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Sex hormone-binding globulin predicts the incidence of hyperglycemia in women: interactions with adiponectin levels

Endocrinology Unit, Department of Medicine, CHU Rennes, Université Rennes 1, INSERM U625, 35000 Rennes, France¹ INSERM U780, Epidemiological and Statistical Research, Villejuif, France² INSERM U695, Xavier Bichat Medical School, Université Paris 7, Paris, France³ Department of Biochemistry, Hospices Civils de Lyon, Lyon, France⁴ IRSA, La Riche, France⁵ Endocrinology and Diabetology Unit, Department of Medicine, CHRU Bretonneau, Tours, France⁶ Endocrinology Unit, Department of Medicine, INSERM U, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon, France

(Correspondence should be addressed to F Bonnet who is now at Department of Endocrinology, CHU Rennes, University of Rennes 1, 35002 Rennes, France; Email: fabrice.bonnet{at}chu-rennes.fr)

Objective: Previous evidence has suggested that a low sex hormone-binding globulin (SHBG) concentration is associated with insulin-resistance and a low adiponectin concentration. We investigated the association between SHBG and the risk of hyperglycemia in each sex and we determined potential interactions between SHBG and adiponectin levels in the development of dysglycemia.

Design: We used a nested case–control design in the large prospective study, Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). We studied 227 men and women who were normoglycemic at baseline but hyperglycemic at 3 years (glycemia6.1 mmol/l or type 2 diabetes). They were matched for sex, age, and body mass index with 227 subjects who remained normoglycemic at 3 years.

Results: At baseline, the concentration of SHBG was significantly lower in women who subsequently developed hyperglycemia than in those who remained normoglycemic, with no difference for men. In multiple regression, SHBG at baseline was as an independent determinant of plasma adiponectin levels, in both women (P<0.0001) and men (P=0.002). In multivariate conditional logistic regression taking into account physical activity and changes in waist circumference over the follow-up, plasma SHBG remained significantly associated with the development of hyperglycemia in women but not in men. These associations persisted after adjustment for fasting insulinemia, high fasting glucose, and adiponectin levels.

Conclusions: These findings suggest that a low SHBG level is a strong risk marker for dysglycemia in women, independently of both adiponectinemia and insulinemia. SHBG may therefore improve the identification of women at risk of diabetes.