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\def\RunningAuthor{Hasanain F. Hasan Al-Timimi et al.}
\firstPage{2433}
\articleType{Original Article}
\receivedDate{10 Feb 2020}
\acceptedDate{27 Mar 2020}
\revisedDate{04 Mar 2020}
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\journalDoi{ijrps.v11i2.2236}
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\title{Urodynamic findings of bladder dysfunction in patients with Type 2 DM}
\author{Hasanain~F.~Hasan~Al-Timimi\textsuperscript{*}\textsuperscript{1},  
            Mohammed~B.~Ismail\textsuperscript{2}, 
            Mustafa~Mohsin~Al-Musawi\textsuperscript{3}~\\[5pt]{\textsuperscript{1}FICMS (Urology), SNBHW (Urology), College of Medicine, University of Baghdad, Iraq}~\\{\textsuperscript{2}CABMS (Urology), College of Medicine, University of Baghdad, Iraq}~\\{\textsuperscript{3}Department of Urology, Al-Karkh General Hospital, Baghdad, Iraq}}

\begin{abstract}
Bladder dysfunction is one of the most common complications of diabetes, even exceeding nephropathy or peripheral neuropathy. Diabetic cystopathyaffects patients in both sexes, and its prevalence increases over time with diabetes; our concern is to evaluate the urodynamic findings of bladder dysfunction in diabetic patients. A cross sectional study conducted at Ghazi Al-Hariri Surgical specialized hospital during the period from the firsts of January 2018 to the end of Mar 2019, in which 118 diabetic patients (71 female and 47 male) with lower urinary tract symptoms were enrolled in the current study. The mean age (62\ensuremath{\pm}13) years old, 37.3\% of patients presented with urgency as the main type of dysfunction. Diabetic cystopathy were found in (40,4\%) of the male and (43.7\%) of the female, while detrusor over activity were found in (15.5\%) of the male and (18.3\%) of the female, bladder outlet obstruction were represent (8.5\%) of the male with significant association. Highly significant ({\textless}0.001) increase in female compliance and flow rate than that in male but highly significant decrease were found in female filling IV pressure. We concluded that Bladder over activity of the patients in the current study was found in more than half of the patients and diabetic cystopathy is the most common urodynamic finding in diabetic bladder dysfunction in patients with DM.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Type 2 diabetic mellitus,\newline Bladder dysfunction,\newline Diabetic cystopathy,\newline detrusor over activity
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Hasanain~F.~Hasan~Al-Timimi~\\ Phone:\ 07801620188~\\  Email:\ drghassan1993@yahoo.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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\section{Introduction}
Diabetes, a disease that affects blood glucose control, is a growing problem worldwide. In 2000, the global prevalence of the disease was estimated at 2.8\% for all age groups and it is estimated to reach 4.4\% in 2030 of the total of the world population \unskip~\citep{730536:17335587}.\ensuremath{^{}}

\unskip~\cite{730536:17335583} mentioned that according to International Diabetes Federation (IDF) Diabetes Atlas, the diabetes mellitusrate in population does not stop or decrease in the future, andin the year 2040; the number of diabetics worldwide is expected to rise to 642 million, representing a potential future health crisis for patients and providers \unskip~\citep{730536:17335583}.\ensuremath{^{}}

The majority of patients with diabetes mellitus experience various pathological changes at varying intervals during the evolution of the illness. The complications that happened in the body (nephropathy, retinopathy and diabetic neuropathy) commonly was due to microvascular damage \unskip~\citep{730536:17335598}. The risk of diabetic neuropathy is proportional to the magnitude and duration of hyperglycemia \unskip~\citep{730536:17335589}.\ensuremath{^{}}

This alteration appears in 10-15\% of cases at the time of diagnosis of diabetes mellitus and in approximately 50\% of those who have suffered from the disease for more than 25 years \unskip~\citep{730536:17335600}. Diabetic neuropathy can be prevented by optimal control of serum glucose concentrations \unskip~\citep{730536:17335582}.

Bladder dysfunction is one of the most common complications of diabetes, even exceeding nephropathy or peripheral neuropathy. No accurate data are currently available on the incidence and risk factors of bladder dysfunction (diabetic cystopathy). Diabetic voiding dysfunction (DVD) found to be a far more common complication of the diabetic patients than the commonly documented complications such as peripheral neuropathy (60\%) and nephropathy (50\%) \unskip~\citep{730536:17335599}.

