Metabolic basis of sudden sensorineural hearing loss in diabetes mellitus: From epidemiological association to mechanistic understanding

Abstract

Sudden sensorineural hearing loss (SSNHL) is an otologic emergency that necessitates prompt intervention; however, its pathogenesis remains elusive in most cases. Diabetes mellitus, a prevalent systemic metabolic disorder, has been increasingly implicated in the onset and unfavorable prognosis of SSNHL. Although epidemiological studies have consistently reported this association, the biological plausibility and causal direction of this relationship remain poorly understood and require further investigation. This review demonstrated that dysglycemia contributes to hearing impairment. The underlying mechanisms include vascular injury, auditory neuropathy, microcirculatory dysfunction, chronic inflammation driven by oxidative stress, and the accumulation of advanced glycation end products. Microcirculatory dysfunction may act as a critical nexus that integrates these diverse pathological pathways, ultimately leading to hearing loss. The potential role of prediabetes as an early driver of auditory damage, however, remains to be fully elucidated. Current management of SSNHL involves the use of glucocorticoids, vasodilators, neurotrophic agents, and adjunctive therapies, such as hyperglycemic control and hyperbaric oxygenation. Strengthening basic and translational research is essential to bridge mechanistic insights with clinical practice to develop precise therapeutic strategies to improve outcomes for patients with diabetes mellitus or prediabetes who present with SSNHL.

Key Words: Sudden sensorineural hearing loss; Diabetes mellitus; Prediabetes; Mechanisms; Dysglycemia

Core Tip: Growing evidence indicates that diabetes mellitus is not merely a comorbidity but an important contributor to sudden sensorineural hearing loss. Chronic hyperglycemia and early metabolic dysregulation lead to cochlear microvascular injury, neuropathy, oxidative stress, and impaired microcirculation, all of which increase susceptibility to hearing loss and hinder recovery. Emerging data suggest that prediabetes may already induce subclinical auditory damage. Elucidating these mechanisms provides a pathophysiological basis for risk stratification, early detection, and more individualized, mechanism-informed treatment strategies in patients with sudden sensorineural hearing loss.

INTRODUCTION

Sudden sensorineural hearing loss (SSNHL) is defined as an unexplained hearing loss developing within 72 h with a severity of 30 decibels or greater across a minimum of three consecutive frequencies[1]. Common clinical manifestations include rapid-onset unilateral or bilateral hearing impairment, frequently accompanied by tinnitus, aural fullness, vertigo, or dizziness[2]. It represents a time-sensitive otologic emergency that severely impacts the patient’s quality of life and poses a formidable clinical challenge owing to its frequently idiopathic nature. More than 90% of SSNHL cases are classified as idiopathic. SSNHL is a potentially self-limiting disorder. The global incidence of SSNHL is approximately 5-30 cases per 100000 people annually with no major sex predilection and occurrence across all age groups[3,4]. The condition has been linked to systemic diseases such as diabetes mellitus (DM) as well as to psychological and lifestyle factors like mental stress and excessive fatigue[5].

Despite its prevalence, the exact etiology of SSNHL remains unclear. Proposed mechanisms include vascular compromise, impaired inner ear microcirculation, immune-mediated processes, stress responses, and chronic inflammation[6]. The inner ear is uniquely vulnerable to microcirculatory dysfunction. As a terminal organ with high metabolic demand and limited collateral blood supply, even minor circulatory disturbances can precipitate ischemia, hypoxia, and metabolic failure. Consequently, any disorder that disrupts cochlear blood flow may precipitate functional decline and SSNHL.

DM is a chronic metabolic disorder characterized by persistent hyperglycemia. It is primarily classified into two forms: Type 1 DM caused by autoimmune destruction of pancreatic β cells leading to absolute insulin deficiency; and type 2 DM (T2DM) characterized by insulin resistance and relative insulin deficiency[7]. Globally, the burden of DM has surged dramatically from an estimated 108 million cases in 1980 to 589 million in 2024, largely driven by the increasing prevalence of T2DM[8].

