Obesity is a state of chronic low-grade inflammation which may lead to impaired insulin signaling and type 2 diabetes. Whether a structured lifestyle intervention combined with metformin therapy ameliorates raised levels of inflammatory markers in obese children with insulin resistance and/or prediabetes is unknown. 

111 free-living obese children with insulin resistance and/or prediabetes (45 boys; mean age= 13.1±1.9y; mean BMI z score= 2.4±0.3) participated in a 12 month randomised control trial of metformin therapy with two structured lifestyle interventions, differing in dietary macronutrient content (high- carbohydrate or moderate- carbohydrate, increased protein). Inflammatory markers chemokine ligand 2 (CCL2), high-sensitivity c-reactive protein (hsCRP) and interleukin 6 (IL6) were measured at baseline, 3, 6 and 12 months. Mixed modeling analyses were performed and data are presented as estimated marginal means (95% CI).

At 12 months, BMI expressed as a percent of the 95th centile, percent body fat, and body weight decreased by 6.8, 2.4 and 4.9% respectively and insulin sensitivity index increased by 0.23; there were no differences between diet groups. There were no significant effects of diet group on inflammatory markers after the 12 month intervention, thus results have been pooled. CCL2, a chemokine secreted predominantly from macrophages [Baseline= 179.5 (162.9-197.7); Month 3= 171.4 (154.2-190.5); Month 6= 175.4 (158.1-195.0); Month 12= 146.2 (129.1-165.2)pg/ml; p=0.004], and hsCRP, a classical marker of inflammation and predictor of cardiovascular risk [Baseline= 2.4 (2.0-3.0); Month 3= 2.1 (1.7-2.6); Month 6= 2.0 (1.6-2.6); Month 12= 2.0 (1.6-2.6)mg/L; p=0.01] were both significantly lower after 12 months. There were no significant effects of time on IL-6.

In conclusion, our study showed that a 12 month lifestyle intervention with metformin therapy resulting in modest weight loss improved markers of inflammation in obese children with prediabetes.