Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: Impact of obesity and ethnicity

[Guest guest]

http://www3.interscience.wiley.com/journal/123319754/abstract

Hepatology

Early View (Articles online in advance of print)

Published Online: 15 Mar 2010

American Association for the Study of Liver Diseases

Viral Hepatitis

Comparison of surrogate and direct measurement of insulin resistance in chronic

hepatitis C virus infection: Impact of obesity and ethnicity

Khoa D. Lam 1, Bacchetti 2, Fahim Abbasi 3, E. Ayala 1, M.

Loeb 1, Vidhi Shah 1, J. Wen 1, Gerald M. Reaven 3, Jacquelyn J. Maher

1, Mandana Khalili 1 *

1Department of Medicine and Biostatistics, University of California San

Francisco (UCSF), San Francisco, CA

2Department of Epidemiology and Biostatistics, University of California San

Francisco (UCSF), San Francisco, CA

3Department of Medicine, Stanford University Medical Center, Palo Alto, CA

email: Mandana Khalili (Mandana.khalili@...)

*Correspondence to Mandana Khalili, University of California San Francisco, San

Francisco General Hospital, 1001 Potrero Avenue, NH-3D, San Francisco, CA 94110

Potential conflict of interest: Nothing to report.

fax: 415-641-0745

Funded by:

National Institutes of Health (NIH); Grant Number: R01 DK074673

NIH/NCRR UCSF-CTSI; Grant Number: UL1 RR024131

UCSF Liver Center; Grant Number: P30 DK 026743

UCSF Dean's Office Medical Student Research Program

American Diabetes Foundation; Grant Number: 1-08-CR-30

Abstract

Studies using surrogate estimates show high prevalence of insulin resistance in

hepatitis C infection. This study prospectively evaluated the correlation

between surrogate and directly measured estimates of insulin resistance and the

impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic,

noncirrhotic patients with hepatitis C virus (age = 48 ± 7 years, 74% male, 44%

white, 22% African American, 26% Latino, 70% genotype 1) were categorized into

normal-weight (body mass index [bMI] < 25, n = 30), overweight (BMI = 25-29.9, n

= 38), and obese (BMI 30, n = 18). Insulin-mediated glucose uptake was measured

by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin

suppression test. Surrogate estimates included: fasting glucose and insulin,

glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin

sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under

the curve during oral glucose tolerance test, and the Belfiore and Stumvoll

indexes. All surrogate estimates correlated with SSPG, but the magnitude of

correlation varied (r = 0.30-0.64). The correlation coefficients were highest in

the obese. I-AUC had the highest correlation among all ethnic and weight groups

(r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the

normal weight group. The common HOMA-IR cutoff of 3 to define insulin resistance

had high misclassification rates especially in the overweight group independent

of ethnicity. HOMA-IR> 4 had the lowest misclassification rate (75% sensitivity,

88% specificity). Repeat HOMA-IR measurements had higher within-person variation

in the obese (standard deviation = 0.77 higher than normal-weight, 95%

confidence interval = 0.25-1.30, P = 0.005). Conclusion: Because of limitations

of surrogate estimates, caution should be used in interpreting data evaluating

insulin resistance especially in nonobese, nondiabetic patients with HCV.

HEPATOLOGY 2010

--------------------------------------------------------------------------------

Received: 11 January 2010; Accepted: 5 March 2010

Digital Object Identifier (DOI)

10.1002/hep.23670