Sex modifies the association between insulin resistance and psychiatric comorbidities among individuals with type 2 diabetes
- 1Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Colonia Sección XVI, Tlalpan, Mexico City, Mexico
- 2Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, 64710 México
Abstract
Introduction: The co-occurrence of neuropsychiatric disorders and type 2 diabetes (T2D) is well-documented. Insulin resistance (IR) has emerged as a potential biological mechanism associated with psychiatric disorders. However, the influence of sex on this relationship remains underexplored. This study aimed to determine whether sex modifies the association between insulin resistance, assessed using the METS-IR Index, and psychiatric comorbidities in patients with type 2 diabetes.
Methods: Comparative cross-sectional study of 4,699 individuals (2689 females, 2010 males) with T2D (duration < 10 years) who attended a multidisciplinary care center in Mexico City. IR was estimated using the METS-IR index (cutoff ≥ 50). Psychiatric comorbidities, including affective, anxiety, and eating disorders, were evaluated using standardized clinical assessments. Multiple logistic regression models were constructed to evaluate the association between the sex-insulin resistance interaction and four distinct psychopathological outcomes.
Results: Females exhibited a significantly higher prevalence of all psychiatric comorbidities compared to males: affective (27.8% vs. 13.5%), anxiety (25.9% vs. 17.5%), and eating disorders (28.9% vs. 20.1%) (all p < 0.001). In females, high IR (METS-IR ≥ 50) was significantly associated with a higher frequency of affective disorders (30.5% vs. 26.0%, p = 0.011), anxiety disorders (28.0% vs. 24.5%, p = 0.040), and eating disorders (38.3% vs. 22.7%, p < 0.001). Conversely, in males, high METS-IR was only associated with eating disorders (27.0% vs. 14.4%, p < 0.001), showing no significant impact on affective or anxiety symptoms. Females with METS-IR ≥ 50 were two-fold more likely to have any psychiatric disorder (OR = 2.40; IC95%:1.85–3.11).
Conclusion: Higher METS-IR was associated with psychiatric comorbidities in a sex-specific manner. These findings suggest that the relationship between insulin resistance and psychiatric disorders differs between females and males. While IR broadly increases the risk for multiple psychiatric domains in females, its impact in males is primarily restricted to eating behaviors. These findings underscore the critical need for sex-stratified metabolic monitoring to improve mental health screening and integrated care in T2D.
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BibTeX
@article{alcantaragarces2026modifies,
title = {{Sex modifies the association between insulin resistance and psychiatric comorbidities among individuals with type 2 diabetes}},
author = {María Teresa Alcántara-Garcés and Alejandra Monserrat Estefanía Rodríguez-Ramírez and Victoria Landa-Anell and Marco Antonio Melgarejo-Hernández and Ana Cristina García-Ulloa and Sergio Hernández-Jiménez},
journal = {BMC Psychiatry},
year = {2026},
month = aug,
doi = {10.1186/s12888-026-08502-2},
url = {https://doi.org/10.1186/s12888-026-08502-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sex modifies the association between insulin resistance and psychiatric comorbidities among individuals with type 2 diabetes
AU - María Teresa Alcántara-Garcés
AU - Alejandra Monserrat Estefanía Rodríguez-Ramírez
AU - Victoria Landa-Anell
AU - Marco Antonio Melgarejo-Hernández
AU - Ana Cristina García-Ulloa
AU - Sergio Hernández-Jiménez
PY - 2026
DA - 2026/08/11
JO - BMC Psychiatry
DO - 10.1186/s12888-026-08502-2
UR - https://doi.org/10.1186/s12888-026-08502-2
AB - Introduction: The co-occurrence of neuropsychiatric disorders and type 2 diabetes (T2D) is well-documented. Insulin resistance (IR) has emerged as a potential biological mechanism associated with psychiatric disorders. However, the influence of sex on this relationship remains underexplored. This study aimed to determine whether sex modifies the association between insulin resistance, assessed using the METS-IR Index, and psychiatric comorbidities in patients with type 2 diabetes. Methods: Comparative cross-sectional study of 4,699 individuals (2689 females, 2010 males) with T2D (duration < 10 years) who attended a multidisciplinary care center in Mexico City. IR was estimated using the METS-IR index (cutoff ≥ 50). Psychiatric comorbidities, including affective, anxiety, and eating disorders, were evaluated using standardized clinical assessments. Multiple logistic regression models were constructed to evaluate the association between the sex-insulin resistance interaction and four distinct psychopathological outcomes. Results: Females exhibited a significantly higher prevalence of all psychiatric comorbidities compared to males: affective (27.8% vs. 13.5%), anxiety (25.9% vs. 17.5%), and eating disorders (28.9% vs. 20.1%) (all p < 0.001). In females, high IR (METS-IR ≥ 50) was significantly associated with a higher frequency of affective disorders (30.5% vs. 26.0%, p = 0.011), anxiety disorders (28.0% vs. 24.5%, p = 0.040), and eating disorders (38.3% vs. 22.7%, p < 0.001). Conversely, in males, high METS-IR was only associated with eating disorders (27.0% vs. 14.4%, p < 0.001), showing no significant impact on affective or anxiety symptoms. Females with METS-IR ≥ 50 were two-fold more likely to have any psychiatric disorder (OR = 2.40; IC95%:1.85–3.11). Conclusion: Higher METS-IR was associated with psychiatric comorbidities in a sex-specific manner. These findings suggest that the relationship between insulin resistance and psychiatric disorders differs between females and males. While IR broadly increases the risk for multiple psychiatric domains in females, its impact in males is primarily restricted to eating behaviors. These findings underscore the critical need for sex-stratified metabolic monitoring to improve mental health screening and integrated care in T2D.
SN - 1471-244X
ER -