Diabetes and Audiological Monitoring of Oral and Injectable Medications Robert M. DiSogra, AuD, FAAA Audiology Consultant Millstone, NJ www.drbobdisogra.com Disclosure I There are no non-financial relationships to disclose for this presentation Disclosure II Dr. DiSogra is not a Endocrinologist Pharmacist 1 2 3 Disclosure III The content of this program is for informational purposes only Diabetes ~30 million Incidence HL ~35 million Incidence Type 2 >20% of persons over 65 y.o. Ogden, et al, 2014 4 5 6 1
Diabetes Diabetes A disease The body s ability to produce or respond to the hormone insulin is impaired A metabolic disorder The body is unable to regulate levels of glucose in the blood 7 8 9 WHY? A lack of insulin in the body OR Failure of cells in the body to respond properly to insulin Diabetes GLUCOSE Cochlear function is affected by hyperglycemia GLUCOSE Hyperglycemia Reduces dendritic branching Creates oxidative stress Produces free radicals 10 11 12 2
GLUCOSE Hyperglycemia results in Neural Damage Microglial Activation Microglial Activation Microglia The resident immune cells of the CNS Normally respond to neuronal damage Activation of microglia is a hallmark of brain pathology Dheen, St et al. Microglial activation and its implications in the brain diseases. Curr Med Chem. 2007;14(11):1189-97. Changes associated with Degradation of the vasa vasorum* surrounding CN VIII *a network of small blood vessels that supply the walls of large blood vessels 13 14 15 Diabetes Diabetes Diabetes Results: Abnormal metabolism of carbohydrates Elevated levels of glucose in the blood and urine Results: Neuropathy Microvascular damage Damage to arteries, nerves, kidneys and retinas Results: Neuropathy Microvascular damage Damage to arteries, nerves, kidneys and retinas 16 17 18 3
3 Types of Diabetes Type 1 Type 2 Gestational Type 1 Diabetes Body does not make insulin The immune system attacks and destroys the cells in the pancreas that make insulin 19 20 21 Type 1 Diabetes Usually diagnosed in children and young adults Type 1 Diabetes Can appear at any age Type 1 diabetics need to take insulin every day to stay alive 22 23 24 4
Type 2 Diabetes Body does not make or use insulin well Can develop at any age (even during childhood) Occurs most often in middle-aged and older people Type 2 Diabetes The most common type of diabetes 20% of adults >65 25 26 27 Can develop during pregnancy Clears after the baby is born Gestational Diabetes Mom has a greater chance of developing Type 2 diabetes later in life Sometimes GD is actually Type 2 diabetes Gestational Diabetes 28 29 30 5
High Blood Glucose Levels Leads To: Heart Disease Stroke Kidney Disease Glaucoma Dental Disease Foot Problems Peripheral Neuropathy and HEARING LOSS! Diabetes and the Auditory System outer middle inner auditory ear ear ear cortex Diabetes and the Auditory System outer ear middle ear 31 32 33 Types of Hearing Loss Types of Hearing Loss Types of Hearing Loss Conductive Hearing Loss 15-16% CHL (1% otosclerosis) inner ear Sensorineural Hearing Loss More common (42%) with diabetes pts than with non-diabetes patients Genevey Hlayisi, et al 2018, Swain, et al, 2014; Thimmasettaiah, et al, 2012 Genevey Hlayisi, V. et al, 2018; Swain SK, et al, 2014; Kakarlapudi, V., et al., 2003 34 35 36 6
