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.
The study was carried out in adult subjects with type 2 diabetes mellitus. They were recruited from the Diabetes Outpatient Clinic at our institution. The subjects included newly diagnosed diabetics and those on follow-up attending the clinic. The control group consisted of individuals with fasting blood glucose levels less than 6.1 mmol/l and with no known history of diabetes mellitus.
Written informed consent was obtained from both subjects and controls.
The subject group included individuals attending the Diabetes Outpatient Clinic of OAUTHC in Ile-Ife that are above 40 years of age, diagnosed with Type 2 diabetes mellitus by an endocrinologist based on the WHO 1997 criteria which include any of the following(28):
Fasting plasma glucose of 126 mg/dl (7.0 mmol/L) or higher on two separate tests.
Symptoms of diabetes plus a random blood glucose of 200 mg/dl (11.1 mmol/L) or higher.
Two-hour plasma glucose >200 mg/dl (11.1 mmol/L) during an oral glucose tolerance test.
Glycated haemoglobin (HbA1c) of >48 mmol/L (>6.5 DCCT Diabetes Control and Complications Trial %).
History of urologic disease, for example urethral stricture, meatal narrowing, and posterior urethral valve.
History of spinal cord operation or previous pelvic operation that might have injured the presacral nerve plexus, such as surgical correction of imperforate anus.
Neurologic disease such as transverse myelitis, meningomyelocele, Parkinson’s disease, multiple sclerosis, spinal cord injury or stroke.
Urinary tract infection.
Patients on medication that could affect bladder function, such as diuretics or calcium channel blockers.
Patients who currently use or previously used antimuscarinics were also excluded to avoid a likely effect on bladder wall thickness.
Women with evidence of significant pelvic lesion/mass or genital prolapse.
Pregnancy.
Patients with signs of bladder outlet obstruction; or with residual volume over 20 ml.
Patients with obvious neurogenic disorders, stone disease, genitourinary malignancies and/or a history of lower urinary tract injury or surgery were excluded from the study.
Persons who did not give their consent for whatever reason.
Healthy volunteers comprising hospital staff, patient relatives and individuals presenting to the Radiology Department for other investigations (e.g. routine medical check-up).
Fasting blood glucose in the range of 4.0–5.6 mmol/L.
No known history of DM.
Subjects who did not meet the inclusion criteria for the control group.
Subjects with any exclusion criterion for cases.
Persons who did not give their consent for whatever reason.
Versana Essential real-time ultrasound machine: manufactured by GENERAL ELECTRICS® GE Medical Systems (China) Co. Ltd with Serial No. 6023098WX0, equipped with a 3.5–3.8 MHz curvilinear transducer.
A written consent was obtained from all study participants.
The following general information were collected and recorded: age, gender and date of diagnosis of diabetes (or duration of diabetes). Clinical history was obtained from DM subjects to know the duration of their illness (or age at diagnosis).
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).
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.
Various parameters of the examination were recorded in the patient data sheet and entered into the computer spreadsheet using Statistical Package for Social Science (SPSS Inc., Chicago, IL, USA) software, version 20.0 (2016) for Windows.
Quantitative data for descriptive analysis were described in mean, median, standard deviation (SD), and minimum and maximum values, while categorical variables were summarised in simple and relative frequencies.
Independent t-test was applied to compare the means of the urinary bladder wall thickness of diabetic subjects with the control group.
The relationship between glycated haemoglobin levels and urinary bladder wall thickness was determined using Spearman’s correlation coefficient. Spearman’s rank correlation was also used to test the relationship between other continuous variables. Possible correlations between the urinary bladder wall thickness and gender, age, BMI, HBA1c, FBG, and duration of diabetes mellitus were evaluated using multiple regression analysis.
The statistical level of confidence was set at ≤0.05, and the results were presented in tables and charts.
A total of 160 study subjects were recruited, comprising 80 adult subjects with diabetes mellitus aged 40 years and above; in order to ensure the exclusion of type 1 DM; and an equal number of age- and sex-matched apparently healthy controls.
