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.

BACKGROUND: 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, IL-1β and IFN-γ were significantly decreased with exenatide treatment ( < 0.001 and  = 0.001, respectively), but increased with insulin ( = 0.009 and  = 0.026, respectively). However, pioglitazone treatment had no impact on ADICs. No significant change in leptin or FGF21 was detected with any of the treatments. After adjustment for baseline values and changes of body weight, waist and HbA1c, the between-group differences were found in ΔIL-1β (exenatide vs. insulin:  = 0.048; and exenatide vs. pioglitazone:  = 0.003, respectively) and ΔIFN-γ (exenatide vs. insulin:  = 0.049; and exenatide vs. pioglitazone:  < 0.001, respectively). Multiple linear regression analysis indicated that Δweight was associated with ΔIL-1β ( = 0.753; 95 % CI, 0.137-1.369;  = 0.017). After adjusting for treatment effects, Δweight was also be correlated with ΔFGF21 ( = 1.097; 95%CI, 0.250-1.944;  = 0.012); furthermore, ΔHOMA-IR was correlated with Δleptin ( = 0.078; 95%CI, 0.008-0.147;  = 0.029) as well. However, ΔHOMA-IR was not significantly associated with ΔIL-1β after adjusting for treatment effects ( = 0.513). 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.