Population-based cohort studies and meta-analyses confirm DM as an independent risk factor for SSNHL. Individuals with DM exhibit approximately twice the risk of SSNHL compared with those without DM[9,10]. Complications of long-term hyperglycemia, such as retinopathy, nephropathy, neuropathy, and cardiovascular disease, are the leading causes of disability and mortality worldwide[11]. Anatomically and physiologically, the inner ear is a key target organ in DM[12]. This shifts SSNHL from being viewed solely as a localized otologic disorder to a potential manifestation of systemic metabolic disease in patients with DM. However, to translate this perspective into clinical benefit, the underlying mechanisms linking DM and SSNHL must be more clearly delineated.

Therefore, this review aimed to: (1) Systematically synthesize recent epidemiological evidence linking DM and SSNHL; (2) Elucidate the interacting cellular and molecular mechanisms by which DM impairs inner ear function; (3) Comprehensively analyze the clinical phenotypes and prognostic features of SSNHL in patients with DM; and (4) Develop a mechanism-informed and evidence-based management framework while highlighting future research priorities.

ASSOCIATION BETWEEN DM AND SSNHL

To comprehensively evaluate the existing evidence on the association between DM, prediabetes, and SSNHL, we conducted a systematic literature search of the PubMed, Web of Science, and Elsevier databases for records published between January 2000 and October 2025. The search strategy employed the following keywords: “diabetes mellitus” OR “prediabetes” OR “insulin resistance” AND “sudden sensorineural hearing loss” OR “hearing loss” OR “sudden deafness”. The inclusion criteria were as follows: Peer-reviewed studies published in English that investigated the association between DM or prediabetes and SSNHL. Eligible study types included original research (encompassing both human populations and animal models), systematic reviews, and meta-analyses. Exclusion criteria included conference abstracts and publications for which the full text was unavailable. Through a stepwise screening process based on titles, abstracts, and full-text review, we ultimately identified the core literature referenced in this manuscript.

Robust epidemiological evidence has established a significant link between DM and SSNHL, supporting its recognition as a well-substantiated clinical observation (Table 1). Clinical studies report a higher incidence of SSNHL in individuals with T2DM than in populations without DM with an odds ratio (OR) of 1.59[13]. Patients requiring three or more classes of glucose-lowering agents or those with diabetic microvascular complications such as retinopathy exhibit a markedly elevated SSNHL risk with hazard ratios of 2.06 and 1.57, respectively[13]. A meta-analysis corroborated these findings, reporting an overall OR of 2.15 for SSNHL in individuals with DM[14].

Table 1 Key epidemiological evidence linking metabolic dysfunction and auditory system disorders.

Ref.	Study type	Population	Outcome	Key finding	Grade
Lin et al[13]	Clinical study	Individuals with T2DM	SSNHL risk	OR = 1.59 (T2DM vs non-diabetic); HR = 2.06 (with ≥ 3 glucose-lowering agents); HR = 1.57 (with retinopathy)	Moderate
Horikawa et al[14]	Meta-analysis	Patients with diabetes	SSNHL risk	Overall OR = 2.15	Moderate
Fukui et al[15]	Cohort study	General population	SSNHL risk	Significant association with DM	High
Zhou et al[16]	Clinical analysis	26556 patients with diabetes	SSNHL risk and severity	Risk correlates with DM severity	Low
Costa[17]; Fukushima et al[18]	Clinical studies	SSNHL patients with T2DM	Hearing recovery	Negative prognostic factor for recovery	Low
Zhu et al[23]	Clinical study	General population	SSNHL risk	Progressive increase in risk with HbA1c > 5%	Low

T2DM: Type 2 diabetes mellitus; SSNHL: Sudden sensorineural hearing loss; OR: Odds ratio; HR: Hazards ratio; DM: Diabetes mellitus; HbA1c: Glycated hemoglobin A1c.

Clinical studies have identified DM as a risk factor for SSNHL[13]. After adjusting for demographic variables, occupational noise exposure, lifestyle, and other metabolic conditions, a large-scale Korean cohort study demonstrated a significant association between DM and SSNHL[15]. Furthermore, an analysis of 26556 patients revealed that DM not only increases SSNHL risk but also correlates with greater severity of auditory impairment[16]. Notably, SSNHL patients with T2DM often present with more severe hearing loss at onset, and DM is considered a negative prognostic factor for hearing recovery[17,18].

