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Published in final edited form as: Hear Res. 2024 Jun 20;450:109072. doi: 10.1016/j.heares.2024.109072

Associations Between Diabetes Mellitus and Sensorineural Hearing Loss from Humans and Animal Studies

Essence DeVine Williams 1, María Eulalia Rubio 1,2,*
PMCID: PMC12175331  NIHMSID: NIHMS2084719  PMID: 38936171

Abstract

There is controversy regarding the association and etiopathogenesis of diabetes mellitus (DM) and sensorineural hearing loss (SNHL). Some studies support that SNHL develops because of angiopathy and/or neuropathy caused by DM, but many of the findings have been inconsistent. This review aims to highlight a select number of studies that effectively describe the relationship between DM and SNHL, thus bringing more attention and awareness to this area of research. This review also describes animal models to understand better the mechanisms of DM contributing to SNHL in the inner ear. The goal of this narrative review is for researchers and healthcare professionals to further their understanding and investigation of the etiopathogenesis of both DM and SNHL, therefore leading to the development of effective treatments for diabetic patients displaying symptoms of SNHL.

Keywords: cochlea, angiopathy, neuropathy, stria vascularis, modiolar artery

1. Incidence of Type 1 and Type 2 diabetes mellitus

An estimated 537 million adults worldwide have diabetes mellitus (DM); this number is expected to increase to 783 million by 2045 (Gedawy et al., 2023). DM is a chronic disorder that is caused by insufficient insulin secretion and action and is considered the leading cause of cardiovascular disease morbidity and mortality, blindness, renal failure, and amputations (Wu et al., 2014; Schmidt, 2018). DM is categorized into two forms: type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) (Wu et al., 2014).

T1DM affects two million people in Europe and North America and accounts for 10% of cases in people of European descent, with an increasing incidence in children (Gillespie, 2006). The global incidence is increasing, which suggests that the environment's action on susceptibility genes may play a role in the rise (Gillespie, 2006). The onset of T1DM can occur at any age, but typically manifest between 7 and 15 years of age (Dalton et al. 1998). In T1DM individuals, insulin-producing beta cells in the pancreas are destroyed by infiltrating CD4+, CD8+ T cells, and macrophages (Fig.1A) (Gillespie, 2006). Frequently, a combination of genetic and environmental risk factors contributes to the development of T1DM. In response, there is a continuous search for therapeutic strategies and agents aimed at both treating and preventing the disease.

Figure 1. Schematic of the etiopathogenesis and effects of diabetes.

Figure 1.

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A) In T1DM, T cells attack and destroy pancreatic beta cells, which halts the production of insulin. In T2DM, the pancreas produces insulin, however, insulin becomes resistant to receptors and beta cells fail to respond to insulin properly due to insufficient signaling. In both types of diabetes, there is an excess of glucose in the blood, which can ultimately lead to the buildup of fatty material and cause the blood vessels to narrow. High blood glucose levels result in diabetic angiopathy and neuropathy. B) Schematic of a cochlea turn highlighting the blood vessels supply within the stria vascularis, the organ of Corti, and the spiral ganglion. The angiopathy caused by T1DM and T2DM damages the small blood vessels within the stria vascularis and the modiolar artery within the modiolus region leading to SNHL. SM: Scala Media; ST: Scala Tympani; SV: Scala Vestibuli