Diabetes and the Auditory System Types of Hearing Loss Types of Hearing Loss outer middle inner auditory ear ear ear cortex Mixed Hearing Loss (combo. of CHL & SNHL) 26% Genevey-Hlayisi et al, 2018 18% Swain et al, 2014 Central Hearing Loss (cortical HL) No research identifying central HL with insulin dependent or non-insulin dependant patients 37 38 39 Types of Hearing Loss Types of Hearing Loss Types of Hearing Loss Cannot be ruled out! Central Hearing Loss Sensorineural Hearing Loss Fluctuating Hearing Loss (altered sodium/potassium gradients and reduced endocochlear potentials) Sudden S/N Hearing Loss Cases of sudden HL have been reported Jung, et al. 2018, Weng, et al 2005 40 41 42 7
The Tour Continues The Cochlea outer middle inner auditory ear ear ear cortex X Capillary network is extensive especially in the stria vascularis, medial and lateral walls of cochlea 43 44 45 3 Dominant Pathways Microangiopathy Neuropathy Mitochondrial Damage 3 Dominant Pathways Microangiopathy Neuropathy Mitichondrial Damage MICROANGIOPATHY A disease of the arteries veins capillaries 46 47 48 8
CAUSE: MICROANGIOPATHY build-up of sugar-based substances on vessel walls RESULT: reduces blood flow throughout the body For Type II, the cochlea is the main structure that is affected Fukushima, et al. Cochlear changes in patients with Type 1 diabetes mellitus. Otol. Head Neck Surg. Vol 133, No. 1 July 2005, pp. 100-106. STRIA VASCULARIS *Produces endolymph (scala media) *Susceptible to microangiopathy Helzner, EP, Contrera, KJ. Type 2 diabetes and hearing impairment. Curr Diab Rep. 2016;16:3 49 50 51 STRIA VASCULARIS Stria vascularis was 10-20 times thicker than usual in diabetes patients Jorgensen MB, Buch NH. Studies on inner-ear and cranial nerves in diabetes. Acta Otolaryngol. 1961;107:179-82 Thicker vessel walls of the SV Sclerosis of the internal aud. artery SpringerLink Makihima K, Tanaka P. Pathological changes of the inner ear central auditory pathway in diabetic patients. Ann Otol Rhinol Laryngol, 1971: 80(2); 218-228. HISTOPATHOLOGICAL STUDIES Loss of outer hair cells (OHC) Fukushima, et al. Cochlear changes in patients with Type 1 diabetes mellitus. Otol. Head Neck Surg. Vol 133, No. 1 July 2005, pp. 100-106. 52 53 54 9
3 Dominant Pathways Microangiopathy Neuropathy Mitichondrial Damage Diabetic Neuropathy Chronic, symmetrical, sensory polyneuropathy Affecting the nerves of the lower limbs and often affecting autonomic nerves 3 Dominant Pathways Microangiopathy Neuropathy Mitichondrial Damage 55 56 57 Jorgensen MB, Buch NH. Studies on inner-ear function and cranial nerves in diabetes. Acta Otolaryngol. 1961;53:350-64. Mitochondrial Damage (accelerated aging) There is a degradation of the spiral canal and the basement membrane of the stria vascularis Helzner, EP, Contrera, KJ. Type 2 diabetes and hearing impairment. Curr Diab Rep. 2016;16:3 Mitochondrial Damage (accelerated aging) Oxidative stress and atherosclerotic processes are augmented by the onset of DM Helzner, EP, Contrera, KJ. Type 2 diabetes and hearing impairment. Curr Diab Rep. 2016;16:3 Incidence of HL and Diabetes HL is twice as common in diabetic pts with proliferative retinopathy Jorgensen MB, Buch NH. Studies on inner-ear function and cranial nerves in diabetes. Acta Otolaryngol. 1961;53:350-64 58 59 60 10
Incidence of HL and Diabetes Microvascular blood supply of the EAR is similar to that of the EYE Retinopathy = Hearing Loss Incidence of HL and Diabetes Type I: 32% Botelho CT, et al. Increased prevalence of early cochlear damage in young patients with type 1 diabetes detected by distortion product otoacoustic emissions. Int J Audiol. 2014 Jun;53(6):402-8 Incidence of HL and Diabetes Type I: Significant HF SNHL (n=63) Elamin A, et al. Hearing loss in children with type 1 diabetes. Indian Pediatr. 2005 Jan;42(1):15-21 61 62 63 Incidence of HL and Diabetes Type II: 44% - 69% Duration of Diabetes and HL Decrease in neuronal and vascular function + presbycusis Under 60 Age Mais CA, Campos, CA. Diabetes mellitus as etiological factor of hearing loss. Braz J Otolaryngol. 2005 Mar-Apr;71(2):208-14 Unexplained HF HL might lead to a diabetes diagnosis (after lab tests) 64 65 66 11