However, the evidence regarding the impact of DM on the prognosis of SSNHL is divergent. While DM has been linked to greater hearing loss severity and poorer recovery, especially with microvascular complications, some studies suggest it may not independently predict prognosis[19,20]. Despite these discrepancies T2DM has consistently been identified as a risk factor for SSNHL, and the use of hypoglycemic agents may attenuate this risk. Furthermore, T2DM accompanied by microvascular complications likely indicates a worse prognosis in patients with SSNHL[21]. Glycated hemoglobin A1c (HbA1c), which reflects the average glycemic control over the preceding 2-3 months, is associated with a 37% increased risk of microvascular complications for every 1% rise[22]. Higher HbA1c levels, particularly those exceeding 5%, are associated with a progressive increase in the risk of hearing impairment[23]. However, direct evidence specifically linking HbA1c levels to SSNHL remains limited.

Beyond clinical observations experimental models provide further evidence supporting an association between DM and SSNHL. In streptozotocin-induced diabetic rats, elevated brainstem auditory evoked potential thresholds at 8 kHz and 16 kHz, prolonged wave IV latency, and reduced amplitudes of distortion product otoacoustic emissions (OAEs) were observed, reflecting functional impairments in both the cochlear and central auditory pathways[24]. Altered expression of calretinin further suggests selective vulnerability of cochlear afferent fibers under hyperglycemic conditions, potentially representing an early biomarker of SSNHL[25]. Diabetic rats also exhibited impaired recovery from noise-induced hearing loss compared with controls, indicating that DM hinders restorative processes and exacerbates acoustic injury[26]. Interestingly, ribbon synapse loss was less pronounced in these animals, suggesting heterogeneous mechanisms of auditory injury in DM; in Akita diabetic mice, significant cellular loss and mitochondrial damage were observed in the spiral ganglion neurons. Additionally, the stria vascularis exhibited reduced thickness, loss of intermediate cells, disorganization of capillary morphology, and a reduction in type I, II, and IV fibrocytes and Na+-K+-ATPase expression in the spiral ligament was also observed. Elevated cleaved caspase-3 expression further implicates apoptosis as a central mechanism of DM-related auditory degeneration[27]. Another study found that diabetic mice developed elevated auditory thresholds as early as 6 weeks of age even though hair cell survival in the apical and middle turns was preserved. The basal turn shows significant ribbon synapse loss, reduced auditory brainstem response amplitudes, and mitochondrial damage along with elevated inflammatory cytokines, indicating that mitochondria-mediated apoptosis contributes to early auditory decline[28].

ASSOCIATION BETWEEN PREDIABETES AND SSNHL

Prediabetes, which includes impaired fasting glucose and impaired glucose tolerance, already affects hundreds of millions of people worldwide. Recent research has shown a significant association between prediabetes and SSNHL. Studies using the triglyceride-glucose (TyG) index, a reliable marker of insulin resistance, have shown a positive, dose-dependent relationship between TyG levels and the prevalence of SSNHL (OR = 2.10)[29]. An earlier study also identified an L-shaped relationship among the TyG index, fasting glucose, and the risk of SSNHL. When the TyG index exceeds 9.07 or fasting glucose exceeds 94 mg/dL, the risk of SSNHL increases sharply (OR = 3.60)[29]. This threshold effect indicates that auditory vulnerability emerges well before glucose levels reach the diabetic range.

Clinical evidence further reinforces this association. Compared with individuals with normal glucose levels, those with impaired fasting glucose show a markedly higher prevalence of high-frequency hearing loss (42.2% vs 24.5%). The prevalence of low-frequency and mid-frequency hearing loss is also nearly doubled (14.7% vs 7.8%)[30]. Even among patients with early-stage DM who maintain good glycemic control and in children with normal standard pure-tone thresholds, hearing thresholds in the extended high-frequency range (> 8 kHz) are significantly elevated[31]. Many patients with DM exhibit substantially reduced OAE amplitudes despite normal audiometric thresholds, indicating that cochlear injury may precede measurable threshold shifts[32]. Collectively, these findings imply that prediabetes affects not only high-frequency but also lower-frequency hearing and that such impairment can arise before a formal diagnosis of DM is made.

