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Original Research

Effect of Ezetimibe on Hepatic Fat, Inflammatory Markers, and Apolipoprotein B-100 Kinetics in Insulin-Resistant Obese Subjects on a Weight Loss Diet

  1. Dick C. Chan, PHD,
  2. Gerald F. Watts, MD, DSC,
  3. Seng Khee Gan, MD, PHD,
  4. Esther M.M. Ooi, PHD and
  5. P. Hugh R. Barrett, PHD
  1. From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
  1. Corresponding author: Gerald F. Watts, gerald.watts{at}uwa.edu.au.
Diabetes Care 2010 May; 33(5): 1134-1139. https://doi.org/10.2337/dc09-1765
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    Figure 1

    Effects of weight loss and ezetimibe plus weight loss on intrahepatic triglyceride content in obese subjects. There was no significant group difference in preintervention intrahepatic triglyceride content (P > 0.05). *P < 0.05, value significantly different from baseline value. **Value significantly different using general linear modeling after adjustment for weight loss group.

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  • Table 1

    Clinical and biochemical characteristics before and after intervention in the weight loss and ezetimibe plus weight loss groups

    Weight lossEzetimibe plus weight loss
    022 weeks022 weeks
    n1015
    Body weight (kg)100 ± 694 ± 5*94 ± 387 ± 3*
    BMI (kg/m2)33 ± 131 ± 1*32 ± 131 ± 1*
    Waist (cm)107 ± 498 ± 4*106 ± 296 ± 2*
    Total fat mass (kg)39 ± 435 ± 4*37 ± 332 ± 3*
    Fat-free mass (kg)60 ± 359 ± 356 ± 355 ± 3
    Visceral fat at L3 vertebra (cm2)278 ± 38228 ± 36†257 ± 25213 ± 22*
    Subcutaneous fat at L3 vertebra (cm2)358 ± 43316 ± 36†278 ± 30257 ± 28†
    Intrahepatic triglyceride content (%)22 ± 516 ± 4*18 ± 310 ± 2*‡
    Alanine aminotransferase (U/l)32 ± 526 ± 429 ± 230 ± 3
    Cholesterol (mmol/l)5.8 ± 0.25.5 ± 0.25.8 ± 0.34.9 ± 0.3*‡
    Triglyceride (mmol/l)1.7 ± 0.31.3 ± 0.2†2.0 ± 0.21.5 ± 0.1*
    Nonesterified fatty acids (mEq/l)0.62 ± 0.070.56 ± 0.060.74 ± 0.110.75 ± 0.10
    HDL cholesterol (mmol/l)1.3 ± 0.21.3 ± 0.11.1 ± 0.11.1 ± 0.1
    LDL cholesterol (mmol/l)3.7 ± 0.23.7 ± 0.23.8 ± 0.33.1 ± 0.2*‡
    Lathosterol (μmol/l)12 ± 110 ± 2*12 ± 115 ± 2†
    Campesterol (μmol/l)5.4 ± 0.94.9 ± 0.79.1 ± 1.53.2 ± 0.5*
    ApoA-I (g/l)1.5 ± 0.11.5 ± 0.11.4 ± 0.11.4 ± 0.1
    ApoB-100 (g/l)1.2 ± 0.11.1 ± 0.11.2 ± 0.10.9 ± 0.1*‡
    ApoC-III (mg/l)176 ± 15153 ± 16*186 ± 12160 ± 13*
    Glucose (mmol/l)5.5 ± 0.25.7 ± 0.25.5 ± 0.25.6 ± 0.1
    Insulin (mU/l)12 ± 210 ± 2†12 ± 19 ± 1†
    HOMA score3.1 ± 0.52.6 ± 0.4†2.9 ± 0.32.2 ± 0.3†
    • Data are means ± SEM. There was no significant group difference in the variables at baseline.

    • ↵*P < 0.01, value significantly different from baseline value.

    • ↵†P < 0.05.

