Low Levels of Sex Hormone Protein Indicate Higher Risk of Type 2, Says Study

Researchers have recently reported that people with the lowest levels of a protein that regulates sex hormones, “sex hormone-binding globulin,” were 10 times more likely to develop type 2 diabetes than those with the highest levels of SHBG. In short, the lower a person’s SHBG levels, the higher his or her risk of developing the disease.

The finding about SHBG, which regulates testosterone and estrogen levels, presents the diabetes community with one of the clearest predictors yet of risk for type 2. Lead researcher Dr. Simin Liu said that SHBG appeared to predict the risk of type 2 diabetes better than such traditional factors as weight, smoking habits, exercise, and high blood pressure, and that it “significantly outperformed” such currently touted risk predictors as A1c and C-reactive protein.

The study team, located at the David Geffen School of Medicine at the University of California, Los Angeles, examined SHBG levels in 718 postmenopausal women. Half had recently been diagnosed with type 2, and half didn’t have type 2. The women had participated in a large-scale cardiovascular study, the Women’s Health Study, that began in 1993. The team also examined a group of 340 men, divided between those with and without type 2, who had participated in a similar study called the Physicians’ Health Study II.

Because of the two studies’ extent and duration, the UCLA team was able to track the patients’ SHBG levels and match them to the incidence of type 2 diabetes. In addition to discovering that SHBG was a marker for diabetes risk, they found that the amount of SHBG in a person’s bloodstream may be genetically determined.

For example, people in the study who carried one of two different alleles had either 10 percent higher or 10 percent lower levels of SHBG than people who carried the most common allele. (An allele is one member of a pair of genes that is an alternative form of the gene and is located at a specific position on a specific chromosome.)

The alleles, called rs6259 and rs6257, lower and increase the risk of developing type 2, respectively. The discovery of their effects on the actions of SHBG has created speculation that SHBG may also play an active role in the disease’s development. If so, the ability to manipulate the protein genetically could open the door to a therapy or even vaccine that prevents the onset of type 2.

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

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