Bladder dysfunction in adolescents with type 1 diabetes.

BACKGROUND: It is increasingly significant that adults with diabetes experience lower urinary tract symptoms, however, there has been limited research in younger individuals with type 1 diabetes. OBJECTIVE: To investigate bladder function using non-invasive urodynamics as a potential indicator of autonomic neuropathy in adolescents with type 1 diabetes. This involved examining the association between urinary flow disturbances, reported symptoms, and results from other autonomic tests. STUDY DESIGN: Cross-sectional study enrolling 49 adolescents with type 1 diabetes and 18 control subjects. All participants underwent uroflowmetry and ultrasound scanning, completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire, and were instructed to record their morning urine volume and voiding frequencies and report them back. Cardiovascular reflex tests (CARTs) and the quantitative sudomotor axon reflex test (QSART) were performed. RESULTS: The main results are shown in the Summary figure. DISCUSSION: In this study, urological abnormalities were not significantly more frequent in adolescents with diabetes, however, urological issues were observed. This is supported by previous findings of Szabo et al. who found that adolescents with type 1 diabetes had reduced flow acceleration and time to maximum flow compared to control subjects. In our study, we observed cases with reduced acceleration and prolonged uroflow curves, possibly indicating detrusor underactivity. People with diabetes had a higher risk of nocturia than healthy controls, which our results supported. Some adolescents reported urination twice per night. Based on these findings, it is considered beneficial to ask about urological symptoms annually to determine if more examinations (frequency-volume charts and uroflowmetry) are necessary and/or if any opportunities for treatment optimization exist. However, uroflowmetry has limitations, as bladder filling and emptying is a complex process involving multiple pathways and neurological centers, making it difficult to standardize and evaluate. Another limitation of this study was that our control group was smaller and consisted of fewer males than females, which could affect the results due to differences in anatomy and physiology in the lower urinary tract system. CONCLUSION: In conclusion, adolescents with type 1 diabetes, as well as healthy adolescents, frequently experience urological symptoms. Although urological abnormalities were not significantly more frequent in adolescents with diabetes in this study, the focus on nocturia and risk for bladder dysfunction seems relevant, even in adolescents without any other tests indicating autonomic dysfunction.

Cross-sectional study investigating the association between inflammatory biomarkers and neuropathy in adolescents with type 1 diabetes.

OBJECTIVES: The aims of this study were to investigate circulating levels of inflammatory markers in adolescents with type 1 diabetes with and without different types of neuropathies and evaluate the association between inflammatory biomarkers, nerve function and clinical parameters. DESIGN: Cross-sectional study. SETTING: Hospitals and Steno Diabetes Center in Denmark. PARTICIPANTS: Adolescents with more than 5 years of diabetes duration were investigated for large fibre, small fibre and autonomic neuropathy as a part of the T1DANES study. Blood samples from the participants were analysed for inflammatory biomarkers by Meso Scale Discovery multiplexing technology. PRIMARY AND SECONDARY OUTCOME MEASURES: Inflammatory biomarkers and results of diagnostic nerve tests. RESULTS: Fifty-six adolescents with type 1 diabetes and 23 healthy controls were included. The adolescents with diabetes had significantly higher interferon-gamma, tumour necrosis factor-alpha (TNF-a), interleukin (IL)-10 and soluble urokinase plasminogen activator receptor (suPAR) compared with healthy controls (p values<0.05). TNF-a was higher in the adolescents with large fibre neuropathy (LFN) (p=0.03) compared with those without LFN in the group with diabetes. A negative correlation was seen between TNF-a and conduction velocity in nervus tibialis (p=0.04), and higher TNF-a and IL-6 were associated with higher gastric motility index (TNF-a, p value=0.03; IL-6, p value=0.02). There were no significant associations between inflammatory markers and expressed symptoms, haemoglobin A1c, diabetes duration or body mass index standard derivation score (p values>0.05). The receiver operating characteristic (ROC) curves for the inflammatory markers suggested them as poor screening methods for all types of neuropathies with an area under the curve between 0.47 and 0.67. CONCLUSION: Our results confirm increased low-grade inflammation in adolescents with type 1 diabetes. TNF-a was higher in adolescents with LFN and correlated negatively with nervus tibialis conduction velocity. The other inflammatory biomarkers fail to support differences in those with and without different types of diabetic neuropathies. However, TNF-a and IL-6 were positively correlated to gastric motility index.

Sweat gland nerve fiber density and association with sudomotor function, symptoms, and risk factors in adolescents with type 1 diabetes.

