Urinary bladder wall thickness in type 2 diabetes mellitus patients

Diabetes mellitus is an endocrine disease that affects many people across the world. Diabetes mellitus, also called diabetes, is a long-standing condition that occurs when there are elevated levels of sugar in the blood circulation because the pancreas cannot produce any or enough of the hormone insulin or use insulin effectively⁽¹⁾. Insulin is an essential hormone produced in the pancreas, and it aids in the uptake of glucose in the bloodstream into the body cells where glucose is converted into energy. The inability of the body cells to respond to insulin or lack of insulin leads to elevated levels of blood glucose, or hyperglycaemia, which is a special mark of diabetes.

Hyperglycaemia, if left unchecked over the long term, can cause damage to various body organs, leading to the development of disabling and life-threatening complications such as cardiovascular disease, neuropathy, nephropathy and eye disease, leading to retinopathy and blindness. However, if an appropriate treatment of diabetes is initiated, these serious complications can be delayed or averted.

The classification and diagnosis of diabetes are complex and have been the subject of much consultation, debate and revision stretching over many decades, but it is now widely accepted that there are three main types of diabetes: type 1 diabetes, type 2 diabetes and gestational diabetes (GDM).

Some less common types of diabetes also exist which include monogenic diabetes and secondary diabetes. Monogenic diabetes is caused by a single genetic alteration in an autosomal dominant gene rather than the contributions of many genes and environmental factors as seen in type 1 and type 2 diabetes. Examples of monogenic diabetes include conditions like maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus. Around 1–5% of all diabetes cases are due to monogenic diabetes^{(2, 3, 4, 5, 6, 7)}. Secondary diabetes arises as a complication of other diseases such as hormone disturbances (e.g. Cushing’s disease or acromegaly), pancreatic diseases (for example, pancreatitis) or due to medications (e.g. corticosteroids).

The incidence of diabetes is increasing at a fast rate, with an expected global incidence of not less than 640 million people by 2040. Four hundred and twenty five million people worldwide, or 8.8% of adults aged 20–79 years, are estimated to have diabetes, and about 79% of these live in low- and middle-income countries.

If the age range is expanded to 18–99 years, the number of people with diabetes increases to 451 million. Given the current trend, it is estimated that by 2045, 693 million people aged between 18 and 99 years, or 629 million of people aged between 20 and 79 years, will have diabetes.

The vast majority of persons with diabetes have type 2 diabetes, which occurs when insulin resistance is present in fat and muscle cells, hepatic glucose output is enhanced, and insulin secretion fails to compensate⁽⁸⁾. Genetic studies have identified more than 150 so-called risk alleles for type 2 diabetes-variations in genes that increase a person’s susceptibility to diabetes⁽⁸⁾. Diabetes and urologic diseases are very common health problems that markedly grow in prevalence and incidence with increasing age^{(9, 10, 11)}. Diabetes is seen with an earlier onset and increased severity of urologic diseases, resulting in costly and debilitating urinary system complications. Urologic complications, including bladder dysfunction, sexual and erectile dysfunction, as well as urinary tract infections (UTIs), have a great effect on the quality of life of men and women with diabetes⁽¹²⁾. Over half of men and women with diabetes develop urinary bladder dysfunction^{(13, 14)}. According to the current understanding of bladder dysfunction, it refers to a progressive condition encompassing a broad spectrum of lower urinary tract symptoms including urinary urgency, frequency, nocturia, and incontinence. Previously, the dysfunction has been classically described as diminished bladder sensation, poor contractility, and increased post-void residual urine, termed bladder cystopathy⁽¹⁵⁾. However, bladder cystopathy most likely represents end-stage bladder failure with symptoms of infrequent micturition, difficulty initiating voiding, and post-void fullness, and it is relatively uncommon⁽¹²⁾.

A number of clinical studies in people with diabetes have reported bladder instability or hypersensitivity as the most common findings, ranging from 39–61% of subjects^{(14, 16)}. Diminished bladder contractility or sensation has been found less often⁽¹⁴⁾, and a non-contractile bladder appears to be quite uncommon.

Evidence suggests an increased prevalence of urgency with or without urge urinary incontinence among women with type 2 diabetes⁽¹⁷⁾ and an increasing trend with longer duration of diabetes⁽¹⁸⁾. Overactive bladder (OAB), a highly prevalent and disturbing disease, is also based on the symptoms of urgency, with or without urge urinary incontinence, usually with frequency and nocturia⁽¹⁹⁾. Although urodynamic studies are widely used in patients with symptoms of OAB, only 54% show detrusor overactivity on conventional urodynamics⁽²⁰⁾. Similarly, 55% of diabetic patients with OAB and 25% of asymptomatic patients with diabetes show detrusor overactivity during urodynamic studies^{(14, 21)}.

