Adipocytokines as a Novel Target for the Anti-inflammatory Effect of Atorvastatin in Patients With Type 2 Diabetes
Recently, Shetty et al. (1) reported a positive correlation of resistin with C-reactive protein (CRP) in a cross-sectional study of patients with type 1 or type 2 diabetes and patients in a pre-diabetic state. Collectively, however, little is known about the role of proinflammatory adipocytokines. The adipocyte-secreted hormones leptin and resistin have recently been regarded as pro-inflammatory cytokines positively associated with CRP in healthy subjects (2) and patients with diabetes (1). Shetty et al. therefore investigated whether atorvastatin may mediate part of its beneficial effects by altering resistin levels. They did find a 20% reduction of plasma resistin after statin treatment. Due to a concomitant decrease in the placebo group, however, this reduction was not statistically significant (1).
In this study, we report that atorvastatin significantly reduced plasma levels of resistin and leptin in patients with type 2 diabetes. In contrast to the Shetty et al. study, we investigated the effect of atorvastatin in a homogeneous population, including patients with type 2 diabetes only. We also investigated a larger number of patients and administered a two-fold higher dose of atorvastatin (40 mg/day).
We studied the effect of atorvastatin on plasma resistin, leptin, and CRP in 87 patients with type 2 diabetes (60 men and 27 women) in a randomized, open, placebo-controlled study, designed with an 8-week intervention period to either atorvastatin (n = 52) or placebo (n = 35). The relationships between paired variables before and after intervention were analyzed with the paired Student’s t test. Two-tailed bivariate correlations were determined by the Pearson coefficient. Results were expressed as means ± SE.
At baseline, resistin levels were positively correlated with plasma CRP (r = 0.35, P < 0.005) and negatively with HDL cholesterol (r = −0.26, P < 0.02). Leptin levels were higher in women (22.2 ± 3.7 ng/ml) than in men (15.2 ± 1.3 ng/ml, P = 0.03) but did not correlate with plasma CRP. Atorvastatin treatment resulted in a significant reduction in resistin of almost 20% (3.5 ± 0.4 vs. 2.9 ± 0.4 ng/ml, P < 0.001) and was furthermore accompanied by a significant decrease in leptin by 40% (20.7 ± 2.3 vs. 12.5 ± 1.1 ng/ml, P < 0.01) and in CRP by 39% (3.8 ± 0.6 vs. 2.3 ± 0.3 mg/l, P < 0.001). No significant alterations of resistin, leptin, or CRP levels were observed in the placebo group.
These results show, for the first time, a statin-mediated significant reduction in two important adipocytokines in type 2 diabetes. The reduction of resistin, we observed, is similar to the one reported by Shetty et al. In that study, however, the change was not statistically significant because of a similar decrease in the placebo group that was most likely due to chance.
It has been shown that patients with type 2 diabetes benefit from low-dose atorvastatin therapy (3) and that the magnitude of protection may be larger than that observed in nondiabetic populations. This suggests that anti-inflammatory effects, referred to as pleiotropic effects, augment the lipid-lowering effect of atorvastatin therapy. Because proinflammatory adipocytokines are known to be dysregulated in patients with type 2 diabetes (4), it is tempting to speculate that, based on our findings, patients with type 2 diabetes might receive added benefits from a statin-mediated reduction of resistin and leptin.
The study was supported by a research grant from Pfizer (ATV-d-01-006G).
- DIABETES CARE