PURPOSE: To quantify sweat gland nerve fiber density in adolescents with diabetes. Additionally, to investigate associations between sudomotor innervation, sweat responses, and possible risk factors for sudomotor neuropathy. METHODS: Cross-sectional study where 60 adolescents with type 1 diabetes (duration > 5 years) and 23 control subjects were included. Clinical data, quantitative sudomotor axon reflex test, and skin biopsies were obtained. Skin tissue was immunostained and imaged by confocal microscopy. Quantification of the sweat gland volume and three-dimensional reconstruction of the nerve fibers was performed using a design-unbiased technique. RESULTS: Adolescents with diabetes had a significant reduction of maximum and mean values of nerve fiber length and nerve fiber density in sweat glands compared to controls (p values < 0.05). No association between nerve fiber density and sweat responses was found (p = 0.21). In cases with reduced sweat gland nerve fiber length, nerve fiber density, and volume, the sweat response was reduced or absent. Height, systolic blood pressure, time in hypoglycemia, and total daily and basal/total insulin dose were positively correlated to sweat response, while low-density lipoprotein, and HbA1c were negatively correlated with sweat response (p values < 0.05). Other microvascular complications and high cholesterol levels increased the relative risk for reduced sweat gland nerve fiber density. CONCLUSION: Our findings of reduced sweat gland innervation in a selected group of adolescents add new knowledge about the structural changes that occur in autonomic nerves due to diabetes. Evaluating both the sweat gland innervation and sweat gland volume was important for understanding the association with sweat responses. Further research is needed to understand its clinical relevance.

Neuropathy in adolescents with type 1 diabetes: Confirmatory diagnostic tests, bedside tests, and risk factors.

AIMS: To estimate the prevalence of large fiber (LFN), small fiber (SFN), and autonomic neuropathy in adolescents with type 1 diabetes using confirmatory tests known from adults and to identify risk factors and bedside methods for neuropathy. METHODS: Sixty adolescents with type 1 diabetes (diabetes duration > five years) and 23 control subjects underwent neurological examination and confirmatory diagnostic tests for neuropathy, including nerve conduction studies, skin biopsies determining intraepidermal nerve fiber density, quantitative sudomotor axon reflex test (QSART), cardiovascular reflex tests (CARTs), and tilt table test. Possible risk factors were analyzed. Bedside tests (biothesiometry, DPNCheck®, Sudoscan, and Vagus®device) were compared with the confirmatory tests using ROC analysis. RESULTS: The prevalence of neuropathies in the adolescents with diabetes (mean HbA1c 7.6% (60 mmol/mol)) was as follows: 14% confirmed/26% subclinical LFN, 2% confirmed/25% subclinical SFN, 20% abnormal QSART, 8% abnormal CARTs, and 14% orthostatic hypotension. Higher age, higher insulin dose, previous smoking, and higher triglycerides level were found to increase the relative risk for neuropathy. The bedside tests showed poor to acceptable concordance with the confirmatory tests (all, AUC ≤ 0.75). CONCLUSIONS: The diagnostic tests confirmed the presence of neuropathy in adolescents with diabetes and underscore the importance of prevention and screening.

Early Gastrointestinal Neuropathy Assessed by Wireless Motility Capsules in Adolescents with Type 1 Diabetes.

BACKGROUND: To assess the prevalence of objective signs of gastrointestinal (GI) autonomic neuropathy (AN) in adolescents with type 1 diabetes (T1D). In addition, to investigate associations between objective GI findings and self-reported symptoms or other findings of AN. METHODS: Fifty adolescents with T1D and 20 healthy adolescents were examined with a wireless motility capsule to assess the total and regional GI transit times and motility index. GI symptoms were evaluated with the GI Symptom Rating Scale questionnaire. AN was evaluated with cardiovascular and quantitative sudomotor axon reflex tests. RESULTS: There was no difference in GI transit times in adolescents with T1D and healthy controls. Adolescents with T1D had a higher colonic motility index and peak pressure than the controls, and GI symptoms were associated with low gastric and colonic motility index (all p < 0.05). Abnormal gastric motility was associated with the duration of T1D, while a low colonic motility index was inversely associated with "time in target range" for blood glucose (all p < 0.01). No associations were found between signs of GI neuropathy and other measures of AN. CONCLUSIONS: Objective signs of GI neuropathy are common in adolescents with T1D and it seems to require early interventions in patients at high risk of developing GI neuropathy.

Treatment-induced neuropathy of diabetes in an adolescent with rapid reduction in HbA1c and weight loss: Persistent neuropathic findings at follow-up after 1.5 years.

Treatment-induced neuropathy of diabetes (TIND) is a condition occurring within weeks after a rapid decline in blood glucose. This case report illustrates consequences in an adolescent with TIND. Gold standard methods diagnosing large fiber, small fiber, and autonomic neuropathy were abnormal at 1.5 years of follow-up. Awareness of TIND is important.

Large fibre, small fibre and autonomic neuropathy in adolescents with type 1 diabetes: A systematic review.

AIMS: To estimate the prevalence of neuropathy in adolescents with type 1 diabetes. METHODS: Systematic collection of published studies exploring the prevalence of large fibre neuropathy (LFN), small fibre neuropathy (SFN), and autonomic neuropathy in adolescents with type 1 diabetes. Following prospective registration (Prospero CRD42020206093), PubMed, EMBASE, and Cochrane Library were searched for studies from 2000 to 2020. PICO framework was used in the selection process (Population: adolescents aged 10-19 years with type 1 diabetes; Intervention: diagnostic methods for neuropathy; Comparison: reference data; Outcome: data on prevalence or comparison). Data were extracted concerning study quality based on available data and established methods for determining and diagnosing various neuropathy types. RESULTS: From 2,017 initial citations, 27 studies (7589 participants) fulfilled eligibility criteria. The study population (47% males) had a diabetes duration between 4.0 and 10.6 years, and HbA1c level between 7.3 and 10.8%, 56-95 mmol/mol. The prevalence of LFN, based on nerve conduction studies, was 10-57%. Based on other tests for neuropathy, the prevalence of LFN and SFN was 12-62%, and that of cardiac autonomic neuropathy was 12-75%. CONCLUSION: The described prevalence of neuropathy in adolescents with type 1 diabetes varied, which can be methodological due to different screening methods and classifications of neuropathy.

