Adiponectin is an abundant plasma protein, mainly secreted by adipocytes and closely linked to insulin sensitivity (1–4). Plasma adiponectin independently correlates with insulin sensitivity (5). Since women have greater plasma adiponectin levels than men (5–7), we determined sex-specific differences in associations between plasma adiponectin and tissue-specific insulin sensitivity in skeletal muscle, liver, and fat.

Plasma adiponectin concentrations were measured (intra-assay coefficient of variation <4%) in 28 men and 28 women (6 men and 6 women had impaired glucose tolerance according to World Health Organization criteria). Insulin sensitivity in skeletal muscle, liver, and fat was determined by insulin-mediated whole-body glucose disposal (M values), suppression of hepatic glucose output evaluated during a hyperinsulinemic-euglycemic clamp, and suppression of free fatty acid (FFA) concentrations during an oral glucose tolerance test (OGTT), respectively.

The BMI and body weights of men and women were similar (mean ± SD for BMI 32.11 ± 6.89 vs. 34.24 ± 6.44 kg/m2, P = 0.24; weight, 100.77 ± 23.83 vs. 94.19 ± 19.43 kg, P = 0.26). Men were 9 years older than women (52.64 ± 5.29 vs. 43.89 ± 4.22 years, P < 0.001). The percentage body fat measured by bioimpedance in women (44.56 ± 5.59%) was 54.5% greater than that in men (28.84 ± 7.85%, P < 0.001). It is also important to note that M values in men (6.75 ± 3.39 mg · kg −1 · min−1) and in women (6.81 ± 2.56 mg · kg −1 · min−1) were similar (P = 0.94).

Fasting plasma adiponectin concentrations were negatively correlated with hepatic glucose output in men (r = −0.384, P = 0.022) and women (r = −0.312, P = 0.05) and were strongly correlated with M values in men (r = 0.58, P = 0.001), whereas this correlation did not reach statistical significance in women (r = 0.229, P = 0.242). Fasting plasma adiponectin concentrations were correlated with age, BMI, and percentage body fat in men (r = 0.39, P = 0.038; r = −0.467, P = 0.006; r = −0.41, P = 0.02, respectively), but not in women (r = 0.027, P = 0.89; r = −0.13, P = 0.26; r = −0.06, P = 0.77, respectively).

Plasma adiponectin concentrations were strongly correlated with percentage FFA suppression at 40 min in both men (r = 0.50, P = 0.006) and women (r = 0.50, P = 0.006) during an OGTT. Those correlations were examined at 40 min during the OGTT because percentage FFA suppression at 40 min correlated significantly with M values for both men and women.

When the data were stratified by sex, stepwise multivariate linear regression showed that in men, M value was a strong independent predictor (adjusted R2 = 0.31, P = 0.001) and remained a strong independent predictor of adiponectin concentration (adjusted R2 = 0.39, P = 0.002) when age was also included in the model. In women, however, the percentage FFA suppression was the only independent variable predicting plasma adiponectin concentration, and this model explained ∼26.5% (R2 = 0.27, P = 0.005) of the variance in plasma adiponectin concentration. When the data sets for men and women were combined, FFA suppression (P < 0.001) and sex (P = 0.023) were the only independent predictors of plasma adiponectin concentration. The association with sex was independent of body fat and age percentages.

In conclusion, plasma adiponectin is independently predicted by muscle insulin sensitivity in men but by fat insulin sensitivity in women. Of note is the relationship between plasma adiponectin and FFA suppression, rather than total fat mass, suggesting that fat function is more important than total fat mass in determining plasma adiponectin concentrations, particularly in women. Given that visceral adiposity alters insulin sensitivity, any differences in the relationship between plasma adiponectin and measures of fat function and fat location will require further investigation.

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