Possible hearing implications of diabetes mellitus : a literature review

The purpose of this research is to review the literature to find the relation between diabetes mellitus, types I and II, and possible hearing disorders. According to the studies analyzed, was possible to conclude that there is a relation between hearing alteration and diabetes mellitus. It is believed there are several factors that contribute for this association, being needed more studies with more details to establish the true role of these factors.


INTRODUCTION
Diabetes mellitus is a metabolic disorder, in which there is uncontrolled sugar levels of the organism, affecting all sectors of the body.The pancreas does not produce insulin or produces inefficiently, failing to perform its biological purpose.
The main types of diabetes mellitus are type I and type II.In type I, there is an autoimmune destruction of beta pancreatic cells leading to insulin production inability, requiring insulin injections.Type II is characterized by affections to insulin action or secretion, with possible predominance of an event, usually being both present 1 .The metabolic control of type II diabetes is usually achieved with diet, physical exercises and/or concomitant use of oral hypoglycemic agents, insulin may be used in the treatment 1 .
This study aims to analyze the relationship between diabetes mellitus, type I and II, and possible hearing disorders.This curiosity arose from the fact that audiological anamnesis, as applied in clinical audiology practice, questions patients about the very controversial and may be related to diffuse microangiopathy that would affect nourishment of peripheral nerves 7 .

Audiological implications
The association between hearing loss and diabetes mellitus (type I and type II) has been debated since it was first mentioned by Jordan in 1857, being subject of debate and remaining controversial to this day, despite numerous previous studies [8][9][10][11] .
In 1864, it was identified the first scientific documentation connecting glucose metabolism disorders to inner ear diseases; observing the relation between sensorineural deafness and diabetes, thus establishing the link between hearing loss and hyperglycemia.Since then, several authors reported vestibular-cochlear secondary alterations to diabetes mellitus 11,12 .
Among glucose metabolism disorders, diabetes mellitus is the affection most commonly related with auditory disorders 13 , and the incidence of neurosensory hearing loss in patients with diabetes mellitus varies from 0% to 80% 11 .
When it comes to diabetes mellitus, there are different opinions about the pathological affections caused in the auditory system.The hearing acuity may be compromised in patients with glucose metabolism alterations and insulin action alterations, regardless of age 14 .Researches have suggested a higher risk of hearing loss in diabetic patients, but other factors such as exposure to noise, ototoxic drugs and presbycusis, known to affect both glucose metabolism and cochlear function, make it difficult to establish this association 10 .Studies in humans are complicated for the variety of factors, in addition to the variations related to diabetes, such as duration of disease, metabolic control and the presence and degree of complications 10 .
Ganança states that the metabolic changes that occur in diabetes mellitus, such as hyperglycemia, hyperinsulinemia and hypoglycemia, can cause various types of hearing loss and vestibular changes 15 .
Patients with glucose metabolism disorders may experience auditory, vestibular or mixed symptoms.Dizziness may be of the rotatory kind, but it is not unusual to find complaints of instability, floating or a feeling of faint.Hearing complaints are varied and can be presented from fluctuating hearing loss to sensorineural hearing loss.Still occur tinnitus and aural feeling of fullness 14.
Glucose metabolism has great influence in the physiology of the inner ear and this stands out for its intense metabolic activity 13 .The underlying pathophysiology associated with diabetes and hearing

