Bladder dysfunction secondary to metabolic diseases related to insulin resistance
Date Issued
2009
Date
2009
Author(s)
Lee, Wei-Chia
Abstract
Backgroundnsulin resistance related metabolic disease have become an important worldwide public health problem because the prevalence has risen steadily during recent decades, particularly in the Asian and female populations. Rapid economic development and urbanization have increased the prevalence of metabolic syndrome and type 2 diabetes in Asia. Both metabolic syndrome and type 2 diabetes are known to be risk factors for the development of bladder dysfunction. Metabolic diseases are likely to result in major economic burdens for countries in Asia, the most populous area in the world. iabetic bladder dysfunction is one of the most frequent complications of diabetes mellitus. Over 50 % of patients with diabetes exhibit diabetic bladder dysfunction.lthough the complications of diabetes mellitus have been well studied, the development and severity of lower urinary tract disorders in patients with diabetes mellitus are still poorly understood. The bladder dysfunction secondary to metabolic syndrome is the other interesting issue. The patients with metabolic syndrome also have a higher risk of lower urinary tract symptoms. To study the bladder dysfunction secondary to metabolic syndrome plays an important role in the prevention and early treatment of diabetic complications. nsulin resistance is the core metabolic perturbation of the metabolic syndrome and can result in type 2 diabetes. Moderate degrees of insulin resistance are closely linked to a range of common disease, such as polycystic ovary syndrome, obesity, hypertension and benign prostatic hyperplasia. Currently, metabolic syndrome is considered as a pre-diabetic status. n this dissertation, we present our observations on the bladder dysfunction secondary to metabolic diseases related to insulin resistance. In human study, the urodynamic studies along with the intravesical CPT test were used to evaluate the lower urinary tract function in type 2 diabetic women. We also established an animal model of fructose-fed rats to study the bladder dysfunction secondary to metabolic syndrome. ims, materials and methodslinic study: The relationship between urodynamic findings and intravesical current perception thresholds testing among diabetic bladder women. ighty-six consecutive type 2 diabetic women followed-up at a diabetes clinic with minimal confounders of voiding dysfunction were prospectively enrolled and subjected to urodynamic studies. The sensory response of Aδ- and C-fibers of the bladder was measured by intravesical current perception threshold (CPT) testing at frequencies of 250 and 5 Hz, respectively.asic study: Bladder dysfunction in rats with metabolic syndrome induced by long-term fructose feeding. emale Wistar rats were fed with fructose-enriched (60%) or control diet for three and six months. In vitro contractile responses to electric field stimulation, KCl, carbachol, adenosine triphosphate and in vivo cystometry were used to evaluate bladder function. Tissue staining and electron microscopy were also performed to evaluate the structural changes in rats subjected to metabolic syndrome. The western blotting was used to evaluate the protein amount of M2-muscarinic、M3-muscarinic and P2X1-purinergic receptors in the bladder. Biochemical and physiological data were compared between fructose-fed rats and age-matched controls. esults: art I: Clinic studyf these 86 women, 30 (34.9%) were classified as detrusor underactivity, 12 (14.0%) presented signs of detrusor overactivity, 11 (12.8%) were referred as bladder outlet obstruction, and 33 (38.4%) showed a normal detrusor function in urodynamics. The normal detrusor function group was the reference group. The detrusor underactivity group showed impaired emptying function and decreased sensation both in cystometry and intravesical CPT testing. The detrusor overactivity group showed impaired storage and emptying function, but had no significant changes in intravesical CPT values. When the normal detrusor function group and detrusor underactivity group were pooled to perform multivariate analysis, an increase in CPT values was associated with a decrease in bladder voiding efficiency in both 5 Hz and 250 Hz CPT testing. art II: Basic studyll rats fed with fructose-enriched diet for three months developed insulin resistance, hyperinsulinemia, hypertriglycemia, and hypertension. These fructose-fed rats showed a decreased contractile response to high concentrations of KCl, but not to other parameters tested when compared to controls. Eight of the twelve (66.7%) rats showed abnormal cystometry, mainly by increased phasic contractions. In the six-months fructose-fed rats, contractile responses to electric field stimulation, KCl and carbachol were decreased significantly. However, responsiveness to high concentrations of adenosine triphosphate was significantly increased. Morphologic studies on fructose-fed rats showed swollen mitochondria of bladder smooth muscle, increased leukocyte infiltration between interstitial tissue, and neutrophil adhesion around the endothelium of vessels. An up-regulation of M2-muscarinic and M3-muscarinic receptors was observed in 3-month and 6 month fructose-fed rats. The increase amount of P2X1-purinergic receptors in the bladder was also noted in 6 month fructose-fed rats.onclusion: ladder dysfunction secondary to metabolic diseases related to insulin resistance has prominent morbidity and affected deeply. Our data of human study provided the electrophysiological evidence that indicates an association between impaired Aδ- as well as C-fiber bladder afferent pathways and poor emptying function in diabetic women with detrusor underactivity. Our animal model showed that a significant proportion of fructose-fed rats develop time-related alterations in the biochemical, morphological and functional properties of the bladder. The proinflammation and myopathy of the bladder induced by metabolic perturbations play important roles in causing bladder dysfunction.
Subjects
metabolic syndrome
diabetes
bladder
urination disorders
rat
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