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Original Research

Triglyceride/High-Density Lipoprotein Cholesterol Ratio: A Surrogate to Predict Insulin Resistance and Low-Density Lipoprotein Cholesterol Particle Size in Nondiabetic Patients With Schizophrenia

Xiaoduo Fan, MD, MS; Emily Y. Liu, MD; Vicki Poole Hoffman, PharmD; Alison J. Potts, PhD; Bikash Sharma, MD; and David C. Henderson, MD

Published: November 2, 2010

Article Abstract

Objective: Insulin resistance, changes in lipid parameters, and cardiometabolic adverse events have been reported in some patients during clinical trials of antipsychotic agents. The present study examined whether the triglyceride/high-density lipoprotein (HDL) ratio can be used as a better surrogate than other conventional lipid measures (low-density lipoprotein [LDL], HDL, triglyceride) in predicting insulin resistance and LDL particle size in nondiabetic patients with schizophrenia.

Method: Outpatients 18 to 75 years old diagnosed with schizophrenia or schizoaffective disorder (DSM-IV criteria) and receiving olanzapine, risperidone, or typical antipsychotics participated in a multicenter, cross-sectional study. Fasting blood samples were obtained to determine the levels of glucose, insulin, lipids, and lipid particle size. The study was conducted from July 2001 to March 2002.

Results: In the sample of 206 patients, significant correlations were found between various lipid measures (LDL, HDL, triglyceride, and triglyceride/HDL ratio) and the homeostasis model of assessment of insulin resistance (P < .05). However, stepwise multiple regression analysis suggested that the triglyceride/HDL ratio is a stronger predictor of insulin resistance and of LDL particle size than other conventional lipoprotein measures after other potential confounding variables, including age, gender, race, family history of diabetes, body mass index, and antipsychotic agent, were taken into consideration (P < .001). Further, logistic regression analysis indicated that the triglyceride/HDL ratio and male gender predict the existence of a small LDL particle size pattern (pattern B LDL phenotype), with a sensitivity of 75.9% and a specificity of 85.4%.

Conclusions: The triglyceride/HDL ratio, a simple, readily available and inexpensive measure, can be a useful surrogate to identify those with insulin resistance as well as those with more atherogenic small LDL particles in nondiabetic patients with schizophrenia.

J Clin Psychiatry

Submitted: February 2, 2009; accepted November 19, 2009.

Online ahead of print: November 2, 2010 (doi:10.4088/JCP.09m05107yel).

Corresponding author: Xiaoduo Fan, MD, MS, Freedom Trail Clinic, 25 Staniford St, Boston, MA 02114 (

Volume: 71

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