Context: Age-related declines in testosterone and insulin-growth factor (IGF-1) are associated with deposition of visceral fat, a component of the metabolic syndrome (MES).

Objective: Testosterone and IGF-1 may interact with familial disposition to diabetes mellitus to increase the association with MES.

Design: A cross-sectional cohort study

Setting: A university teaching hospital

Subjects: 179 middle-aged men with a family history of diabetes (FH) [aged 39.1 ± 8.1 yr] and 128 men without FH [aged 43.8 ± 8.5 yr].

Main Outcome Measures: Clinical characteristics, frequency of MES using the WHO criteria with Asian definitions of obesity (BMI 25 kg/m²), serum levels of total testosterone, IGF-1 and high-sensitive C-Reactive Protein (hs-CRP).

Results: Men with FH had higher frequency of MES than those without FH [39.1% vs. 23.4% (P = 0.004)]. On multivariate analysis, smoking (ex and current), low total testosterone and IGF-1 but elevated hs-CRP levels explained 35% of the MES variance in men with FH, The frequency of MES increased with declining tertiles of total testosterone and IGF-1 but increasing tertiles of hs-CRP. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES than those without hormonal and inflammatory risk factors. These risk associations were not found in men without FH in whom only smoking (ex and current) and low total testosterone level were independent predictors for MES which explained 14% of the variance.

Conclusions: Clustering of a family history of diabetes, hormonal abnormalities and high hs-CRP is associated with MES in Chinese middle-aged men.