Links between lower urinary tract symptoms, intermittent hypoxia and diabetes: Causes or cures?

Abstract

Bothersome lower urinary tract symptoms (LUTS) manifest as urinary frequency, urgency, incontinence and incomplete bladder emptying. Existing treatments ameliorate but do not eliminate most symptoms, leading to financial and personal burdens attributable to sustained medical therapies that may last a lifetime. The purpose of this review is to highlight evidence of causal associations between LUTS and several common comorbidities, including intermittent hypoxia (IH) concomitant with obstructive sleep apnea (OSA), obesity, metabolic syndrome and type 2 diabetes. Links between these conditions, including therapies targeted to co-occurring complications that have demonstrated benefits for LUTS, suggest compelling avenues of research and also underscore critical gaps in understanding the mechanisms underlying urinary dysfunction. These gaps are prominent in the IH field, where an acknowledged link between OSA and LUTS has gone largely uninvestigated. New tools, models, or reappropriation of existing ones, especially rodent models, is required to parse the associations between IH/OSA, LUTS and obesity/diabetes and to elucidate their underlying, and potentially shared, etiologies.

Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research

“…Recent studies connect LUTD to other diseases. For example, people with cardiovascular disease, diabetes and obstructive sleep apnea are at increased risk of developing LUTD [176][177][178][179]. A common thread linking these diseases is a change in hemodynamics connected to ischemic injury [180][181][182], a factor that independently drives LUTD in mice [174].…”

Don't let sleeping men lie

“…Of all LUTS, nocturia, defined as waking to pass urine more than once during the night, is strongly associated with OSA (Figure 1), with an odds ratio of 1.64 in multivariate analysis 10 . The severity of LUTS and OSA are directly associated 11 . The effective treatment of OSA results in prompt resolution of nocturia 12 …”

“…10 The severity of LUTS and OSA are directly associated. 11 The effective treatment of OSA results in prompt resolution of nocturia. 12…”

Phases of decompensation during acute ischemia demonstrated in an ex vivo porcine bladder model

“…Phases of decompensation during acute ischemia demonstrated in an ex vivo porcine bladder model understanding of a possible etiology of LUTS and have identified novel treatment targets (7)(8)(9)(10)(11)(12)(13). However, a recent review focuses on the lack of mechanistic treatments as current therapies are mainly focused on improving symptoms, rather than addressing the underlying pathophysiology (14). In this regard, a mechanistic proposal postulates that pelvic ischemia leads to progressive deterioration of detrusor muscle function, presenting initially as detrusor overactivity (DO) and ultimately leading to detrusor underactivity (DU) (15)(16)(17)(18).…”

“…However, because chronic ischemia may lead to irreversible structural damage to the detrusor muscle, there is a pressing need to study the pathophysiology of acute ischemia to identify reversible points where potential interventions could restore both structure and function. This is especially true because of the strong association of LUTS with other comorbid conditions including erectile dysfunction, anxiety, depression, as well as the financial and personal burdens that come with a lifetime of symptom management (14).…”