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

Insulin resistance plays a major role in the pathophysiology of diabetes an d 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 larg e population studies, and, thus, surrogate estimates of insulin sensitivity based on measurements in a single blood sample have been developed. Recent ly an index based on the logarithm and the reciprocal of the insulin-glucos e product (QUICKI) has been proposed. QUICKI correlated with insulin sensit ivity across the entire spectrum of glucose tolerance, but its performance was less satisfactory in normal subjects. Aim of this study was to ascertai n whether the inclusion of fasting plasma free fatty acids concentration in to QUICKI improves its association with insulin sensitivity in nonobese sub jects. 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 diabet es (the former group being an in vivo model of mild insulin resistance). We then compared the clamp-based index of insulin sensitivity with both QUICK I and a revised QUICKI, the latter index including the contribution of fast ing 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 add ition, the revised QUICKI revealed a reduction of insulin sensitivity in th e offspring of type 2 diabetes (10%; P < 0.006) that QUICKI was unable to d etect (3%; P = 0.28). In conclusion, this study suggests that the incorpora tion of fasting free fatty acid level into QUICKI is useful to improve its correlation with the clamp-based index of insulin sensitivity and its discr iminatory power in case of mild insulin resistance. Further investigation i s needed to ascertain its applicability to patients with obesity and type 2 diabetes.