Investing Fascia Release Modulates Glucose Metabolism: A Hypothesis of a Sympathetic–Islet Axis Mechanism Mediated by Mechanical Coupling of the Carotid Sheath Complex

Abstract The core mechanisms of type 2 diabetes are insulin resistance and β-cell failure. The classical model explains how hyperglycemia is maintained and amplified, but it does not answer an upstream question: in some patients, is there a physical–mechanical trigger layer independent of classical metabolic pathways that contributes to elevated fasting blood glucose and glycemic variability? This article proposes a mechanistic hypothesis titled “Investing Fascia Release Modulates Glucose Metabolism.” The investing fascia is the superficial layer of the deep cervical fascia; together with the pretracheal fascia and the prevertebral fascia, it forms a continuous mechanical system and contributes to the formation of the carotid sheath (Zhang & Lee, 2002; Bond et al., 2023). The cervical sympathetic trunk lies closely posterior to the carotid sheath, runs deep to the prevertebral fascia, and forms a close anatomical relationship with the posterior wall of the sheath (Chen M et al., 2021; Civelek et al., 2008). The hypothesis takes the sympathetic nervous system as its core axis, with the vagus nerve, hypothalamic–pituitary–adrenal (HPA) axis, lymphatic system, carotid artery mechanics, PIEZO1, and oxidative stress as auxiliary or parallel components. Chronic forward head posture, stress, aging, inflammation, and diabetes itself can drive fibrosis of the investing fascia (Cyron & Humphrey, 2017; Pirri et al., 2023; Ugwoke et al., 2026a, 2026b). After the investing fascia loses its elasticity, abnormal tension is transmitted along the continuous fascial network to the carotid sheath, leading to fibrotic thickening of the sheath and surrounding tissues (Pires et al., 2025; Bond et al., 2023). Thickening of the posterior wall of the sheath directly compresses the cervical sympathetic trunk, activating sympathetic outflow (Struthoff et al., 2024; Williamson et al., 1996; Joshi et al., 2019; Bolton et al., 2014; Chen M et al., 2021; Civelek et al., 2008), while also affecting the vagus nerve within the sheath and leading to decreased parasympathetic tone (Cunningham & Martínez, 2021; Tahiri et al., 2025). Sympathetic overactivation promotes hepatic glucose output through the hypothalamic–brainstem–liver pathway (Zsombok et al., 2024; Drougard et al., 2014), inhibits β-cell insulin secretion through α2-adrenergic receptors (Prates et al., 2018; Ogawa et al., 2026), and aggravates insulin resistance through α-adrenergic vasoconstriction (Smith et al., 2024; Gamboa et al., 2014; Sakamoto et al., 2025; Thorp & Schlaich, 2015). Cervical mechanical intervention can also activate the HPA axis (Valera-Calero et al., 2019; Amjad et al., 2025; Farrell et al., 2023). Diabetes itself can exacerbate sympathetic activation through the protein kinase C–mitogen-activated protein kinase (PKC-MAPK) pathway (Singh et al., 2026). PIEZO1 and changes in extracellular matrix (ECM) stiffness can directly impair β-cell function (Ye et al., 2022; Johansen et al., 2024; Chen AW et al., 2025). Oxidative stress serves as a central hub, linking mechanical stress, metabolic disorders, and neuroendocrine activation (Drougard et al., 2014; Ugwoke et al., 2026a; Pirri et al., 2023; Caroccia et al., 2025). Investing fascia release, through mechanical unloading, may acutely reduce sympathetic tone, restore vagal tone, and ameliorate oxidative stress, thereby producing a blood glucose-lowering effect in some patients. Faber et al. (2021) demonstrated through a randomized controlled trial (RCT) that reducing pressure pain sensitivity can improve HbA1c. Staats et al. (2025) combined vagus nerve stimulation to reduce HbA1c in patients with type 2 diabetes (T2D) from 8.9% to 5.8%, whereas the RCT by Kufaishi et al. (2025) showed that transcutaneous auricular vagus nerve stimulation (taVNS) alone produced no significant improvement, suggesting that fiber type selection and target combination determine therapeutic efficacy. Lu et al. (2019) demonstrated that spinal manipulation can reduce fasting blood glucose, 2-hour postprandial blood glucose, and HbA1c. Wändell et al. (2013) demonstrated that tactile massage can improve metabolic markers such as adiponectin; Xie et al. (2022) demonstrated that abdominal massage can improve HbA1c and gut microbiota; Lyu et al. (2019) demonstrated that self-acupoint massage can significantly reduce HbA1c in older adults with T2D; Licciardone et al. (2013) demonstrated that osteopathic manual treatment can reduce tumor necrosis factor-α (TNF-α); Cao et al. (2021) demonstrated that lymphatic dysfunction can directly promote insulin resistance; Antoniak et al. (2022) demonstrated that manual lymphatic drainage can reduce HbA1c and 2-h postprandial glucose (2-h PG). This hypothesis is a mechanistic hypothesis, not a clinical treatment recommendation; investing fascia release serves only as a tool for mechanistic verification. This article proposes testable predictions and a three-stage validation framework, and emphasizes that confounders such as diet, medication, stress, pain, sleep, placebo, and natural fluctuations must be excluded.