Diabetic cystopathy affects patients in both sexes, and its prevalence increases over time with diabetes \unskip~\citep{730536:17335600}. Most patients with diabetic bladder dysfunction usually have long-term complications from diabetes. Symptoms of diabetic bladder dysfunction are insidious and characterized by a progressive deficiency in the ability to empty the bladder. The proprioceptive sensitivity of intravesical volume usually changes in the early stages of the disease. Patients start with urinary retention, concomitant with lower sensitivity, prolonging intermittent intervals, and have difficulty emptying the bladder, in addition to increasing the amount of residual urine \unskip~\citep{730536:17335590}.

This can cause complete urinary retention with overflow incontinence, including renal failure. Detrusor hyperactivity (urodynamically determined by involuntary contractions, not inhibited during filling) and bladder hyperactivity (clinically determined by urgency with or without incontinence, frequency and nocturia) \unskip~\citep{730536:17335591} they usually appear in patients with diabetic bladder dysfunction before detrusor hypo contractility, it has even been described that they may be more frequent \unskip~\citep{730536:17335584}.

Urodynamic is a general term to describe the study of the dynamics of storage and the evacuation of urine through the urinary tract. It could be considered an examination of provocation of vesico-urethral function. It is the functional study of the lower urinary tract. It allows the direct measurement of the function of the urinary tract through physiological parameters. Currently, urodynamic is considered the reference standard for the diagnosis of voiding dysfunction. However, the results obtained depend on the operator and have interobserver variability \unskip~\citep{730536:17335588}. The objective of the urodynamic study is to reproduce the symptoms while accurate measurements made in order to identify the underlying causes of the symptoms and the related pathophysiological processes. In addition, an effective urodynamic practice requires theoretical understanding of the physics and operation of the measurement, experience in the use of equipment and procedures, quality control of the recorded data and ability to interpret the results \unskip~\citep{730536:17335591}.\ensuremath{^{}}

\textbf{Aim of the study}

To evaluate urodynamic findings of bladder dysfunction in type 2 diabetic patients.
    
\section{Patients and Methods}
A cross sectional study conducted at Ghazi Al-Hariri Surgical specialized hospital during the period from the firsts of January 2018 to the end of Mar 2019, in which 118 diabetic patients (71 female and 47 male) with lower ureteral tract symptoms were enrolled for the current study. 


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\makeatother 
\caption{\boldmath {Gender distribution }}
\label{f-ae3b2c4175ac}
\end{figure}
\egroup

