Han ZG, Yang Y, Huang PY, Yang M, Zhang GD, Yang X, Song CY, Lu JS, Wang KY. Hidden metabolic crisis in lean youth: Waist-to-height ratio uncovers endoplasmic reticulum stress-driven insulin resistance in platelets. World J Diabetes 2026; 17(6): 119998 [DOI: 10.4239/wjd.119998]
Corresponding Author of This Article
Kai-Yang Wang, Assistant Professor, Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai 200233, China. ortho_wang@163.com
Research Domain of This Article
Endocrinology & Metabolism
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review-article
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Han ZG, Yang Y, Huang PY, Yang M, Zhang GD, Yang X, Song CY, Lu JS, Wang KY. Hidden metabolic crisis in lean youth: Waist-to-height ratio uncovers endoplasmic reticulum stress-driven insulin resistance in platelets. World J Diabetes 2026; 17(6): 119998 [DOI: 10.4239/wjd.119998]
World J Diabetes. Jun 15, 2026; 17(6): 119998 Published online Jun 15, 2026. doi: 10.4239/wjd.119998
Hidden metabolic crisis in lean youth: Waist-to-height ratio uncovers endoplasmic reticulum stress-driven insulin resistance in platelets
Zeng-Gao Han, Yang Yang, Peng-Yan Huang, Min Yang, Guo-Dong Zhang, Xu Yang, Chen-Yu Song, Jing-Shun Lu, Kai-Yang Wang
Zeng-Gao Han, Yang Yang, Peng-Yan Huang, Guo-Dong Zhang, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe State, Honghe Hani and Yi Autonomous Prefecture 661000, Yunnan Province, China
Min Yang, Department of Traditional Chinese Medicine, Meilong Community Health Service Center of Minhang District, Shanghai 200233, China
Xu Yang, Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China
Chen-Yu Song, Kai-Yang Wang, Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Jing-Shun Lu, Department of Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 241000, Anhui Province, China
Author contributions: Han ZG wrote and edited the manuscript; Huang PY, Yang Y, Zhang GD and Yang X contributed to review and edit; Yang M, Lu JS and Song CY reviewed this paper; Wang KY conceived, reviewed, and revised this paper.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Kai-Yang Wang, Assistant Professor, Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai 200233, China. ortho_wang@163.com
Received: February 12, 2026 Revised: March 8, 2026 Accepted: May 6, 2026 Published online: June 15, 2026 Processing time: 119 Days and 20.8 Hours
Abstract
The rising prevalence of insulin resistance (IR) among metabolically unhealthy normal-weight youth represents a critical public health challenge, often missed by conventional body mass index (BMI)-based screening. Numerous studies have suggested that the waist-to-height ratio (WtHR) may be more effective than BMI for the early prediction of IR. This superiority likely stems from WtHR’s capacity to more accurately reflect abdominal fat accumulation. However, the precise underlying molecular mechanisms remain to be fully elucidated. In this article, we synthesize evidence linking elevated WtHR to visceral adiposity, systemic inflammation, and endoplasmic reticulum stress, a convergent molecular mechanism driving IR across liver, adipose, and vascular tissues. Notably, emerging data implicate platelets as accessible biosensors of endoplasmic reticulum stress, offering a novel window for early detection. Supported by epidemiological, clinical, and molecular studies - including recent findings in young adults with normal BMI but high WtHR - this paradigm shift underscores the urgency of integrating WtHR into routine youth health assessments to enable precision prevention and mitigate lifelong metabolic disease burden.
Core Tip: The waist-to-height ratio, with a threshold of > 0.5, offers a simple yet powerful anthropometric tool to unmask hidden insulin resistance and cardiometabolic risk in metabolically unhealthy normal-weight youth - a population routinely missed by body mass index-centric screening. This paradigm shift is grounded in mechanistic links among visceral adiposity, systemic inflammation, and endoplasmic reticulum stress, with emerging evidence positioning platelets as accessible biosensors of endoplasmic reticulum stress. Integrating waist-to-height ratio into routine youth health assessments enables early, precise intervention and holds potential to curb the lifelong burden of metabolic disease.
