OBJECTIVE: Compared with Caucasians, obese African-American adolescents have a higher risk for type 2 diabetes. Subclinical inflammation and reduced glucagon-like peptide 1 (GLP-1) concentration are linked to the pathogenesis of the disease. We determined the relationship between insulin resistance, beta-cell activity, and subclinical inflammation with GLP-1 concentrations and whether racial disparities in GLP-1 response were present in 49 obese adolescents (14 +/- 3 years; 76% African American; 71% female). RESEARCH DESIGN AND METHODS: Subjects underwent physical examination and an oral glucose tolerance test. We measured levels of high-sensitivity CRP (CRP(hs)), fibrinogen, glucose, GLP-1(total), GLP-1(active), and insulin. Insulin and glucose area under the curve (AUC), insulinogenic index (DeltaI30/DeltaG30), and composite insulin sensitivity index (CISI) were computed. Subjects were categorized by race and as inflammation positive (INF+) if CRP(hs) or fibrinogen were elevated. RESULTS: No racial differences were seen in mean or relative BMI. Thirty-five percent of subjects had altered fasting or 2-h glucose levels (African American vs. Caucasian, NS), and 75% were INF+ (African American vs. Caucasian, P = 0.046). Glucose and insulin, CISI, and DeltaI30/DeltaG30 values were similar; African Americans had lower GLP-1(total) AUC (P = 0.01), GLP-1(active) at 15 min (P = 0.03), and GLP-1(active) AUC (P = 0.06) and higher fibrinogen (P = 0.01) and CRP(hs) (NS) compared with Caucasians. CONCLUSIONS: African Americans exhibited lower GLP-1 concentrations and increased inflammatory response. Both mechanisms may act synergistically to enhance the predisposition of obese African Americans to type 2 diabetes. Our findings might be relevant to effective deployment of emerging GLP-1-based treatments across ethnicities.