Out of the 80 diabetic subjects, 30 (37.5%) were males, while 50 (62.5%) were females; of the 80 non-diabetic controls, 40 (50%) were males and 40 (50%) were females. There was no statistically significant difference in the numbers of males and females between the diabetic subjects and the control group (
The mean age of the diabetic subjects was 59.5 ± 10.4 years (Tab. 1) with a range of 40–82 years, while that of the controls was 60.2 ± 7.4 years with a range of 40–85 years (
Demographic characteristics of study subjects
Variables | Diabetic | Non- | Statistics | Df | |
---|---|---|---|---|---|
59.5 ± 10.4 | 60.2 ± 7.4 | 0.473 | 158 | 0.6368 | |
(40–82) | (42–85) | ||||
61.6 ± 8.4 | 60.1 ± 8.2 | 0.7606 | 68 | 0.4495 | |
58.2 ± 11.4 | 60.2 ± 6.5 | 1.0034 | 88 | 0.3184 | |
<50 | 15 (18.75) | 7 (8.75) | 0.473 | 158 | 0.6368 |
50–59 | 17 (21.25) | 28 (35.0) | |||
60–69 | 33 (41.25) | 37 (46.25) | |||
≥70 | 15 (18.75) | 8 (10.0) | |||
Male | 30 (37.5) | 40 (50.0) | 2.5397 | 1 | 0.111 |
Female | 50 (62.5) | 40 (50.0) | |||
27.06 ± 6.08 | 27.77 ± 4.39 | 0.8313 | 158 | 0.4071 | |
(17.58–39.84) | (18.69–37.37) | ||||
Underweight | 5 (6.25) | 0 (0.0) | 1.282 | 2 | 0.108 |
Normal | 25 (31.25) | 21 (26.25) | |||
Overweight | 25 (31.25) | 37 (46.25) | |||
Obese | 25 (31.25) | 22 (27.5) |
* Independent sample t-test was used to compare the means,
** chi square
The mean height of the diabetic subjects was 1.63 ± 0.1 m, while that of controls was 1.58 ± 0.08 m. The range of height of the diabetic subjects was between 1.3 m and 1.9 m, while that of the control subjects was between 1.4 m and 1.8 m.
The mean weight of the diabetic subjects was 71.9 ± 14.5 kg and that of the controls was 69.1 ± 10.4 kg with a range of 40.5–108 kg for the diabetic subjects and 50–108 kg for the control subjects. There is, however, no statistical significant difference in the BMI between the diabetic and non-diabetic subjects of this study (
Mean fasting blood glucose was 7.6 ± 3.5 mmol/L and 4.42 ± 0.4 mmol/L in the diabetic and control groups, respectively, with a range of 3.3–21.3 mmol/L and 2.4–4.5 mmol/L, respectively (Tab. 2). Forty-seven (58.75%) of them had good fasting blood glucose control (FBG <7.0 mmol/L) while 41.25% (33) had poor FBG (FBG >7.0 mmol/L). The mean fasting blood glucose in the control subjects was 4.42 ± 0.4 mmol/L.
Clinical parameters in type 2 diabetes mellitus patients
Variables | Diabetic | Non-diabetic |
---|---|---|
7.6 ± 3.5 | 4.42 ± 0.4 | |
(3.3–21.3) | (2.4–4.5) | |
47 (58.75) | ||
33 (41.25) | ||
7.0 ± 2.71 | ||
(4.0–15.0) | ||
44 (56.41) | ||
34 (43.59) |
* Independent sample t-test was used to compare the means
# chi square test was used to compare the proportions SD – standard deviation; BMI – body mass index; FBG – fasting blood glucose; HbA1c – glycated haemoglobin
The mean glycated haemoglobin level (HbA1c) among the people with diabetes was 7.0 ± 2.7% (Tab. 2) with a range of 4–15%. 56.41% (44) of these subjects had good control (HBA1c <6.5%), while 43.59% (34) had poor control (HBA1c >6.5%). Three patients among the diabetics presented with urinary symptoms ranging from urgency, incomplete bladder emptying, frequency, nocturia, to difficulty initiating voiding. All of them were females with poor glycaemic control (9–11%).