    • ↵‡P< 0.05, value significantly different using general linear modeling after adjustment for relative changes in the weight loss group.

  • Table 2

    Plasma hs-CRP, adipocytokine, and fetuin-A concentrations before and after intervention in the weight loss and ezetimibe plus weight loss groups

    Weight lossEzetimibe plus weight loss
    022 weeks022 weeks
    n1015
    hs-CRP (mg/l)2.2 ± 0.42.4 ± 0.53.9 ± 1.02.2 ± 0.7*†
    Interleukin-6 (ng/l)0.87 ± 0.080.91 ± 0.141.1 ± 0.10.91 ± 0.14*†
    Tumor necrosis factor-α (ng/l)5.4 ± 0.55.4 ± 0.66.3 ± 0.55.4 ± 0.6*
    Retinol-binding protein-4 (mg/l)27 ± 1624 ± 8‡27 ± 1725 ± 20‡
    Adiponectin (mg/l)5.9 ± 0.76.8 ± 0.8‡4.9 ± 0.76.1 ± 0.9*
    Fetuin-A (mg/l)303 ± 31189 ± 15*284 ± 24221 ± 18‡
    • Data are means ± SEM.

    • ↵*P <0.01, value significantly different from baseline value.

    • ↵†P < 0.05.

    • ↵‡P< 0.05, value significantly different using general linear modeling after adjustment for relative changes in the weight loss group.

  • Table 3

    Kinetic indices for apoB-100 before and after intervention in the weight loss and ezetimibe plus weight loss groups

    Weight lossEzetimibe plus weight loss
    022 weeks022 weeks
    n1015
    VLDL–apoB-100
        Concentration (mg/l)142 ± 123123 ± 19†134 ± 12109 ± 11†
        Fractional catabolic rate (pools/day)4.8 ± 1.13.8 ± 0.43.9 ± 0.44.2 ± 0.3
        Production rate (mg/kg FFM/day)41 ± 529 ± 7†38 ± 332 ± 4†
    IDL–apoB-100
        Concentration (mg/l)76 ± 1074 ± 1282 ± 965 ± 9§
        Fractional catabolic rate (pools/day)3.9 ± 0.73.6 ± 0.33.5 ± 0.44.5 ± 0.5§
        Production rate (mg/kg FFM/day)20 ± 318 ± 220 ± 218 ± 2
    LDL–apoB-100
        Concentration (mg/l)957 ± 61885 ± 36952 ± 76774 ± 62*‡
        Fractional catabolic rate (pools/day)0.35 ± 0.030.34 ± 0.030.31 ± 0.020.39 ± 0.03*‡
        Production rate (mg/kg FFM/day)26 ± 322 ± 222 ± 121 ± 2
    • Data are means ± SEM.

    • ↵*P <0.01, value significantly different from baseline value.

    • ↵†P < 0.05.

    • ↵‡P< 0.05, value significantly different using general linear modeling after adjustment for relative changes in the weight loss group.

    • ↵§P = 0.06, value different from baseline value.

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Diabetes Care: 33 (5)

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Effect of Ezetimibe on Hepatic Fat, Inflammatory Markers, and Apolipoprotein B-100 Kinetics in Insulin-Resistant Obese Subjects on a Weight Loss Diet
Dick C. Chan, Gerald F. Watts, Seng Khee Gan, Esther M.M. Ooi, P. Hugh R. Barrett
Diabetes Care May 2010, 33 (5) 1134-1139; DOI: 10.2337/dc09-1765

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Effect of Ezetimibe on Hepatic Fat, Inflammatory Markers, and Apolipoprotein B-100 Kinetics in Insulin-Resistant Obese Subjects on a Weight Loss Diet
Dick C. Chan, Gerald F. Watts, Seng Khee Gan, Esther M.M. Ooi, P. Hugh R. Barrett
Diabetes Care May 2010, 33 (5) 1134-1139; DOI: 10.2337/dc09-1765
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