Mechanistically, the auditory consequences of prediabetes appear to differ from those driven by chronic hyperglycemia in established DM and are more closely tied to insulin resistance and early metabolic dysregulation. Insulin acts as a natural vasodilator; thus, impaired insulin signaling reduces vascular dilation and may activate sympathetic and inflammatory pathways. This leads to microvascular constriction, endothelial dysfunction, and diminished cochlear perfusion. Given the high metabolic demands of the cochlea, especially the stria vascularis, these disturbances render the auditory system highly susceptible to ischemia and hypoxic injury. Subclinical microcirculatory disruption can impair the energy supply and survival of hair cells and supporting cells, ultimately elevating hearing thresholds.

In states of insulin resistance, glucose metabolism abnormalities increase mitochondrial reactive oxygen species (ROS) production and weaken antioxidant defenses. This oxidative imbalance arises early in prediabetes, preceding overt hyperglycemia. Cochlear hair cells with their high metabolic rate and lipid-rich membranes are particularly vulnerable to oxidative damage, which can trigger hair cell apoptosis, synaptic dysfunction, and progressive neural injury. Consistent with this, diabetic rat models show early-stage outer hair cell loss[33]. These anatomical findings correlate with functional deficits observed in individuals with prediabetes, including reduced OAE amplitudes and elevated auditory brainstem response thresholds.

For individuals at high risk of prediabetes, such as those who are overweight or have a family history of DM, routine pure-tone audiometry, extended high-frequency testing, and OAE assessments can provide sensitive and noninvasive methods for detecting subclinical cochlear dysfunction and systemic microvascular injury before subjective symptoms appear. Early intervention in prediabetes through lifestyle modification, dietary regulation, and increased physical activity not only helps delay or prevent the onset of DM but may also play a meaningful role in protecting auditory function.

PATHOPHYSIOLOGICAL MECHANISMS

Long-term hyperglycemia, which is inherent in DM, leads to a spectrum of pathological complications. Beyond acute metabolic crises, such as recurrent hypoglycemia and ketoacidosis, patients often develop severe vascular sequelae, including macrovascular diseases such as atherosclerosis and thrombosis in the heart, peripheral arteries, and cerebrovascular system along with microvascular injuries manifesting as nephropathy, neuropathy, and retinopathy[34]. Notably, DM has emerged as a significant contributor to SSNHL, and the pathogenic mechanisms of DM-associated auditory dysfunction are primarily linked to hyperglycemia-induced microangiopathy, neuropathy, microcirculatory dysfunction, and oxidative stress (Figure 1).

Figure 1 Pathophysiological mechanisms of sudden sensorineural hearing loss. AGEs: Advanced glycation end-products; ROS: Reactive oxygen species; Trx: Thioredoxin; TXNIP: Thioredoxin-interacting protein; SSNHL: Sudden sensorineural hearing loss.

Microangiopathy

Patients with DM, particularly those with long-standing disease or poor glycemic control, frequently suffer from concurrent inner ear microangiopathy. This condition is characterized by thickening of the microvascular basement membrane, dysfunction of the vascular barrier, and progressive occlusion of the lumen. These pathological changes promote the formation of microthrombi, inducing local ischemia and further compromising auditory function. Additionally, hyperglycemia enhances platelet aggregation, reduces erythrocyte deformability, and increases blood viscosity, collectively slowing cochlear blood flow and exacerbating inner ear perfusion deficits. This results in metabolic disturbances within the cochlea, negatively impacting the function of the stria vascularis and hair cells, and ultimately contributing to hearing loss[35].

Although direct observation of inner ear microcirculatory dysfunction is challenging due to the intricate anatomy of the cochlea, substantial clinical and pathological evidence supports its occurrence. Patients with T2DM who develop microvascular complications often experience severe hearing loss, frequently presenting with profound deafness on audiometry along with comorbid conditions like diabetic retinopathy, nephropathy, and neuropathy. The systemic involvement of microvascular disease suggests concomitant damage to the inner ear vasculature[36]. Similarly, patients with SSNHL and underlying microvascular complications tend to show more pronounced hearing loss and poorer prognosis[19].

