Incorporation of the fasting plasma FFA concentration into QUICKI improves its association with insulin sensitivity in nonobese individuals

Insulin resistance plays a major role in the pathophysiology of diabetes and is associated with obesity and cardiovascular disease. Excellent methods exist for the assessment of insulin sensitivity in the laboratory setting, such as the glucose clamp. However, these methods are not suitable for large population studies, and, thus, surrogate estimates of insulin sensitivity based on measurements in a single blood sample have been developed. Recently an index based on the logarithm and the reciprocal of the insulin-glucose product (QUICKI) has been proposed. QUICKI correlated with insulin sensitivity across the entire spectrum of glucose tolerance, but its performance was less satisfactory in normal subjects. Aim of this study was to ascertain whether the inclusion of fasting plasma free fatty acids concentration into QUICKI improves its association with insulin sensitivity in nonobese subjects. To test this hypothesis, we performed a euglycemic hyperinsulinemic clamp [40 mU/(m(2).min)] in 57 young, healthy, nonobese individuals with (n = 17) or without (n = 40) first-degree relatives affected by type 2 diabetes (the former group being an in vivo model of mild insulin resistance). We then compared the clamp-based index of insulin sensitivity with both QUICKI and a revised QUICKI, the latter index including the contribution of fasting free fatty acid concentration as well. The revised QUICKI considerably improved the relationship with the clamp-based index of insulin sensitivity (r = 0.51, P < 0.0001) with respect to QUICKI (r = 0.27, P < 0.05). In addition, the revised QUICKI revealed a reduction of insulin sensitivity in the offspring of type 2 diabetes (10%; P < 0.006) that QUICKI was unable to detect (3%; P = 0.28). In conclusion, this study suggests that the incorporation of fasting free fatty acid level into QUICKI is useful to improve its correlation with the clamp-based index of insulin sensitivity and its discriminatory power in case of mild insulin resistance. Further investigation is needed to ascertain its applicability to patients with obesity and type 2 diabetes.