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IntroductionThe aim of this study was to investigate serum Neurofilament Light polypeptide (NfL) as a biomarker for diabetic polyneuropathy (DPN) in adolescents with type 1 diabetes (T1D). Secondarily, to investigate vitamin B12 (B12) deficiency as a cause for DPN in adolescents with T1D.Research design and methodsCross-sectional study. Sixty Danish adolescents with T1D (age 15–18 years, diabetes duration >5 years) and 23 age-matched control subjects were included. Based on nerve conduction studies (NCS), intraepidermal nerve fibre density (IENFD) and neurological examination, patients were divided into three groups: (1) T1D without DPN, (2) T1D with subclinical DPN and (3) T1D with confirmed DPN. Blood levels of NfL, B12, B12-binding protein holotranscobalamin (HoloTC) and methylmalonic acid (MMA) were determined.ResultsTwenty-four of the adolescents were without DPN, twenty-one had subclinical DPN and eight had confirmed DPN. NCS was not conducted in three participants and four patients did not have blood samples taken. There were no significant differences in NfL levels or any of the B12 parameters between any of the groups.ConclusionsNfL used in a cross-sectional manner was not found useful to distinguish between the adolescents with DPN and those without. Vitamin B12 deficiency did not contribute to neuropathy in Danish adolescents with T1D.

ObjectivesThe 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.DesignCross-sectional study.SettingHospitals and Steno Diabetes Center in Denmark.ParticipantsAdolescents 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 measuresInflammatory biomarkers and results of diagnostic nerve tests.ResultsFifty-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.ConclusionOur 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.

Aim: This study is aimed at assesing the impact of neuropathy on well‐being and health‐related quality of life (HRQoL) in adolescents with Type 1 diabetes (T1D). Methods: In a cross‐sectional study, 60 adolescents with T1D (15–18 years, diabetes duration > 5 years) were enrolled. Clinical and biochemical data were collected, and well‐being and HRQoL were assessed using the WHO‐5 well‐being index and DISABKIDS questionnaires, including diabetes‐specific modules. Diagnostic tests for large fiber neuropathy (LFN), small fiber neuropathy (SFN), and autonomic neuropathy were performed as part of the T1DANES study. The participants were divided into groups depending on the presence or absence of specific forms of neuropathy. Those with autonomic neuropathy were further divided depending on reported autonomic symptoms (Composite Autonomic Symptom Scale 31 (COMPASS‐31) score ≥ 24 or < 24). Additionally, the data was compared to 23 healthy control subjects. Results: The median diabetes duration was 8.5 years (range 5–17), and the HbA1c was 60 mmol/mol (7.6%) (range 41–93 [5.9%–10.6%]). Adolescents who had abnormal autonomic function test(s) and a COMPASS‐31 score ≥ 24 exhibited lower WHO‐5 well‐being index compared to the following groups: those with abnormal autonomic test(s) and fewer autonomic symptoms (COMPASS‐31 < 24), the remaining adolescents with T1D, and the control subjects ( p values < 0.05). There was no significant difference in the total score of DISABKIDS between the groups; however, the subdomain social inclusion was lowest in the group with COMPASS‐31 ≥ 24. Gastric motility index ( p = 0.04) and uroflow acceleration ( p = 0.02) were positively associated with the total score of DISABKIDS. Females reported lower well‐being and HRQoL than males ( p values < 0.05); in total, 28% had a WHO‐5 well‐being index < 50. Conclusion: In conclusion, adolescents with diabetic autonomic neuropathy who also reported autonomic symptoms had lower well‐being and impaired social inclusion. Adolescents with symptoms of neuropathy and females appear to be at higher risk of lower well‐being, and using standardized screening tools helps to identify the subjects at risk.

Aim. To determine whether adolescents with type 1 diabetes (T1D) have morphological changes of the corneal nerve fibers and reduced smell and taste function compared to healthy control subjects as a sign of cranial nerve affection and to evaluate possible associated risk factors for cranial nerve affection. Methods. The study was a part of the T1DANES study including 60 adolescents (15–<19 years) and 23 healthy age-matched controls. First, clinical and biochemical data on the participants were obtained, and the second step involved a test day with neurological examinations including corneal confocal microscopy (CCM), olfactory testing with Sniffin’ Sticks, and gustatory assessment with taste-drop test. Results. The adolescents with T1D (mean diabetes duration 9.8 years, mean HbA1c 61 mmol/mol) had lower CCM parameters (corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, and corneal nerve fiber fractal dimension) compared to control subjects (all p<0.05). No differences in total score for smell test (p=0.66) and taste test (p=0.47) were found, but adolescents with T1D had reduced ability to taste sweet (p<0.01). In total, 24% had two or more reduced CCM parameters, 12% had reduced smell test, and 23% had abnormal taste test. Higher waist to height ratio (WHtR) was the only risk factor found for reduced corneal nerve fiber density, and higher BMI-SDS and WHtR were found for impaired taste function. Having abnormal smell test increased the risk for having abnormal taste perception, and vice versa. Conclusion. Up to 29% of adolescents with T1D had abnormal test scores indicating cranial nerve affection. Lower corneal nerve fiber density and reduced ability to taste sweet were found in adolescents with T1D compared to control subjects. Clinical attention to smell and taste function seems important because it requires intervention for advising adolescents with impaired smell and taste function.

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.

The aim of this study was to investigate serum Neurofilament Light polypeptide (NfL) as a biomarker for diabetic polyneuropathy (DPN) in adolescents with type 1 diabetes (T1D). Secondarily, to investigate vitamin B (B ) deficiency as a cause for DPN in adolescents with T1D. Cross-sectional study. Sixty Danish adolescents with T1D (age 15-18 years, diabetes duration >5 years) and 23 age-matched control subjects were included. Based on nerve conduction studies (NCS), intraepidermal nerve fibre density (IENFD) and neurological examination, patients were divided into three groups: (1) T1D without DPN, (2) T1D with subclinical DPN and (3) T1D with confirmed DPN. Blood levels of NfL, B , B -binding protein holotranscobalamin (HoloTC) and methylmalonic acid (MMA) were determined. Twenty-four of the adolescents were without DPN, twenty-one had subclinical DPN and eight had confirmed DPN. NCS was not conducted in three participants and four patients did not have blood samples taken. There were no significant differences in NfL levels or any of the B parameters between any of the groups. NfL used in a cross-sectional manner was not found useful to distinguish between the adolescents with DPN and those without. Vitamin B deficiency did not contribute to neuropathy in Danish adolescents with T1D.

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. Treatment‐induced neuropathy of diabetes (TIND) causes persistent neurological deficits with definite large fiber, small fiber, and autonomic neuropathy even after 1.5 years in an adolescent with diabetes. Clinical awareness of TIND is important.

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.