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Sex Hormone Protein May Predict Type 2 Diabetes

Whether it causes the disease or is simply a marker for obesity is unclear ,,

WEDNESDAY, Aug. 5 (HealthDay News) -- A protein that carries and activates sex hormones throughout the body may also predict those at high risk of developing type 2 diabetes, a new study finds.

The protein, called sex hormone-binding globulin (SHBG), regulates the levels of testosterone and estrogen in the blood. Researchers suspect it also plays a role in the development of type 2 diabetes.

"Basically, we have identified plasma SHBG as a strong and significant marker for type 2 diabetes development in initially healthy men and women," said lead researcher Dr. Simin Liu, professor and director of the Center for Metabolic Disease Prevention in the School of Public Health at the University of California Los Angeles, David Geffen School of Medicine.

Low levels of SHBG were a significant predictor for the risk of development of type 2 diabetes, the researchers found.

"To our knowledge, there are few biomarkers for type 2 diabetes prediction that have presented both genetic and plasma phenotypic evidence like ours," Liu said.

The report was published in the Aug. 5 online edition of the New England Journal of Medicine.

For the study, Liu's group looked at SHBG levels in 718 postmenopausal women -- 359 with type 2 diabetes and 359 without -- who participated in the Women's Health Study, a large-scale cardiovascular trial begun in 1993. In a separate investigation, they confirmed their findings in a group of 340 men who participated in the Physicians' Health Study II, a similarly large study.

Besides the inverse relationship between levels of SHBG and type 2 diabetes, they identified two genetic variants in the gene coding for SHBG -- one increases type 2 diabetes risk while the other decrease diabetes risk.

"Plasma SHBG appeared to predict type 2 diabetes risk beyond traditional risk factors," Liu said. "In direct comparison, it significantly outperformed some newer risk predictors such as HbA1c (glycated hemoglobin) and C-reactive protein."

The researchers also used genetic data to confirm that SHBG may play a causal role in the development of type 2 diabetes.

"Our findings provide further support of the importance of the sex-hormone biology, an area of diabetic pathogenesis which has been relatively less well-studied," Liu said.

While the exact causal mechanism involved in SHBG levels and type 2 diabetes are unclear, it appears that SHBG is involved in complex chemical interactions that can increase or decrease the risk for the disease, the researchers say.

Until now, classical thinking and teaching in medicine have never focused on the potential causal role of SHBG in the development of disease, Liu noted. "By directly linking SHBG with diabetes risk at both genetic and plasma levels, our data suggest that SHBG may have important biological effects that go beyond simply regulating sex-hormones in the blood," he said.

These findings provide new insights into the mechanisms underlying the relationship between sex-steroid hormone metabolism and type 2 diabetes, Liu said.

About 24 million Americans have diabetes, mostly type 2, and another 57 million have pre-diabetes, according to the U.S. Centers for Disease Control and Prevention.

"If our initial findings are confirmed, it is our hope that someday SHBG would serve as a critical screening tool for diabetes as well as a target for developing treatment and preventive measures," he said.

Dr. Robert Rapaport, chief of the division of pediatric endocrinology and diabetes at Mount Sinai School of Medicine in New York City, said much is still unknown about the precise association between SHBG and type 2 diabetes.

"SHBG is emerging from a role as just a carrier protein to being a player on its own," Rapaport said.

Rapaport noted that SHBG has been linked to obesity. "So you don't know which came first. Are these genes expressed more in the framework of obesity or not? Clearly, obesity is the main risk factor for type 2 diabetes. Whether or not this is an additional risk factor will be interesting to know," he said.

More information

For more information on type 2 diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCES: Simin Liu, M.D., Sc.D., professor and director, Center for Metabolic Disease Prevention, School of Public Health, University of California Los Angeles, David Geffen School of Medicine; Robert Rapaport, M.D., director, Hall Family Center for Pediatric Endocrinology and Diabetes, Emma Elizabeth Sullivan Professor of Pediatric Endocrinology and Diabetes, Mount Sinai School of Medicine, New York City; Aug. 5, 2009, New England Journal of Medicine, online

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