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Metabolism. 2009 Mar;58(3):304-10. doi: 10.1016/j.metabol.2008.09.029.

Repeatability and reproducibility of the hyperinsulinemic-euglycemic clamp and the tracer dilution technique in a controlled inpatient setting.

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Obesity and Diabetes Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ 85016, USA.


The objective of the study was to evaluate the reproducibility and repeatability of the combined use of the hyperinsulinemic-euglycemic (H-E) clamp and tracer dilution techniques. Ten nondiabetic men underwent a low-dose (40 mU/[m(2) min]) H-E clamp that was repeated within 3 to 4 days using porcine or human insulin in a double-blinded, randomized, crossover design. Coefficients of variation (CVs) for intraindividual differences and repeatability coefficient were calculated to evaluate reproducibility and repeatability. The Bland and Altman method was used to quantify repeatability. The CVs for intraindividual differences were 5.7% +/- 3.5% for steady-state (SS) insulin; 6.7% +/- 6.2% and 54.2 +/- 38.3% for basal and SS endogenous glucose product (EGP), respectively; and 10.3% +/- 8.5% for total insulin-stimulated glucose disposal (M) values. Basal EGP, SS EGP, and SS glucose and insulin concentrations were similar for the 2 clamps; but glucose infusion rate (P = .02) and M (borderline significant, P = .06) were higher in the first clamp than the second clamp. No significant correlations between mean of differences and average of basal and SS EGP, SS insulin concentration, and M between the 2 clamps were observed. We also found that the different values were less than the repeatability coefficients of these parameters and that the 95% limits of agreement and the interval of repeatability coefficient of these parameters were similar. There were no differences in metabolic responses between clamps when compared by the type of insulin (porcine vs human) infused. Our findings indicate that, although SS EGP has a high CV, the clamp, which measures insulin action (ie, SS insulin, M), and the tracer dilution technique for assessing basal EGP are repeatable and reproducible. Decreased glucose infusion rate and M over a short period in the second clamp may reflect an accumulative effect of continued physical inactivity.

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