Introduction:
Involuntary contractions of the detrusor cause an overactive bladder during the filling phase of the micturition cycle (the process of eliminating waste); it can develop with or without incontinence and is commonly characterized by urine frequency and nocturia. Diabetic bladder dysfunction is a form of autonomic neuropathy that presents due to the involvement of the lower urinary tract or an overactive bladder (OAB). Urinary urgency, generally associated with frequent nocturia (frequent urination in the night), with or without urgency urinary incontinence (UUI), in the absence of urinary tract infection or other evident pathological diseases, was described as OAB syndrome.
Diabetes and its consequences have a substantial influence on the patient’s quality of life. However, the degree of the effect of various diabetes complications on life quality varies. Overactive bladder (OAB) development in diabetic individuals is caused by systemic inflammation, diabetic angiopathy (disease of the blood vessels), and neuropathy (nerve damage due to diabetes), all of which result in prolonged ischemia (reduced blood supply) of the bladder and central nervous system. As a result, early identification of risk factors for OAB progression in diabetic patients would improve the therapeutic care of these two disorders.
What Is the Pathophysiology of Bladder Dysfunction in Diabetes?
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Diabetic bladder dysfunction is a collection of bladder symptoms that occur in diabetic individuals. Diabetic bladder dysfunction manifests as a variety of clinical symptoms, from overactive bladder to decreased bladder contractility. Its frequency is estimated to be between 25 percent to 87 percent (Frimodt-Mller,1980).
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Moreover, because diabetes is more common in the elderly, other factors such as benign prostatic hyperplasia (enlargement of the prostate), neurological disorders, and aging may also play a significant role in voiding dysfunction, making it difficult to determine the specific cause contributing to voiding dysfunction in diabetic patients.
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Diabetic bladder dysfunction, in contrast, can manifest as an overactive bladder syndrome characterized by urgency, with or without incontinence, frequency of urine, and nocturia.
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Hypersensitivity and hypercontractility (excessive contraction of the muscles) of the bladder are far more prevalent than hypo-contractility. More than half (55 percent) of diabetes individuals exhibit micturition cycle, 23 percent have diminished detrusor contractility, ten percent have detrusor areflexia, and the other 11 percent have inconclusive results.
What Is Pathogenesis?
Diabetes-induced bladder dysfunction has a complex etiology. Participating components include changes in detrusor muscle physiology, neuronal damage, and urothelial dysfunction.
What Is the Role of the Detrusor Muscle?
Modifications in detrusor muscle physiology are linked to various processes, including alterations in intercellular connections and excitability, the density and distribution of the receptors, intracellular signaling, and genetic changes. For example, in diabetes, the detrusor muscle responds more strongly to muscarinic agonists (will mimic the action of acetylcholine on muscarinic receptors and slows down the muscle contraction). It might be attributed to increased muscarinic receptor density (Saito et al., 1997) or enhanced smooth muscle calcium sensitivity.
What Is the Role of Neuronal Damage?
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Hyperglycemia can cause neuronal damage by activating polyol pathway (which leads to the buildup of sorbitol and fructose), increasing the release of free radicals, activating protein kinase C, and enhancing the development of advanced glycation end products (Fedele, 2005).
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These metabolic disturbances cause axonal degeneration and impaired nerve transmission, resulting in bladder hypotension. In addition, axonal degeneration may reduce the activity of acetylcholinesterase in bladder biopsies of patients with diabetes, and significantly Schwann cell proliferation takes place in to use a regenerative rescue following demyelination or axonal degeneration.
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Diabetic neuropathy and bladder dysfunction are related to reduced production of nerve growth factor in the bladder or poor transportation of nerve growth factor to the lumbosacral dorsal root ganglia (Brown et al., 2005).
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Nerve growth factors, particularly neurotrophin factor family members, are required for the appropriate function of mature sensory and sympathetic neurons and its capacity to enhance neuron survival throughout development.
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Pressure from an overly-dilated bladder can suppress parasympathetic activity, a stimulant for fecal retention and soiling. Struggling to defecate, on the other hand, can injure pelvic floor muscles and result in rectocele, cystocele (conditions that involve pelvic organs shifting out of place because of a weakened pelvic floor in women), and an elevated chance of stress incontinence and incomplete bladder emptying. Should also note that vesicourethral dysfunction is caused by somatic and autonomic neuropathy.
What Is the Role of Urothelium?
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There are at least three layers in the urothelium: basal, middle, apical, or surface layer (umbrella cells). These cells' barrier role is an early acknowledgment of one of their functions.
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The urothelium can adapt to substantial urine volume changes as the bladder empties. Exocytosis and fusion of a subapical pool of discoidal-shaped vesicles with the apical plasma membrane of the superficial umbrella cells occur at the cellular level, resulting in increased mucosal surface area (Wang et al., 2005).
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The urothelium also serves as a sensor for bladder function, releasing various mediators that alter afferent neurons, thereby contributing to various diabetic bladder disorders.
What Is the Diagnosis?
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Both physicians and patients are concerned about several diabetic consequences, such as neuropathy, retinopathy, or nephropathy, as well as uncomfortable bladder functions associated with diabetes, such as polyuria (increased urination).
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Almost 25 percent to 50 percent of patients do not report voiding issues unless expressly questioned. Understanding the symptoms that the patient is experiencing is a vital first step. Patients may ignore early signs and symptoms of diabetic bladder dysfunction because the illness progresses slowly and insidiously.
What Are the Treatment Modalities?
The therapy for diabetic cystopathy is determined by urodynamic abnormalities. Management aims at:
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Symptom alleviation.
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Treatment and prevention of urinary tract infections.
