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Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes

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Abstract

Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m2) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = −68 %, insulin Δ = −58 %, pioglitazone Δ = −49 %). Exenatide reduced VF (Δ = −36 %) and SF (Δ = −13 %), and pioglitazone decreased VF (Δ = −30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.

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Acknowledgments

The authors would like to thank all the participating patients. This study was sponsored by Grants from National Natural Science Foundation of China Grant Award (81270906, 81070636), 973 project (2012CB517506), the China postdoctoral Science Foundation (2012M521050), Jiangsu postdoctoral Science Foundation, Jiangsu Province’s Key Provincial Talents Program (RC2011011), the Key Project of Nanjing Medical Science and Technology Development Foundation (ZKX11017, YKK11092), the Project of National Key Clinical Division, Jiangsu Province’s Key Discipline of Medicine (XK201105), National Science Fund for Distinguished Young Scholars (81025005), and New Drug Development, Construction and management of Clinical Biobank for Major Disease (2011ZX0907-001-08).

Conflict of interest

Yan Bi, Bing Zhang, Wen Xu, Huijie Yang, Wenhuan Feng, Cuiliu Li, Guoyu Tong, Ming Li, Xin Wang, Shanmei Shen, Bin Zhu, Jianping Weng, and Dalong Zhu declare that they have no conflict of interest.

Human and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China

    Yan Bi, Huijie Yang, Wenhuan Feng, Cuiliu Li, Guoyu Tong, Shanmei Shen & Dalong Zhu

  2. Department of Radiology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China

    Bing Zhang, Ming Li, Xin Wang & Bin Zhu

  3. Department of Endocrinology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Wen Xu & Jianping Weng

  4. Key Lab of Diabetology of Guangdong Province, Guangzhou, China

    Jianping Weng

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  1. Yan Bi
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Correspondence to Bin Zhu, Jianping Weng or Dalong Zhu.

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Yan Bi and Bing Zhang contributed equally to the paper.

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Bi, Y., Zhang, B., Xu, W. et al. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes. Acta Diabetol 51, 865–873 (2014). https://doi.org/10.1007/s00592-014-0638-3

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