Casillas OE, Hernández-Aguirre CA, Leija-Montoya AG, Romero-García T, Vázquez-Jiménez JG. Association between high waist-height ratio and endoplasmic reticulum stress of young adults with insulin resistance. World J Diabetes 2026; 17(5): 116053 [DOI: 10.4239/wjd.v17.i5.116053]
Corresponding Author of This Article
J Gustavo Vázquez-Jiménez, MD, PhD, Department of Physiology, Faculty of Medicine and Nutrition, Autonomous University of Baja California, Centro Cívico, Mexicali 21000, Baja California, Mexico. gustavo.vazquez@uabc.edu.mx
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Endocrinology & Metabolism
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Basic Study
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May 15, 2026 (publication date) through May 14, 2026
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World Journal of Diabetes
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1948-9358
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Casillas OE, Hernández-Aguirre CA, Leija-Montoya AG, Romero-García T, Vázquez-Jiménez JG. Association between high waist-height ratio and endoplasmic reticulum stress of young adults with insulin resistance. World J Diabetes 2026; 17(5): 116053 [DOI: 10.4239/wjd.v17.i5.116053]
World J Diabetes. May 15, 2026; 17(5): 116053 Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.116053
Association between high waist-height ratio and endoplasmic reticulum stress of young adults with insulin resistance
Oscar E Casillas, César A Hernández-Aguirre, Ana Gabriela Leija-Montoya, Tatiana Romero-García, J Gustavo Vázquez-Jiménez
Oscar E Casillas, César A Hernández-Aguirre, Ana Gabriela Leija-Montoya, J Gustavo Vázquez-Jiménez, Department of Physiology, Faculty of Medicine and Nutrition, Autonomous University of Baja California, Mexicali 21000, Baja California, Mexico
Tatiana Romero-García, Blood Chemistry Laboratory, Faculty of Sports, Autonomous University of Baja California, Mexicali 21289, Baja California, Mexico
Author contributions: Casillas OE and Vázquez-Jiménez JG conceptualized the study, designed the methodology and performed the analysis; Leija-Montoya AG, Casillas OE and Hernández-Aguirre CA performed the research; Leija-Montoya AG, Romero-García T, and Vázquez-Jiménez JG performed the data curation; Casillas OE, Romero-García T, and Vázquez-Jiménez JG wrote the original draft; Romero-García T, and Vázquez-Jiménez JG reviewed and edited the manuscript; Vázquez-Jiménez JG received the funding; all authors have read and agreed to the published version of the manuscript.
Supported by Program of Universidad Autónoma de Baja California, No. 106/2/C/27/25.
Institutional review board statement: The study was reviewed and approved by the Autonomous University of Baja California, Sports Faculty-Ethics Committee (Approval No. 265/2023-1).
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Corresponding author: J Gustavo Vázquez-Jiménez, MD, PhD, Department of Physiology, Faculty of Medicine and Nutrition, Autonomous University of Baja California, Centro Cívico, Mexicali 21000, Baja California, Mexico. gustavo.vazquez@uabc.edu.mx
Received: November 2, 2025 Revised: December 12, 2025 Accepted: January 30, 2026 Published online: May 15, 2026 Processing time: 191 Days and 15.2 Hours
Abstract
BACKGROUND
In our search to unravel the pathophysiological mechanisms underlying the development of insulin resistance (IR) in the young population, we evaluated the waist-to-height ratio (WtHR) in 39 participants, setting 0.5 as the cut-off value. A high WtHR has been associated with metabolic alterations and increased risk of developing IR.
AIM
To explore the relationship between WtHR and IR in young individuals with endoplasmic reticulum (ER) stress molecular mechanisms.
METHODS
This was a cross-sectional study conducted at the Faculty of Medicine of the Autonomous University of Baja California (Mexico). A total of 39 young participants (18-25 years old, both sexes) were recruited from the general community. All measurements and sample analyses were performed in a single study visit per participant. According to their WtHR, 0.5 is used as the threshold to define high or low WtHR. The degree of IR was estimated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Additionally, we analyzed ER stress markers in platelets, including SERCA protein expression and phosphorylation levels of PERK and JNK. Data were analyzed using one-way ANOVA followed by Dunn’s post-hoc test.
RESULTS
Young individuals with high WtHR showed greater body weight, body mass index, and visceral fat area percentage; additionally, high-density lipoprotein cholesterol (HDL-C) levels were lower, and the triglyceride/HDL-C ratio was higher (P < 0.05). Fasting insulin was higher in the high-WtHR group (18.76 ± 2.35 µU/mL vs 13.54 ± 1.5 µU/mL; P < 0.05), resulting in elevated HOMA-IR (4.34 ± 0.54 vs 2.90 ± 0.3; P < 0.05). Moreover, platelets from participants with high WtHR exhibited elevated SERCA protein expression (297.3 ± 39.4 vs 98.8 ± 14.9; P < 0.0002) and increased PERK phosphorylation (532.0 ± 98.9 vs 127.8 ± 29.6; P < 0.001), indicating activation of the unfolded protein response. These platelets also showed greater JNK phosphorylation than those from individuals with low WtHR (604.9 ± 216.3 vs 126.7 ± 25; P < 0.04), confirming JNK activation, a negative regulator of the insulin signaling pathway.
CONCLUSION
High-WtHR in young people is associated with IR and ER stress, driven by JNK activation in platelets, suggesting molecular alterations in early metabolic dysfunction.
Core Tip: Insulin resistance (IR), a health complication commonly associated with advanced age, is increasingly affecting the young population due to poor eating habits and a sedentary lifestyle. In this study, conducted with 39 young adults, participants with a waist-to-height ratio greater than 0.5 showed elevated insulin levels, higher Homeostatic Model Assessment of Insulin Resistance, and altered body composition. Likewise, these participants exhibited platelet molecular disturbances, including IR and activation of proteins associated with endoplasmic reticulum stress. The results suggest that excessive central adiposity in the young population triggers early activation of molecular mechanisms underlying the development of metabolic diseases, such as type 2 diabetes mellitus.