Bladder wall thickness has been shown to be significantly increased in women with detrusor overactivity⁽²²⁾. This variable has also been applied in the assessment of voiding dysfunction, bladder outlet obstruction, and as a screening tool in the assessment of upper urinary tract deterioration in children with myelodysplasia^{(23, 24)}. This is why urinary bladder dysfunction is to be assessed in type 2 diabetes mellitus by measuring the urinary bladder wall thickness using sonography in this study. Bladder wall hypertrophy is caused by the thickening of the detrusor⁽²⁵⁾. It was hypothesised that detrusor wall thickness (DWT) or bladder wall thickness (BWT) reflects the workload of the bladder similar to the heart, whereby the cardiac wall thickens due to arterial hypertension or cardiac valve stenosis⁽²⁶⁾. In animal studies, diabetes has been shown to result in hypertrophy of the bladder wall with an increase in smooth muscle and urothelium thickness⁽²⁷⁾. Diabetes mellitus patients with OAB may also have an increased risk for bladder wall thickness, which may have a prognostic potential.

Ultrasound is a fast, readily available, and inexpensive modality, and it does not produce a claustrophobic effect like MRI. Ultrasonography is effective in evaluating the urinary bladder wall thickness and it does not utilise ionizing radiation like cystography and abdominal computed tomography which can also be used to evaluate the urinary bladder. However, cystography cannot adequately assess the urinary bladder wall thickness, while CT is quite expensive.

The aim of this study is to evaluate the urinary bladder wall thickness in type 2 diabetes mellitus patients with or without overactive bladder syndrome. The findings will be correlated with the relevant clinical and laboratory parameters.

This was a case-control cross-sectional study carried out at the Departments of Radiology of our institution.

Sonographic assessment technique

The patients were asked to drink an adequate volume of water until they felt a strong desire to void.

The bladder was moderately distended to stretch the wall and better visualise the mucosal surface and bladder lumen. Images were obtained in the transverse and longitudinal planes (Fig. 1)⁽²⁹⁾.

Fig. 1

The bladder wall thickness (BWT) was measured from the interface of the anechoic urine and bladder mucosa to the outer part of the muscle layer. It was measured perpendicular to the luminal surface of the bladder in the anterior bladder wall. Estimated urinary bladder volume was obtained⁽³⁰⁾. Post-void residual (PVR) urine was measured after toilet voiding. Wipes were used to clean off the gel from the examined areas upon completion of the examination.

The age range distribution in this study (40–85 years) was similar to a related study by Uzun et al.⁽³¹⁾ who also carried out their study among patients aged 40 to 75 years.

Among the 80 diabetic mellitus patients included in this study, only three (3.75%), who were females, presented with urinary tract symptoms. This is similar to the findings in the study done by Salem et al.⁽³²⁾, where only two (10%) of the 20 non-neuropathy diabetic patients had obstructive and overactive symptoms. Also, 22 (36.7%) out of the 60 neuropathy diabetic patients presented with lower urinary tract symptoms. 20% of the diabetic neuropathy patients presented with obstructive urinary symptoms, while none of the non-neuropathy patients suffered from these symptoms. Urgency was the most common symptom in all the patients in the study done by Ali et al.⁽³³⁾; urinary frequency which was the second common symptom, was recorded in 93.5% of the 62 patients with overactive bladder (OAB) and 63.9% (23) of the control group.

A common finding in the majority of reviewed studies was that the urinary bladder wall thickness was higher in the diabetics, patients with detrusor overactivity and urinary tract infection than in the non-diabetics. In the study carried out by Uzun et al⁽³¹⁾, it was found out that women that were diabetic and had OAB syndrome had significantly increased bladder wall thickness compared with the controls (p = 0.000), which was similar to the findings in this study, whereby the mean urinary bladder wall thickness in the diabetic patients was 3.18 ± 1.50 mm greater than in the non-diabetic patients, which was 2.18 ± 0.41 mm, with a statistically significant difference between the two groups (p <0.001). In the study done by Ali et al.⁽³³⁾, bladder wall thickness (BWT) in the patients with documented detrusor overactivity was significantly higher than in the patients with normal cystometry. Bladder wall thickness values in patients diagnosed with cystitis cystica via cystoscopy and those with recurrent urinary tract infection (UTI) almost completely overlapped and were very similar. That of the patients with an episode of cured UTI (Group C) and the healthy controls (Group D) were almost the same in Milosevic et al.’s study⁽³⁴⁾. The authors suggested that by measuring the BWT, one can differentiate between the patients with endoscopically verified cystitis cystica and healthy subjects.

The range of urinary bladder wall thickness in men (1.52– 4.15 mm) was similar to that of women (1.46–3.57 mm) in this study population, and there was no statistically significant difference in the urinary bladder wall thickness (p = 0.159) between the males and females who participated in this study (Tab. 4). This is similar to the findings reported by Blatt et al.⁽³⁵⁾, where even though the males (2.1 ± 0.54 mm) had a slightly thicker bladder wall than the females (1.9 ± 0.45 mm), there was no statistically significant difference between the male and female patients with a p value of 0.064. Also, a study carried out by Kanyilmaz et al.⁽³⁶⁾ among 95 healthy volunteers in Turkey showed that there was no statistically significant difference (p = 0.16) in the BWT of the men and women. This is contrary to the findings of the study done by Oelke et al.⁽³⁷⁾ (Germany and the Netherlands) that reported higher BWT in males than in females in a healthy population.

