Posted on Tue, Apr. 1, 2008
When doctors told 28-year-old Nakia East that her 1-year-old's sudden weight loss and unusual thirst were caused by diabetes, she found herself thrust into a whole new level of parenting.
"They told me everything was going to change," said East, who lives in Upper Darby. Since then, she has learned to inject her son, Yanaan, with insulin four times every day. She tracks every ounce of food he eats and measures his blood sugar after each meal. And then there are the terrifying moments when the readings plunge far too low.
"They told me he's going to have this his whole life," she said recently, resigned to her son's fate.
But the scientific community is not so resigned. At a recent Philadelphia meeting on the genetics of diabetes, a flurry of discoveries offered new leads in the search for better treatments and strategies to prevent the disease in the first place.
Some of the newly discovered diabetes-associated genes - some involved in fighting infection, others in Vitamin D metabolism - could help scientists understand how genes and environment conspire to cause diabetes.
While the more common Type 2 diabetes is closely connected to obesity, Type 1 is an autoimmune disorder, in which the body's immune system malfunctions and attacks insulin-secreting cells in the pancreas.
People with Type 1 eventually produce no insulin of their own and depend on injections or an insulin pump for survival. They must keep a near-constant watch on their blood sugar. If it is too high, it can slowly damage tiny blood vessels, sometimes leading to blindness, kidney damage and amputations. High blood sugar can also damage larger blood vessels, raising the risk of heart disease.
Scientists have been searching for both Type 1 and Type 2 diabetes genes since the 1980s, but only in the last several years have they started finding them. Last July, a new Type 1-associated gene was discovered by a team led by Hakon Hakonarson, director of the new Center for Applied Genomics at Children's Hospital of Philadelphia.
Both types of diabetes run in families, so scientists long assumed that a combination of genetic and environmental factors was at play. They just couldn't find the specific genes.
Efforts surged ahead after 2005, said Francis Collins, director of the Human Genome Research Institute and a speaker at the recent diabetes conference at the Rittenhouse Hotel. That's when new technology allowed scientists to scan human DNA many times faster.
Using "genome-wide association studies," researchers can now take hundreds or even several thousand people with the disease, scan over hundreds of genes, and seek out any genetic variants that show up more often in the disease group than in a group of healthy controls.
The bad news is that of the roughly 10 odd genes identified with these studies, each one confers only a tiny effect on an individual's probability of developing Type 1 diabetes.
But that doesn't mean the genes can't offer clues to the cause of diabetes.
John Todd, a geneticist from Cambridge University, started looking for diabetes genes back in the 1980s. Certain combinations of genes make some children more vulnerable than others, he said, but it's something in the environment that actually triggers the disease.
At the meeting, Todd outlined the unknowns that surround Type 1, which affects about a million Americans. What they do know is that Type 1 starts when the body's own immune system attacks the insulin-producing cells. Insulin is necessary for digesting sugar and clearing it from the bloodstream.
What they don't know is why the number of new cases has been rising at about 3 percent per year since 1950.
Another puzzle: It strikes more often in winter than in summer. "There's something about winter that induces diabetes," Todd said. It also strikes more in Northern climates, which he illustrated using shaded maps of the United Kingdom, highlighting higher rates in Scotland and northern England.
Then there's a higher-than-average incidence of other autoimmune diseases among relatives of those with Type 1. "We often see an aunt with thyroid disease or an uncle with rheumatoid arthritis," Todd said. "All these are clues."
But by figuring out what each of the genes does, he said, he hopes to add another cache of clues. Some connect to Vitamin D metabolism, for example. These may explain the connection with winter and Northern climates. People get much of their Vitamin D from a reaction triggered by sunlight on the skin.
So people hit a Vitamin D low in winter, and many in Northern regions never get enough.
Children who take Vitamin D supplements have a somewhat reduced risk of developing diabetes, according to a review of the medical literature published in March, just a week before the diabetes meeting.
"This provides more justification for doing proper clinical studies assessing the vitamin" and its potential as a diabetes fighter, Todd said.
Other genes connected to diabetes function in the immune system, including one that confers resistance to AIDS. "Our immune systems evolved to be good fighting machines against infection," he said, and our ancestors until very recently faced a much bigger threat than people today.
His favorite hypothesis: "The immune system in infancy isn't being stimulated as much in developed countries," thanks to vaccination and better hygiene, with the unintended consequence that juvenile diabetes started rising after 1950.
More diabetes cases are appearing in the developing world, paralleling improvements in other public-health arenas. "It's a pandemic rise," he said.
Waiting to see his doctor at Children's Hospital of Philadelphia, East's son, Yanaan, now almost 3, was spinning in the doctor's chair and playing with every piece of furniture within reach.
Easter was tough for him, East said, with so much candy around, so she plans to find a sugar-free cake for his third birthday.
In an interview, Yanaan's doctor, Children's Hospital endocrinologist Steve Willi, said diabetics and their families were expected to keep much closer watch over their blood sugar than ever before as the technology has improved for monitoring it.
Insulin is still the only treatment, he said, but researchers are testing drugs that might work in the very first weeks after diagnosis to halt the autoimmune attack and preserve at least a few of the insulin-producing "beta" cells.
The genetics work is looking further ahead.
A cure remains the ultimate goal, though it's taken longer than some of the scientists had estimated a decade ago.
During a break at the meeting, New Jersey radiologist Don Meltzer held back from a midafternoon spread of brownies, cream puffs and mini-pastries. He's had Type 1 since about 1950, when he was 12.
Though he's lived with the disease for all those years, he still envisions a cure. "I'm an eternal optimist," he said. "The genetics is opening up a whole new world."
Contact staff writer Faye Flam
at 215-854-4977 or fflam@phillynews.com.
