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World J Diabetes. Feb 15, 2022; 13(2): 70-84
Published online Feb 15, 2022. doi: 10.4239/wjd.v13.i2.70
Metabolically healthy obesity: Is it really healthy for type 2 diabetes mellitus?
Qi Wu, Ming-Feng Xia, Xin Gao
Qi Wu, Ming-Feng Xia, Xin Gao, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Qi Wu, Ming-Feng Xia, Xin Gao, Fudan Institute for Metabolic Disease, Fudan University, Shanghai 200032, China
Author contributions: Wu Q wrote the paper; Xia MF provided the core topic, outlined the manuscript, and modified the paper; Gao X provided the core topic, wrote and revised the manuscript, and provided funding.
Supported by Shanghai Municipal Science and Technology Major Project, No. 2017SHZDZX01 (to Gao X).
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Feng Xia, MD, Associate Professor, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China. dr_xiamingfeng@163.com
Received: February 26, 2021
Peer-review started: February 26, 2021
First decision: April 20, 2021
Revised: April 27, 2021
Accepted: January 20, 2022
Article in press: January 20, 2022
Published online: February 15, 2022
Abstract

Metabolically healthy obese (MHO) individuals are reported to have a lower risk of developing cardiovascular diseases in comparison with individuals with metabolic syndrome. However, the association between MHO and type 2 diabetes (T2DM) is still controversial. Some studies indicated that MHO is a favorable phenotype for T2DM, but more studies showed that MHO individuals have an increased risk of developing T2DM compared with metabolically healthy normal-weight individuals, especially among those who would acquire metabolically unhealthy obesity. This has been supported by finding insulin resistance and low-grade inflammatory responses in MHO individuals with a tendency for impaired beta-cell dysfunction. Studies also showed that liver fat accumulation increased the risk of incidence of T2DM in MHO. Here, we reviewed current literature on the relationship between MHO and T2DM, discussed the determinants for the development of diabetes in MHO, and summarized the measures for the prevention of T2DM in MHO.

Keywords: Metabolically healthy obesity, Type 2 diabetes, Non-alcoholic fatty liver diseases, Insulin resistance, Low-grade inflammatory status, Beta-cell dysfunction

Core Tip: Metabolically healthy obese individuals have already developed impaired insulin sensitivity with dysfunction of insulin action on subcutaneous tissue, as well as a tendency for beta-cell dysfunction and a chronic low-grade inflammatory status compared with metabolically healthy normal-weight individuals. Thus, it is an unfavorable phenotype for type 2 diabetes, with metabolic changes preceding the incidence of diabetes. Liver fat content might be an important contributor to the development of diabetes in metabolically healthy obesity among all risk factors. More attention should be paid to the weight management and metabolic status of these individuals.