Altered adipokines in obese adolescents: A cross-sectional and longitudinal analysis across the spectrum of glycemia

Obesity and type 2 diabetes is rapidly increasing in the adolescent population. We sought to determine whether adipokines, specifically leptin, C1q/TNF-related proteins 1 (CTRP1) and CTRP9, and the hepatokine fibroblast growth factor 21 (FGF-21), are associated with obesity and insulin resistance in a cohort of lean and obese adolescents, across the spectrum of glycemia. In an observational, longitudinal study of lean and obese adolescents, we measured fasting labs, oral glucose tolerance tests, and adipokines including: Leptin, CTRP1, CTRP9, and FGF-21. Participants completed baseline and 2-year follow-up study visits, and were categorized as lean (n=30), obese normoglycemic (ONG) (n=61), and obese hyperglycemic (OHG) (n=31) adolescents at baseline, and lean (n=8), ONG (n=18), and OHG (n=4) at follow-up. Results showed that at baseline, leptin was higher in all obese groups (p<0.001) compared to LC. FGF-21 was higher in OHG participants compared to LC (p<0.001) and ONG (p<0.001), and positively associated with fasting glucose (p<0.001), fasting insulin (p<0.001), HOMA-IR (p<0.001), and HbA1c (p=0.01). CTRP1 was higher in OHG compared to ONG (p=0.03). CTRP9 was not associated with obesity or hyperglycemia in this pediatric cohort. At 2 years, leptin decreased in ONG (p=0.003) and FGF21 increased in OHG (p=0.02), relative to lean controls. Altered adipokine levels are associated with the inflammatory milieu in obese youth with and without hyperglycemia. In adolescence, the novel adipokine CTRP1 was elevated with hyperglycemia, while CTRP9 was unchanged in this cohort.