Diabetes is a disease which elevates normal levels of blood sugar and affects multiple physiological systems in the body. There are two major types of diabetes: type one diabetes mellitus (T1DM) and type two diabetes mellitus (T2DM). It is estimated that five to 10 percent of Americans who are diagnosed with diabetes have T1DM, which is due to dysfunction of cells in the pancreas that normally produce insulin. The American Diabetes Association has cited T2DM as the most common form of diabetes, which is very prevalent in elderly populations, affecting more than 20 percent of people over the age of 60. Many of the complications from T2DM in older people are associated with natural aging but these complications can appear earlier in diabetic patients. The most serious long-term health complications include heart, kidney, eye, leg and foot circulation problems, and nerve damage which can result in numbness and abnormal sensations. T2DM is becoming a national health problem – even now in many of our children and young adults.
The association between hearing loss and diabetes has been debated since first reported in 1857, although doctors often observe that patients with T2DM exhibit significant hearing loss. However, the precise biological mechanisms of how diabetes diminishes hearing in young adults or the elderly are not well understood. There are several common theories or hypotheses of why people with diabetes may have accelerated age-related hearing loss: 1) neuropathy – problems with nerve cells; 2) angiopathy – problems with the circulatory system (heart, blood vessels, including capillaries and microvasculature of sensory organs such as the inner ear); and 3) associations or interactions between neuropathy and angiopathy.
A main focus of our research group is to understand the neuronal and molecular bases of age-related hearing loss, also called presbycusis. Considerable progress has been made in understanding correlations between common medical conditions in humans and lab animals (rodents) and age-related hearing loss. Recently our Rochester hearing research group discovered that older diabetic patients exhibited significant hearing loss compared with same-age individuals without diabetes (age 60 and above). In this study, we used two groups of elderly people. One group consisted of elderly people with T2DM who did not have any other significant health problems; the other group was healthy people matched by sex and age with the first group. Both groups went through a battery of comprehensive hearing tests (about three hours of testing) to evaluate peripheral (inner ear) and central (brain) hearing capabilities.
The results demonstrated that older people with T2DM exhibited significantly worse hearing for both the inner ear (peripheral hearing system, cochlea) and some parts of the brain used for hearing (central auditory system). For example, understanding speech was more difficult and the levels at which they could hear white noise and pure tones (Fig. 1) were significantly elevated in the T2DM group. The cochlear outer hair cell function was also impaired, as shown by a significant decrease in the amplitudes of otoacoustic emissions recorded with tiny microphones placed in the ear canal. We also conducted a hearing-in-noise test. Speech recognition in background noise was significantly worse in the diabetics. These findings indicate that age-related hearing loss in people with T2DM is more severe than expected by taking into account aging alone.
The nature of diabetes-related hearing loss is an extremely important issue, so we have begun examining possible neural and biological causes in laboratory mice. But how can mice have diabetes symptoms that mimic human symptoms? We can model T1DM by injecting a chemical that impairs the insulin-producing cells of the mouse pancreas. We can induce T2DM by feeding mice a high-fat, high-carbohydrate diet. Utilizing these lab methods, we can study the anatomy, chemistry and genetics of the mouse inner ear and parts of the brain used for hearing. Determining these biological effects of diabetes paves the way for future biomedical interventions, such as medications, to improve hearing in persons with diabetes.
Many studies have shown that a certain type of mouse, the inbred CBA/CaJ mouse strain, serves as an excellent animal model for human presbycusis, since it shows hearing loss that progresses on a time frame similar to most humans. The age-related hearing loss of this strain of mouse probably corresponds most to a sensory-neuronal type of age-related hearing loss in which high-frequency tones are lost, along with changes in parts of the brain used for hearing.
We took a group of middle-aged mice, induced diabetes and then measured changes in structure and function of the inner ear (cochlea) and parts of the brain used for hearing. The duration of the experiment was six months, approximately corresponding to 15 years of human life (average mouse lifespan is about two and a half to three years versus 70 to 80 years for humans). Body weights and fasting blood glucose levels were measured at the start of the experiment to create a baseline of data and then we took measurements every other month for six months. Both diabetic groups (T1DM and T2DM) exhibited significant elevation of fasting blood glucose and T2DM mice gained weight. Hearing tests showed accelerated hearing loss by two months after the start of the study for T1DM, while in T2DM hearing loss was evident after six months of the experiment. In both cases the diabetic mice showed elevations in auditory brainstem response (ABR) thresholds, similar to the human diabetic pure-tone audiogram changes – in order for the mice to hear them, pure tones had to be louder than they were when the experiment began.
Thanks to lab mouse models, we have learned a good deal about the relationship between diabetes and hearing loss. There is still much to learn and these same lab mouse models will enable future investigation of anatomical, chemical and molecular changes in the inner ear and parts of the brain used for hearing to determine underlying biological mechanisms of diabetes-related hearing loss. For example, one big question is: Does hearing loss associated with diabetes improve when a diabetic is treated with medications or exercise/lifestyle improvements? These findings and future research will pave the way for biomedical interventions to preserve or improve sensory functioning, like hearing loss, in persons suffering from diabetes or other metabolically-deficient medical conditions, including those linked to aging.