\begin{table*}[!htbp]
\caption{\boldmath {Clinical characteristics of the studied group} }
\label{tw-bd0036e35278}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1981\linewidth-2\tabcolsep}p{\dimexpr.3019\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\multicolumn{2}{p{\dimexpr(.50\linewidth-2\tabcolsep)}}{\cAlignHack Variables} & No. & \%\\
\tblmidrule 
\multicolumn{1}{p{\dimexpr(.1981\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{Age Group}} &
  \ensuremath{\leq }50 &
  17 &
  14.4\%\\
 &
  51-60 &
  22 &
  18.6\%\\
 &
  61-70 &
  51 &
  43.2\%\\
 &
  {\textgreater}70 &
  28 &
  23.7\%\\
 &
  Mean\ensuremath{\pm}SD &
  \multicolumn{2}{p{\dimexpr(.50\linewidth-2\tabcolsep)}}{62\ensuremath{\pm}13}\\
\multicolumn{1}{p{\dimexpr(.1981\linewidth-2\tabcolsep)}}{\multirow{8}{\linewidth}{Type }} &
  urgency &
  44 &
  37.3\%\\
 &
  frequency &
  16 &
  13.6\%\\
 &
  ROU &
  6 &
  5.0\%\\
 &
  nocturia &
  2 &
  1.7\%\\
 &
  SI &
  32 &
  27.1\%\\
 &
  continuous &
  1 &
  0.8\%\\
 &
  overflow &
  5 &
  4.2\%\\
 &
  mixed &
  7 &
  5.9\%\\
\multicolumn{1}{p{\dimexpr(.1981\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{}} &
  intermittency &
  1 &
  0.8\%\\
 &
  hesitancy &
  1 &
  0.8\%\\
 &
  poor stream &
  1 &
  0.8\%\\
 &
  incomplete evacuation  &
  2 &
  1.6\%\\
\multicolumn{1}{p{\dimexpr(.1981\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{bladder over activity}} &
  Yes &
  70 &
  59.3\%\\
 &
  No &
  48 &
  40.7\%\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Association between genders in the studied group according to the Urodynamic findings results } }
\label{tw-2f00b3505c65}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1765\linewidth-2\tabcolsep}p{\dimexpr.26090000000000003\linewidth-2\tabcolsep}p{\dimexpr.182\linewidth-2\tabcolsep}p{\dimexpr.1806\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\multicolumn{2}{p{\dimexpr(.4374\linewidth-2\tabcolsep)}}{\cAlignHack Variables} & Male (n=47) & Female (n=7) & P value\\
\tblmidrule 
\multicolumn{2}{p{\dimexpr(.4374\linewidth-2\tabcolsep)}}{Normal} &
  15 (31.9\%) &
  21 (29.6\%) &
  Ns\\
\multicolumn{2}{p{\dimexpr(.4374\linewidth-2\tabcolsep)}}{Diabetic cystopathy} &
  19 (40.4\%) &
  31 (43.7\%) &
  Ns\\
\multicolumn{2}{p{\dimexpr(.4374\linewidth-2\tabcolsep)}}{Detrusor over activity} &
  9 (15.5\%) &
  13 (18.3\%) &
  Ns\\
\multicolumn{2}{p{\dimexpr(.4374\linewidth-2\tabcolsep)}}{Bladder outlet obstruction} &
  4 (8.5\%) &
  - &
  0.05\\
\multicolumn{1}{p{\dimexpr(.1765\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{Incontinence}} &
  Urge incontinence &
  - &
  3 (4.2\%) &
  0.1\\
 &
  Stress urinary incontinence &
  - &
  3 (4.2\%) &
  0.1\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Association between patient's characteristics and gender} }
\label{tw-c27d3d896b9b}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.31919999999999998\linewidth-2\tabcolsep}p{\dimexpr.2535\linewidth-2\tabcolsep}p{\dimexpr.2275\linewidth-2\tabcolsep}p{\dimexpr.1998\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor} & Male (N=47) \mbox{}\protect\newline Mean\ensuremath{\pm}SD & Female(N=71) \mbox{}\protect\newline Mean\ensuremath{\pm}SD & P value\\
\tblmidrule 
Age &
  63\ensuremath{\pm}13 &
  62\ensuremath{\pm}13 &
  0.6\\
Duration of DM &
  11.3\ensuremath{\pm}3.7 &
  12.2\ensuremath{\pm}4.1 &
  0.2\\
BMI &
  27.8\ensuremath{\pm}3.02 &
  28.9\ensuremath{\pm}4.57  &
  0.1\\
bladder capacity &
  415\ensuremath{\pm}220 &
  426\ensuremath{\pm}414 &
  0.8\\
compliance &
  77.22\ensuremath{\pm}26.39 &
  95.04\ensuremath{\pm}22.19 &
  {\textless}0.001\\
urethral pressure profile &
  75\ensuremath{\pm}44 &
  62\ensuremath{\pm}32 &
  0.06\\
filling iv pressure &
  36\ensuremath{\pm}30 &
  20\ensuremath{\pm}15 &
  {\textless}0.001\\
flow rate &
  12\ensuremath{\pm}2.8 &
  14\ensuremath{\pm}1.3 &
  {\textless}0.001\\
post voiding residual (PVR) &
  132\ensuremath{\pm}16.1 &
  127\ensuremath{\pm}15 &
  0.08\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
The inclusion criteria were (1) diagnosed with type 2 diabetes based on World Health Organization Criteria \unskip~\citep{730536:17335596}  for at least 5 years;(2) presenting lower urinary tract symptoms (LUTS). 

