Friday, December 19, 2014

Five promising local diabetes projects

Cynthia Cheng, a Jefferson Medical College family physician has spent the last five years studying prediabetes. (Charles Fox / Staff Photographer)
Cynthia Cheng, a Jefferson Medical College family physician has spent the last five years studying prediabetes. (Charles Fox / Staff Photographer)

Quest for a new pancreas

For people with Type 1 diabetes, managing blood sugar can be a full-time gig. Jeffrey Joseph, director of Jefferson Medical College's Artificial Pancreas Center, is trying to change that.

An artificial pancreas, Joseph explained, would be like a pacemaker for blood sugar. The device would consist of a continuous blood-sugar monitor communicating with a "smart" insulin pump to give just the right dose of insulin. Instead of having to draw blood from four to 12 times a day - and still never knowing if their blood sugar is going up or down - diabetics could go about their day like the rest of us, without the fear of becoming hyper- or hypoglycemic.

Joseph spent his childhood inventing things, including "a solar-heated doghouse that got so hot, the dog wouldn't go in it."

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  • An anesthesiologist, he holds 11 medical-device patents. Some of his inventions are on the market, including a ventilator breathing tube that halves patients' risk of pneumonia.

    Three firms - Medtronic Diabetes, Abbott Laboratories and Dexcom - make real-time monitors that can be implanted under the skin for up to a week. Joseph's lab works with these and others as well as academic labs. He says an automatic monitor/insulin-pump combo may come in five years, so Type 1 diabetics can stop "living their diabetes."

    Reading capillaries for risk

    Forget about reading palms. What if patterns in your fingers could predict your future?

    Jefferson Medical College family physician Cynthia Cheng thinks they can.

    She has spent the last five years studying how prediabetes - where blood-sugar levels are higher than normal, but not high enough to be Type 2 diabetes - affects capillaries, the body's tiniest blood vessels. To do it, she enrolled 200 participants, including prediabetics and healthy control subjects. Then she used a special microscope to take pictures of the capillaries just below the skin bordering the bottom edge of their fingernails.

    Normal capillaries are slightly curved, like bobby pins, Cheng said. But in prediabetics, they looked twisted and curled-up.

    It's not surprising that prediabetes would take a toll on capillaries. These vessels deliver oxygen and nutrients, including glucose, to every cell, and insulin, which prediabetics produce at a higher-than-normal rate, controls how the capillaries do their job.

    Does damage to large blood vessels "trickle down" to smaller ones, or does the disease hit capillaries first? Cheng hoped to answer this by tracking participants for the last five years to see if those with abnormal capillaries were likelier to get diabetes. So far, no participant has. But the abnormal capillaries were related to high albumin levels in the urine, a well-known sign of damaged, leaky blood vessels.

    Cheng plans to keep following her participants to see who eventually develops diabetes.

    Her technique could replace or augment current tests for diabetes risk and cardiovascular damage, such as blood pressure. But that might take decades. Meanwhile, Cheng who devotes half her time to clinical care, says the most valuable part of her work is the chance to educate patients about prevention. "The bottom line is helping patients," she said.

    Tracking hunger hormones

    Why do we eat?

    Rexford Ahima is trying to answer that question by studying the hormones that regulate hunger and appetite.

    "Our main research question is how fat cells communicate with the brain, liver and muscle," said Ahima, who directs the obesity unit of the University of Pennsylvania's Institute for Diabetes, Obesity and Metabolism. Disrupting these messages can cause overeating, obesity and diabetes.

    Hormones - chemicals made by one type of body tissue that affect how another tissue, organ or organ system functions - make this communication happen. For example, the stomach produces not only acid, which aids in digestion, but also ghrelin, "the hunger hormone," which prompts the stomach's owner to eat.

    Known for its role in stimulating the release of growth hormones, ghrelin peaks before meals and decreases after them - especially if the meal includes high-fat, sugary foods.

    Studies of obese patients getting bariatric weight-loss surgery showed that afterwards, patients' ghrelin levels fell. Reduced hunger feelings may have helped them lose weight.

    "Drugs targeting ghrelin are being developed,"Ahima said. They may help people who have lost their appetites - and a dangerous amount of weight - due to aging, cancer or infections.

    In a recent study, Ahima's colleague Anne Cappola showed that frail elderly women with unexplained weight loss ate more after receiving ghrelin.

    And ghrelin-blocking drugs hold promise as weight-loss aids for people with obesity and diabetes. But Ahima cautioned, these drugs would suppress only physical hunger. If people overeat from habit or for social or cultural reasons, behavioral treatment would also be necessary.

    In mice, beta cells grow back

    Beta cells are like little brains, says pediatric endocrinologist Jake Kushner, of Children's Hospital of Philadelphia.

    Set in the pancreas, these sophisticated neuronlike cells regulate the body's glucose level by adjusting the amount of insulin they release. But in Type 1 diabetes, the immune system turns against beta cells, eliminating nearly all of them within 10 years and leaving patients dependent on daily insulin injections for life.

    Kushner wants to figure out how to make beta cells grow back. But "we need to know the basics" to drive the work, he said, citing the success of AIDS researchers who used their understanding of HIV to attack it.

    In a study published in the journal Diabetes in June, Kushner and Children's colleague Matthew Rankin showed that mice can grow new beta cells if necessary - but only when they are young.

    His ultimate goal, Kushner said, is to help develop drugs to prevent beta cell destruction or promote their growth, with minimal side effects. That drug may still be decades away.

    But, he said, "we've learned a tremendous amount in the last 20 years. So I'm very hopeful."

    The skinny on fatty acids

    Scientists have long known that obesity and Type 2 diabetes often go hand-in-hand. But exactly how extra weight reduces the body's sensitivity to blood-sugar-regulating insulin remains unclear.

    Temple endocrinologist Guenther Boden has spent the last 20 years trying to shed light on these mechanisms. "If you understand the process, you can pick a spot that's rate-controlling, and either inhibit it or speed it up," he said.

    Much of Boden's work has focused on the role of fatty acids in causing obese people to develop diabetes. Fatty acids, which can enter the bloodstream from body fat or from food, are important fuel for the body. Most obese people have high blood levels of fatty acids, and Boden's group showed that these acids promote insulin resistance, a condition that increases Type 2 diabetes risk.

    Recently, Boden has focused on the endoplasmic reticulum, a network of membranes in each cell that folds proteins. It works like a car plant inspector, Boden said, identifying the faulty units and fixing them or taking them off line.

    When people eat too much, more proteins have to be folded to store that energy as fat. The assembly line speeds up, and more unfolded or poorly folded proteins - which can promote cancer in vitro - make it through.

    But Boden remains skeptical about prospects for a "miracle pill" to replace a healthy diet. "Eating less works like a charm to get rid of these problems," he said.

    Contact Karen Knee through kstark@phillynews.com

    KAREN KNEE For The Inquirer
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