T2DM is considered the most prevalent form of diabetes mellitus, accounting for 90-95% of all diabetic patients (Wu et al., 2014). More than nine percent of Americans (29.1 million) were reported to have T2DM in 2014, and the risk of developing the disorder has continued to increase (Schmidt, 2018). In addition, T2DM is becoming more prevalent in developing countries, and the largest number of diabetic patients are found in low-middle-income countries, such as India, China, Russia, Brazil, and Pakistan (Wu et al., 2014). T2DM is primarily caused by changes in insulin secretion due to dysfunctional pancreatic beta cells and a loss of sensitivity of insulin signaling that leads to insulin resistance (Galicia-Garcia et al., 2020; Wu et al., 2014). The changes result in elevated blood glucose levels or hyperglycemia, an important risk factor that can lead to microangiopathy and microvascular complications that affect every tissue in the body (Fig.1A) (Marcovecchio, 2017; Akinpelu et al., 2014; Schmidt, 2018). Some other important factors that increase the risk of developing T2DM include obesity, family history, racial or ethnic background, and age (Wu et al., 2014). Younger and middle-aged men display a higher prevalence of T2DM than women, however, aging women with postprandial hyperglycemia tend to have a higher prevalence of undiagnosed T2DM (Kautzky-Willer et al., 2023). Additionally, African American, Asian-American/Pacific Islander, Latino/Hispanic American, or Native American populations are at a higher risk of developing T2DM. Although certain factors remain beyond control, individuals can effectively manage T2DM through dietary choices, regular physical activity, or the use of oral hypoglycemic drugs. In instances where blood glucose levels are not adequately controlled, supplementation with exogenous insulin may be necessary (Wu et al., 2014).

2. Diabetes and hearing loss

430 million people worldwide currently have hearing impairment that hinders individuals from participating in social activities and conversation (Giraudet et al., 2022; Bagai et al., 2006). Peripheral hearing loss can be classified as conductive or sensorineural (SNHL) (Bagai et al., 2006). SNHL stands as the predominant form of hearing loss, characterized by the functional impairment of the inner ear. This sensory disorder can arise from various factors, including noise exposure, the intake of ototoxic drugs, systemic diseases like diabetes, and the natural aging process. With age being a pivotal factor, it is projected that, by the year 2050, at least 700 million people worldwide will experience some degree of hearing loss (Bing et al., 2023; Bagai et al., 2006; Giraudet et al., 2022). Because no current therapies can restore normal hearing or cure SNHL, it is important to identify potential risk and prevention factors (Cunningham and Tucci, 2017).

It is uncertain how DM is associated with SNHL because the relationship between the two and etiopathogenesis of hearing loss are described as controversial. Researchers have supported the idea that SNHL develops due to angiopathy, neuropathy, or a combination of both but have often yielded inconsistent findings and results (Maia & Campos, 2005). Studies have shown that diabetes leads to microvascular changes that may affect the arteries, nerves, kidneys, and retina (Davies et al., 2018). The cochlea is a highly vascular structure dependent on its blood supply from the spiral modiolar artery and cochlear branch of the vestibule cochlear artery, which then supplies the areas enriched with capillaries, such as the spiral ganglion and the stria vascularis (Fig.1B) (Nakashima et al., 2003; Mei et al., 2020). When this blood supply is disrupted, several morphological and microvascular changes to the inner ear ensue (Kimmura & Perlman, 1956; Lawrence, 1966).

Researchers have debated the relationship between DM and SNHL over time, however, previous literature (research and review studies) have concluded that there is limited evidence to describe DM as a cause of SNHL (Maia & Campos, 2005; Gioacchini et al., 2023; Samocha-Bonet et al., 2021). There is a call for more studies to address confounding factors and variables like noise exposure that have weakened past conclusions (Maia & Campos, 2005; Samocha-Bonet et al., 2021). PubMed, ScienceDirect, and Google Scholar databases were used to source research articles published within the last 20 years that include findings related to DM on human temporal bones and cochlear changes in animal models of DM, as well as sex and age differences. This review covers the most significant findings associated to the causes of SNHL in DM observed in the studies from humans and animal models. Reports in the literature have found that diabetic patients are at an increased risk of SNHL (Izuora & Ng, 2022), which is why it is critical to investigate this topic in more depth to further our understanding of the factors that influence this risk and develop better prevention strategies.

3. Human Studies

Overall, previous studies have indicated that the SNHL of diabetic patients is often caused by neuropathy, spiral ganglion atrophy, and thickening of the stria vascularis walls (Ren et al., 2017; Lerman-Garber et al., 2012; Elamin et al., 2005). Here we review the human studies that seek to understand the mechanisms underlying the associations between DM and SNHL. To understand the potential mechanisms, the researchers either analyzed temporal bones from type 1 and 2 diabetic patients or performed hearing tests on DM patients with a self-reported diagnosis of hearing loss (see Table 1 for reference).