General considerations
Diabetes mellitus is a metabolic disease of multiple etiologies.It is characterized by chronic hyperglycemia resulting from disorders in the metabolism of carbohydrates, proteins and fats, due insufficient secretion function and/or insulin absence, as well as for defects of its action on insulin target tissues (liver, muscle and adipose tissues) 2 .
In Brazil is quite high the incidence of chronic complications of diabetes.It is known that the number of individuals with the disease grows every year and it is estimated that half of these individuals are unaware of the diagnosis 3 .
In this work will be focused possible audiological implications of diabetes type I and type II.
The type I diabetes mellitus is the most common form among children and adolescents, caused by partial or total destruction of pancreatic beta cells, resulting in progressive inability to produce insulin.This aggression is usually of the autoimmune nature, resulting from genetic and/or environmental processes.Insulin is always necessary in the treatment of type I diabetes mellitus and should be established as soon as the diagnosis is established 4,5 .
The type II diabetes mellitus results from the action of insulin resistance mechanisms associated with a defect in hormone secretion, corresponding to the most prevalent form of diabetes worldwide 4 .These individuals still have some endogenous insulin, but their levels are insufficient to maintain normoglycemia due to resistance to its action 6 .It can happen at any age, but is most often diagnosed after age of 40 4 .
The main goal of the diabetic patient's treatment is prevention of chronic complications since the disease is not curable, but controllable.In a large number of individuals, especially children and adolescents, the diagnosis of diabetes is made in face of health complications, especially infections 3 .
Complete clinical manifestation of diabetes is characterized by metabolic disorders, vascular and neuropathic complications 3 .
One of the most consistent morphological aspects of diabetes mellitus is diffuse thickness of basal membrane, which also occurs in the vascular endothelium and is called diabetic microangiopathy.Its pathogenesis is still unclear, however it is clearly associated with hyperglycemia 7 .
Other morphological alterations refer to the impairment of both motor nerves as the sensory nerves of lower extremities, characterized by damage to Schwann cells, degeneration of myelin and axon damage.The cause of neuropathy is still there are those who understand that diabetes mellitus and hearing loss could be an integral part of a genetic syndrome and not dependent upon each other 21 .
Angiopathy and neuropathy are diabetes complications, well recognized, but not fully understood, and are considered important factors responsible for vestibulocochlear manifestations 21 .It is believed that metabolic factors, vascular abnormalities and other mechanisms besides the peripheral nerves' vulnerability, could affect the inner ear and/or the eighth nerve and cause decreased hearing 8 .
Diabetic angiopathy has been characterized by endothelial proliferation, glycoproteins accumulation in the intima and thickening of the basal membrane of capillaries and small blood vessels.Angiopathy may occur both directly by interfering with the blood supply to the cochlea by reducing transport through the thickened walls of capillaries, and indirectly, by reducing the flow in a narrowed vasculature, or even by secondary degeneration of the eighth cranial nerve 23 .Several authors have previously suggested that microangiopathy could be responsible for functional changes in the inner ear associated with diabetes mellitus 10 .There appears to be a relationship between hearing loss severity and disease progression, and this may be due to microangiopathic disease in the inner ear 22 .
Diabetic neuropathy, one of the main complications that appear from time of diabetes mellitus chronic evolution, is characterized by progressive degeneration of nerve fibers' axons 24 .The main electrophysiological change in diabetic neuropathy seems to be a decrease in the amplitude of sensory and motor responses in peripheral nerves.However, it also seems to exist a demyelinating action by hyperglycemia, which leads to a decrease in nerve conduction velocity 25 .
Regardless of the etiology and pathogenesis of hearing loss, it can be noted that several studies of auditory function in diabetic patients showed that hearing loss attributed to diabetes mellitus (type I and type II) is usually of the progressive bilateral neurosensorial type, predominantly in high frequencies 13,14,26 , especially in the elderly 13,26 .Another study also mentions the possibility of an early neurosensorial hearing loss 10 .
Several researches revealed hearing loss, sensorineural in most cases, with a predominance of light to moderate degree and affecting higher frequencies 27 .Hearing loss present at higher frequencies could be explained by the fact that the basal region of the cochlea is more vascularized, which predisposes it to more obvious effects of vascular damage 28 .The hyperglycemia, in turn, could be further present in this region and therefore, loss is subject to speculation.The main explanation would be the effect of diabetes in microvascular disease of the cochlea 9 .Unlike the retina, cochlea is virtually impossible to visually examine and its microvasculature is incorporated into the temporal bone, which can not be analyzed effectively, even under surgical conditions.Previous studies on cadavers have shown microvascular disease affecting the vascular groove, which is responsible for generating endolymph that serves as driving force for mechanical transduction of hair cells 16 .
The involvement of the blood vessels supplying the inner ear and the changes occurring in the vascular striae in patients with diabetes mellitus are facts proven by several authors, who believe that such changes are strong evidence that diabetes mellitus may cause hearing loss 14 .
Specifically in the auditory system, it may occur atrophy of spiral ganglion, degeneration of the eighth nerve myelin sheath, decrease on the number of nerve fibers in the spiral blade, or thickening of the capillary walls of the groove vascular and small arteries inside the ear canal 17 .
Vascular and nerve tissues have predominant role in auditory function and any disease capable of causing damage its cells has the potential to negatively affect various hearing organs.In fact, the connection between hearing and diabetes seems likely if the blood supply to the cochlea and/or nerve centers in the auditory path, including the brain, are affected 18 .Both hypoglycaemia as hyperglycemia can alter the normal functioning of the cochlea, causing metabolic deafness through floating blood glucose, essential in the chemical constitution of endolymph 5 .
The inner ear is especially sensitive to fluctuations in blood glucose and insulinemia.The vascular stria depends on constant glucose concentration and it is glycemic oscillation that triggers changes to balance as well as to hearing 19 .However, inner ear has no energy reserves in storage, which means that minor glycemic variations influence its function, causing alterations 13 .