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Proper bladder emptying.
Management strategies can be divided into:
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Behavioral.
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Pharmacological.
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Surgical categories.
What Are the Behavioral Modalities?
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Non-invasive techniques should be explored as the first stage of treatment. For example, recent research examined the findings of the diabetes prevention program trial. It determined that a lifestyle change consisting of a five to ten percent weight loss significantly reduced symptoms of incontinence (Brown et al., 2006).
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Changes in nutrition, monitoring the quantity and timing of fluid consumption, and bladder and pelvic muscle exercise may also be recommended. In addition, patients should be instructed to reduce nocturnal polyuria (urination frequently at night) by limiting fluid consumption to the morning or early afternoon, limiting irritants to the bladder like caffeine, and urination before going to bed.
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Alcohol is a diuretic, patients should expect increased urine volume if they take it. Should also prioritize normal bowel movements by boosting fiber consumption through suitable meals or supplements particularly in constipated individuals.
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In such individuals, emphasizing improved glucose management, enhancing blood pressure control, and promoting smoking cessation are also major elements.
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Pelvic floor exercises, also known as Kegel exercises, are beneficial for strengthening the pubococcygeus muscles of the pelvic floor, which stabilize the bladder and urethral structures. In addition, these exercises can assist with stress incontinence due to stress, urge, and mixed incontinence.
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Simple suggestions to locate and contract specific muscles may be given to patients.
One method involves inserting a finger into the vagina or rectum (in men) and instructing the individual to tighten the muscles surrounding the finger, almost like holding back urine. Keep the abdomen and thigh muscles relaxed. Patients may benefit from a referral to a physical therapist who specializes in pelvic floor physical therapy.
What Are the Pharmacological Treatments?
Antimuscarinic Drugs: These drugs are the foundation of treatment for individuals with overactive bladder. These medicines block acetylcholine binding to muscarinic M2 and M3 receptors on detrusor smooth muscle cells and other structures inside the bladder wall, lowering detrusor muscle spasms and managing involuntary detrusor contractions without interfering with regular voiding.
Anticholinergic Agents: 1. Trospium Chloride: This is a non-selective antimuscarinic anticholinergic drug having an immediate action peripherally. This medication has three distinct pharmacokinetic features;
- Firstly, It is a quaternary ammonium compound that reduces central nervous system penetration and has fewer negative cognitive consequences.
- Second, it is not metabolized by the cytochrome P450 system, leading to a lower likelihood of drug-to-drug interactions.
- Finally, it is eliminated as the active parent drug in urine, leading to an early onset local impact.
It has demonstrated encouraging results in treating overactive bladder and is now being investigated as an option for individuals who do not handle oxybutynin (used to treat overactive bladder) well.
2. Fesoterodine: This is an anticholinergic medication that also functions as a prodrug. Fesoterodine's effectiveness and safety in managing an overactive bladder are comparable to Tolterodine.
Anticholinergic medications can cause dry mouth, impaired vision, drowsiness, dizziness, cognitive impairments, and constipation. Therefore, anticholinergic therapy is contraindicated in patients with glaucoma of close angle (Chapple et al., 2005). Dry mouth is the most prominent adverse effect and cause of noncompliance. Therefore, patients should be evaluated for retention and post-void retention despite symptomatic improvement on follow-up appointments.
3. Propiverine Hydrochloride: This is an antimuscarinic drug with calcium-antagonistic properties. Inhibiting calcium influx, which supports musculotropic spasmolytic, is a significant aspect in the management of an overactive bladder and may cause a decrease in micturition frequency.
4. Imipramine: This is a tricyclic antidepressant that has been widely employed in the management of overactive bladder and seems to be beneficial in managing diabetic autonomic dysfunction like incontinence (Duby et al., 2004). This medication blocks noradrenaline and serotonin reuptake by adrenergic nerve terminals, resulting in greater noradrenaline contractile effects on urethral smooth muscle and improved detrusor muscle relaxation.In the management of detrusor areflexia, medication has a limited role. The use of parasympathomimetic medications has been used to replicate detrusor muscle. These medications raise intravesical pressure and reduce the bladder's capacity by stimulating autonomic effector cells and postganglionic parasympathetic receptors.
Cholinergic drugs have adverse effects (such as sweat, salivation, tachycardia, and flushing (sudden reddening of the face), limiting daily usage. However, treating Bethanechol (10 to 20 milligrams taken orally three to four times a day) may be useful in individuals with constant residual volumes of more than 100 milliliters but less than 500 milliliters.
This medication has a reasonably specific effect on the urinary bladder and has also been used to aid reflex bladder contraction in individuals with supra-sacral spinal cord damage.
What Are the Surgical Treatments?
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Patients with the characteristic symptoms of diabetic cystopathy (impaired detrusor contractility) but do not benefit from non-pharmacological or pharmacological therapies are candidates for surgery.
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These treatments are designed to reduce the incidence of urinary tract infections. Vesical neck excision is done transurethrally and maintains the external sphincter intact to maintain urinary continence.
Conclusion:
Diabetic bladder dysfunction is prevalent and can appear in various ways, ranging from detrusor instability to impaired bladder sensation and contraction. The cornerstone of assessment is a urodynamic examination, which identifies the kind of bladder dysfunction and the therapy techniques. As non-pharmacological therapy, lifestyle adjustments such as weight loss, dietary changes, fluid intake amount and timing, and pelvic muscle exercise are indicated. Anticholinergic medicines may be an alternative for individuals who present with overactivity of the detrusor muscle, but pharmacotherapy has limited performance in the management of detrusor areflexia. In rare cases, surgical intervention may be advantageous.