Table 1.

Studies in humans and animal models showing a clear association between DM and hearing loss

Species Age/Range Sex Hearing Assessment Major findings
Temporal Bones
Fukushima et al. (2005) --- 18-68 years old Males and Females Morphometric measurements of the cochlea T1DM patients showed atrophy of the stria vascularis which capillaries had thicker walls
Fukushima et al. (2006) --- 44-65 years old Males and Females Morphometric measurements of the cochlea T2DM patients had thicker walls of the blood vessels of the basilar membrane and loss of OHCs
Human Studies
Friedman et al. (1975) --- 22-70 years old Males and Females Audiometry and bone and air conduction tests Diabetic patients had significantly higher hearing thresholds at some frequencies
Mitchell et al. (2009) --- 30 years or older Males and Females Questionnaire and pure-tone audiometry T2DM is associated with an increased prevalence of hearing loss in older populations
Horikawa et al. (2013) --- Unknown Udetermined Meta-analysis of observational studies A strong association between DM and hearing impairment is observed in younger participants
Treviño-González et al. (2015) --- 6-18 years old Males and Females Tonal audiometry and speech audiometry SNHL is more prevalent in patients who have had T1DM for more than 5 years
Kim et al. (2017) --- Avg. 37.6 years old Males and Females Pure-tone audiometric test Young and middle-aged diabetic patients are more likely to have an increased risk of future hearing loss
Gupta et al. (2019) --- Unknown Females Self-reported hearing loss Women with T2DM have a higher risk of hearing loss than those without
Wang et al. (2022) --- 45 years or older Males and Females Self-reported hearing loss Diabetic women are more likely to have SNHL than men
Animal Studies
Fujita et al. (2012) Mouse 8 weeks Males ABR/Blood flow measurements/Histology Diabetic mice were more vulnerable to noise, had decreased blood flow and had thicker walls of the modiolar blood vessels
Pålbrink et al. (2020) Mouse 8 weeks Females Endolymphatic fluid compartment size analysis Hyperglycemia in mice can lead to the development of endolymphatic hydrops
Lyu et al. (2021) Mouse 6 weeks Males ABR/ Blood flow measurements/Histology Diabetic mice showed a decrease in wave I amplitude, altered mitochondria within the sensory epithelium and stria vascularis and the cochlear blood flow was decreased
Akcay et al. (2022) Rat 3 months Females ABR/DPOAE High blood glucose levels cause cochlear dysfunction in the initial stages of diabetes (increased ABR and DPOAE thresholds; prolonged wave I-V latencies)
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3.1. Cochlear changes in type 1 diabetic patients

The effects of diabetes on the cochlea were evaluated in a study by Fukushima et al. (2005) using 26 temporal bones from 13 patients (7 males, 6 females; ages ranging from 18-68 years) with type 1 diabetes and 30 age-matched controls from 17 patients (9 males, 8 females; ages ranging from 12-67 years) without diabetes. Authors performed qualitative and quantitative morphometric measurements of the walls of the blood vessels of the basilar membrane in all turns of the cochlea at the midmodiolar level. Results showed that the diabetic group had significant thickening of the walls of the vessels of the basilar membrane in all turns, and overall thickness increased with aging more rapidly (Fukushima et al., 2005). Diabetics also displayed significantly thickening of the walls of the blood vessels of the stria vascularis in all turns compared to controls. Cochlear reconstructions and cytocochleograms were prepared to analyze the presence or absence of hair cells and compare the percentage of hair cell loss in each turn. Diabetics were shown to have a greater loss of outer hair cells (OHCs) in the lower basal turn, and the loss increased more rapidly with aging (Fukushima et al., 2005). Comparisons between diabetics and controls showed no significant difference in the total number of spiral ganglion neurons, and the total number decreased with age in both groups. Measurements of the area of the stria vascularis and the walls of its capillaries showed that the atrophy of the stria vascularis was higher in diabetics, and that the walls of the blood vessels were thicker in the diabetic stria. In addition, some patients showed a total occlusion of blood vessel walls, and others had complete loss of the stria vascularis. The area of the stria vascularis was shown to decrease with age more rapidly in the diabetic group (Fukushima et al., 2005). These findings suggest that T1DM can result in morphological changes of the cochlea and that diabetic microangiopathy is associated with vascular atrophy of the stria vascularis.

