Adipose insulin resistance in obese adolescents across the spectrum of glucose tolerance

CONTEXT: Adipocytes represent an important insulin-responsive tissue taking an active part in glucose metabolism. OBJECTIVE: This study sought to assess adipose tissue insulin resistance (IR) across the spectrum of glucose tolerance and to test its relation with free fatty acid (FFA) suppression during an oral glucose tolerance test (OGTT). DESIGN AND SETTING: A cross-sectional analysis of a pediatric clinic-derived cohort of obese adolescents. PATIENTS OR OTHER PARTICIPANTS: Participants age 7-20 y with a body mass index that exceeded the 95th percentile for their age and sex. INTERVENTION(S): A standard oral glucose tolerance test. MAIN OUTCOME MEASURES: The adipose tissue insulin resistance index (calculated as the product of fasting insulin and FFA concentrations) (Adipose IR) and the area under curve of FFAs during the OGTT were compared between glucose tolerance categories. RESULTS: A total of 962 obese children and adolescents participated in this study. Adipose IR significantly increased across glucose tolerance categories (P for trend < .001). Within the normal glucose tolerance participants, an increase in adipose IR was observed related to an increase in 2-hr glucose levels. In a subsample of participants who underwent abdominal imaging for determination of lipid partitioning (n = 115), a tight relation of visceral fat (r = 0.34; P < .001) and the visceral/sc fat ratio (r = 0.55; P < .001) with the Adipose IR index was evident. Greater area under the curve FFAs (lower FFA suppression) during the OGTT was evident with worsening glucose tolerance (P for trend < .001). Glucose tolerance category, degree of obesity (body mass index-z score), IL-6, and low adiponectin emerged as significant predictors of the Adipose IR. CONCLUSIONS: Adipose IR is associated with reduced suppression of FFAs during the OGTT and with an altered adipocytokine profile. The negative relation with insulin secretion deserves further longitudinal investigation in the context of deteriorating glucose tolerance.