RBP4 Predicts Type 2 Diabetes

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Source: Beth Israel Deaconess Medical Center

Released: Tue 13-Jun-2006, 09:00 ET

Embargo expired: Wed 14-Jun-2006, 17:00 ET

http://www.newswise.com/articles/view/521226/?sc=dwhp

RBP4 Predicts Type 2 Diabetes

Description

BOSTON – A study in the June 15 issue of The New England Journal of

Medicine (NEJM) reveals that elevated levels of a molecule called RBP4

(retinol binding protein 4) can foretell early stages in the development

of insulin resistance, a major cause of type 2 diabetes as well as

cardiovascular disease.

Newswise — A study in the June 15 issue of The New England Journal of

Medicine (NEJM) reveals that elevated levels of a molecule called RBP4

(retinol binding protein 4) can foretell early stages in the development

of insulin resistance, a major cause of type 2 diabetes as well as

cardiovascular disease.

The new findings, led by researchers at Beth Israel Deaconess Medical

Center (BIDMC), offer a potential new target for the development of

anti-diabetic therapies to lower serum RBP4 levels as well as an early

means of identifying individuals who are at risk of developing diabetes

– before the onset of overt disease.

“Type 2 diabetes is a rapidly increasing epidemic in the Western world,”

explains senior author Barbara Kahn, MD, Chief of the Division of

Diabetes, Endocrinology and Metabolism at BIDMC and Professor of

Medicine at Harvard Medical School. “Since it is now occurring even in

childhood, predictions indicate that it could shorten lifespan in the

U.S. for the first time in more than a century.”

Insulin resistance develops when the body’s muscles, fat and liver cells

lose the ability to respond to the hormone insulin. Because insulin is

necessary to enable the body to take up sugar from blood and convert it

into energy, this impairment results in a buildup of glucose in the

bloodstream.

“Insulin resistance not only predisposes individuals to type 2 diabetes,

it is also a major risk factor for cardiovascular disease,” adds co-lead

author Graham, MD, an investigator in the Kahn laboratory.

“Unfortunately, in the clinical setting, it is often difficult to

distinguish individuals with and without insulin resistance.”

Last year, in a study conducted in animals, Kahn’s laboratory made the

discovery that RBP4, a protein secreted from fat, can cause insulin

resistance. Prior to this, the molecule was recognized only for its role

in the transport of vitamin A.

In this new research, Graham, together with co-lead author Qin Yang, MD,

PhD, set out to determine whether levels of RBP4, as measured in blood,

correlate with the presence or absence of insulin resistance. (Study

subjects represented three separate cohorts from San Diego, California;

Goteberg, Sweden; and Leipzig, Germany.)

They first studied individuals with either obesity, impaired glucose

tolerance (a “pre-diabetic” state), or with type 2 diabetes, comparing

the blood levels of RBP4 in these insulin-resistant subjects with levels

found in non-obese healthy subjects. Their results showed that not only

were RBP4 levels higher in all cases in which insulin resistance was

high, but that elevated serum RBP4 was also closely associated with

components of the metabolic syndrome, including increased body mass

index, waist-to-hip ratio, serum triglyceride levels, and systolic blood

pressure, as well as decreased levels of high-density lipoprotein (HDL),

or good, cholesterol.

The study was then extended to subjects with normal body weight and

normal blood glucose, but with a strong family history of type 2

diabetes. “These are people who appear healthy, but have a high risk of

developing diabetes due to their genetic background,” explains Ulf

, MD, PhD, of Sahlgrenska Hospital, Goteberg, Sweden, where this

group of subjects was based. As predicted, the investigators found

elevated RBP4 levels among this group as well.

Finally, the authors tested whether a therapeutic intervention – in this

case, exercise – could lower RBP4 levels and increase insulin

sensitivity. They found that all of the people who improved their

insulin sensitivity with exercise also lowered their serum RBP4 levels.

Among the one-third of the subjects who did not improve their insulin

sensitivity, neither did RBP4 levels go down.

“Collectively, these findings tell us that RBP4 is a useful marker for

therapeutic improvement and that this protein could play a causal role

in insulin resistance in humans, just as our lab previously showed in

mice,” says Kahn. Furthermore, she adds, because RBP4 levels

consistently corresponded with insulin resistance -- even among lean

subjects whose genetic risk for the development of diabetes might

otherwise be overlooked -- this protein could be an important marker for

type 2 diabetes among the general population.

“Being able to determine diabetes risk well before the onset of symptoms

could provide an important opportunity for patients to take preventive

measures,” she adds. “For those who are overweight or sedentary, this

could mean making changes to their diet and fitness routines. For those

who are lean and fit, but have a family history of type 2 diabetes, this

could mean taking antidiabetic medication. Either way, these findings

could help clinicians to better manage this growing epidemic.”

In addition to Kahn, Graham and Yang, study coauthors include

of BIDMC; Matthias Bluher, MD and s Oberbach,

MD, of the University of Leipzig Medical Center, Germany; Ann

Hammarstedt, PhD, Per-Anders Jansson, MD, PhD, and Ulf , MD, of

Sahlgrenska University Hospital, Goteborg, Sweden; and Theodore

Ciaraldi, PhD and Henry, MD, of the Veterans Affairs San Diego

Healthcare System.

This study was funded, in part, by grants from the National Institutes

of Health, the American Diabetes Association, the Swedish Diabetes

Association, and the Takeda Pharmaceutical Company, LTD.

Beth Israel Deaconess Medical Center is a patient care, research and

teaching affiliate of Harvard Medical School and ranks fourth in

National Institutes of Health funding among independent hospitals

nationwide. BIDMC is clinically affiliated with the Joslin Diabetes

Center and is a research partner of the Dana-Farber/Harvard Cancer

Center. BIDMC is the official hospital of the Boston Red Sox. For more

information, visit http://www.bidmc.harvard.edu.

--

ne Holden, MS, RD < fivestar@... >

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