Indices of Insulin Suppression of Non-Esterified Fatty Acids Measured During an Oral Glucose Challenge and Their Association with the Insulin-Glucose Clamp Index and Central Adiposity

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To determine the indices of insulin-induced NEFA suppressibility derived from the oral glucose tolerance test (OGTT) that are best associated with the standard measure derived from the insulin-glucose clamp and with central adiposity. Sixteen men and 10 women, aged 20 to 35 years, without any disease or family history of type 2 diabetes, underwent a 75 g OGTT and a 2-step euglycemic clamp with low- and high-dose insulin infusions (10 and 40 mU/kg/min). OGTT indices of NEFA suppressibility were: area under the curve (AUC) of NEFA, AUCNEFA×AUCinsulin, NEFA T50, insulin concentration at T50 (EC50) and negative slope of the log-linear portion of NEFA suppression curve corrected by AUCinsulin (NegSlopeLnNEFA/AUCIns). NEFA insulin suppression during the clamp was calculated by ΔNEFA/Δinsulin at low-dose insulin (from baseline=positive results). Central adiposity was estimated mainly by the waist-to-hip ratio (WHR) and glucose insulin sensitivity, by the M/I value (clamp, high-dose insulin). OGTT-derived indices of insulin-induced NEFA suppression significantly associated with clamp ΔNEFA/Δinsulin: AUCNEFA×AUCinsulin (r=0.54), EC50 (r=0.50), NegSlopeLnNEFA/AUCIns (r=–0.44) and %reductionNEFA/AUCinsulin (r=–0.42). The only index significantly associated with WHR: AUCNEFA×AUCinsulin (r=0.55). Based on a step-wise regression analysis, the variables significantly and independently associated with WHR were: AUCNEFA×AUCinsulin (p=0.002) and AUCglucose (p=0.01) (model R2=0.49). AUCNEFA×AUCinsulin may represent the best OGTT-derived parameter to estimate sensitivity to insulin suppression of lipolysis because, in our sample, it was the only one significantly correlated with central adiposity. Moreover, among all metabolic parameters measured in our study, AUCNEFA×AUCinsulin and AUCglucose were the two main factors independently associated with central adiposity.