Metabolic changes in the inner ear cause a potassium displacement from the endolymph to the perilymph, and sodium displacement in the opposite direction.This mechanism would cause vertigo, tinnitus, hearing loss and aural feeling of fullness 19 .It is also observed that there is a reduction of hair cells and a smaller oxygenation on them, due to these vascular abnormalities of the inner ear 20 .
There is controversy regarding the etiology and pathogenesis of hearing loss.Some researchers support that it occurs due to neuropathy; others attribute the disease to angiopathy; and another group claim it's a combination of the two 21,22 .But 32,33 since diabetes mellitus is known can cause microvascular damage, as well as other microcirculation disorders involving sudden increase of blood viscosity and thromboembolic episodes 32 .According to Weng et al., diabetic patients with idiopathic sudden hearing loss tend to be predominantly male, elderly and have a high prevalence of hypertension and hyperlipidemia 33 .
In relation to the vestibular system, it is experimentally shown that Labyrinthic structures, and especially the vascular groove, present intense metabolic activity and thus depends on constant and adequate supply of oxygen and glucose 34 .Klagenberg et al. observed the prevalence of changes in the peripheral vestibular system and the peripheral vestibular deficit syndrome 35 .This result is consistent with other studies that also found changes in the vestibular exam 36,37 .
It is also known that the metabolic disorders can affect the homeostasis of the vestibular organ faster than the auditory portion 38 .Gawron et al. noted that the detection of disorders present in the central nervous system in patients with diabetes mellitus seems to be more sensitive through vestibular assessment than by audiological evaluation.In the same study, the authors found that auditory tests and measures of acoustic impedance were within the normal range, although most of them had central change in the vestibular assessment 38 .
In contrast, findings from Biurrun et al., point out that patients with newly diagnosed diabetes mellitus showed no abnormality in vestibular assessment.This led to consider that the effect of diabetes on vestibular function could possibly be mediated with diabetic complications such as neuropathy and angiopathy, which are absent at disease onset 36 .
However, other authors have reported minimal cellular changes and functional impairment of the central labyrinthic pathways as complications of initial diabetes mellitus, with no relation to neuropathy or microangiopathy 9 .This is probably because the labyrinth is particularly sensitive to small variations in glucose and insulin plasma levels, and evidenced by the presence of insulin receptors in the endolymphatic sac 39 .
As previously mentioned, it is known that patients with diabetes mellitus often show symptoms such as dizziness, tinnitus and hearing loss.It is called attention to the difficulty in distinguishing hearing loss in diabetics from senile hearing loss, in non-diabetic individuals.Some studies indicate that a reduction in auditory acuity, which is similar to that shown in presbycusis, is greater than expected for its effects would be greater than those observed in other regions of the cochlea 29 .
Perhaps, as seen in aging and ototoxic subjects, the basal or high frequency region in the cochlea is susceptible to certain diseases, such as diabetes.Although routine clinical tests usually run only in the frequencies of speech, when they identify sensitivity beyond this region (at higher frequencies), we obtain a more complete picture of cochlear status, which may indicate declining hearing in the high frequencies 10 .
In a study by Maia and Campos, there is no consensus regarding audiological and histopathological aspects of type I diabetes mellitus 21 .In this study, there were three cases (10.0%) of sensorineural hearing loss, in which one case (3.3 %) was of flat bilateral moderate sensorineural hearing loss kind and two cases (6.6%) were of descending bilateral moderate sensorineural hearing loss.
Conventional audiometric tests are not sensitive enough to detect the earliest stages of sensorineural hearing loss.For this, it can be used electrophysiological methods and otoacoustic emissions 11 .
The otoacoustic emissions test is a physiological objective test of outer hair cells.A study indicates that the distortion product otoacoustic emissions can detect early hearing loss in diabetic patients because they are more sensitive than routine behavioral audiometry to detect cochlear dysfunction in these patients 30 .A smaller amplitude of distortion product otoacoustic emissions of 4.0 kHz was reported by Lisowska et.al 11 .
Several studies have revealed alterations in auditory brainstem evoked potential in individuals with diabetes mellitus showing a prolonged latency of waves III and V 11,30 .Bayazit et al. also reported in its research on 59 diabetic patients an increase in latency of the main components of the responses of the brain stem 31 .
In order to investigate the relationship between diabetes mellitus and hearing, another study used the P300 cognitive potential, which has been used as an objective procedure to assess cerebral cognitive function.The results of this study showed that the decrease in blood glucose level in diabetic individual leads to increased latency and decreased amplitude of the P300 component, suggesting a dysfunction in the central auditory system.Considering that the nervous tissue is glucose-dependent, i.e., dependent on a stable level of glucose in ideal situations, extended periods of hypoglycemia episodes can lead to significant individual neurological alterations 1 .
Other findings related to diabetes and hearing loss indicate that diabetes can be considered one of the causes of idiopathic sudden hearing loss

CONCLUSION
According to the analyzed studies, we can conclude that there is a relation between hearing disorders and diabetes mellitus.We also believe that there are a number of contributing factors to such an association, and more discerning studies are required to establish the true role of these factors.
Considering the above, it can be noticed that people with diabetes mellitus are more likely to have hearing loss.Thus, this possibility should be investigated by health professionals working with diabetic patients so that such patients might benefit if audiologically monitored.the age, in elderly and diabetic patients 10 .After age 60, the difference in hearing loss between diabetics and non-diabetics was reduced 10 .
However, other studies have reported that hearing loss found in diabetes does not follow a pattern similar to presbycusis, due to the fact that the distribution of frequencies is more linear 40 .
To the present time, we have not found specific studies that showed data related to speech recognition tests in diabetic patients.Some authors refer only that changes in brain cells on some diabetics can result in slower processing of complex sounds, such as of speech 18 .