Intermittent Hypoxia and Urologic Complications of Diabetes
Persons with type 2 diabetes have a high risk of developing bothersome lower urinary tract symptoms (LUTS), including incomplete emptying, urinary frequency, urgency and incontinence. These urinary symptoms impair quality of life and are costly to manage, especially since most type 2 diabetic patients seeking treatment for LUTS require lifetime therapy for their urinary symptoms. Prolonged treatment is necessary because few LUTS are cured by existing therapies. Effective treatments for LUTS are lacking because the underlying basis of most urinary symptoms is not known at this time. The risk of developing bothersome lower urinary tract symptoms is increased in patients experiencing obstructive sleep apnea, which exists in as many as 87% of type 2 diabetic patients. This pilot study is the first of a series of studies to test the hypothesis that physiological manifestations of sleep apnea underlie urinary complications in many type 2 diabetic patients. One physiological hallmark of obstructive sleep apnea is intermittent hypoxia. We will test whether intermittent hypoxia is sufficient to alter voiding behavior and bladder physiology in mice and whether intermittent hypoxia also causes further deterioration of lower urinary tract function when combined with type 2 diabetes. We will use an innovative custom-designed, computer-controlled chamber to achieve specific patterns of inspired oxygen in order to isolate and test the variable of intermittent hypoxia on urinary function in diabetic mice. We will use BTBR-wild type mice and BTBR.V(B6)-Lepob/WiscJ (BTBR ob/ob) mice that harbor a spontaneous mutation in the leptin gene and progressively develop obesity, hyperglycemia, and insulin resistance. Urinary function will be assessed in wild type and mutant mouse strains following normoxia or chronic intermittent hypoxia exposures. We expect to reveal intermittent hypoxia as an underlying contributor to lower urinary tract symptoms. These results will drive the design of future studies, which will incorporate one of the world’s largest population-based prospective studies on sleep disordered breathing and health, to determine whether sleep studies are warranted for type 2 diabetics with lower urinary tract symptoms.

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