Urodynamics can provide a fine and early diagnosis of bladder dysfunction not only in urological, but also in non-urological diseases. Uroflowmetry is a non-invasive, quick and easy-to-use urodynamic diagnostic tool in the evaluation of voiding function. In bladder dysfunction caused by impaired detrusor muscle contraction (e.g. in autonomic neuropathy), both maximal urine flow (Qmax) and acceleration of the detrusor muscle contraction (Qacc) decrease. Recent studies suggest that uroflowmetry might determine autonomic neuropathy earlier than cardiovascular autonomic neuropathy symptoms occur, therefore it seems to be a better indicator of diabetic autonomic neuropathy than cardiovascular dysfunction tests (Ewing tests). Therefore, our aim is to assess the use of urodynamics in non-urological diseases.

To do so, first a meta-analysis was performed to evaluate the urodynamic parameters of diabetic women. The study was in line with the protocol registered in PROSPERO. Our primary aim was to compare the urodynamic parameters of diabetic women to those of healthy women, but the eligible studies according to our inclusion criteria did not provide sufficient raw data on healthy female population. Since a direct comparison could not be implemented in diabetic and non-diabetic patients, we conducted a single-arm meta-analysis and positive event rates were pooled for statistical analysis. For data synthesis, the random-effects model with restricted maximum-likelihood estimation was used in all cases; means and 95% confidence intervals (CIs) were calculated. The calculated effect sizes were visualized in forest plots. Heterogeneity was tested using Cochrane's Q and the I2 statistics. Cohen kappa was calculated to test interrater reliability. The risk of bias of the studies were using the Quality In Prognostic Studies (QUIPS) tool. The result of the assessment was graphically demonstrated. 
Then, a prospective, observational, single-centre clinical trial (INTACT trial) was designed to evaluate the diagnostic accuracy (sensitivity, specificity, positive and negative predictive value) of uroflowmetry in the detection of autonomic neuropathy in diabetic and healthy children. The inclusion criteria are children aged 5–18 years with type 1, type 2 and monogenic diabetes mellitus. Baseline characteristics (age, gender, race, weight, height, body surface, body mass index, diet, alcohol consumption, smoking habits, regular medicine, physical status, vital parameters), clinical symptoms (urgency, daytime urine incontinence, nocturnal urination, nocturnal enuresis, frequency of bowel movement, consistency of stool), diabetes anamnesis (type of diabetes, time of diagnosis, treatment, method of insulin administration, use of sensor–pump, the total number of diabetic ketoacidosis, HgA1c value, fasting glucose value, postprandial glucose value), fluid balance in the past 48 hours, laboratory and uroflowmetry parameters will be recorded. Cardiovascular autonomic dysfunction tests will be executed, and peripheral neuropathy will be evaluated by a nerve conduction test. After the first 50 patients, sample size calculation will be carried out. The study was registered in ClinicalTrials.gov.

Out of 1750 records (MEDLINE, n = 454; Embase, n = 773; CENTRAL, n = 63; and Web of Science, n = 460), a total of 140 articles were assessed for eligibility by full text, of which 10 studies were used in the quantitative synthesis, that reported on a total of 2342 diabetic patients. The mean Qmax (n = 1620) is 18.80 mL/sec [95% CI: 15.27–22.33] with a considerable level of heterogeneity (I2 = 99%). The mean maximal detrusor pressure at Qmax (PdetQmax, n = 1211) is 30.13 cmH2O [95% CI: 25.53–34.73],(I2 = 90%). The mean first sensation of bladder filling (n = 1201) is 178.66 mL [95% CI:150.59–206.72],(I2 = 97%). The mean maximal cystometric capacity (n = 1178) is 480.41 mL [95% CI:409.32–551.50],(I2 = 98%). 
The primary endpoint of the INTACT trial is the diagnostic accuracy of the uroflowmetry tests compared to the cardiovascular autonomic dysfunction tests in the detection of autonomic neuropathy. The secondary endpoints are (1) the existence of peripheral and autonomic neuropathy in diabetic children in parallel with the metabolic status (prevalence and incidence of peripheral and autonomic neuropathy), (2) differences in metabolic status (weight, height, body surface, BMI, laboratory parameters, body composition), (3) fluid turnover, and (4) clinical symptoms of diabetic patients comparing to healthy children.

Lower mean voided volume, Qmax and PdetQmax; as well as higher mean postvoid residual volume, first sensation of bladder filling, and cystometric capacity in the diabetic group was detected compared to healthy women.

Diabetes is an important independent risk factor for lower urinary tract symptoms. As urodynamics can detect early alterations in voiding function, it might help to apply interventions to delay or prevent the onset of diabetes to limit difficulties in voiding. We believe that the results of urodynamic studies in diabetic cystopathy and autonomic neuropathy will support the early diagnosis of autonomic neuropathy in other non-urological diseases as well.

Continence 7S1 (2023) 100923
DOI: 10.1016/j.cont.2023.100923