3.2. Cochlear changes in type 2 diabetics

Poor control and longer duration of diabetes are reported risk factors for SNHL (Gupta et al., 2019). Those with T2DM often develop hearing loss much faster than individuals without DM (Mitchell et al., 2009). For instance, Fukushima et al. (2006) compared cochlear changes between 18 patients with T2DM (10 men and 8 women) and 26 age-matched controls (12 men and 14 women). Temporal bones from the 18 diabetic patients (44-65 years of age) were divided into two groups: insulin management group (11 patients) and oral hypoglycemic agent management group (7 patients). In both insulin and oral hypoglycemic agent groups when compared to controls, and authors found an increase in the thickness of the walls of the blood vessels of the stria vascularis. Furthermore, the diabetic patients in the insulin group, had also an increase in the thickness of the walls of the vessels of the basilar membrane. In both the insulin management and the oral hypoglycemic agent management diabetic groups, there was also a significantly greater loss of OHCs compared to controls. In contrast, no significant difference in the total number of spiral ganglion neurons was found among all three groups (Fukushima et al., 2005; 2006).

3.3. Sex-specific associations between DM and hearing loss in humans

While studies describe the relationship between DM and SNHL, disparities between sex and humans and animals are not well addressed. Evidence indicates that sex differences could account for the inconsistent results across studies of DM and hearing loss. The Baltimore Longitudinal Study on Aging found that men show a rapid decline in hearing function compared to women (Pearson et al., 1995). It has been assumed that men are more susceptible to hearing loss when exposed to loud noise over a long period of time (Villavisanis et al., 2020). In addition, it has been suggested that sex differences in hearing loss may be related to risk factors like hypertension or smoking (Izuora & Ng, 2022). Helzner et al. (2005) found that men with DM were more likely to have hearing loss than their female counterparts. Gupta et al. (2019) observed a higher prevalence of hearing loss in diabetic women compared to women without DM; however, the study did not include men. Wang et al. (2022) addressed these inconsistencies in the sex-specific associations between DM and SNHL in a cohort study consisting of 16,140 Chinese middle-aged adults (8,011 men and 8,129 women). Findings indicated that women with DM were more likely to have SNHL than men. Authors also found that females had other potential confounders including overweight, obesity, and had hypertension, while men were more likely to smoke and drink.

It should be noted that sex hormones like estrogen appear to play an important role in protecting auditory function against hearing loss (Villavisanis et al., 2020; Charitidi et al., 2009; Hultcrantz et al., 2006). Estrogen also has beneficial effects on the vascular walls (Kautzky-Willer et al., 2016). However, when women experience a drastic decline in the production of estrogen following menopause (Villavisanis et al., 2020), the protective effects of estrogen in auditory function are likely weakened. Menopause women may suffer of an escalating progression of their hearing loss as well as may have increased their vulnerability to the damaging effects of hyperglycemia on hearing (Izuora & Ng, 2022; Wang et al., 2022). These results are similar to previous studies that have shown that females with DM were more likely to develop hearing loss than men because the risk of microvascular complications were greater and more prevalent in women with DM (Orchard et al., 1990; Monti et al., 2007; Liu et al., 2010; Izuora and Ng, 2022). None of these studies differentiated between T1DM and T2DM.