The molecular mechanisms underlying auditory nerve damage are intricately linked to hyperglycemia-induced oxidative stress and metabolic disturbances. Under high-glucose conditions, the activation of the polyol pathway releases reactive molecules, triggering oxidative stress, contributing to the development of diabetic neuropathy. Elevated glucose also stimulates mitochondrial ROS production, accelerating axonal degeneration and reducing cell membrane elasticity. These processes ultimately damage peripheral auditory nerve fibers and impair hearing function. Furthermore, hyperglycemia disrupts the nutrient supply to peripheral nerves, activating aberrant metabolic pathways, compromising myelin structure, and promoting inflammation-related gene expression. The upregulated expression of inducible nitric oxide synthase catalyzes the production of neurotoxic nitric oxide, further damaging auditory nerve axons[37].

Chronic hyperglycemia also inflicts damage to the labyrinthine artery, often leading to stenosis or occlusion, severely reducing inner ear perfusion. The reliance of the cochlea on end arteries with negligible collateral circulation makes it especially vulnerable to ischemic damage when these arteries are obstructed. Standard vasodilators and microcirculatory agents are often ineffective as the disrupted blood flow pathway is structurally compromised, and the irreversible loss of hair cells leads to poor hearing recovery[38]. This endothelial injury is a hallmark of T2DM-associated microangiopathy, contributing to atherosclerosis and further impairing cochlear blood supply. Notably, postprandial glucose levels, a risk factor for microvascular complications, may inversely correlate with the severity of hearing loss[39]. Single-photon emission CT imaging has supported this theory, revealing cerebral hypoperfusion in patients with DM who have SSNHL, offering imaging evidence for microcirculatory deficits[40]. Thus, hearing impairment in DM is not restricted to the cochlea but may also affect the auditory brainstem, delay neural impulse transmission, and manifest as sensorineural hearing loss or auditory decline.

Neuropathy

SSNHL in DM can be attributed to diabetic peripheral neuropathy affecting the vestibulocochlear nerve (VIII). Diabetic auditory nerve damage can be primarily explained by two hypotheses, one of which emphasizes microangiopathy. This hypothesis proposes that patients with T2DM who have SSNHL often exhibit microvascular abnormalities, such as cochlear vascular stenosis and reduced blood flow. These abnormalities cause local ischemia and hypoxia, ultimately resulting in distal axonal degeneration of the intralabyrinthine nerve, thereby inducing neuropathy and directly impairing auditory function[41].

The second hypothesis implicates diabetic peripheral neuropathy in hearing loss. This suggests that neuropathy impairs auditory function through direct damage to the relevant cranial nerves, manifesting as pathological changes, such as Schwann cell thinning, axonal degeneration, and myelin sheath abnormalities that disrupt neural signaling. Supporting evidence from animal models includes scanning electron microscopy, which reveals clear injury to the cochlear outer hair cells, spiral ganglion cells, and nerve fibers in diabetic rats[42]. Human histopathological studies have corroborated these findings, revealing injury to the organ of Corti, loss of spiral ganglion neurons, and demyelination of the auditory nerve[43,44].

The pathogenesis of auditory nerve damage involves key molecular mechanisms initiated by hyperglycemia. High glucose activates the polyol pathway, generating reactive molecules and oxidative stress, which are central to diabetic neuropathy. Elevated glucose levels also stimulate mitochondrial ROS production, promoting axonal degeneration and reducing cell membrane elasticity, contributing to damage to auditory nerve fibers and hearing loss. These dysregulations lead to structural demyelination and increased expression of inflammation-related genes. Additionally, the upregulation of inducible nitric oxide synthase facilitates the production of neurotoxic nitric oxide, causing further auditory nerve damage[45].

Microcirculatory dysfunction

The microcirculation of the inner ear, vital for nutrient supply and waste clearance, is highly sensitive to blood glucose levels. Chronic hyperglycemia leads to microcirculatory impairment, which disrupts cellular metabolism. The limited energy reserves of the inner ear make it particularly vulnerable to even minor glycemic instability, which can fail the Na⁺-K⁺-ATPase pump, triggering potassium accumulation in the perilymph and the emergence of auditory abnormalities[46].

Comorbid lipid metabolism disorders in DM exacerbate this dysfunction. A hyperlipidemic state enhances red blood cell aggregation and platelet adhesion, reduces erythrocyte deformability, and diminishes perfusion efficacy, contributing to further microcirculatory deficits. Lipid deposition within cochlear hair cells induces direct cytological injury, and the resultant prothrombotic milieu promotes the formation of intracochlear microthrombi[47]. Lipid-associated microangiopathy is thus a significant contributor to inner ear damage in patients with DM, and this pathology is compounded by early subclinical injury to the auditory neural system, increasing the clinical complexity and therapeutic resistance commonly observed in diabetic SSNHL cases.

