Coffee, that morning elixir, may give us an
early jump-start to the day, but numerous studies have shown that it also may
be protective against type 2 diabetes. Yet no one has really understood why.
Now, researchers at UCLA have discovered a
possible molecular mechanism behind coffee’s protective effect. A protein
called sex hormone–binding globulin (SHBG) regulates the biological activity of
the body’s sex hormones, testosterone and estrogen, which have long been thought
to play a role in the development of type 2 diabetes. And coffee consumption,
it turns out, increases plasma levels of SHBG.
Reporting with colleagues in the current
edition of the journal Diabetes, first author Atsushi Goto, a UCLA doctoral
student in epidemiology, and Dr. Simin Liu, a professor of epidemiology and
medicine with joint appointments at the UCLA School of Public Health and the
David Geffen School of Medicine at UCLA, show that women who drink at least
four cups of coffee a day are less than half as likely to develop diabetes as
When the findings were adjusted for levels
of SHBG, the researchers said, that protective effect disappeared.
The American Diabetes Association estimates
that nearly 24 million children and adults in the U.S—nearly 8% of the
population—have diabetes. Type 2 diabetes is the most common form of the
disease and accounts for about 90% to 95% of these cases.
Early studies have consistently shown that
an “inverse association” exists between coffee consumption and risk
for type 2 diabetes, Liu said. That is, the greater the consumption of coffee,
the lesser the risk of diabetes. It was thought that coffee may improve the
body’s tolerance to glucose by increasing metabolism or improving its tolerance
“But exactly how is elusive,” said
Liu, “although we now know that this protein, SHBG, is critical as an
early target for assessing the risk and prevention of the onset of
Earlier work by Liu and his colleagues
published in the New England Journal of
Medicine had identified two mutations in the gene coding for SHBG and their
effect on the risk of developing type 2 diabetes; one increases risk while the
other decreases it, depending on the levels of SHBG in the blood.
A large body of clinical studies has
implicated the important role of sex hormones in the development of type 2
diabetes, and it’s known that SHBG not only regulates the sex hormones that are
biologically active but may also bind to receptors in a variety of cells,
directly mediating the signaling of sex hormones.
“That genetic evidence significantly
advanced the field,” said Goto, “because it indicated that SHBG may
indeed play a causal role in affecting risk for type 2 diabetes.”
“It seems that SHBG in the blood does
reflect a genetic susceptibility to developing type 2 diabetes,” Liu said.
“But we now further show that this protein can be influenced by dietary
factors such as coffee intake in affecting diabetes risk—the lower the levels
of SHBG, the greater the risk beyond any known diabetes risk factors.”
For the study, the researchers identified
359 new diabetes cases matched by age and race with 359 apparently healthy
controls selected from among nearly 40,000 women enrolled in the Women’s Health
Study, a large-scale cardiovascular trial originally designed to evaluate the
benefits and risks of low-dose aspirin and vitamin E in the primary prevention
of cardiovascular disease and cancer.
They found that women who drank four cups of
caffeinated coffee each day had significantly higher levels of SHBG than did
non-drinkers and were 56 percent less likely to develop diabetes than were
non-drinkers. And those who also carried the protective copy of the SHBG gene
appeared to benefit the most from coffee consumption.
When the investigators controlled for blood
SHBG levels, the decrease in risk associated with coffee consumption was not
significant. This suggests that it is SHBG that mediates the decrease in risk
of developing type 2 diabetes, Liu said.
And there’s bad news for decaf lovers.
“Consumption of decaffeinated coffee was not significantly associated with
SHBG levels, nor diabetes risk,” Goto said. “So you probably have to
go for the octane!”
Other authors of the study included Brian
Chen, of UCLA, and Julie Buring, JoAnn Manson and Yiqing Song, of Brigham and
Women’s Hospital and Harvard
Funding was provided by the National Institutes of Health. No conflicts of
interest were reported by the authors.