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Response: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J 2020;44:267–76)
Hokyou Lee1,2, Gyuri Kim3, Yong-ho Lee1,4orcid
Diabetes & Metabolism Journal 2020;44(3):486-487.
DOI: https://doi.org/10.4093/dmj.2020.0127
Published online: June 29, 2020
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1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

2Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.

3Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

4Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea.

Corresponding author: Yong-ho Lee. Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. yholee@yuhs.ac

Copyright © 2020 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

See the Original "Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus" on page 267.
We would like to thank Dr. Yu for showing great interest in and providing insightful comments on our article, entitled “Association between non-alcoholic steatohepatitis and left ventricular diastolic dysfunction in type 2 diabetes mellitus,” which was published in Diabetes & Metabolism Journal [1].
In our study, we observed a smaller odds ratio with significant heterogeneity for left ventricular (LV) diastolic dysfunction associated with nonalcoholic fatty liver disease (NAFLD) or liver fibrosis in the presence of insulin resistance. This is a form of a negative multiplicative interaction between insulin resistance and hepatic steatosis/fibrosis in association with LV diastolic dysfunction [2]. The direction of the additive interaction, although not statistically significant, was also consistent with a negative interaction. Therefore, competing antagonism may exist between insulin resistance and hepatic steatosis/fibrosis, which share several common biological mechanisms and may compete with regard to outcomes [34]. The clinical implications of our study suggest that the presence of hepatic steatosis or fibrosis may be a “red flag” for subclinical cardiac dysfunction and diabetic cardiomyopathy among type 2 diabetes mellitus patients without severe systemic insulin resistance or other overt cardiometabolic diseases, seemingly low-risk patients.
We agree with Dr. Yu that long-term exposure to high blood pressure is an important risk factor for LV dysfunction and remodeling [5]. Although there is limited evidence on the association between the duration of hypertension and NAFLD or liver fibrosis, it may be reasonable for future studies to include the duration of hypertension as a potential confounder.
We also agree that randomized controlled trials should evaluate the beneficial effects of NAFLD intervention on LV diastolic dysfunction and remodeling. Prospective cohort studies as well as animal studies should seek to establish the underlying mechanisms and causality between NAFLD and diastolic dysfunction in type 2 diabetes mellitus. We are again grateful for Dr. Yu's invaluable comments.

CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

  • 1. Lee H, Kim G, Choi YJ, Huh BW, Lee BW, Kang ES, Cha BS, Lee EJ, Lee YH, Huh KB. Association between non-alcoholic steatohepatitis and left ventricular diastolic dysfunction in type 2 diabetes mellitus. Diabetes Metab J 2020;44:267-276. ArticlePubMedPDF
  • 2. VanderWeele TJ. The interaction continuum. Version 2. Epidemiology 2019;30:648-658. PubMedPMC
  • 3. VanderWeele TJ, Knol MJ. Remarks on antagonism. Am J Epidemiol 2011;173:1140-1147. ArticlePubMedPMC
  • 4. Smith BW, Adams LA. Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol 2011;7:456-465. ArticlePubMedPDF
  • 5. Kishi S, Teixido-Tura G, Ning H, Venkatesh BA, Wu C, Almeida A, Choi EY, Gjesdal O, Jacobs DR Jr, Schreiner PJ, Gidding SS, Liu K, Lima JA. Cumulative blood pressure in early adulthood and cardiac dysfunction in middle age: the CARDIA Study. J Am Coll Cardiol 2015;65:2679-2687. PubMed

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    • Association of Metabolic Dysfunction-Associated Fatty Liver Disease With Left Ventricular Diastolic Function and Cardiac Morphology
      Dandan Peng, Zhenqiu Yu, Mingwei Wang, Junping Shi, Lei Sun, Yuanyuan Zhang, Wenbin Zhao, Chen Chen, Jiake Tang, Chunyi Wang, Jie Ni, Wen Wen, Jingjie Jiang
      Frontiers in Endocrinology.2022;[Epub]     CrossRef

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      Response: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J 2020;44:267–76)
      Diabetes Metab J. 2020;44(3):486-487.   Published online June 29, 2020
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