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

Khoa D Lam, Peter Bacchetti, Fahim Abbasi, Claudia E Ayala, Samuel M Loeb, Vidhi Shah, Michael J Wen, Gerald M Reaven, Jacquelyn J Maher, Mandana Khalili, Khoa D Lam, Peter Bacchetti, Fahim Abbasi, Claudia E Ayala, Samuel M Loeb, Vidhi Shah, Michael J Wen, Gerald M Reaven, Jacquelyn J Maher, Mandana Khalili

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 > or = 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 < or =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.

Conflict of interest statement

Potential conflict of interest: Nothing to report.

Figures

Fig. 1
Fig. 1
Relationship between SSPG and (A) HOMA-IR and (B) I-AUC by BMI category.
Fig. 2
Fig. 2
Relationship between SSPG and (A) HOMA-IR and (B) I-AUC by ethnicity.
Fig. 3
Fig. 3
Receiver operator characteristic (ROC) curve and sensitivity, specificity, and misclassification rate of HOMA-IR in identifying subjects with insulin resistance. ROC curve for HOMA-IR performance is shown, where SSPG > 10 mmol/L is used to define insulin resistance. The area under the curve is 0.845. The table at the bottom of this figure outlines the sensitivity, specificity, and the misclassification rates of HOMA-IR. The HOMA-IR > 4 has the lowest misclassification rate.

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