Liu, Guiming , PhD
Bladder dysfunction in diabetes
General Research Subject: Both Type 1 And Type 2 Diabetes
Type of Grant: Junior Faculty
Project Start Date: January 1, 2010
Project End Date: June 30, 2013
This proposal will lay out the scientific road map for the early career development of the PI as an independent investigator of urologic complications of diabetes. Diabetes causes devastating complications that lead to severe morbidity among patients. One of the most common consequences of diabetes is diabetic bladder dysfunction (DBD), which leads to poor emptying of the bladder and urinary incontinence, and has a major impact on the quality of life of diabetic patients. However, it is unknown how diabetes causes DBD.
In the PI's previous work, changes in bladder function induced by diabetes have been examined. Complications such as enlarged bladder capacity and thickened bladder wall develop relatively early after the onset of diabetes, whereas complications such as decreased sensation of a full bladder and residual urine after urination develop later in the course of diabetes. Early changes seem to result from the markedly increased production of urine (polyuria), while the later loss of bladder function appears to be due to the direct damage from high levels of sugar in the blood (hyperglycemia). Using that temporal pattern as a guide, we will investigate the mechanisms underlying the time-dependent alterations in the bladder in diabetes. We will: 1) distinguish the contributions of polyuria and hyperglycemia to the manifestations of DBD progression in rats. 2) examine if these mechanisms are potential therapeutic targets for the treatment of DBD. Our experiments should uncover important steps leading to DBD, and suggest pharmacological approaches to prevent or alleviate the harsh morbidity of DBD.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Diabetes mellitus causes debilitating and devastating complications. Indeed, it is the complications of diabetes, and not the disease itself, which lead to devastating morbidity and mortality among patients. Diabetic bladder dysfunction is among the most common and costly consequences of diabetes-which leads to poor emptying of the bladder, urinary incontinence, and has a major impact on the quality of life of a large portion of diabetes patients. In some series clinical studies, 52-87% of randomly evaluated diabetic patients were found to have urologic symptoms. This project will cover the bladder dysfunction in diabetes.
This project will uncover important pathogenesis and molecular steps leading to the early and late changes in the bladder characteristic of diabetic bladder dysfunction, and suggest pharmacological approaches to interfere with those steps and thereby prevent or alleviate the harsh morbidity of diabetic bladder dysfunction.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
In some series clinical studies, 52-87% of randomly evaluated diabetic patients were found to have urologic symptoms. The classic symptoms associated with diabetic bladder dysfunction include decreased bladder sensation, increased bladder capacity, and impaired detrusor contractibility with resultant increased postvoid residual urine. Recent clinical and experimental evidence indicate a strong presence of storage problems such as urgency, and urge incontinence in both type I and II diabetes. Studies of diabetic bladder dysfunction from our and other investigators on small animal models of diabetes, indicate the presence of a temporal effect on diabetic bladder dysfunction: Early phase of diabetes causes compensated bladder function; and late phase of diabetes causes decompensated bladder function.
We expect to uncover the important steps leading to early and late changes in the bladder that lead to ultimate dysfunction of the bladder causing severe urinary incontinence and poor emptying. Further, we expect to find the evidence for how to interfere with the process of disease in the DBD and hence prevent or stop the development of urinary incontinence and poor bladder emptying.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I was impressed by realizing the medical, personal, and societal burden of diabetic complications on patients and the potential impact of my research. I have developed a strong interest in this area and have been inspired to seek a better understanding of the pathophysiology of bladder dysfunction in diabetes. My enthusiasm is motivated by the fact that the prevalence of diabetes mellitus rose from 4.9% in 1990 to 7.3% in 2000 - an increase of 49%. The Centers for Disease Control and Prevention reported that 18 million Americans are estimated to have diabetes. In some series clinical studies, 52-87% of randomly evaluated diabetic patients are found to have urologic symptoms. Therefore, it became quite clear to me that the high prevalence of diseases and paucity of investigation in diabetic bladder dysfunction would offer me a unique opportunity to use my training and interest in a deeply needed line of research. I could apply my previous education and research experience to a new and relatively unexplored field of basic science research.
ADA Junior Faculty Award will allow me to conscientiously investigate the paths by which we might understand and explore the causes of diabetic bladder dysfunction. I expect to apply successfully for R01 type NIH grants within the next 2-3 years using the results of this research proposal. Further, I am confident that with the support of this award, I will be able to build a solid foundation for a career as a successful researcher in the filed of the lower urinary tract complications in diabetes.
In what direction do you see the future of diabetes research going?
Research on the prevention and control of diabetes: medications and insulin injections only suppress the symptoms of diabetes without addressing its causes. New treatments need to be developed. Stem cell research holds great promise in the search for a cure and better treatments for diabetes.
Research on the prevention, alleviate, or reverse diabetic complications including heart disease, stroke, kidney disease, blindness, nerve damage, foot problems: obviously, controlling the blood glucose level ideally is the strategy in the treatment of diabetes. However, it is often difficult to maintain at a level that can completely prevent the diabetic complications. It was reported that the prevalence rate of diabetic bladder dysfunction in patients on oral hypoglycemic treatment is 25%. Therefore, it is necessary to use the processes leading to diabetic complications as a framework for designing novel therapeutic targets.
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