3.4. Prevalence of sensorineural hearing loss in type 1 diabetic children

Studies have reported that hearing loss is more prevalent in younger rather than in older individuals with DM (Kim et al., 2017; Horikawa et al., 2013). Treviño-González et al. (2015) conducted a longitudinal study in Mexico from January 2011 to December 2012, to analyze the prevalence of SNHL in 84 patients ranging from 6 to 18 years of age with a T1DM diagnosis. Hearing function was tested using tone audiometry, and SNHL was defined at any frequency more than 25 dB. Out of the 84 patients with T1DM, 72 patients displayed normal hearing, while 12 presented SNHL. In addition, SNHL was found more prevalent in patients who had type 1 diabetes for more than 5 years. The data indicate a cumulative effect of T1DM on SNHL. Out of the patients with normal hearing, only 11% had T1DM for more than 5 years, while 33% of those with SNHL had T1DM for more than 5 years (Treviño-González et la., 2015).

4. Animal Studies

Researchers seek to investigate the association and pathophysiology between DM and SNHL in animal models. To induce T1DM, some researchers have injected mice or rats with streptozotocin (STZ), a cytotoxic glucose analogue that induces diabetes by damaging the pancreatic beta cells, thus causing hyperglycemia (Graham et al., 2011; Lenzen, 2008). T2DM has been induced through a high-fat diet (HFD), which is a commonly used animal model to study the pathophysiology of insulin resistance and impaired glucose homeostasis (Vasilyeva et al., 2009; Winzell & Ahrén, 2004). To understand the mechanisms underlying the association between DM and SNHL, the animal studies in this review will describe both types of induction methods (see Table 1 for reference).

4.1. Assessing hearing sensitivity in STZ-induced T1DM-like diabetic mice

Fujita et al. (2012) assessed the changes in the cochlea of mice with STZ-induced T1DM and hypothesized that diabetes increased the inner ear’s sensitivity to environmental stress. One, three, and five months after induction, auditory-evoked brainstem responses (ABRs) were used to compare the sensitivity to noise-induced hearing loss in normal and STZ-induced diabetic mice. ABRs were also measured in normal and diabetic mice exposed to noise before and after five months following injection of STZ or physiological saline. Cochlear blood flow and cochlear blood vessels were evaluated after the preceding measurements. Results throughout the 5-month observation period revealed that, with aging, ABR thresholds increased at all frequencies in both diabetic and control groups. However, it is noteworthy that the diabetic group exhibited significantly higher thresholds at 4 kHz just one month after induction. Both groups also had greater ABR threshold shifts after noise exposure, which indicates greater hearing loss. Additionally, five months after the injection, the walls of the modiolar blood vessels were broader and thicker in diabetic mice, and they showed a decrease in cochlear blood flow after noise exposure compared to normal mice (Fujita et al., 2012). These findings suggest that morphological changes in the walls of the modiolar vessels potentially induce circulatory disturbances in cochleae affected by diabetes. Similar findings were observed in the human study conducted by Fukushima et al. (2005). Fujita and colleagues (2012) concluded that diabetic mice were more vulnerable to noise exposure than controls, and that after noise exposure, mice with long-term diabetes status could develop damaging morphological changes, such as thickening of the walls of the modiolar blood vessels.

4.2. Microangiopathy, synaptopathy, and mitochondrial dysfunction are associated with SNHL in a T2DM mouse model

The human studies described in Section 3 of this review suggested that hyperglycemia and hyperlipidemia were associated with impairments in cochlear microcirculation, which as a result, may increase blood viscosity and lead to circulation disorders in the inner ear (Lyu et al., 2021). In their 2021 study Lyu and colleagues investigated the pathophysiology of diabetes-associated SNHL, cochlear synaptopathy, and cochlear flow by examining morphological changes in the cochlea and testing hearing sensitivity in 22 hyperglycemic, insulin-resistant male B6.BKS(D)-Leprdb/J diabetic mice and 20 control mice. Lower ABR wave I amplitudes were observed in diabetic mice, suggesting cochlear synaptopathy. In addition, morphological observations showed a marked reduction of synaptic ribbons in the inner hair cells (IHC), vacuolated mitochondria with disrupted cristae in the synapses on the IHCs and OHCs, and swollen mitochondria with reduced cristae in the stria vascularis in diabetic mice. These results suggested that microangiopathy, mitochondrial dysfunction, and synaptopathy were the main causal factors leading to SNHL in the insulin-resistant B6.BKS(D)-Leprdb/J diabetic male mice (Lyu et al., 2021). In addition, immunofluorescence assays and laser Doppler flowmetry were used to confirm whether diabetes influenced changes in cochlear blood flow and the expression of PECAM-1 (Lyu et al., 2021). PECAM-1 is a cell-surface protein expressed on the surface of the endothelial cells of the stria vascularis, which plays specific roles in regulating vascular integrity and transmitting survival signals into the blood (Gao et al., 2003; Falati et al., 2006). Authors found that PECAM-1 expression and cochlear blood flow were decreased in the cochlea, indicating that cochlear microcirculation was compromised in diabetic mice and prolonged hyperglycemia had adverse effects on protein activity/expression in the cochlea (Lyu et al., 2021).

