Effects of rosiglitazone and metformin treatment on apelin, visfatin, and ghrelin levels in patients with type 2 diabetes mellitus

Abstract 

Visfatin, ghrelin, and apelin are the most recently identified adipocytokines; but their response to insulin-sensitizing agents is poorly clarified. We aimed to assess the differential effects of either rosiglitazone or metformin monotherapy on the aforementioned adipocytokines in patients with type 2 diabetes mellitus (T2DM). One hundred T2DM patients (30 men, 70 women), with poor glycemic control (glycosylated hemoglobin >6.5%) while taking 850 mg of metformin daily, were enrolled. All participants were randomized to receive either adjunctive therapy with rosiglitazone (8 mg/d, n = 50) or the maximum dose (2550 mg/d) of metformin (MET group, n = 50). Anthropometric parameters, glycemic and lipid profile, high-sensitivity CRP (hs-CRP), insulin resistance (homeostasis model assessment of insulin resistance index [HOMA-IR]), visfatin, ghrelin, and apelin were assessed at baseline and after 14 weeks of therapy. Both rosiglitazone and metformin led to similar, significant improvement in glycemic profile and apelin levels, whereas lipid parameters, fat mass, and visfatin remained almost unaffected (P > .05). Insulin resistance was significantly attenuated in both groups, but to a lesser degree in the MET group (P = .045). Rosiglitazone-treated patients experienced a significant decrease in hs-CRP and systolic blood pressure compared with baseline values and those of the MET group (P < .05). Besides, rosiglitazone treatment considerably increased plasma ghrelin (3.74 ± 1.52 ng/mL) in comparison with either baseline (P = .034) or metformin monotherapy values (−2.23 ± 1.87 ng/mL, P = .008). On the other hand, the MET group, rather than the rosiglitazone group, had decreased body mass index (−0.79 ± 0.47 vs 0.56 kg/m², P = .009). The aforementioned changes in apelin and ghrelin were independently associated with HOMA-IR changes. Both rosiglitazone and metformin favorably changed glycemic indexes and apelin levels. The addition of rosiglitazone seemed to confer greater benefits in ghrelin, hs-CRP, systolic blood pressure, and HOMA-IR regulation than metformin monotherapy. Although these results reflect improvement in cardiovascular risk profile, the overall clinical importance of insulin sensitizers must be further assessed.