The study population included 884 young adults (570 men and 314 women; mean ± SD age 30.1 ± 0.8 years). Men had greater BMI than women (25.1 ± 3.6 vs. 23.8 ± 3.9 kg/m2; P < 0.001), whereas women had greater adiponectin (8.9 ± 3.4 vs. 6.4 ± 2.6 mg/l; P < 0.001) and leptin concentrations (13.2 ± 8.3 vs. 5.1 ± 3.5 μg/l; P < 0.001).
Adiponectin was associated with lipoprotein mean particle size in both sexes. Its strongest relation in men was an inverse association with VLDL size (r = −0.39; P < 0.001) that persisted after adjustment for BMI, waist circumference, and homeostasis model assessment of insulin resistance (HOMA-IR) (r = −0.28; P < 0.001). This relation was weaker in women (r = −0.21; P < 0.001) and was attenuated by adjustment (r = −0.12; P < 0.05). A positive association of adiponectin with HDL and LDL particle size evident in both sexes (r = ~0.30–0.35) remained significant after adjustment.
VLDL, LDL, and HDL particle sizes were introduced separately as dependent variables in backward stepwise multivariable linear regression models that included sex, BMI, waist circumference, HOMA-IR, the relevant plasma lipid or lipoprotein (triglycerides, HDL cholesterol, or LDL cholesterol), leptin, and adiponectin. Adiponectin was significantly inversely associated with VLDL size (B = −0.12; P < 0.001), whereas waist circumference (B = 0.12; P < 0.001), HOMA-IR (B = 0.09; P = 0.002), and triglycerides (B = 0.58; P < 0.001) were positively associated (model R2 = 0.57). Adiponectin was associated with larger LDL particle size (B = 0.20; P < 0.001), whereas waist circumference (B = −0.31; P < 0.001) and sex (B = −0.20; P < 0.001) were associated with smaller particle size (model R2 = 0.32). Adiponectin (B = 0.06; P = 0.013) and leptin (B = −0.10; P = 0.001) showed opposite associations with HDL particle size. HDL cholesterol was strongly associated with larger HDL particle size (B = 0.58; P < 0.001), whereas waist circumference (B = −0.14; P < 0.001), HOMA-IR (B = −0.04; P = 0.06), and male sex (B = −0.25; P < 0.001) were associated with smaller HDL particles (model R2 = 0.69).
We stratified the study sample into tertiles of lipoprotein subclasses and displayed the concentration of adiponectin in each tertile of a lipoprotein subclass (i.e., large, intermediate, and small) while adjusting for sex, waist circumference, BMI, and HOMA-IR. As shown in A, the adiponectin concentrations differed substantially between tertiles of large VLDLs and were inversely associated with increasing concentrations of large VLDL particles (B = −0.19; P for trend < 0.001). In contrast, adiponectin was highest in the upper small VLDL tertile within each large VLDL tertile category (P for trend = 0.02). Adiponectin was highest in the upper large LDL tertile (P for trend < 0.001) (B). In contrast, within each large LDL tertile, adiponectin decreased consistently with increasing concentrations of small LDL particles (P for trend = 0.009). Adiponectin was positively associated with concentrations of large HDLs (P for trend < 0.001) (C) but was not related to small HDL particle concentrations. Thus, adiponectin concentration showed significant contrasting associations with small and large VLDL and LDL subclasses but was associated with only large HDL and not small HDL particles.
Figure 1 Adjusted plasma adiponectin concentration as a function of lipoprotein subclass tertiles adjusted for sex, waist circumference, BMI, and HOMA-IR. A: The cohort divided into tertiles of large VLDL concentrations is shown. Each of these tertiles is subdivided (more ...)
We modeled adiponectin and leptin separately as dependent variables in a backward stepwise procedure that included all lipoprotein subclasses, anthropometric measures (BMI and waist circumference), and HOMA-IR. In men, adiponectin was independently inversely associated with concentrations of large VLDLs and positively associated with small VLDLs and large and intermediate HDLs. Leptin was positively associated only with small VLDLs and adiponectin after adjustment for anthropometric measures and HOMA-IR. In women, adiponectin showed an independent positive association only with large HDLs, whereas leptin was inversely associated with large VLDLs and positively with small and intermediate HDLs.