QUICKI Is a Useful and Accurate Index of Insulin Sensitivity

A recent article by Duncan, Hutson, and Stacpoole (1) examined the ability of QUICKI, an index of insulin sensitivity based upon fasting glucose and insulin levels (2), to accurately reflect changes in insulin sensitivity associated with exercise training. In their study, the authors performed an unmodified frequently sampled iv glucose tolerance test (FSIVGTT) with a reduced sampling schedule (14 blood samples) in 15 nondiabetic sedentary adults before and after 6 months of exercise training. QUICKI was compared with SIMM, an index of insulin sensitivity derived from minimal model analysis of the FSIVGTT (3). Although QUICKI and SIMM were significantly correlated both before and after exercise training, changes in QUICKI after training were not significantly correlated with changes in SIMM. SIMM increased in 12 subjects and decreased in 3 subjects after exercise training, whereas QUICKI increased in 9 subjects and decreased in 6. Based upon this data, the authors concluded that QUICKI does not accurately reflect changes in insulin sensitivity associated with exercise training. While the data presented may be sound, the conclusions are not. The main problem with the interpretation of the data comes from not having a reference standard for insulin sensitivity to compare with QUICKI and SIMM. When compared with a direct measure of insulin sensitivity such as that derived from the glucose clamp, the correlation of QUICKI with SIClamp is significantly stronger than the correlation between SIMM and SIClamp (2). Thus, discordance between changes in QUICKI and changes in SIMM most likely reflects problems associated with the minimal model approach rather than inaccuracies manifested by QUICKI. Indeed, the implementation by Duncan et al. (1) of an unmodified FSIVGTT and a reduced sampling schedule is quite suboptimal for minimal model analysis. It is well established that the SIMM derived from the unmodified FSIVGTT does not correlate well with glucose clamp measurements of insulin sensitivity (4). Although modifications to the standard FSIVGTT that add either tolbutamide or insulin infusion significantly improve the correlation between minimal model and glucose clamp estimates of insulin sensitivity (5–9), systematic errors in minimal model estimates of glucose effectiveness and insulin sensitivity still remain even when modified FSIVGTTs are employed (10–12). Moreover, using a reduced sampling schedule of 14 blood samples instead of the usual 30 samples for the FSIVGTT is likely to introduce additional error (13, 14). Because Duncan et al. (1) do not include a reference standard for measuring insulin sensitivity, it is difficult to ascertain from their data whether or not QUICKI is a useful index for following changes in insulin sensitivity after exercise training. However, in patients with polycystic ovary syndrome (15) or in obese adolescents (16), QUICKI is able to discern significant improvements in insulin sensitivity after therapy with insulin sensitizers. Of note, close inspection of the data from obese adolescents also reveals discordance between changes in QUICKI and changes in SIMM in that study (16). Finally, a number of independent groups have found excellent correlations between QUICKI and reference glucose clamp measurements in normal, obese, and diabetic populations (15, 17, 18) as well as in pregnant women and women with gestational diabetes (19). QUICKI is also a useful index of insulin sensitivity in subjects with hyperandrogenism (20), young girls with premature adrenarche (21), and patients with nonalcoholic steatohepatitis (22). In summary, from the fact that changes in QUICKI after exercise training do not correlate with changes in SIMM derived from suboptimal FSIVGTT data, it is incorrect to conclude that QUICKI does not accurately reflect changes in insulin sensitivity with exercise. Judging by the utility of QUICKI as an accurate index of insulin sensitivity in a variety of other contexts, it seems plausible that QUICKI may also be useful for assessing changes in insulin sensitivity due to exercise. However, QUICKI must be compared with the reference glucose clamp before and after exercise to make a definitive conclusion.