Methods for quantifying insulin resistance in human immunodeficiency virus-positive patients

Various indirect indices have been used in human immunodeficiency virus (HIV)-infected individuals to assess insulin resistance, but the validity of these measures has not been rigorously assessed by comparison with physiologic methods of quantifying insulin-mediated glucose uptake (IMGU). We directly measured IMGU in 50 nondiabetic HIV-positive subjects by determining the steady-state plasma glucose (SSPG) concentration in response to a 3-hour continuous infusion of insulin, glucose, and somatostatin. Because steady-state plasma insulin concentrations were similar (approximately 60 microU/mL) in all subjects, the SSPG concentrations provided direct assessments of insulin action. Relationships between SSPG levels and various surrogate measures of IMGU derived from the 75-g oral glucose tolerance test (OGTT) were determined. The indirect measure of IMGU most closely related to SSPG concentrations was the total integrated insulin response to a 75-g glucose load (r=0.78, P<.01), accounting for approximately two thirds of the variability in SSPG (r2=0.61). Other indirect measures of IMGU, including the homeostasis assessment for insulin resistance (HOMA-IR), were also significantly related to SSPG values, but had lower magnitudes of correlation (r=0.43 to 0.61), thereby possessing limited ability to predict SSPG variability (r2=0.18 to 0.37). In conclusion, indirect measures of IMGU need to be applied with caution when evaluating insulin action in HIV-infected patients.