Date:
03/17/2008 01:43 PM HEALTHBEAT: Scientists hunting how to turn diabetes
gene revolution into better care
By LAURAN NEERGAARD
AP Medical Writer
WASHINGTON (AP) _ You've heard of Type 1 and
Type 2 diabetes, but what about a kind called MODY?
Diabetes is undergoing a genetics revolution
that suggests there actually are many subtypes of the disease.
The discoveries already trigger important
changes in treatment for a fraction of patients with some
rare diabetes types caused by single genes gone awry —
if they have a doctor aware of the findings.
"We've got a whole group of diabetologists
who have never heard of this," laments Dr. Andrew Hattersley,
a British physician-scientist who pioneered how to treat single-gene
subtypes collectively known as MODY.
Yet the vast majority of diabetes is caused
by complex interactions among numerous genes and modern lifestyles
— and a flurry of genetic discoveries in the past year
finally points to new ways of attacking the epidemic.
So this week, U.S. health officials are bringing
20 drug companies together with international gene specialists
to jump-start the hunt for new therapies.
"We're trying to inspire some really
creative thinking," says Dr. Francis Collins, gene chief
at the National Institutes of Health, who organized the first-of-a-kind
meeting.
Why does diabetes strike one person who's
overweight but not another who's equally heavy? Why does one
diabetic need dialysis while another has healthy kidneys despite
decades of bad blood sugar? The newest gene work suggests
there likely are even more subtypes that explain those differences,
and that in turn may require personalized treatment just as
MODY does.
Some 21 million Americans have diabetes, meaning
their bodies cannot properly turn blood sugar into energy.
Either they don't produce enough insulin or don't use it correctly.
With the Type 1 form, the body's immune system
attacks insulin-producing pancreatic cells, so that patients
require insulin injections to survive. It usually, but not
always, strikes in childhood.
With the most common Type 2 form, the body
gradually loses its ability to use insulin, so the confused
pancreas churns out extra until eventually its cells wear
out. Most at risk are the overweight.
Genetics research is showing diabetes is far
more complicated than those simple demarcations:
—First there's MODY, shorthand for six
different subtypes thought to account for 2 percent of all
diabetes. Each is caused by a single, different gene. Suspicions
arise when patients are extra hard to treat, especially skinny
people diagnosed with Type 2 diabetes or young adults with
diabetic relatives who abruptly seem to develop Type 1.
Consider Dan Humphries of Shawbury, England,
who at age 16 was diagnosed with Type 1. His mother, a nurse
with diet-controlled diabetes, questioned the diagnosis. But
doctors insisted he was too skinny for other diabetes. They
prescribed insulin that had Humphries passing out from low
blood sugar even with small doses.
His mother sought out Britain's Peninsula
Medical Center in Exeter, where Hattersley performed a gene
test that showed Humphries' pancreas actually can make its
own insulin. But a gene called HNF1-alpha was essentially
putting that production to sleep.
Over a decade of research, Hattersley had
found that old diabetes drugs called sulfonylureas neutralize
that gene so insulim production resumes. Sure enough, Humphries,
now 19, is fine with a quarter-tablet morning and night.
—That brings us to the 16 genes discovered
so far to play a role in Type 2 diabetes, and at least 14
in Type 1.
Surprisingly, the Type 2 genes don't affect
how the body uses insulin, thought to be the trigger. Instead,
they alter how the pancreas makes insulin in the first place,
explains Dr. David Altshuler of Harvard and the Massachusetts
Institute of Technology.
So how healthy your pancreas starts out could
determine how vulnerable you are to other diabetes triggers,
like getting fat.
Collins points to one potential drug target:
A gene with the sole job of getting zinc to insulin-creating
cells. Zinc's a key part of the recipe; too little or too
much, and insulin isn't secreted.
But randomly choosing a gene to target is
"a shot in the dark," cautions Eric Schadt of Merck
& Co., who will urge another approach at this week's meeting,
hosted by the National Disease Research Interchange.
Monday in the journal Nature, Schadt reports
finding how multiple genes work together in computer-like
networks that suggest which will be master control switches
— and thus good drug targets. Already, Merck has begun
checking whether one network of obesity genes really might
predict which overweight people get diabetes.
———
EDITOR's NOTE — Lauran Neergaard covers
health and medical issues for The Associated Press in Washington.
———
Gene info: http://www.diabetes.niddk.nih.gov/dm/pubs/mody/
and http://www.diabetesgenes.org