There was a statistically significant difference in the urinary bladder wall thickness between the diabetic subjects and the control group (
Comparison of urinary bladder wall thickness among diabetic and non-diabetic patients
Urinary bladder wall thickness in mm | Study participant Mean ± SD | ||
---|---|---|---|
80 (50.0) | 3.18 ± 1.50 | ||
80 (50.0) | 2.18 ± 0.41 |
* Independent t-test was used to compare the means
SD – standard deviation
The ranges of urinary bladder wall thickness among the men and women included in this study were 1.52–4.15 mm and 1.46–3.67 mm, respectively. The mean urinary bladder wall thickness of all male and female participants of the study were 2.84 ± 1.31 mm and 2.90 ± 1.37 mm, respectively. There was no statistically significant difference in the urinary bladder wall thickness (
Comparison of the urinary bladder wall thickness among all the study participants
70 (43.75) | 2.84 ± 1.31 | 0.159 | |
90 (56.25) | 2.9 ± 3.67 |
t* Independent t-test was used to compare the means
SD – standard deviation 1`
Comparison of urinary bladder wall thickness among diabetic men and women
Urinary bladder wall thickness in mm | Study participant Mean ± SD | p value | |
---|---|---|---|
30 (37.5) | 3.66 ± 1.61 | ||
50 (62.5) | 2.9 ± 1.37 |
t* Independent t-test was used to compare the means
SD – standard deviation
Using Spearman’s rank correlation to test the relationship between the glycaemic control of diabetic subjects and the mean urinary bladder wall thickness, there was no correlation between these variables (Spearman’s rho = 0.119,
The mean duration of diabetes mellitus in the diabetic subjects was 7.15 ± 5.62 years with a range of 0.3–34 years, while the median was 6 years. The skewed distribution of the duration of DM led to the use of the median of 6 years in the grouping of DM patients to those with a duration of diabetes mellitus below 6 years and those above 6 years. Comparing the mean urinary bladder thickness of diabetic patients whose duration of diabetes mellitus was below 6 years with those above 6 years showed that there was no statistically significant difference between them (
Relationship of diabetes mellitus duration with urinary bladder wall thickness
Urinary bladder wall thickness in mm | T2DM Mean ± SD | P value | |
---|---|---|---|
43 (53.75) | 1.16 ± 0.37 | 0.231 | |
37 (46.25) | 1.22 ± 0.42 |
* Independent t-test was used to compare the means
SD – standard deviation
Association between urinary bladder wall thickness, glycaemic control, urinary bladder volume and duration of diabetes mellitus in type 2 diabetes mellitus patients
Variables | rho* | ||
---|---|---|---|
78 | 0.119 | 0.309 | |
78 | |||
80 | –0.009 | 0.937 | |
80 | |||
80 | –0.163 | 0.148 | |
80 |
* Spearman’s rank correlation was used to check the relationship
BWT – bladder wall thickness; HBA1c – glycated haemoglobin; UBV – urinary bladder volume; DDM – duration of diabetes mellitus
A multiple regression analysis was run to predict urinary bladder wall thickness from age, gender, BMI, duration of diabetes mellitus, fasting blood glucose and glycated haemoglobin level. Among all six variables, only gender added statistically significantly to the prediction,
Predictors of urinary bladder wall thickness
Variables | |||
---|---|---|---|
80 | 0.44 | 0.665 | |
80 | –2.33 | 0.023 | |
80 | –0.62 | 0.537 | |
80 | –0.92 | 0.362 | |
80 | 0.90 | 0.369 | |
80 | 1.04 | 0.300 |
* Multiple regression analysis was used to determine the predictor of UBW BMI – body mass index; UBW – urinary bladder wall thickness; DDM – duration of diabetes mellitus; HBA1c – glycated haemoglobin; FBG – fasting blood glucose
The age range distribution in this study (40–85 years) was similar to a related study by Uzun
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
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
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 (
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 (
This is contrary to the findings in the study done by Salem
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
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 (
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 (
In the study by Ali
The BWT of the T2DM patients was statistically higher than that of the non-diabetic controls (
Gender was the only variable that significantly predicted the BWT on multiple regression analysis.