Antilipolytic Insulin Sensitivity Indices Measured during an Oral Glucose Challenge: Associations with Insulin-Glucose Clamp and Central Adiposity in Women without Diabetes.

Abstract

Background: Tissue overexposure to non-esterified fatty acids (NEFA) contributes to the development of metabolic conditions, with insulin-mediated suppression of lipolysis being an important mechanism in limiting this overexposure. We investigated which dynamic NEFA insulin-suppression indices derived from the oral glucose tolerance test (OGTT) were best associated with those derived from the insulin-glucose clamp, as well as with central adiposity and glucoregulatory parameters.

Methods: This cross-sectional study recruited 29 women without diabetes, 15 healthy women, and 14 women with polycystic ovary syndrome. The OGTT indices of NEFA insulin-suppression were the decremental NEFA area under the curve, negative log-linear NEFA slope, percentage of NEFA suppression (%NEFAsupp) and time to suppress NEFA levels by 50% (T50NEFA). The indices derived from the two-step euglycemic-hyperinsulinemic clamp (low-dose insulin step) were delta NEFA and %NEFAsupp.

Results: Among the OGTT and clamp indices, T50NEFA[OGTT] and %NEFAsupp[clamp] showed the closest associations in both subgroups (r=-0.58). Additionally, T50NEFA correlated significantly in all women with waist circumference (r=0.64), body fat percentage (r=0.60), fasting insulinemia (r=0.53), and M-value insulin sensitivity index (r=-0.45). Similarly, %NEFAsupp[clamp] correlated significantly in all women with waist circumference (r=-0.57), body fat percentage (r=-0.54), fasting insulinemia (r=-0.55), and M-value insulin sensitivity index (r=0.51). T50NEFA and %NEFAsupp[clamp] also correlated with other anthropometric and metabolic parameters associated with lipotoxicity.

Conclusion: For dynamic testing of NEFA insulin-suppression in women, T50NEFA was the OGTT-derived index best correlated with a clamp index (%NEFAsupp). These indices were also the most closely associated with anthropometric and glucoregulatory parameters. Thus, the OGTT-derived T50NEFA appears valid for assessing dynamic antilipolytic insulin action.