Background The aim was to investigate if autonomic symptoms questionnaire Composite Autonomic Symptom Score (COMPASS) 31 has different association with cardiovascular autonomic neuropathy (CAN) and diagnostic performance between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).
Methods Seventy-nine participants with T1DM and 140 with T2DM completed COMPASS 31 before cardiovascular reflex tests (CARTs) for CAN, and assessment of symptoms, signs, vibration, and thermal perception thresholds for diabetic polyneuropathy (DPN) diagnosis.
Results COMPASS 31 total weighted score (TWS) was similar in the two groups, but significantly associated with confirmed CAN only in T1DM (P=0.0056) and not T2DM group (P=0.1768) and correlated with CARTs score more strongly in T1DM (rho=0.356, P=0.0016) than in T2DM group (rho=0.084, P=0.3218) (P=0.016). Only in T1DM and not T2DM group, the area under the receiver operating characteristic curve (AUC) reached a fair diagnostic accuracy (>0.7) for confirmed CAN (0.73±0.07 vs. 0.61±0.08) and DPN (0.75±0.06 vs. 0.68±0.05), although without a significant difference. COMPASS 31 TWS (cut-off 16.44) reached acceptable diagnostic performance in T1DM, with sensitivity for confirmed CAN 81.2% and sensitivity and specificity for DPN 76.3% and 78%, compared to T2DM group (all <70%). AUC for DPN of orthostatic intolerance domain was higher in T1DM compared to T2DM group (0.73±0.05 vs. 0.58±0.04, P=0.027).
Conclusion COMPASS 31 is more weakly related to CAN in T2DM than in T1DM, with a fair diagnostic accuracy for confirmed CAN only in T1DM. This difference supports a multifactorial origin of symptoms and should be considered when using COMPASS 31.
Citations
Citations to this article as recorded by
Corneal confocal microscopy identifies early and definite diabetic cardiac autonomic neuropathy Shazli Azmi, Maryam Ferdousi, Alise Kalteniece, Ioannis N Petropoulos, Uazman Alam, Georgios Ponirakis, Omar Asghar, Andrew Marshall, Andrew JM Boulton, Nathan Efron, Rayaz A Malik Diabetes Research and Clinical Practice.2025; 224: 112172. CrossRef
Features of short-term heart rate variability in internally displaced people with type 2 diabetes mellitus V.A. Serhiyenko, V.B. Sehin, V.I. Pankiv, A.A. Serhiyenko INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2025; 21(3): 243. CrossRef
Article commentary on: ‘impact of autonomic dysfunction on cardiovascular outcomes among patients with ATTR cardiomyopathy: insights from the COMPASS-31’ Jonas Wixner Amyloid.2025; 32(4): 311. CrossRef
Frequency and severity of autonomic dysfunction assessed by objective hemodynamic responses and patient-reported symptoms in individuals with myasthenia gravis Monika Zawadka-Kunikowska, Mirosława Cieślicka, Jacek J. Klawe, Małgorzata Tafil-Klawe, Wojciech Kaźmierczak, Łukasz Rzepiński Frontiers in Neuroscience.2024;[Epub] CrossRef
Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.
Citations
Citations to this article as recorded by
Interplay between cardiomyocytes and nonmyocytes plays a vital role in cardiac metabolism and function: early-phase metabolic syndrome and short QT Belma Turan, Yasemin Atici, Deniz Billur Canadian Journal of Physiology and Pharmacology.2026; 104: 1. CrossRef
Role of neddylation in diabetes metabolism: potential therapeutic target Hui Li, Ruiyin Zeng, Jing Liu, Huiwen Wang Journal of Diabetes & Metabolic Disorders.2026;[Epub] CrossRef
Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF Hyeong Rok Yun, Manish Kumar Singh, Sunhee Han, Jyotsna S. Ranbhise, Joohun Ha, Sung Soo Kim, Insug Kang International Journal of Molecular Sciences.2026; 27(2): 879. CrossRef
Association between free fatty acids and adverse outcomes in patients with and without diabetes undergoing percutaneous coronary intervention Qinxue Li, Guyu Zeng, Deshan Yuan, Tianyu Li, Peizhi Wang, Ce Zhang, Sida Jia, Pei Zhu, Ying Song, Xiaofang Tang, Ping Liu, Yuejin Yang, Runlin Gao, Jingjing Xu, Xueyan Zhao, Jinqing Yuan Journal of Translational Internal Medicine.2026; 14(1): 53. CrossRef
Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review) Yongchun Liang, Xinbiao Fan, Xiaofei Geng, Yunfeng Jia, Wenyu Shang, Xitong Sun, Jun Ge, Guijun Ye, Boyu Zhu, Zheng Zhang, Yuxin Kang, Xiaoyu Shan, Junping Zhang International Journal of Molecular Medicine.2026; 57(4): 1. CrossRef
From Metabolism to Mind: The Cardio–Metabolic–Brain Axis and the Role of Insulin Resistance—A Review Joanna Cielecka, Zuzanna Szkamruk, Maciej Walędziak, Anna Różańska-Walędziak Biomedicines.2026; 14(2): 394. CrossRef
Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression Seung-Hwan Lee, Kyu Na Lee, Jong-Chan Youn, Hun Sung Kim, Kyungdo Han, Mee Kyoung Kim Diabetes & Metabolism Journal.2025; 49(1): 105. CrossRef
Predictive value of TG/HDL-C and GFR-adjusted uric acid levels on cardiovascular mortality: the URRAH study Elisa Russo, Francesca Viazzi, Roberto Pontremoli, Fabio Angeli, Carlo Maria Barbagallo, Bruno Berardino, Michele Bombelli, Federica Cappelli, Edoardo Casiglia, Rosario Cianci, Michele Ciccarelli, Arrigo F. G. Cicero, Massimo Cirillo, Pietro Cirillo, Lanf Lipids in Health and Disease.2025;[Epub] CrossRef
Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias Pegah Bahrami, Kelly A. Aromolaran, Ademuyiwa S. Aromolaran Journal of Cellular Physiology.2025;[Epub] CrossRef
Cardiovascular abnormalities already occurred in newly-diagnosed patients with early-onset type 2 diabetes Hong Lian, Qian Ren, Wei Liu, Rui Zhang, Xiantong Zou, Simin Zhang, Yingying Luo, Wei Deng, Qiuping Wang, Lin Qi, Yufeng Li, Wenbo Wang, Liyong Zhong, Pengkai Zhang, Chengcheng Guo, Li Li, Yating Li, Tianhao Ba, Chaochao Yang, Lili Huo, Yan’ai Wang, Chunx Cardiovascular Diabetology.2025;[Epub] CrossRef
Association of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in population with cardiovascular-kidney-metabolic syndrome stages 0–4: evidence from a large cohort study Fan-Shun Guo, Jia-Hao Dou, Jun-Xiang Wang, Chen Guo, Rui-Yun Wu, Xue-Lu Sun, Yi-Wei Hu, Jin Wei Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
Traditional Chinese medicine in the prevention of diabetes mellitus and cardiovascular complications: mechanisms and therapeutic approaches Caixia Chen, Hui Gao, Ying Wei, Yaxi Wang Frontiers in Pharmacology.2025;[Epub] CrossRef
Micronized Purified Flavonoid Fraction (Diosmin/Hesperidin) Ameliorates Cardiac Structural and Functional Integrity in Cisplatin-treated Male Wistar Rats by Modulating NLRP3/Caspase-1/-3 Signaling W. A. Saka, P. A. Oyedokun, C. A. Adegbola, T. M. Akhigbe, P. J. Ashonibare, O. R. Kolawole, A. A. Oladipo, R. E. Akhigbe Cell Biochemistry and Biophysics.2025; 83(4): 4415. CrossRef
Interaction between mitochondrial oxidative stress and myocardial fibrosis in the context of diabetes Pu-Hua Zhang, Nuo-Nan Li, Xiang Gu, Chun-Xia Zhou, Zhen-Zhen Jiang, Xian-Jun Luo, Hong-Wen Zhu, Xiao-Yong Zhu Frontiers in Endocrinology.2025;[Epub] CrossRef
Liposomal Nanoparticle Delivery of Ginkgo Flavone Glycosides Enhances SIRT1 Activation and Improves Diabetic Cardiomyopathy Wei Gao, Ruoran Chen, Huixin Tong, Yu Wang, Linlang Liang, Yiyao Li, Hao Yu International Journal of Nanomedicine.2025; Volume 20: 7295. CrossRef
A user-friendly sugar stevia: Role in diabetes-associated health adversities Sanjay, Hae-Jeung Lee Food Bioscience.2025; 71: 107121. CrossRef
Network pharmacology-based insights into the role of gut microbiota metabolites in insulin resistance Bing Xiao, Xin Chen, Ruiyu Zong, Yiming Guan, Zhu Zhu, Siling Bi Frontiers in Microbiology.2025;[Epub] CrossRef
Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank Kun Liu, Jinling Hu, Yueqing Huang, Dingliu He, Jing Zhang Cardiovascular Diabetology.2025;[Epub] CrossRef