4.3. Assessing the impact of insulin resistance in a high-fat diet-induced T2DM mouse model

Pålbrink et al. (2020) investigated the impact of insulin resistance on the inner ear in HFD-fed mice to further understand the mechanisms underlying the association between T2DM and inner ear impairment. C57BL/6J mice (n = 12) were fed an HFD, or control diet, and the size of the inner ear endolymphatic fluid compartment was measured 30 days after. The effect of HFD on the size of the endolymphatic fluid compartment was also measured in 8 mice before and after being fed an HFD. The insulin-resistant HFD-fed mice had larger endolymphatic fluid compartments than the control group and developed endolymphatic hydrops in both ears. Larger endolymphatic fluid compartments and the presence of endolymphatic hydrops could lead to cochlear dysfunction in the HFD T2DM mice. In addition, Pålbrink and colleagues (2020) suggested that the development of endolymphatic hydrops could be related to systemic hyperglycemia or insulin resistance. Valenzuela et al. (2020) showed in guinea pigs, that endolymphatic hydrops developed after insulin administration. Studies reported that insulin reduces [K+] and increases [Na+] in the endolymph, therefore increasing osmotic pressure and resulting in endolymphatic hydrops (Albernaz, 2016; Mendelsohn & Roderique, 1972).

4.4. Increased blood glucose levels lead to oxidative stress in the cochlea and induce SNHL

Studies have suggested that DM is strongly associated with the oxidative stress produced by reactive oxygen species that can lead to changes in protein structure and function and lipid peroxidation, thus causing cell damage (Halliwell et al., 1986; Kakkar et al., 1995; Ihara et al., 1999; Opara, 2002; Turk et al., 2002; Davì & Patrono, 2005; Matsunami et al., 2010). A study conducted by Akcay et al. (2022) investigated the effects of blood glucose on ABRs and Distortion Product Otoacoustic Emissions (DPOAE). In addition, the authors determined whether oxidative stress was associated with hearing function in STZ-induced diabetic rats. The rats were divided into three groups: control, high blood glucose, and DM. Authors observed that blood glucose levels were higher in both high blood glucose and DM groups compared to controls, but the DM group displayed the highest levels. To evaluate oxidative stress, brainstem tissue levels of thiobarbituric acid reactive substance were measured fluorometrically. Elevated levels were observed in both high blood glucose and DM groups, with the latter exhibiting the highest levels, suggesting a potential involvement of increased oxidative stress in the pathogenesis of diabetes. The DM group also showed increased threshold values at 8 kHz in the ABR recordings compared to the control group, but at 16 kHz, threshold values were higher in both DM and high blood glucose groups compared to controls. The authors also showed when compared to controls, that the DM rats had prolonged wave I-V latencies at 8 and 16 kHz, while the latencies in the high blood glucose group were only longer at 8 kHz. Lower DPOAE amplitudes at frequency values from 4,000 to 10,000 Hz were seen in the DM group compared to the control group, while the high blood glucose group had lower DPOAE amplitudes at slightly higher frequencies (8,000-10,000 Hz). These findings suggest that high blood glucose levels can cause damage to auditory pathways in the initial stages of diabetes and deficits in both ABRs and DPOAEs are indicative of cochlear dysfunction affecting IHCs and OHCs and the auditory nerve (Akcay et al., 2022).