Unexplained HF SNHL might lead to a diabetes diagnosis Under 60 55% with diabetes have HF SNHL Age Females >males Gender 20% have HL w/o diabetes Hlayisi, VG et al. High prevalence of disabling hearing loss in young to middle aged adults with diabetes. Int J Diabetes in Devel Countries. Published online, June, 2018 Sharashennidz N, et al. Age related hearing loss: gender differences. Georgian Med News. 2007;144:14-8 67 68 69 Males >females Gender No difference between the sexes Gender Gender: The Jury Is Still Out Vera-Genevey Hlayisi, et al. High prevalence of disabling hearing loss in young to middle aged adults with diabetes. Int J Diabetes in Devel Countries. Published online, June, 2018 Liu. B. et al. Investigation and analysis of tinnitus in diabetic patients. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2018 Apr;32(8):566-569 70 71 72 12
Tinnitus with Diabetic Patients Tinnitus may be related to age and not diabetes (n = 112) 51-60 year: 43% >60 year: 55% Thorough Case History Get to know your pharmacist Liu B. et al. Investigation and analysis of tinnitus in diabetic patients. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2018 Apr;32(8):566-569 73 74 75 Audiometric Monitoring Audiometric Monitoring for Patients with Diabetes Screening Recommendations Soon After the Diabetes Diagnosis No formal guidelines exist for monitoring hearing loss, tinnitus or balance disorders for Patients with diabetes DiSogra, RM. The Audiology Project, www.theaudiologyproject.com, 2018 76 77 78 13
Baseline A/C (incl. extended HFs >8k) Tymps DPOAEs ABR ABR: Normal I Abn Wave III & V Audiometric Monitoring for Patients with Diabetes Kavanagh KT, Beardsley JV. Brain stem auditory evoked response. Ann Otol Rhinol Laryngol Suppl. 1979;88 (4 Pt 2 Suppl 58) page(s):1-28 Initial visit (baseline) - Review findings - Review symptoms suggesting changes in hearing 79 80 81 Audiometric Monitoring for Patients with Diabetes Initial visit (baseline) - Tinnitus Handicap Inventory (THI) (if warranted) Tinnitus is NOT a Reported Side Effect of Any of the 75 FDA Approved Drugs for Diabetes Management DiSogra, RM. The audiology project, 2018. www.theaudiologyproject.com Audiometric Monitoring for Patients with Diabetes 2-3 months after baseline - to monitor any progression of the loss; THI if warranted - review symptoms of changes in hearing 82 83 84 14
Audiometric Monitoring for Patients with Diabetes 6 months after 1 st follow-up - to monitor any progression of the loss - repeat THI if warranted Audiometric Monitoring for Patients with Diabetes Annually (or sooner if further changes are suspected) - to monitor stability or any progression of the loss - repeat THI if warranted Vestibular Monitoring for Patients with Diabetes 85 86 87 39% of PWD (T2) Are A FALL RISK! www.theaudiologyproject.com Vestibular Monitoring for Patients with Diabetes No formal guidelines exist for monitoring vestibular function for patients with diabetes DiSogra, RM. The audiology project, www.theaudiologyproject.com, 2018 Vestibular Monitoring for Patients with Diabetes Obtain a comprehensive baseline to rule out any co-morbidities 88 89 90 15
