Role of plasma testosterone on the association between obesity, inflammation, and insulin resistance in Indonesian male adolescents

Objective This cross-sectional study aimed to investigate the role of plasma testosterone in the association between obesity, inflammation, and insulin resistance in male adolescents. Methods A total of 192 boys aged 15–18 years (112 obese and 80 non-obese) from a previously established school-based cohort were included. Anthropometric measurements, blood cell counts and fasting plasma insulin data were obtained from the existing database, whereas plasma hs-CRP and testosterone concentrations were measured specifically for the present study. Insulin resistance was calculated using Homeostatic model assessment of insulin resistance (HOMA-IR). Statistical analyses included group comparisons and regression analysis. Path analysis and exploratory mediation analyses were performed to assess the direct and indirect relationships between obesity, inflammation, testosterone, and insulin resistance. Results The plasma testosterone level was 50% lower in obese boys (mean 2.96 ng/mL; 95% confidence interval (CI) 2.5; 3.4) compared to non-obese boys (mean 6.04 ng/mL; 95% CI 5.3;6.8; p < 0.001). Testosterone deficiency was found in 55% of obese boys compared to 15% of non-obese boys (odds ratio 6.54; p < 0.001). Obese male adolescents had a 20 times increased chance of insulin resistance. The association between WtHR and fasting plasma insulin was the strongest found between obesity and insulin resistance indices. Plasma testosterone had a lower direct impact on insulin resistance, whereas exploratory mediation analyses identified C-reactive protein and white blood cell count, but not insulin resistance or monocyte count, as significant indirect mediators of the association between WtHR and plasma testosterone. Its association with fasting plasma insulin was not strengthened within pathways involving inflammation indices. Conclusions Plasma testosterone deficiency is prevalent in obese male adolescents. Plasma testosterone, C-reactive protein, and white blood cell count appear to mediate the relationship between central obesity and insulin resistance through distinct pathways.