Relationships of Circulating Sex Hormone–Binding Globulin With Metabolic Traits in Humans
- Andreas Peter1,
- Konstantinos Kantartzis1,
- Jürgen Machann2,
- Fritz Schick2,
- Harald Staiger1,
- Fausto Machicao1,
- Erwin Schleicher1,
- Andreas Fritsche1,
- Hans-Ulrich Häring1 and
- Norbert Stefan1
- 1Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, member of the German Center for Diabetes Research (DZD), Tübingen, Germany;
- 2Section on Experimental Radiology, University of Tübingen, Tübingen, Germany.
- Corresponding author: Norbert Stefan, .
OBJECTIVE Recent data suggested that sex hormone–binding globulin (SHBG) levels decrease when fat accumulates in the liver and that circulating SHBG may be causally involved in the pathogenesis of type 2 diabetes in humans. In the present study, we investigated mechanisms by which high SHBG may prevent development to diabetes.
RESEARCH DESIGN AND METHODS Before and during a 9-month lifestyle intervention, total body and visceral fat were precisely measured by magnetic resonance (MR) tomography and liver fat was measured by 1H-MR spectroscopy in 225 subjects. Insulin sensitivity was estimated from a 75-g oral glucose tolerance test (ISOGTT) and measured by a euglycemic hyperinsulinemic clamp (ISclamp, n = 172). Insulin secretion was measured during the OGTT and an ivGTT (n = 172).
RESULTS SHBG levels correlated positively with insulin sensitivity (ISOGTT, P = 0.037; ISclamp, P = 0.057), independently of age, sex, and total body fat. In a multivariate model, these relationships were also significant after additional adjustment for levels of the adipokine adiponectin and the hepatokine fetuin-A (ISOGTT, P = 0.0096; ISclamp, P = 0.029). Adjustment of circulating SHBG for liver fat abolished the relationships of SHBG with insulin sensitivity. In contrast, circulating SHBG correlated negatively with fasting glycemia, before (r = −0.17, P = 0.009) and after (r = −0.14, P = 0.04) adjustment for liver fat. No correlation of circulating SHBG with adjusted insulin secretion was observed (OGTT, P = 0.16; ivGTT, P = 0.35). The SNP rs1799941 in SHBG was associated with circulating SHBG (P ≤ 0.025) but not with metabolic characteristics (all P > 0.18).
CONCLUSIONS Possible mechanisms by which high circulating SHBG prevents the development of type 2 diabetes involve regulation of fasting glycemia but not alteration of insulin secretory function.
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- Received February 4, 2010.
- Accepted September 3, 2010.
- © 2010 by the American Diabetes Association.
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