy range can have dire consequences. Hypoglycemia, or too little glucose, can get "very dangerous, very quickly," says Hipszer, because the brain runs only on glucose. Low levels can cause loss of consciousness and eventually death.

Too much glucose, hyperglycemia, over time can have serious long-term effects including kidney failure and blindness.

The artificial pancreas aims to prevent such extremes by continuously monitoring glucose and dosing the right amount of insulin - a hormone normally produced by the pancreas - to keep blood sugar levels stable.

That amount isn't easy to gauge, however. It takes an immense amount of planning for diabetics to properly dose insulin. They have to count carbs before every meal or snack, while also accounting for activity level, stress, and overall health.

"If I didn't eat, then I can give myself a little bit of insulin minute-by-minute and everything will be cool. But in the real world, I eat three meals a day, exercise - it is challenging to keep it nice and stable," Hipszer said.

Indeed, Joseph tells his medical students that even for a diabetes researcher who has been studying his disease for more than a decade - wearing an insulin pump and a sensor and pricking his finger - Hipszer's glucose still bounces "all over the place."

Hipszer, 37, grew up in the foothills of Barto, between Reading and Allentown, next to his grandfather's dairy farm. He has a boyish appearance, yet speaks in a deep and meticulous monotone, and often steers the conversation from personal matters toward science.

He was diagnosed with type 1 diabetes in 1984, after a physical exam at Boy Scout camp showed elevated levels of glucose. "Type 1" distinguishes patients who cannot produce their own insulin and is much less common than type 2, in which the body gradually becomes insulin-resistant.

A two-year "honeymoon period" followed Hipszer's diagnosis - before the remaining insulin-producing cells in his pancreas died. Throughout high school, his family helped him manage his disease.


Diabetes takes hold

But after starting college at Drexel, everything changed. He was living on his own for the first time, and paying little attention to diet and fitness. His glucose control and overall health began to suffer.

A blood test, hemoglobin A1C, is used to gauge a person's average glucose level over several months. A normal nondiabetic's A1C level is about 4.5 to 6 percent, while "someone who's had uncontrolled diabetes for a long time" can have levels above 9 percent, the Mayo Clinic says.

During his freshman and sophomore years, Hipszer's was up to 12 percent, putting him at risk for severe kidney, nerve, and blood vessel damage.

"I was a little angry at that point," he recalls. "I guess everybody with a chronic disease struggles with the issue that it will be a part of their life."

For many diabetics, it can take months, or even years, to accept reality. Hipszer says, for him, two people made him finally snap out of it. The first, his endocrinologist: "It got to a point where he said, 'If you can't do this on your own, maybe we should hospitalize you.' That made me start paying attention." The second was his future wife, Laurel, now a pharmacist, whom he met while they were at Drexel.


Moving into research

Hipszer initially shied away from diabetes research because it felt "too personal" and he "didn't want [diabetes] to be any larger than it had to be" in his life. But as his health improved, he thought more about devoting his career to the condition.

His strengths were in computer engineering and math, and after being introduced to Joseph, they decided he could use that expertise to artificially mimic the regulation of glucose in a healthy body. He spent the next 10 years with this as the focus of his doctoral research, investigating equations that model how the body regulates glucose.

Today, what Hipszer calls his "unique perspective" remains invaluable: "I make sure people are grounded and understand the realities of the disease."

His dual role as researcher and patient also comes in handy while planning studies. For instance, Hipszer was curious about where he could "comfortably" harpoon hospital patients with multiple needle-tipped glucose sensors.

His own body provided the answer: three in his abdomen, two in his biceps. Originally, he tried a sixth in his thigh but it was too painful going into that large muscle, so he took it out after a few hours. The other five he wore for three days.

Hipszer also volunteered to be a subject in one of the early closed-loop trials for Medtronic, a company that uses the center to test products.

Founded in 1998, the Jefferson center consists of Joseph, Hipszer, and a handful of research coordinators.

The center relies mostly on industry funding - it now has eight industry sponsors, including insulin pump manufacturers Medtronic and West Chester-based Animas Corp. - but also has National Institutes of Health and U.S. Army grants. It typically works with a total of about $500,000 per year.

Joseph and his team often test products and present their results to the Food and Drug Administration to help with decisions about approving medical devices.


A device that helps

Joseph recently returned from FDA headquarters, where he showed data from a Medtronic insulin delivery system built with a feature called "low glucose suspend," a step toward a closed-loop system, he says. It protects only against low blood sugar.

If the sensor recognizes that glucose is plunging to dangerous levels, the system will attempt to alert the diabetic. If, after multiple alarms, the person does not respond due to deep sleep, the insulin will automatically shut off for a few hours to prevent blood sugar from dropping too low and causing loss of consciousness.

In Europe, the low glucose suspend feature is already available commercially; it should be available in the United States within a year, Joseph said.

While a fully functioning artificial pancreas would not be a cure, it would ease diabetics' daily life immensely. Already, Hipszer uses a glucose sensor that talks to his insulin pump, linking two of the three pieces of an artificial pancreas.

"I have three kids at home. My wife is a working professional, and I'm very busy at work," he says. "This device helps."

His insulin pump, Medtronic's Paradigm Revel 523, is one of a handful that are commercially available, and the only device that combines the insulin pump and glucose monitor display in one unit. The Revel pump sells for $6,900, and it costs about $700 a month to operate. Hipszer said his health insurance covers these expenses.

The last piece would be to allow one of his own computer programs to take full control of his insulin pump.

Would an automated system do a better job than a leading artificial pancreas researcher?

"I know I'm not the worst-controlled diabetic, but I know I'm not the best," he admits with a laugh. "I'd jump off a building if I couldn't eat what I wanted."

Source: Philly.com Health News , By Meeri Kim "Inquirer Staff Writer"