Oxidative stress and advanced glycation end products

The cochlea is highly susceptible to oxidative stress because of its elevated metabolic activity. Evidence strongly suggests that oxidative stress is a common pathological mechanism contributing to SSNHL, whether induced by noise, DM, or aging[48]. Chronic hyperglycemia overwhelms intracellular glucose metabolism and the electron transport chain, leading to excessive ROS production, which disrupts mitochondrial function and bioenergetic failure[49]. Additionally, hyperglycemia impairs autophagy, a key process that removes damaged organelles and protein aggregates. This autophagic impairment exacerbates intracellular oxidative stress and increases apoptotic pressure by preventing efficient removal of dysfunctional mitochondria.

One of the well-established etiologies of SSNHL in patients with DM is the accumulation of advanced glycation end products (AGEs), which result from prolonged hyperglycemia[50]. AGEs contribute significantly to microvascular pathology by compromising vascular integrity, accelerating atherosclerosis (especially in the cochlea), and inducing histopathological changes like basement membrane thickening, providing direct evidence of DM-induced auditory damage[51]. A critical mediator in AGE-related pathology is the thioredoxin (Trx) system, a redox regulatory complex comprising nicotinamide adenine dinucleotide phosphate, Trx, thioredoxin-interacting protein, and Trx reductase. Studies in diabetic animal models and human subjects have revealed dysregulated expression of Trx system components coupled with increased cochlear AGE levels, indicating that redox imbalance is central to the pathogenesis of auditory dysfunction in DM[52]. Collectively, these findings indicated that therapeutic strategies targeting antioxidant pathways may attenuate oxidative stress and protect hearing.

TREATMENT

The management of DM-associated SSNHL centers on both the control of dysglycemia and the restoration of auditory function. Glycemic control, typically achieved using medications such as metformin, sulfonylureas, or insulin, is essential for optimizing systemic metabolic stability. Pharmacological treatment of SSNHL primarily relies on corticosteroids, hemorheological agents, antioxidants, and neurotrophic drugs although therapeutic efficacy varies among individuals and remains the subject of ongoing clinical debate.

Management of SSNHL is challenging for several reasons. First, there is a lack of direct comparative studies evaluating the efficacy of different treatment modalities, leaving uncertainties regarding the optimal strategy. Second, patient responses differ widely, complicating the prediction of outcomes. Although corticosteroids are regarded as the treatment cornerstone, their use may precipitate significant metabolic complications, particularly hyperglycemia, in patients with DM. Third, SSNHL has a narrow therapeutic window, and delays in seeking medical care frequently result in missed opportunities for intervention. Additionally, the absence of a universally accepted gold standard regimen contributes to controversy regarding the ideal administration route, drug combinations, and treatment duration. Finally, even after the acute phase, many patients continue to face long-term challenges, including incomplete recovery, persistent tinnitus, and psychological distress. These factors underscore the need for individualized, precision-based treatment strategies. For cases refractory to medical therapy, auditory rehabilitation through hearing aids or cochlear implantation becomes essential.

Corticosteroids

The American Academy of Otolaryngology suggests administering corticosteroids within 6 weeks of onset, preferably systemically or intratympanically within the first 2 weeks, and reserving intratympanic injections as salvage therapy thereafter[53]. The Chinese guidelines similarly prioritize corticosteroids with optional inclusion of microcirculation-enhancing agents and recommend batroxobin in severe cases[54]. In contrast, the German guidelines place greater emphasis on hemorheological therapy over corticosteroids[55].

Treatment of SSNHL in patients with DM is complicated by high inter-individual variability and the risk of systemic side effects. Consequently, local corticosteroid administration (intratympanic or postauricular) is strongly preferred for patients with T2DM to minimize systemic metabolic disturbances. Intratympanic or posterior auricular injections have been shown to improve pure-tone thresholds and alleviate tinnitus and vertigo while avoiding steroid-induced hyperglycemia and electrolyte abnormalities[56]. Local delivery also achieves higher intracochlear drug concentrations. Posterior auricular injection offers an alternative with potentially fewer adverse effects, including reduced pain and a lower risk of membrane perforation. However, intratympanic injections may cause patient discomfort, transient vertigo, or tympanic membrane injury.

