Insulin sensitivity: gender-related differences in subjects with normal glucose tolerance

BACKGROUND AND AIMS: To verify whether age and the perimenopausal state may herald the onset of the metabolic syndrome (MS) in females as compared to age-matched males, we studied subjects with normal glucose tolerance, according to ADA definition. METHODS AND RESULTS: In 368 eligible subjects subdivided into three age groups we measured insulin sensitivity by ISI-glycaemia, resistance by HOMA-IR, computed, during OGTT, from fasting and 2-h post-load plasma insulin and glucose concentrations. The significance of differences was tested between different age groups and between males and females within corresponding age groups. Insulin sensitivity fell slightly and insulin resistance rose significantly in the perimenopausal group as compared to younger and older female patients, and compared to men of the same age. This pattern remains after excluding patients with high blood pressure, and after adjusting for WHR and BMI by multivariate analysis. HOMA-IR averaged 2.9+/-1.8 in females, 2.2+/-1.2 in men aged 45-54 years (p<0.02), while in the other age groups insulin resistance was higher in men. CONCLUSION: The onset of MS during the menopause is associated with a physiological shift in insulin resistance occurring even in normal glucose tolerant subjects, suggesting that it may depend upon critical metabolic changes occurring specifically in that age period.