Balance Assessment Video NystagmoGraphy (caloric) Vestibular Evoked Myogenic Potentials (VEMP) Balance Assessment Dynamic Visual Acuity Test (DVAT) Rotary Chair Computerized Dynamic Posturography Vestibular Monitoring for Patients with Diabetes Re-evaluation if symptoms increase 91 92 93 High Risk Considerations Diagnostic Considerations Diagnostic Considerations Extended High Frequencies 8k 14kHz T2DM: poorer thresholds up to 14kHz (Konrad-Martin, et al, 2015; Lerman-Garber, et al, 2012) DPOAEs may be abnormal in the presence of normal audiogram Ottaviani, et al, 2002 Shown with permission: University of Mississippi Medical Center 94 95 96 16
Diagnostic Considerations Diagnostic Considerations ABR: Normal I Abn Wave III & V ABR Poor waveform morphology and reproducibility (Dajani, et al, 2015) ABR prolonged latencies of Waves III and V Latency delay of later waves ** (Kern at al, 1994) ** Waves III and V (Wave I WNL) Kavanagh KT, Beardsley JV. Brain stem auditory evoked response. Ann Otol Rhinol Laryngol Suppl. 1979;88 (4 Pt 2 Suppl 58) page(s):1-28 Wave III: deleon-morales et al, 2005 Wave V: deleon-morales et al, 2005; Ren, et al, 2009 Kavanagh KT, Beardsley JV. Brain stem auditory evoked response. Ann Otol Rhinol Laryngol Suppl. 1979;88 (4 Pt 2 Suppl 58) page(s):1-28 97 98 99 Diagnostic Considerations Tinnitus Evaluation (if tinnitus is reported) Tinnitus Handicap Inventory Tinnitus Reaction Questionnaire Degree of Hearing Loss >25dB in the poorer ear Usually mild to moderate V C Frequency Range Low to Mid Frequency (Type I & II) Peripheral neuropathy (feet) associated with low/mid frequency SNHL (but not HF SNHL) Bainbridge KE, et al. Potential mediators of diabetes-related hearing impairment in the U.S. population. National Health and Nutrition Examination Survey 1999 2004. Diabetes Care. 2010 Apr; 33(4): 811 816. 100 101 102 17
Frequency Range Before 1981 the literature showed that diabetes-related HL was: Mild-Moderate and High Frequency High Frequencies Type II patients (Tay, et al, 1995) Frequency Range High Frequencies Frequency Range Follows a similar pattern that of age-related HL (presbycusis) 103 104 105 Frequency Range Co-Morbidities All Frequencies Celik (1996) showed elevated thresholds at all test frequencies with Type I diabetic patients Flat Audiogram Hx of cardiovascular disease Hypertension Duration of the diabetes Drugs and Insulins for Diabetes Management Celik O, et al. Hearing loss in insulin-dependent diabetes mellitus. Auris Nasus Larynx.1996;23:127-32. 106 107 108 18
Drugs and Insulins for Diabetes Management www.drbobdisogra.com Click More Click Diabetes Rx Side Effects 75 FDA-Approved Drugs for Diabetes 51 23 1 15 Essential Oils for Diabetes 109 110 111 Auditory - Vestibular - Cognitive Side Effects Rx Side Effects Summary (n = 75) Vestibular 67 89% Cognitive 53 70% Auditory 21 28% Rx Side Effects Summary (n = 75) Vestibular 67 89% DiSogra, RM. The audiology project, 2018. www.theaudiologyproject.com 112 113 114 19
Amplification or Hearing Assistance Technology Evaluation At any time if the communication problems increase Communication Strategies for Persons with Hearing Loss March 2017 pp. 32-37 Includes Hearing Handicap Inventory for Adults (HHIA) 115 116 117 Communication Strategies www.drbobdisogra.com Click More Click Communication Strategies Counseling By the Audiologist By the Diabetes Educator www.theaudiologyproject.com/ educational-materials 118 119 120 20
Questions? www.drbobdisogra.com www.drbobdisogra.com 121 122 21