For people with advanced diabetes, every day is a balancing act of carefully monitoring their blood sugar and responding by taking insulin through painful injections or cumbersome pumps.
New technology under development in the Joint Department of Biomedical Engineering at UNC-Chapel Hill and N.C. State University could render these invasive and imprecise treatments obsolete.
The research team has designed what it calls a “smart insulin patch.” The dime-sized patch, which it tested on mice, would respond to high blood sugar levels by secreting an appropriate amount of insulin, all without the patient having to prick, or even lift, a finger.
The North Carolina team describes its “smart insulin patch” in a paper published online Monday in the journal Proceedings of the National Academy of Sciences.
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The patch is an exciting move forward in diabetes treatment, said Susan Spratt, director of Diabetes Services at Duke University Hospital, who was not involved in the study. Diabetes typically occurs when the beta cells of the pancreas stop making insulin, or the insulin they make is somehow insufficient. Without insulin, other cells in the body can’t take up glucose from the bloodstream, which they require as an energy source.
With current treatments for diabetes, a patient’s brain must take over the role of the pancreas, said Spratt. Patients must calculate how much insulin to inject and when, depending on what they’re eating and the kind of physical activity they plan to do. Too little insulin and the body’s blood sugar remains high, leading to complications like high blood pressure, stroke, and neuropathy; too much, and the patient risks hypoglycemia, a condition that can lead to fainting, seizures and even death.
“It’s really hard to get excellent glucose control all the time using only the human brain,” said Spratt.
If successful in humans, the patch would sense glucose levels and secrete insulin as needed, just as healthy beta cells do.
Each patch holds more than a hundred tiny needles, or microneedles, each one loaded with specially-made bubbles containing insulin and an enzyme called glucose oxidase. The microneedles painlessly pierce the skin when the patch is first applied but don’t release insulin until there are high levels of glucose in the bloodstream.
As glucose molecules build up, some make their way into the needles and through the bubbles’ permeable membranes. Inside the bubbles, glucose reacts with glucose oxidase, causing a chemical reaction that gobbles up oxygen atoms. This new low-oxygen environment causes the bubbles to burst, releasing insulin through the microneedles and into the bloodstream.
The combination of feedback-controlled insulin delivery and painless skin patches is “exciting and innovative,” said Samir Mitragotri, director of the Center for Bioengineering at the University of California Santa Barbara. “It addresses a tremendous unmet need in the field of diabetes management.”
The patch is one of several new efforts to combat diabetes using nanotechnology, or tiny engineering. Previous research relied on a change in pH to trigger a chemical reaction and subsequent release of insulin. Responding to oxygen levels rather than pH speeds up the chemical reaction, releasing insulin more quickly, said Zhen Gu, a professor in the Joint Department of Biomedical Engineering at UNC-Chapel Hill and NCSU and co-senior author of the paper. The first author is Ph.D. student Jicheng Yu.
Gu envisions the patch being used for days at a time and eliminating the need for any other injections of insulin.
The patch must be tested in other animals, like miniature pigs, before it can begin clinical trials in humans. But, Gu said, “I have the passion to accelerate this process.”
Several members of Gu’s family have been afflicted with diabetes, including his grandmother, who died of diabetes-related complications several years ago. He says he tells his students that in addition to helping the human race as a whole, “sometimes you do research to help the people around you.”
There were 387 million diabetics worldwide last year, according to the International Diabetes Federation; by 2035, that number is expected to be 592 million.
Diabetes treatment has come a long way since the Greek physician Aretaeus described a disease characterized by intense thirst, excessive urination, weight loss, and death in the 2nd or 3rd century A.D. “Diabetes” comes from the Greek term for “siphon,” a reference to the way water seemed to flow through the victims’ bodies.
Researchers at the University of Toronto won the Nobel Prize for the discovery and purification of insulin from dog and cow pancreases in 1923. Now, human insulin is synthesized in E. coli bacteria, and devices like continuous glucose monitors and insulin pumps are available to some diabetics.