Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: a post-hoc study of the CONFIDENCE trial

Abstract

Abstract Purpose Adipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, β-cell function and insulin resistance (IR). Methods Four hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of β-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. Results In total, 281 participants (68% male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, LgIL-1β and LgIFN-γ were significantly decreased with exenatide treatment (P < 0.001 and P = 0.001, respectively), but increased with insulin (P = 0.009 and P = 0.026, respectively). However, pioglitazone treatment had no impact on ADICs. No significant change in Lgleptin or LgFGF21 was detected with any of the treatments. After adjustment for baseline values and changes of body weight and HbA1c, significant differences were seen between the exenatide group and the insulin group and between the exenatide group and the pioglitazone group for both ΔLgIL-1β (P = 0.033 and P < 0.001, respectively) and ΔLgIFN-γ (P = 0.040 and P < 0.001, respectively). Multiple linear regression analysis indicated that Δweight was associated with ΔLgIL-1β (β = 0.753; 95% CI, 0.137–1.369; P = 0.017). After adjusting for treatment effects, Δweight was also found to be correlated with ΔLgFGF21 (β = 1.097; 95%CI, 0.250–1.944; P = 0.012). Furthermore, ΔLgHOMA-IR was associated with ΔLgleptin, both before (β = 0.085; 95%CI, 0.008–0.162; P = 0.030) and after (β = 0.078; 95%CI, 0.008–0.147; P = 0.029) adjusting for treatment effects. ΔLgHOMA-IR was significantly associated with ΔLgIL-1β before (β = 0.067; 95%CI, 0.006–0.127; P = 0.030), but not after (P = 0.513), adjusting for treatment effects. Conclusion Exenatide treatment led to significant changes of inflammatory cytokines levels (IL-1β and IFN-γ), but not adipokines (leptin and FGF21), in newly diagnosed T2DM patients. The exenatide-mediated improvement in weight and IR may be associated with a decrease in inflammatory cytokine levels.