The mean urinary bladder wall thickness of all the male and female participants of this study was 2.84 ± 1.31 mm and 2.90 ± 1.37 mm, respectively. However, the range of the urinary bladder wall thickness was higher in the diabetic males (3.66 ± 1.61 mm) than in the diabetic females (2.9 ± 1.37 mm). There was a statistically significant difference between the urinary bladder wall thickness of the diabetic men and women (p = 0.027) (Tab. 5).

This is contrary to the findings in the study done by Salem et al.⁽³²⁾ among diabetic children, whereby the average value of bladder wall thickness was almost the same in both neuropathic and non-neuropathic diabetic patients probably due to a lesser duration of DM in these type 1 diabetes mellitus patients compared to the type 2 DM in the index study. Also, the mean rise in estimated bladder weight in patients with neuropathy and those without was similar. This observation can be attributable to the difference in the age range of the study population, and the geographical and cultural differences.

There was no correlation between the urinary bladder wall thickness and the urinary bladder volume among the diabetic patients, and no statistical significance was found in this study. Similar findings were reported in the study done by Kanyilmaz et al.⁽³⁶⁾ in Turkey among 95 healthy volunteers, which revealed that the bladder wall thickness was negatively correlated with the urinary bladder volume (r = –0.50) and bladder surface area (r = –0.57). The results obtained in the study were, however, higher and statistically significant. Also, ultrasound estimated bladder weight had a statistically significant correlation with the bladder volume (r = 0.36), bladder surface area (r = 0.48), and the BWT (r = 0.25). This is contrary to the general knowledge that the BWT depends on the degree of bladder filling, which might have been due to the difference in sample size compared to other similar studies. Oelke⁽²³⁾ revealed that in normal women the detrusor wall thickness reduced rapidly between 50 and 250 ml of bladder filling, and reached the peak and maintained the value of thickness thereafter, with unremarkable differences between 250 ml and the maximum bladder capacity.

The relationship between the BWT of the diabetic subjects in this study and their mean glycated haemoglobin levels showed no correlation (Spearman’s rho = 0.119) and no statistical significance (p = 0.309).

The relationship between the duration of diabetes mellitus (DDM) of the diabetic subjects in this study and their mean urinary bladder wall thickness showed no correlation (Spearman’s rho = –0.163) and no statistical significance (p = 0.148). The reason could have been the fact that most of the diabetic patients in the index study were only diagnosed a few years ago, with the median duration of diabetes mellitus being six years, since it is of a non-parametric distribution. Longer duration of DM is associated with the development of thickened bladder wall. About half (53.75%) of the diabetic patients in this study had a DDM of less than six years, with a mean BWT of 1.16 ± 0.37 mm, while the other 46.25% with a DDM exceeding six years from being diagnosed with diabetes mellitus were found to have their mean BWT slightly higher, measuring 1.22 ± 0.42 mm, but with no statistically significant difference (p = 0.231). All the patients in this study that presented with urinary symptoms had poor glycaemic control, with glycated haemoglobin levels in the range of 9–11%. Evidence suggested an increased prevalence of urgency with or without urge urinary incontinence among women with type 2 diabetes in the study done by Brown et al.⁽¹⁷⁾ that involved 7,949 community dwelling women in the USA, and an increasing pattern with a longer duration of diabetes⁽¹⁸⁾. This was not the same in the study done by Salem et al.⁽³²⁾, where the duration of diabetes was found to be statistically significant in relationship with the ultrasound estimated BWT (p = 0.018), but not significantly related to any of the recorded urodynamic parameters in their study.

In the study by Ali et al.⁽³³⁾, using two-way ANOVA, it was revealed that there was a significant relationship between the BWT and DO (p <0.001) and a non-significant relationship between the BWT and gender (p = 0.142). They also noted a positive correlation between the patients’ age and BWT, which was non-significant both in detrusor overactive patients and healthy ones (Pearson correlation: r = 0.266, p = 0.117, and r = 0.090, p = 0.486, respectively). A multiple regression analysis done in the index study was run to predict urinary bladder wall thickness from gender, age, BMI, duration of diabetes mellitus, fasting blood glucose and glycated haemoglobin level. The model had a statistically significant predictive power, as shown in Tab. 8. Among the six variables, only gender was a significant predictor of the urinary bladder wall thickness, p = 0.023 (Tab. 8), while the other variables were not.

The BWT of the T2DM patients was statistically higher than that of the non-diabetic controls (p <0.001). The mean urinary bladder wall thickness of the diabetic patients was significantly higher than that of the healthy controls.

Gender was the only variable that significantly predicted the BWT on multiple regression analysis.