Lower Insulin Clearance parallels a reduced insulin sensitivity in obese youths and is associated with a decline in β-cell function over time

We examined the relationship between insulin clearance, insulin sensitivity and β-cell function and the longitudinal effect of insulin clearance on β-cell function in lean, obese insulin sensitive and insulin resistant adolescents.A hyperinsulinemic-euglycemic and a hyperglycemic clamp were performed in 110 youths to quantify hepatic and peripheral clearance, insulin sensitivity and β-cell function (disposition index, DIh-clamp). Participants underwent an OGTT at baseline and after 2 years to assess glucose tolerance and oral β-cell function (oDIcpep) and were sorted into four groups (lean, obese NGT insulin sensitive and resistant, obese IGT). Insulin sensitivity was defined based on the median of insulin stimulated glucose disposal (M) measured during the hyperinsulinemic- euglyemic clamp.Lean and obese insulin sensitive participants did not differ with respect to hepatic and peripheral clearance, nor for insulin sensitivity. Insulin sensitivity was linearly correlated with whole body insulin clearance. Hepatic insulin extraction at baseline acted as independent determinant of β-cell function at follow-up.The decline in insulin sensitivity, even in the absence of an impairment of glucose tolerance, is associated with lowering of hepatic insulin clearance in obese youth, that in turn may contribute to the decline in β-Cell function over time.