Frailty and depressive symptoms in relation to cardiovascular disease risk in middle-aged and older adults Zheng Zhang, Huijie Xu, Runjia Zhang, Yangxinyu Yan, Xi Ling, Yun Meng, Xilin Zhang, Yuanyuan Wang Nature Communications.2025;[Epub] CrossRef
Appetite adipokines and insulin resistance shape the link between sleep quality and cardiac structure in youths with cardiometabolic risk: the BCAMS study Mengyu He, Ling Zhong, Lanwen Han, Xinghao Yi, Ming Li, Shan Gao Cytokine.2025; 194: 156998. CrossRef
The association between TyG index and hypertension in middle-aged and elderly Chinese patients: Data from CHALRS Jun Wang, Chao Tang, Zhijie Xie, Amirmohammad Khalaji PLOS One.2025; 20(7): e0329234. CrossRef
C-reactive protein-triglyceride glucose index and heart failure in US adults from NHANES 2001–2010 Ningyi Cheng, Zhicheng Ma, Yukun Chen, Lei Jin, Liangwan Chen Scientific Reports.2025;[Epub] CrossRef
The association between triglyceride glucose-waist height ratio index and cardiometabolic multimorbidity among Chinese middle-aged and older adults: a national prospective cohort study Longyan Lv, Ping Zhang, Xuerui Chen, Yan Gao Cardiovascular Diabetology.2025;[Epub] CrossRef
Dexamethasone-induced insulin resistance impaired artemin levels in the hippocampus and altered behavioural patterns Hasan Çalışkan Scripta Medica.2025; 56(6): 695. CrossRef
Arterial stiffness, cardiovascular disease and the risk of type 2 diabetes mellitus A.A. Serhiyenko, M.E. Hotsko, V.V. Sulyma, V.A. Serhiyenko INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2025; 21(5): 548. CrossRef
Interaction between diabetes and osteoporosis: imbalance between inflammation and bone remodeling Xiao Zhang, Dong Xu, Rui Zhang, Hui Wang, Gangyi Yang Osteoporosis International.2025; 36(12): 2401. CrossRef
Estimated glucose disposal rate predicts frailty through diabetes: Evidence from machine learning and mediation models in NHANES Wentao Yang, Qian Cheng, Guoxin Huang, Hongming Lin, Yee Gary Ang PLOS One.2025; 20(10): e0333388. CrossRef
Combined predictive value of triglyceride-glucose index and remnant cholesterol for coronary artery disease in young adults Xi Wu, Mingxing Wu, Haobo Huang, Zhe Liu, He Huang, Lei Wang Frontiers in Cardiovascular Medicine.2025;[Epub] CrossRef
Association between METS-IR and heart failure: a cross-sectional study Xiaozhou Su, Chunli Zhao, Xianwei Zhang Frontiers in Endocrinology.2024;[Epub] CrossRef
Insulin–Heart Axis: Bridging Physiology to Insulin Resistance Alfredo Caturano, Raffaele Galiero, Erica Vetrano, Celestino Sardu, Luca Rinaldi, Vincenzo Russo, Marcellino Monda, Raffaele Marfella, Ferdinando Carlo Sasso International Journal of Molecular Sciences.2024; 25(15): 8369. CrossRef
The web of intrigue: unraveling the role of NETosis within the gut-microbiome-immune-heart axis in acute myocardial infarction and heart failure Tai Yasuda, Kate Deans, Aditi Shankar, Robert Chilton Cardiovascular Endocrinology & Metabolism.2024;[Epub] CrossRef
Relationship between the Mediterranean Diet and Vascular Function in Subjects with and without Increased Insulin Resistance Marta Gómez-Sánchez, Leticia Gómez-Sánchez, Rocío Llamas-Ramos, Emiliano Rodríguez-Sánchez, Luis García-Ortiz, Ruth Martí-Lluch, María Cortés Rodríguez, Inés Llamas-Ramos, Manuel A. Gómez-Marcos Nutrients.2024; 16(18): 3106. CrossRef
Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects Qin Ru, Yusheng Li, Lin Chen, Yuxiang Wu, Junxia Min, Fudi Wang Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
The Role of Insulin Within the Socio-Psycho-Biological Framework in Type 2 Diabetes—A Perspective from Psychoneuroimmunology Anne Wevers, Silvia San Roman-Mata, Santiago Navarro-Ledesma, Leo Pruimboom Biomedicines.2024; 12(11): 2539. CrossRef
Targeting Cardiac Fibrosis in Diabetic Heart Failure: The Role of the EZH2, AMPK, and PPAR-γ Pathways (Diabetes Metab J 2024;48:716-29) Jooyeop Lee, Joon Ho Moon Diabetes & Metabolism Journal.2024; 48(6): 1176. CrossRef