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Examining the Evidence


First-trimester levels of sex hormone binding globulin predict gestational diabetes

October 2004 · Vol. 16, No. 10

Objective

To explore the association between first-trimester levels of sex hormone binding globulin (SHBG) and subsequent gestational diabetes mellitus.

Results

SHBG levels were lower among women who subsequently developed gestational diabetes than among those who didn’t (187±82 nmol/L versus 233±92 nmol/L; P <.01). For every increase of 50 nmol/L in SHBG, the odds of gestational diabetes fell by 31% (odds ratio, 0.69; 95% confidence interval, 0.48–0.99).

Expert commentary

Gestational diabetes or glucose intolerance first recognized during pregnancy complicates approximately 4% of all pregnancies, varying by population studied.1 Although the best management strategy for these patients has yet to be determined, particularly for patients with only mildly elevated blood sugars, certain fetal and maternal risks are well documented. For example, women with a history of gestational diabetes face an increased risk for type 2 diabetes, with a lifetime risk of approximately 50%.2

This nested case-control study included 44 women documented to have gestational diabetes in the third trimester by the 2-step screening process (50-g screen followed by a 100-g glucose tolerance test in women with a positive screen of 140 mg/dL), as well as 94 women who had negative screening.

Serum samples that had been collected in the first trimester were examined to determine SHBG levels.

Need for earlier detection

By definition, gestational diabetes includes women who—though they are first diagnosed during pregnancy—may have had varying degrees of glucose intolerance prior to conception.

Therapeutic intervention may benefit these women and their babies. Unfortunately, women traditionally are screened for gestational diabetes between 24 and 28 weeks’ gestation, when many of the metabolic consequences have already occurred. Thus, investigators have attempted to find a method of earlier diagnosis and treatment.

SHBG and insulin resistance

SHBG is a glycoprotein produced by the liver; it binds to circulating estradiol and testosterone. Secretion is suppressed by insulin, and SHBG levels are inversely related to insulin concentrations and insulin resistance. Lower concentrations of SHBG are predictive of the development of type 2 diabetes.3 During pregnancy, SHBG concentrations are lower in women with gestational diabetes and in those who require insulin therapy.4,5

Bottom line

Measuring SHBG levels in the first trimester may allow earlier intervention or identify a population appropriate for earlier diabetes testing. However, although an association has been established between low first-trimester SHBG and the development of gestational diabetes, this marker has not been fully explored as a screening test. A larger prospective study is required to establish optimal cut points of SHBG for predicting gestational diabetes.

REFERENCES

1. King H. Epidemiology of glucose intolerance and gestational diabetes in women of childbearing age. Diabetes Care 1998;21:B9-13.

2. Dornhorst A, Rossi M. Risk and prevention of type 2 diabetes in women with gestational diabetes. Diabetes Care. 1998;21:B43-49.

3. Haffner SM, Valdez RA, Morales PA, Hazuda HP, Stern MP. Decreased sex hormone-binding globulin predicts noninsulin-dependent diabetes mellitus in women but not in men. J Clin Endocrinol Metab. 1993;77:56-60.

4. Bartha JL, Comino-Delgado R, Romero-Carmona R, Gomez-Jaen MC. Sex hormone-binding globulin in gestational diabetes. Acta Obstet Gynecol Scand. 2000;79:839-845.

5. Kopp HP, Festa A, Krugluger W, Schernthaner G. Low levels of sex-hormone-binding globulin predict insulin requirement in patients with gestational diabetes mellitus. Exp Clin Endocrinol Diabetes. 2001;109:365-369.

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