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Low pre-pregnancy levels of specific protein linked to higher risk of diabetes during pregnancy

Women with low levels of an important protein known to bind to sex hormones prior to pregnancy were five times more likely to develop gestational diabetes than women with higher levels of the protein, according to a Kaiser Permanente study published in the journal Diabetes Care.

“This study is among the first to find that low circulating levels of sex hormone binding globulin, measured years before pregnancy, are associated with increased risk of gestational diabetes,” said Monique M. Hedderson, PhD, principal investigator of the study and research scientist with the Kaiser Permanente Division of Research in Oakland, Calif.

SHBG binds to the sex hormones, including testosterone and estrogen. It controls the amount of testosterone available in the body; lower SHBG levels are associated with higher testosterone levels. In women, higher testosterone is associated with insulin resistance, a risk factor for gestational diabetes. Levels of SHBG change dramatically, even during early pregnancy, in response to the hormonal changes.

For this study, the researchers retrospectively identified 256 women who developed gestational diabetes during pregnancy and 497 who did not. The women had given voluntary blood samples between 1985 and 1996 during routine care and subsequently delivered an infant in Kaiser Permanente’s Northern California Region, on average 6 years later.

The researchers found that the risk of gestational diabetes increased as SHBG levels decreased, regardless of the woman’s body mass index. However, researchers also found a strong association between high body mass index and an increased risk of developing gestational diabetes.

A previous report on the same cohort of mothers found that overweight women (BMI of 25 or greater) with low levels of the hormone adiponectin prior to pregnancy were nearly seven times more likely to develop gestational diabetes compared to normal weight women (BMI less than 25) with high levels of adiponectin.

This study included women who volunteered to participate in Kaiser Permanente’s multiphasic health check-up exam, therefore the population may be more health conscious than the general population. However, the study cohort was diverse in terms of race-ethnicity and education levels. Gestational diabetes, or glucose intolerance during pregnancy, has increased dramatically in recent decades and is now the most common complication of pregnancy, according to recent studies. It can lead to adverse outcomes, including larger-than-normal babies and subsequent delivery complications. Women with gestational diabetes are seven times more likely to develop type 2 diabetes later in life, and their children are at greater risk of becoming obese and developing diabetes themselves.

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In addition to Hedderson, co-authors of the study are: Fei Xu, MA, Jeanne Darbinian, MPH, Charles P. Quasenberry, PhD, Sneha Sridhar, MPH, Erica Gunderson, PhD, and Assiamira Ferrara, MD, PhD, all of the Kaiser Permanente Division of Research, Oakland, Calif.; and Catherine Kim, MD, Departments of Medicine and Obstetrics and Gynecology, University of Michigan, Ann Arbor.

Research reported in this press release was supported in part by the National Institute of Child Health and Human Development of the National Institutes of Health under award number R01HD065904. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Kaiser Permanente Research