Hipoacuzia asociată diabetului zaharat

Introduction

Hearing impairment may affect all age groups, from the newborn to the elderly. According to the World Hearing Report, 1.5 billion people across the globe were affected by this condition in 2021. By 2050, the number is expected to grow to 2.5 billion subjects⁽¹⁾.

Hearing impairment can arise from any structure of the auditory system: external auditory, sound conduction mechanism, cochlea, cochlear nerve and central auditory pathways. For the patients presenting with hearing impairment, it is important to identify the progression of the hearing loss, if it’s unilateral or bilateral, and also the absence of tinnitus and vertigo. Medical conditions such diabetes, atherosclerosis and kidney disease are important⁽²⁾.

Diabetes is an important public health issue. The International Diabetes Federation (IDF) published in 2024 the 11^th Edition of the Diabetes Atlas which states that 589 million adults are living with diabetes, and this number is predicted to rise to 853 million by 2050⁽³⁾. In 2014, Akinpelu et al. have published a meta-analysis regarding diabetes mellitus type 2 (the most prevalent form accounting 90% of all cases). The authors of this meta-analysis, which included 18 studies, reported that the incidence of hearing impairment ranged between 44% and 69.7% for type 2 diabetes, significantly higher compared to controls⁽⁴⁾.

Corti’s organ is placed within the cochlea, the hearing organ, composed of tree structures: scala vestibuli, scala media and scala tympani. It includes two types of hair cells and supporting cells. The hair cells are represented by inner hair cells (IHC), which are responsible for sending impulses via the auditory nerve, and outer hair cells (OHC), which enhance cochlear performances by increasing sensitivity and selectivity. The sound generates a vibration in the basilar membrane, that separates the scala media from the scala tympani. The vibrations of this membrane are detected by the hair cells in the Corti’s organ. The tectorial membrane spirals along the Corti’s organ. The stria vascularis, a highly vascularized area located in the lateral wall of the cochlea, contributes to the cochlear homeostasis by maintaining the endo­cochlear potential which is required for the process of hair cell transduction to occur, along with the cochlear blood-labyrinth barrier, which controls the transfer of material from the stria vascularis capillaries into the endolymph⁽⁵⁾.

This review summarizes information on the association between hearing impairment and diabetes mellitus.

Possible mechanisms involved in hearing impairment in diabetes

Possible mechanisms involved in the association between diabetes and hearing loss are the combination of cochlear microangiopathy and auditory neuropathy⁽⁶⁾, alongside the loss of outer hair cells⁽⁸⁾, and may lead to irreparable sensorineural hearing loss (SNHL)⁽⁹⁾. Genetic and comorbid factors, including diabetes, are more likely to affect both the high and low frequencies, while middle frequencies are less affected^(6,9).

The microangiopathy is characterized by abnormal growth of small blood vessels, resulting in local edema and functional impairment of several tissues. The mechanisms involved in diabetic microangiopathy are not completely elucidated. The proposed mechanisms for the microangiopathy include dysregulated vascular regeneration, oxidative stress and activation of inflammatory pathways triggered by advanced end-products. Diabetic microangiopathy can generate cochlear changes. The affected cochlear structures in diabetic animal model are: significantly thicker basilar membrane compared to healthy individuals, thickened stria vascularis and narrowing of capillaries in the stria vascularis, vessel wall thickening in the modiolus, chronically reduced blood flow in the cochlea, loss of Corti’s organ hair cells⁽⁷⁾ in both genetically diabetic animal models and drug-induced diabetic animal models, and also in human temporal bone studies^(6,7,22). Fukushima et al. included 18 patients with type 2 diabetes (11 patients with insulin treatment and seven patients in treatment with oral hypoglycemic agents) and 26 age-matched controls. Measures of the vessel wall thickness in the basilar membrane and stria vascularis were performed in the cochlea at the mid-modiolar level. The study revealed that in diabetic patients the vessel walls of the stria vascularis were significantly thicker than those of the control group, and also reported a significant loss of the cochlear OHCs, alongside a degeneration of the stria vascularis⁽⁸⁾.

Diabetic neuropathy is a frequent complication of dia­be­tes, and it involves peripheral nerve impairment, in­clu­ding the auditory nerve. Auditory neuropathy is a hea­ring condition characterized by impaired transmis­sion of the sound signals from the inner ear to the auditory centers of the brain. Hyperglycemia, oxidative stress, inflammation and alterations in the cochlear flow are involved in the pathophysiology of the auditory neuropathy in diabetic patients. Hyperglycemia can generate neuronal damage, demyelination of the auditory nerve, and may affect the release of neurotransmitters. Diabetes is characterized by oxidative stress secondary to the increase in production of reactive oxygen (ROS) species that affect important cellular components; the cellular damage can afflict the auditory functions and structures. The formation of advanced end products can contribute to cellular damage and inflammation; the chronic inflammation can disrupt the integrity of blood vessel, generating complications in auditory pathways, and increase the risk of auditory neuropathy. Diabetes can generate microangiopathy, that reduces blood flow and impairs the functioning of hair cells and nerve fibers, contributing to the development of auditory neuropathy⁽⁶⁾.

