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Association of non-alcoholic fatty liver disease with microvascular complications of type 2 diabetes

  • Mohsen Afarideh
    Affiliations
    Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Department of Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
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  • Zahra Aryan
    Affiliations
    Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Student’s Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
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  • Alireza Ghajar
    Affiliations
    Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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  • Morsaleh Ganji
    Affiliations
    Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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  • Fatemeh Ghaemi
    Affiliations
    Department of Transplantation and Specific Diseases, Ministry of Health and Medical Education (MOHME), Tehran, Iran
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  • Mohammad Saadat
    Affiliations
    Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Department of Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
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  • Behnam Heidari
    Affiliations
    Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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  • Jeffrey I. Mechanick
    Affiliations
    Division of Cardiology and Endocrinology, Diabetes, and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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  • Alireza Esteghamati
    Correspondence
    Corresponding author at: Endocrinology and Metabolism, Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, P.O. Box 13145-784, Iran.
    Affiliations
    Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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      Highlights

      • Association of NAFLD with diabetes-related microvascular complications was studied.
      • NAFLD was inversely correlated with certain diabetes microvascular complications.
      • Beneficial adaptations in sicker patients may contribute to this finding.

      Abstract

      Introduction

      Non-alcoholic fatty liver disease (NAFLD) affects risks of type 2 diabetes (T2D), diabetes-related complications, and cardiovascular disease in a complex manner. This study is designed to clarify associations of sonographically-detected NAFLD and serum liver enzymes with diabetes-related microvascular complications.

      Methods

      A matched case-contorl study was designed for 440 patients with T2D and at least one of the chronic diabetes-related microvascular complications and 495 age- and gender-matched control patients with T2D.

      Results

      Considering pre-existing and newly developed chronic microvascular complications, diabetic peripheral neuropathy was found in 347 out of 935 (37.1%) study patients, diabetic retinopathy in 141/935 (15.1%), and diabetic nephropathy in 103/935 (11.0%). Diagnosis of diabetic retinopathy and diabetic nephropathy were inversely associated with the presence of NAFLD in the crude logistic regressions (OR [95% CI] = 0.18 [0.05–0.63], p value = 0.007; OR [95% CI] = 0.17 [0.04–0.59], p value = 0.011, respectively). The subgroup of NAFLD with elevated liver enzymes had lower odds of having diabetic peripheral neuropathy in the fully adjusted model (OR [95% CI] = 0.34 [0.12–0.98], p value = 0.048).

      Conclusion

      Diagnosis of NAFLD with or without elevated serum liver enzymes was inversely correlated with certain chronic diabetes microvascular complications. Possible explanations for this counter-intuitive and unexpected finding are discussed and center on reverse-causality, wherein sicker patients may develop beneficial compensatory physiological and behavioral adaptations. Diversity of studied patients, in particular with regards to the ethnic and racial differences among the Western and Asian populations may also partly account for contrasting findings of the relationship between NAFLD and microvascular complications of diabetes.

      Abbreviations:

      NAFLD (non-alcoholic fatty liver disease), T2D (type 2 diabetes), BMI (body mass index), SBP (systolic blood pressure), DBP (diastolic blood pressure), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), FPG (fasting Plasma Glucose), FPI (fasting plasma insulin), CV (coefficients of variation), HOMA-IR (Homeostasis model assessment for insulin resistance), A1C (Hemoglobin A1c), UAE (Urinary albumin excretion), MDRD (Modification of Diet in Renal Disease), eGFR (estimated glomerular filtration rate), ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALKP (alkaline phosphatase), GGT (γ-glutamyl transpeptidase), IFCC (International Federation of Clinical Chemistry and Laboratory Medicine), DGKC (Deutsche Gesellschaft für Klinische Chemie), EDTRS (Early Treatment Diabetic Retinopathy Study), DNS (Diabetic neuropathy symptom), OR (odds ratio), 95% CI (95% confidence interval)

      Keywords

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