5. Discussion and Future Directions

It is well-established in audiological literature that cochlear blood flow is essential for the normal function along the auditory pathway (Lyu et al., 2021; Fujita et al., 2012; Engdahl et al., 2015). It should also be noted that highly vascularized regions in the cochlea, like the stria vascularis (Fig. 1B), are susceptible to diabetic microangiopathy and ischemic damage, and several factors, such as glucose levels, can account for these causes that lead to eventual SNHL (Engdahl et al., 2015). Thus, several vascular mechanisms may account for hearing loss in diabetic patients, including the cochlea being susceptible to microangiopathy due to endothelial damage, oxidative stress that promotes vasoconstriction, and glycoprotein buildup (Engdahl et al., 2015; Taslipinar et al., 2011; Dantas et al., 2012). Patients can lower their risk of SNHL with good glycemic control, while poor control increases the risk (Cruickshanks et al., 2015). Therefore, it is important that patients not only maintain good glycemic control but also get examined or treated by a physician who specializes in cardiovascular disorders. While there is no existing cure for diabetes potential existing treatments that increase cochlear blood flow could prevent or postpone SNHL. Thus, obtaining a complete blood profile is crucial to accurately diagnose and treat SNHL in patients with DM (Hultcrantz, 1988). Limited studies describe the effects of diabetic neuropathy on hearing. High blood glucose levels can injure and damage the peripheral nerves and the myelin sheaths (see for review Malone, 2016). Studies have shown that abnormal glucose levels can alter the metabolism of any cell type, including neurons (Malone et al., 2008; Tong et al., 2014). However, it appears that the main cause of neuropathy in diabetics is small-vessel abnormalities. Then, damaged nerves can alter the normal sound processing in the cochlea and along the auditory pathway. Friedman et al. (1975) is just one study that showed that diabetic patients with peripheral neuropathy had SNHL.

The studies presented in this review have provided valuable information that will allow researchers and healthcare professionals to better manage and treat diabetic patients at an increased risk for SNHL. Moreover, researchers should continue to explore sex differences in auditory disorders and other diseases when considering treatments and preventative strategies for women and men. While sex differences are highlighted more in studies investigating the relationship between DM and SNHL, there is a lack of studies that target different populations other than Caucasian American or European ones. This review consisted of some studies conducted in China, however, for future studies it would be valuable to define the prevalence of hearing condition in diabetic individuals from more African American, Asian-American/Pacific Islander, Latino/Hispanic American, and/or Native American populations. Many of the human studies were also limited to self-reported blood sugar and hearing tests and were therefore unable to assess the relationship between hearing loss and diabetes.

Additionally, researchers could improve animal models by analyzing histopathological, molecular, and functional changes in younger mice, rats, or even non-human primates to assess whether adolescence plays a role in the association between DM and SNHL and whether there are sex differences. The studies above were conducted in adult mice. Furthermore, all of the animal models were limited to low sample sizes, which could lead to inconsistencies in findings and, therefore, should increase sample size in future studies.

Highlights.

  • The impact of Diabetes Mellitus on hearing loss has been debated for decades, however, the etiopathogenesis of sensorineural hearing loss in the context of Diabetes Mellitus is still controversial

  • Microvascular changes due to diabetic angiopathy can lead to sensorineural hearing loss in both humans and rodents

  • Female diabetic patients are shown to be more vulnerable to sensorineural hearing loss than males

Acknowledgements

This work was supported by NIDCD DC013048 (MER). We thank Nicholas Lozier and Indra Pal for their helpful comments on the review.

List of Abbreviations

ABR

auditory-evoked brainstem response

DM

diabetes mellitus

DPOAE

Distortion product otoacoustic emission

HFD

high-fat diet

IHC

inner hair cell

OHC

outer hair cell

SNHL

sensorineural hearing loss

STZ

streptozotocin

T1DM

type 1 diabetes mellitus

T2DM

type 2 diabetes mellitus

Footnotes

Disclosure and competing interests’ statement

The authors declare no competing financial interests.

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