The combination between microangiopathy alongside metabolic disruptions and persistent inflammation may be the cause of hearing loss in diabetic patients⁽⁹⁾.

The pathogenesis of hearing impairment in diabetes is not completely elucidated, because most pathological studies were performed on animal model or autopsies, due to the inability to perform a biopsy at the level of inner ear in living subjects^(6,8).

Evaluation of hearing impairment in diabetic patients

Systematic reviews and meta-analyses evaluated the audiological alterations in patients with type 1 diabetes. Teng et al. studied in a review the relationship between type 1 diabetes and hearing impairment. Fifteen studies were included, and the authors highlighted that there is a relationship between the two conditions, with an increased risk for developing mild and subclinical hearing impairment⁽¹⁰⁾. Mujica-Mota et al. evaluated 21 articles to assess the evidence of the effects of type 1 diabetes on hearing function. The authors compared the prevalence of hearing impairment in diabetic patients and control subjects: the prevalence of hearing loss ranged between 5.17% and 48% for diabetes patients, which was greater than in controls, which ranged between 0% and 40%⁽¹¹⁾.

Many studies have evaluated the auditory alterations in patients with type 2 diabetes. Ren et al. studied hearing impairment in 160 diabetic patients and 100 age- and sex-matched healthy controls. The results of the study revealed greater mean pure tone audiometry thresholds than those in controls for all of frequencies. The high frequencies were especially affected, and seemed to be more important when progressing to low frequency involvement. However, there are some studies that show greater deterioration at low frequencies⁽¹²⁾.

Gupta et al. performed a longitudinal study with 138,898 women to examine the relationship between type 2 diabetes and self-reported hearing impairment. The authors concluded that the diabetes duration for eight or more years is associated with a higher risk of developing hearing loss. Preventing type 2 diabetes could potentially reduce the burden of the hypoacusia, along with other complications of diabetes⁽¹³⁾.

Al-Rubean et al. analyzed 157 patients with type 2 diabetes, with ages between 30 and 60 years old. Sixty percent of the diabetic patients had different degrees of hearing impairment, with 50% of them having moderate-to-severe degree hearing loss. Other factors which contribute to hearing impairment in diabetic patients are poor glycemic control and comorbidities such hypertension and hyperlipidemia⁽¹⁴⁾.

Management of hearing impairment associated with diabetes mellitus

Hearing impairment may compromise the quality of life in diabetic patients. This is the reason why the American Diabetes Association has recognized hearing loss as a comorbidity of diabetes and recommends comprehensive medical assessment. Controlling the factors that may cause morphological and functional changes in the cochlea are very important in the management of diabetic hearing loss⁽⁵⁾.

Specific treatment of hearing impairment associated with diabetes mellitus includes strict glycemic control and antioxidant treatment.

Studies on the benefits of glycemic control on hearing recovery are controversial. After intensive idiopathic SNHL treatment and strict glycemic control, an improvement in hearing was observed⁽¹⁵⁾. In a study with 144 patients with type 2 diabetes and idiopathic sudden SNHL, Park et al. showed that glycemic control had no significant impact on the hearing recovery⁽¹⁶⁾.

The antioxidant therapy includes astaxanthin, a non-provitamin A carotenoid with a strong antioxidant effect. The administration of astaxanthin in type 1 diabetic rats generates increased antioxidant levels in cochlear tissue and decreased proinflammatory cytokine levels⁽¹⁷⁾. Alpha-lipoic acid has antioxidant properties: it decreases ROS, repairing oxidative damage and regenerating endogenous antioxidants⁽¹⁸⁾. Kim et al. evaluated the protective effects of alpha-lipoic acid on hair cell damage in diabetic zebrafish model. The survival number of hair cells of zebrafish treated with alpha-lipoic acid was significantly higher than in the control group⁽¹⁹⁾. Asiaticoside is a triterpene glycoside with neuroprotective effects⁽²⁰⁾. Xing et al. analyzed the effect of asiaticoside on cochlear hair cells under treatment with high glucose in vitro and the hearing function in vivo. The results suggests that asiaticoside increases the antioxidative activity and suppresses the AGEs/RAGE/NF-kB pathway, protecting the cochlear hair cells from high glucose-induced injury. Antioxidant therapy has only been performed in experimental and animal models, and more clinical studies are needed⁽²¹⁾.

Conclusions

Based on previous studies, diabetic patients have a worse hearing compared to non-diabetic people. The high frequencies were especially affected, and they seemed to be more important when progressing to low frequency. The duration of diabetes, poor glycemic control and comorbidities such hypertension and hyperlipidemia are risk factors in the progression of hearing impairment in diabetic patients.

Specific treatments of hearing impairment associated with diabetes mellitus are explored, and several researchers took into account glycemic control and antioxidant therapy. Studies on the benefits of glycemic control on hearing recovery are controversial. Antioxidant therapy performed well in experimental and animal models, restoring the hearing function by reduction the degeneration of hair cells and improving the level of antioxidant enzymes in the cochlea. If these treatments prove to be effective in diabetic patients, it could represent a therapeutic alternative in hearing loss. 

Autor corespondent: Diana-Loreta Păun E-mail: dianaloreta_paun@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

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