The functioning of otolith organs in individuals with type-II diabetes mellitus

Diabetes mellitus (DM) is a multifactorial metabolic disorder primarily attributed to hyperglycemia and abnormalities in the metabolism of fat, carbohydrates, and lipids (Reed et al., 2021). As of 2021, about 536.6 million adults (10.5 % of the global population) were estimated to be suffering from DM, and this number is expected to rise to 783.2 million by 2045 (Sun et al., 2022). This means that nearly 12.2 % of the global population will be affected by DM 20 years from now, 2045, a figure confirming the alarming rate of rise of the disease in the population.

DM, based on etiological factors, can be subdivided into three major types: Type 1 diabetes, Type 2 diabetes, and Gestational diabetes. However, their prevalence does not show an equal share in the population. Type 2 diabetes mellitus (T2DM) outnumbers the other two types by being prevalent in over 90 % of the population with DM (Reed et al., 2021). A recent epidemiological estimate indicated that approximately 462 million people (6.28 % of the global population) were affected by T2DM until 2017 (Khan et al., 2020), with a rising trend during the years to come.

T2DM is characterized by hyperglycemia resulting from a progressive decline in pancreatic β-cell insulin secretion and impaired insulin sensitivity in target tissues. This condition usually results from malfunctioning feedback mechanisms between insulin action and insulin secretion (Zheng et al., 2018). Among the pathophysiological mechanisms, β-cell dysfunction is associated with more severe repercussions than insulin resistance (Galicia-Garcia et al., 2020). A combination of both aggravates hyperglycemia, thus accelerating the progression of T2DM and related complications (Galicia-Garcia et al., 2020; Zheng et al., 2018).

T2DM leads to severe long-term complications, affecting nearly every organ system. Common clinical complications include macroangiopathy, retinopathy, nephropathy, and neuropathy. Additionally, it increases the susceptibility of an individual to infections, myopathy, osteoporosis, arthropathies, and liver damage (Farmaki et al., 2020). In addition to the above-mentioned complications, a commonly observed yet often neglected and less reported complication of T2DM is inner ear impairment.

The human inner ear houses the sensory systems of hearing (cochlea) as well as balance (vestibule). The key structures of hearing and balance, such as the stria vascularis, spiral ligament, and the maculae of the otolith organs, are highly sensitive to changes in glucose utilization as they involve insulin receptors, glucose transporters, and components of insulin signaling pathways (Agrawal et al., 2010; Degerman et al., 2013; Dsilva et al., 2017; Gioacchini et al., 2018). In fact, the presence of hearing impairment, tinnitus, and vertigo in several individuals with T2DM is primarily attributed to both micro- and macro-vascular compromise that arises due to glucose metabolism (Kumar et al., 2021).

Over the past few decades, several attempts have been made to study the effects of diabetes on hearing function. While some of these investigations have shown evidence for hearing loss in a higher proportion of the T2DM population than the healthy controls (Kumar et al., 2021), there exists no clear consensus between hearing loss and diabetes. Nonetheless, research over the recent years has indicated a positive association between hearing loss and the presence of T2DM (Wang et al., 2024). Given that the vestibular system has similar connective tissues to those seen in the hearing system (Myers and Ross, 1987; Piker and Romero, 2019; Sadeghi and Géléoc, 2022; Takahashi et al., 1970) and that the two of them share a common arterial supply (Fife, 2010), it may be reasonable to hypothesize that T2DM may also have detrimental effects on the vestibular system. In fact, a few studies have shown a 70–84 % higher prevalence of vestibular dysfunction in the T2DM group than in non-diabetic controls (Bakkali et al., 2021). While T2DM might affect various parts of the vestibular system, the extent and the mechanisms of its damage are not completely deciphered yet.

The two otolith organs (saccule & utricle) and three semicircular canals form the peripheral vestibular system. Over the years, several tests were developed for the assessment of the semicircular canals, and a few were also available to assess the utricular function; however, no test could provide an insight into the saccular function, until the discovery of vestibular-evoked myogenic potential (VEMP). This biphasic electromyographic potential can be recorded from various muscles in the body, such as the trapezius (Ferber-Viart et al., 1998), triceps (Cherchi et al., 2009), forearm flexor (Valente et al., 2020), soleus (Cunha et al., 2014), masseter (Deriu et al., 2007; Vignesh et al., 2021), and gastrocnemius muscles (Rudisill and Hain, 2008). However, the two major variants recorded clinically are cervical VEMP (cVEMP) and ocular VEMP (oVEMP). The cVEMP response is recorded from the surface electrodes placed along the course of the tonically contracted sternocleidomastoid (SCM) muscle. It assesses the sacculo-collic reflex pathway from the saccule to the ipsilateral SCM muscle using the medial vestibulospinal tract (Kushiro et al., 1999). On the other hand, oVEMPs are obtained from the electrodes placed over the inferior oblique muscle (IOM). It assesses the utriculo-ocular pathway from the utricle to the contralateral IOM (Curthoys et al., 2011).

Several studies have explored the effects of T2DM on otolith organs (Dsilva et al., 2017; Kalkan et al., 2018; Konukseven et al., 2015; Koura et al., 2023; Li et al., 2019; Omar et al., 2018; Ward et al., 2015; Zhang et al., 2023). However, otolith dysfunction/hypofunction has not always been confirmed in these studies. Further, among the studies investigating the otolith functioning in individuals with T2DM, only 6 studies have investigated both cVEMP and oVEMP in the same cohort (Kalkan et al., 2018; Konukseven et al., 2015; Koura et al., 2023; Omar et al., 2018; Ward et al., 2015; Zhang et al., 2023). While two of these studies reported significantly prolonged latencies (Konukseven et al., 2015; Zhang et al., 2023), and two other studies found significantly reduced amplitude with no significant effect on latencies (Kalkan et al., 2018; Ward et al., 2015), one study reported significantly prolonged latencies as well as reduced amplitude in individuals with T2DM (Koura et al., 2023), and yet one another reported no significant difference in any of the parameters of VEMP tests between T2DM and their healthy counterparts (Omar et al., 2018), thereby showing a full range of possible findings. Given these findings, a few review studies have concluded that the results of the otolith assessment are inconsistent across the published studies (Bakkali et al., 2021; Kumar et al., 2021). The differences in findings may be due to the high heterogeneity observed among the studies, which signifies the need for further studies investigating VEMP outcomes using standardized methods to make definitive statements about their findings in individuals with T2DM (Bakkali et al., 2021). Hence, the present study aimed to investigate the effect of T2DM on the functioning of the otolith organs and behavioural balance.

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