Dexamethasone, a widely used corticosteroid, improves endothelial function, inhibits platelet aggregation, and stabilizes inner ear fluid homeostasis. Evidence suggests that higher concentrations of intratympanic dexamethasone result in more sustained therapeutic effects and improved clinical outcomes[57]. Although the exact mechanisms remain unclear, corticosteroids likely act through ion transport regulation, aquaporin modulation, anti-inflammatory effects, and reduction of inner ear edema.

Hemorheological agents

Microcirculatory dysfunction, vascular spasm, and hypercoagulability are key pathophysiological factors in SSNHL. Dysregulation of cochlear blood flow and microthrombus formation are considered the primary causes, making hemorheological agents a valuable therapeutic option, particularly in patients where a vascular etiology is suspected.

Alprostadil, delivered via a liposomal prostaglandin E1 carrier, targets vascular injury sites and activates the adenylate cyclase-cyclic adenosine monophosphate pathway, thereby inhibiting platelet aggregation, improving erythrocyte deformability, and inducing vasodilation to enhance cochlear perfusion. Clinical studies suggest that alprostadil improves treatment efficacy and reduces excessive platelet activation in patients with SSNHL[58]. Ginkgo biloba extract (Ginaton) also enhances microcirculation and reduces apoptosis and has been associated with improved hearing outcomes as well as reduced tinnitus and vertigo, especially when administered early in patients with basin-shaped, ascending, or flat audiograms. Evidence indicates that adjunctive therapy with Ginaton significantly improves overall effectiveness, cure rate, hearing thresholds, and hemorheological parameters while lowering the rate of adverse reactions compared with standard therapy alone[59].

Additional hemorheological agents include nimodipine, a calcium channel blocker that reduces blood viscosity and enhances cochlear perfusion, and batroxobin, which lowers fibrinogen levels, dissolves thrombi, and improves red blood cell flexibility. In patients with SSNHL combination therapy with batroxobin plus intratympanic dexamethasone demonstrated a significantly higher effective rate (75.90%) than batroxobin alone (59.78%) while reducing inflammatory markers and adverse events[60]. Because vasodilators used during acute ischemia may trigger steal syndrome, they are commonly administered alongside volume expanders to maintain overall perfusion[61]. Therefore, hemorheological therapy represents a fundamental component of SSNHL management, and treatment selection should be tailored to the patient’s vascular status and comorbidities.

Neurotrophic agents

Neurotrophic agents are widely used as adjuvant therapies in SSNHL to support neural repair, enhancing cochlear metabolism, and promoting auditory nerve function. Commonly used agents include mouse nerve growth factor (mNGF), mecobalamin, and citicoline sodium[62-64]. These agents are rarely used as monotherapy and are typically administered in combination with corticosteroids or other pharmacological treatments.

mNGF promotes neural repair and protects the cochlear spiral ganglion, facilitating neuronal survival during reversible ischemic injury. Animal studies demonstrate the presence of mNGF receptors throughout inner ear development, underscoring its role in auditory system maturation[62]. Mecobalamin enhances methylation processes, modulates gene transcription, and supports nucleic acid and protein synthesis, thereby facilitating repair of nerve fibers and regeneration of spiral ganglion neurons. It additionally improves erythrocyte maturation and oxygen transport, benefiting cochlear metabolism and microcirculation. Citicoline sodium promotes phospholipid synthesis, supports membrane repair, and mitigates ischemic injury in cochlear hair cells and auditory neurons. These actions stabilize neural structures, restore function, and support the reconstruction of auditory signaling pathways[64]. Its anti-apoptotic effects further contribute to improved hearing recovery.

Hyperbaric oxygen therapy and alternative treatments

Since its initial use in the late 1960s, hyperbaric oxygen therapy (HBOT) has been evaluated in multiple clinical guidelines for SSNHL. The 2012 American guidelines recommended it as an optional treatment within 3 months of onset (grade B evidence), whereas the 2015 Chinese guidelines considered it controversial and not a first-line therapy although potentially useful as a salvage therapy[65]. More recent 2019 guidelines support HBOT as an adjunct to corticosteroids, particularly when initiated within 2 weeks of onset or used as salvage therapy within 4 weeks[66].

