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Menopause, insulin resistance, and risk factors for cardiovascular disease

Manco, Melania MD, PhD1; Nolfe, Giuseppe PhD2; Calvani, Menotti MD1; Natali, Andrea MD3; Nolan, John MD4; Ferrannini, Eleuterio MD3; Mingrone, Geltrude MD, PhD1on behalf of the European Group for the Study of Insulin Resistance

doi: 10.1097/01.gme.0000233492.38638.74

Objective: In this retrospective analysis of the European Group for the Study of Insulin Resistance database, a clamp data pooling project, a cardiovascular risk score (CVS) was assessed to verify whether hyperinsulinemia and/or insulin resistance were independent cardiovascular risk factors and to investigate how menopause affected CVS and insulin resistance.

Design: Information was obtained on whole-body glucose uptake (M), determined by the euglycemic hyperinsulinemic clamp technique, normalized by fat-free mass (FFM), and insulin concentration (I) at a steady state. Body composition was estimated using a labeled water technique or bioimpedance. Other parameters measured included blood pressure, lipid levels, and waist-to-hip ratio. CVS was computed using a structural equation model that included age, body mass index, blood lipids, and blood pressure. The study population included 523 normal and overweight patients. Women were grouped according to fertility status, and men, according to age (cutoff 50 y).

Results: M/kgFFM/I significantly decreased after menopause (12.41 ± 3.40 vs 10.96 ± 3.68; P < 0.01) and in men 50 years and older (11.39 ± 3.47 vs 10.32 ± 3.77 μmol·min−1·kg−1·μUI/mL; P < 0.02). CVS was lowest in fertile women (−0.414 ± 0.57 vs 0.107 ± 0.43; P < 0.0001) and highest in men 50 years and older (0.045 ± 0.455 vs 0.257 ± 0.51; P < 0.001). CVS significantly correlated with M/kgFFM/I in men 49 years and younger (ro = −0.27, P < 0.0001) and 50 years and older (ro = −0.38, P < 0.0001) and with fasting insulin in fertile women (ro = −0.29, P < 0.01) and in the other groups (ro ranging from 0.37 to 0.45, P < 0.0001).

Conclusions: Menopause does not seem to strictly relate to a decrease in insulin sensitivity as postmenopausal women had the same insulin sensitivity as age-matched men. In the population studied, the best predictor of CVS was fasting insulin rather than insulin sensitivity.

The analysis of the European Group for the Study of the Insulin Resistance database does not sustain the hypothesis of a detrimental effect of estrogen depletion on insulin sensitivity. Fasting insulin predicts the cardiovascular risk in women either before or after menopause, whereas values of insulin resistance do not.

From the 1Institute of Internal Medicine, Catholic University, Rome; 2CNR Institute of Cybernetics "E. Caianiello," Pozzuoli; 3CNR Institute of Internal Medicine, Pisa, Italy; and 4Department of Endocrinology, St. James's Hospital, Dublin, Ireland.

Received September 27, 2005; revised and accepted December 22, 2005.

Address correspondence to: Melania Manco, MD, PhD, Institute of Internal Medicine, Catholic University, Largo Gemelli 8, I-00168 Rome, Italy. E-mail:

©2006The North American Menopause Society