Proportion of Basal to Total Insulin Dose Is Associated with Metabolic Control, Body Mass Index, and Treatment Modality in Children with Type 1 Diabetes-A Cross-Sectional Study with Data from the International SWEET Registry.

OBJECTIVES: To investigate in a large population the proportion of daily basal insulin dose (BD) to daily total insulin dose (TD) (BD/TD) and its association with glycated hemoglobin A1c (HbA1c), body mass index (BMI)- SDS, and treatment modality in children with type 1 diabetes. STUDY DESIGN: Cross-sectional study in subjects with type 1 diabetes, age ≤18 years, and ≥2 years of diabetes duration, registered in the international multicenter Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference registry in March 2018. Variables included region, sex, age, diabetes duration, treatment modality (multiple daily injections [MDI] or continuous subcutaneous insulin infusion [CSII]), self-monitoring blood glucose, HbA1c, BD/TD, and BMI-SDS. BMI was converted to BMI-SDS using World Health Organization charts as reference. Hierarchic linear regression models were applied with adjustment for age, sex, and diabetes duration. RESULTS: A total of 19 687 children with type 1 diabetes (49% female, 49% CSII users) with median age 14.8 (11.5; 17.2) years and diabetes duration 6.0 (3.9; 9.0) years were included. HbA1c was 63 (55; 74) mmol/mol (7.9 [7.2; 8.9]%), and BMI-SDS 0.55 (-0.13; 1.21). Unadjusted, a lower BD/TD was associated with lower HbA1c, male sex, younger age, shorter diabetes duration, lower BMI-SDS, higher numbers of self-monitoring blood glucose and CSII (all P < .01). After adjustment for confounders, lower BD/TD was associated with lower HbA1c (P < .01) and lower BMI-SDS (P < .01) in children on CSII, but not on MDI. CONCLUSIONS: Lower BD/TD is positively associated with lower HbA1c and lower BMI-SDS in children with type 1 diabetes on CSII. It remains to be investigated in a prospective study whether reducing BD/TD insulin will improve metabolic control and normalize body weight in children with type 1 diabetes.

[Gastric perforation in a two-year-old girl].

Gastric perforation is a life-threatening condition and is rarely seen in children. In this case report a two-year-old girl with a two-day history of fever and severe abdominal pain was evaluated in an emergency department. When she was four months old, she had surgery for malrotation. On examination the abdomen was distended, and her condition deteriorated rapidly with signs of shock. A computerised axial tomography scan revealed pneumoperitoneum, and intraoperative findings proved gastric perforation. Surgery was successful. Early diagnosis, surgery, and antibiotic therapy are important in cases of gastric perforation in children to avoid fatal complications.

Prevalence of taste and smell impairment in adults with diabetes: A cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES).

AIM: This study investigates the prevalence of smell and taste impairment in adults with diabetes and potential risk factors for sense deterioration and its influence of daily food intake. METHODS: Data from the NHANES 2013-2014 were analyzed. Smell impairment was defined as failing to identify ≥3 of 8 odors in NHANES Pocket Smell Test. Taste impairment was defined as being unable to identify quinine or NaCl in NHANES Tongue Tip and Whole-mouth Test. RESULTS: A total of 3204 people (428 patients with diabetes, 2776 controls) were suitable to be included. The prevalence of smell impairment in patients with diabetes was higher compared to the controls: 22% versus 15% (p<0.001). The difference prevailed after adjustment for age, BMI, alcohol misuse and smoking status. Taste was not impaired in patients with diabetes (p=0.29). Patients with diabetes and smell impairment had a lower daily calorie intake compared to patients with diabetes and normal smell function. The duration of diabetes, diabetic complications and other potential risk factors were not associated with smell dysfunction. CONCLUSIONS: Smell dysfunction appears with a higher prevalence in patients with diabetes, and this seems to negatively affect daily food intake.

Extreme doses of intravenous methadone for severe pain in two children with cancer.

We describe the effect and side effects in two children with cancer treated with intravenous methadone in extreme doses (>10 mg/kg/day) due to vincristine-induced neuropathy where surgical procedures provoked severe neuropathic pain. The maximum daily dose was 33 and 25 mg/kg/day. Methadone remained effective at adjusted doses. Few side effects were reported. No significant changes in paraclinical data were observed. Prolonged QTc-interval occurred only during concomitant treatment with fluconazole. In conclusion, methadone should be seen as a part of the armamentarium against cancer-related pain. Methadone can be used in extreme doses with appropriate monitoring by clinicians experienced in its use.