HBOT exerts its therapeutic effects by increasing oxygen delivery to the inner ear, alleviating hair cell hypoxia, and improving cochlear microcirculation. It also reduces edema, limits reperfusion injury, and scavenges free radicals, collectively supporting neural and cellular recovery. Clinical outcomes are substantially improved when HBOT is initiated early and combined with corticosteroids or hemorheological agents like alprostadil. Younger patients and those with severe initial hearing loss (> 50 decibels), especially at low frequencies, tend to experience the greatest benefit[67].

For patients with long-standing DM who exhibit refractory SSNHL unresponsive to medication and HBOT, management shifts toward auditory rehabilitation. Hearing aids can improve speech perception and sound quality in moderate-to-severe cases and are associated with enhanced cortical auditory evoked potentials and speech recognition[68]. Cochlear implantation offers effective rehabilitation for bilateral severe-to-profound SSNHL by directly stimulating the auditory nerve. The choice between hearing aids and cochlear implants should be individualized based on hearing severity, speech recognition ability, and the patient’s specific communication needs.

Future directions

At the mechanistic level several high-priority research questions remain unanswered. A central question is the precise mechanism by which DM contributes to the development of SSNHL. Another key question concerns the role of insulin resistance, specifically whether insulin resistance alone, independent of hyperglycemia, can induce metabolic stress in spiral ganglion neurons, synapses, or the stria vascularis. Addressing these gaps will require well-designed clinical studies, including prospective cohort studies, randomized controlled trials, and mechanistic investigations using in vivo and in vitro models.

There is also an urgent need to identify specific and sensitive biomarkers for DM-associated hearing loss. Metabolomic and proteomic profiling may help reveal circulating “metabolic fingerprints” that reflect early cochlear injury or microvascular dysfunction, providing minimally invasive diagnostic tools for early detection. Similarly, imaging techniques that assess cochlear microcirculation or neural integrity may serve as important adjuncts.

From a public health perspective, research should inform policy changes, such as incorporating extended high-frequency audiometry, OAEs, and auditory brainstem response testing into routine monitoring for individuals with prediabetes or DM. Establishing hearing loss as a core microvascular complication of DM may strengthen clinical awareness and improve early intervention strategies. Future therapeutic development should emphasize precision medicine, including targeted antioxidants, anti-inflammatory agents, modulators of AGEs formation, and strategies that improve mitochondrial resilience. Further evaluation of intratympanic drug delivery, combination pharmacotherapy, and HBOT in populations with DM is needed. Large-scale, multicenter clinical trials will be essential for developing standardized and mechanism-driven treatment protocols.

LIMITATIONS

Despite the compelling associations highlighted in current research, several key limitations warrant careful consideration. First, considerable heterogeneity exists among patients with SSNHL across studies, including differences in disease severity, comorbid conditions, and treatment approaches, making direct comparison of findings challenging. Second, although many epidemiological studies adjust for important confounders, residual confounding from factors such as age, hypertension, dyslipidemia, obesity, noise exposure, and ototoxic medication use cannot be fully excluded. Additionally, there remains a lack of standardized criteria for evaluating hearing recovery, which limits comparability across clinical studies. Objective measures such as extended high-frequency thresholds or OAEs are used inconsistently. There is also a notable shortage of prospective interventional studies specifically designed for populations with DM or prediabetes, limiting our ability to establish causality or determine optimal management strategies. Advancing this field will require standardized audiological assessment methods and rigorous study designs that better account for metabolic factors and microvascular status.

CONCLUSION

DM is recognized as a risk factor for SSNHL. Through mechanisms involving microvascular injury, neuropathy, oxidative stress, and AGE accumulation, DM increases both the likelihood of SSNHL and the severity of its presentation. Effective care requires a comprehensive and mechanism-informed approach with local corticosteroid therapy as the cornerstone and adjunctive use of hemorheological and neurotrophic agents as well as hyperbaric oxygen when appropriate. Routine audiological monitoring in patients with long-standing or poorly controlled DM is essential as early detection may prevent irreversible cochlear damage. Integrating metabolic control with targeted otologic treatment will be key to improving long-term outcomes for individuals with DM or prediabetes who develop SSNHL.