The exclusion criteria were (1) Patients with end stage renal disease; (2) any medication known to interfere with function of the bladder or sphincter, \unskip~\citep{730536:17335595} such as calcium channel blockers, anticholinergics, \ensuremath{\alpha } and -adrenergic agonist, narcotics, antidepressants, antipsychotics and diuretics; 

(3) acute metabolic complication of DM including ketoacidosis or hyperosmolar hyperglycemic state; (4) suprapontine, supra-sacral lesions or any root lesion of the sacral and lumbar outflow tracts and diseases related to peripheral neuropathy other than DM; (5) prostate or bladder cancer; (6) previous genitourinary surgery; (7) women who had previous diagnosis of uterine fibroids

Evaluation of patients consisted of detailed history of the duration of diabetes, type of therapy, physical examination, concomitant diabetic retinopathy, nephropathy and neuropathy, genitourinary evaluation, urodynamic investigation.

\textbf{Ethical clearance}

The procedures and importance of the study were informed to each of the patients and after they agreed, we included them in the study
    
\section{Results and Discussion}
The current study included 118 diabetic patients (71 female and 47 male) and the main age group between 61-70 years within the mean age (62\ensuremath{\pm}13) years old, 37.3\% of patients presented with urgency as the main type of dysfunction, 59.3\% with bladder over activity, all these were shown in (Table~\ref{tw-bd0036e35278} and Figure~\ref{f-ae3b2c4175ac}).

Diabetes mellitus disease considered as one of the main disease that lead to many complications to the human body, and one of them is its effect on the bladder dysfunction 

Bladder over activity of the patients in the current study rate is in agreement with that mentioned previously by many studies that ranging from 39\% to 61\% of the diabetic patients \unskip~\citep{730536:17335585,730536:17335581}.

\unskip~\cite{730536:17335586} in a study to measure the bladder dysfunction in a sample of diabetic patients reported that 31\% of female and (25\%) of male had isolated detrusor over activity. Which is more than that in the current study when (15.5\%) of female and (18.3\%) of male had detrusor over activity. 

As shown in (Table~\ref{tw-2f00b3505c65}) the diabetic cystopathy were found in (40, 4\%) of the male and (43.7\%) of the female. While detrusor over activity were found in (15.5\%) of the male and (18.3\%) of the female, bladder outlet obstruction were represent (8.5\%) of the male with significant association. Urge incontinence were found in (4.2\%), also (4.2\%) of them were suffered from stress urinary incontinence. 

Recent evidence suggests that symptoms are more often among men with diabetes, with an estimated increase in risk of 25\% to almost twice in different studies. In a study of men and women with type 2 diabetes, age, duration of diabetes, poor metabolic control, the residual amount remaining after empty \ensuremath{\geq }100 mL parasympathetic autonomic neuropathy (heart, stomach and esophageal), retinopathy and micro-albuminuria all correlated with urodynamic results DBD \unskip~\citep{730536:17335586}.

Diabetic cystopathy was the most frequent urodynamic finding in diabetic women, which is same that found in the present study (43.7\%). The urinary incontinence is the main differential diagnosis of Diabetic cystopathy which was found that UI affects more than half of the middle to older age women \unskip~\citep{730536:17335592,730536:17335580}.

Highly significant ({\textless}0.001) increase in female compliance and flow rate than that in male but highly significant decrease were found in female filling IV pressure (Table~\ref{tw-c27d3d896b9b}).

Ueda and others they studied asymptomatic diabetic patients and found an increase in bladder volume at first sensation of emptiness and a decrease in detrusor contractility followed by an increase in residual volume after vacuum, but also found a 25\% hyperactivity rate \unskip~\citep{730536:17335597}. In a \unskip~\cite{730536:17335585}, study carried on 1995 found that 55\% of patients with diabetes they had detrusor over activity and only 23\% with contractility disorders, with 10\% of patients flexed and 11\% undetermined \unskip~\citep{730536:17335580}. Different symptoms of diabetic bladder dysfunction (DBD) may be associated with gender, age, concomitant obstruction of bladder outflow, and duration of diabetes. Urinary bladder compliance and obstruction of bladder outlet, elderly with low flow velocity and outlet obstruction, instability of detrusor with shorter duration of diabetes, and peripheral somatic neuropathy with low flow velocity \unskip~\citep{730536:17335594}.\ensuremath{^{}}
    
\section{Conclusions}
Bladder over activity of the patients in the current study was found in more than half of the patients and diabetic cystopathy is the most common urodynamic finding in diabetic bladder dysfunction in patients with DM.

\textbf{Ethical clearance}

It was approved by the scientific committee of the Iraqi Ministry of health. 
    

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