The objective of the study was to investigate the effect of long-term (3.2 years)
weight loss on serum levels of the nontraditional cardiovascular risk factors
interleukin (IL)-18 and
matrix metalloproteinase (MMP)-9. Moreover, we wanted to assess the significance of the magnitude of the
weight loss and evaluate the potential effects of 36 months of treatment with the
lipase inhibitor
orlistat on these parameters. Sixty-eight abdominally obese subjects completed 8 weeks of very low energy diet (600-800 kcal/d) followed by 36 months of randomized treatment with either
orlistat or placebo together with lifestyle intervention. Serum levels of
IL-18, MMP-9, and
leptin were measured by flowmetric xMAP technology (Luminex, Austin, TX). Changes in the levels of
IL-18, MMP-9, and
leptin were similar in the
orlistat and the placebo group during this study. Thus, the 2 groups were combined for further analysis. A
weight loss of 8.4 +/- 8.8 kg from baseline to 3.2 years was associated with significant decreases in
IL-18 (P < .001), MMP-9 (P < .01), and
leptin (P < .001).
Matrix metalloproteinase-9 was, however, significantly increased after 8 weeks of very low energy diet-induced
weight loss (P < .05). The long-term changes in
IL-18 were significantly associated with changes in body mass index independent of changes in blood pressure and
lipids (P < .05). Levels and changes of
IL-18 and MMP-9 were significantly positively associated at 3.2 years (P < .01). Long-term changes in
leptin were significantly associated with changes in
IL-18 (P < .01) at 3.2 years. Diet-induced long-term
weight loss decreased
IL-18 and MMP-9. The decrease in
IL-18 was associated with changes in body mass index independent of changes in blood pressure and
lipids, indicating that even a minor
weight reduction (>5%) has beneficial effects on nontraditional cardiovascular risk markers.
Orlistat treatment had no independent effects on
IL-18, MMP-9, or
leptin in the present study.