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 (Delta ADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, beta-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 beta-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), 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-1 beta and IFN-gamma 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 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 Delta IL-1 beta (exenatide vs. insulin: P = 0.048; and exenatide vs. pioglitazone: P = 0.003, respectively) and Delta IFN-gamma (exenatide vs. insulin: P = 0.049; and exenatide vs. pioglitazone: P < 0.001, respectively). Multiple linear regression analysis indicated that Delta weight was associated with Delta IL-1 beta (beta = 0.753; 95 % CI, 0.137-1.369; P = 0.017). After adjusting for treatment effects, Delta weight was also be correlated with Delta FGF21 (beta = 1.097; 95%CI, 0.250-1.944; P = 0.012); furthermore, Delta HOMA-IR was correlated with Delta leptin (beta = 0.078; 95%CI, 0.008-0.147; P = 0.029) as well. However, Delta HOMA-IR was not significantly associated with Delta IL-1 beta after adjusting for treatment effects (P = 0.513).Conclusion: Exenatide treatment led to significant changes of inflammatory cytokines levels (IL-1 beta and IFN-gamma), 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.