Comorbidity of inflammatory bowel disease in children and adolescents with type 1 diabetes.

AIM: To determine the prevalence of inflammatory bowel disease (IBD) in patients with type 1 diabetes (T1D) and to characterise patients with both diseases. METHODS: Data of 65.147 patients with T1D ≤18 years of 379 centres in Germany and Austria participating in the DPV initiative were analysed. A total of 63 children had comorbid IBD; IBD prevalence was 0.1%. Regression models were used to analyse differences in metabolic control, acute complications and steroid intake. RESULTS: Mean BMI-SDS in patients with T1D and IBD was lower (-0.15 ± 0.11) compared to patients with T1D only (0.27 ± 0.00, p < .001). Patients with T1D and IBD had a significantly higher use of steroids (22% ± 0.05% vs. 1% ± 0.00, p < .001) and a significantly higher rate of severe hypoglycaemic events per patient year (0.33 ± 0.07 vs. 0.16 ± 0.00, p = .001). No differences were found in HbA1c levels, insulin dose and occurrence of DKA. CONCLUSION: Although children and adolescents with T1D and IBD take steroids more often, they suffer from severe hypoglycaemia more frequently and have a lower BMI-SDS. These findings might be explained by chronic intestinal inflammation leading to malabsorption, malnutrition and increased severe hypoglycaemia.

Increased tissue factor activity promotes thrombin generation at type 1 diabetes onset in children.

OBJECTIVE: In type 1 diabetes (T1D), a prothrombotic status due to elevated coagulation factors coincides with metabolic derailment. In a previous study, we discovered altered thrombin generation profiles in children with T1D. These alterations are potentially most pronounced at T1D onset and ameliorated after insulin treatment. We tested this hypothesis in a longitudinal study, measuring thrombin generation together with coagulation parameters in children at T1D onset and during follow-up. MATERIALS AND METHODS: Twenty-three children (12 female, age: 9.4 [2.7-17.3] years; median [range]) were tested at T1D onset and after long-term insulin treatment. Thrombin generation was measured using calibrated automated thrombography. Tissue factor (TF) activity and tissue factor pathway inhibitor (TFPI) activity were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: A procoagulant shift was observed in thrombin generation traces at T1D onset compared to follow-up (time to peak: 5.67 [4.11-7.67] min vs 6.39 [4.89-10.44] min, P < .001). These alterations at T1D onset coincided with increased TF activity (5.18 [0.01-12.97] pmol/L vs 2.67 [0.04-10.41] pmol/L, P < .05) and increased TFPI activity (0.051 [0.038-0.074] U/mL vs 0.035 [0.026-0.056] U/mL, P < .05). CONCLUSION: The procoagulant shift in thrombin generation at T1D onset is a result of increased TF activity, but this effect is partially counterbalanced by increased TFPI levels. Elevated TF and TFPI levels hint to a fragile hemostatic balance at the endothelial lining of blood vessels. Additional prothrombotic stimuli may tip over this balance explaining the increased thrombotic risk of children with T1D.

Type 1 diabetes in children and adolescents is not associated with a reduced prevalence of atopy and allergic diseases.

BACKGROUND: Type 1 diabetes mellitus (T1D) as well as allergies in childhood have increased worldwide during the last 2 decades. The reasons for this increase are still unknown but early life origins are being discussed, such as dietary and hygiene factors that may play a role in the development of both diseases. The aim of this study was to compare the prevalence of allergies in children with and without T1D and to define potential influencing factors. MATERIALS AND METHODS: Data were collected from 104 patients with T1D (n = 104; mean age 11.4 ± 4.4 years; m/f: 77/27) and 104 healthy controls (CG) (n = 104; mean age 11.4 ± 4.3 years; m/f: 77/27). A questionnaire on allergic symptoms was obtained from each individual. In parallel, ImmunoCAP tests to detect specific allergen sensitization were performed. RESULTS: Allergen sensitization rates were not significantly different between both groups (T1D: 42% vs CG 38%; P = 0.625). In both groups, a comparable number of patients reported allergic symptoms in the questionnaire (T1D: 20% vs CG 26%; P = 0.43). Allergen sensitization and allergic symptoms were independent of breastfeeding, pets at home or diabetes duration. However, in T1D, fewer family members smoked (T1D: 10% vs CG 56%; P < 0.001). CONCLUSIONS: The present cohort study shows the same prevalence of allergy and atopy in a pediatric diabetes population compared to healthy controls. Diabetes per se does not seem to influence the development of allergies.

Impact of electric cardioversion on platelet activation.

INTRODUCTION: Atrial fibrillation (AF) comes along with high risk of stroke. This risk continues even after re-establishing sinus rhythm with cardioversion. Aim of this study is to evaluate the contribution of electric cardioversion (EC) to platelet activation and procoagulatory tendency. METHODS: Extent of platelet activation before and after electric cardioversion was quantified using flow cytometry, impedance aggregation measurements with Multiplate®, and quantification of serum levels of platelet factor 4 (PF4) and ß-thromboglobulin (ß-TG) in patients with AF (N = 10). RESULTS: No significant differences were observed in any of the measured parameters comparing the values from before and after cardioversion. Geometric means of P-selectin expression and integrin αIIbß3 activation were 0.27 (+/- 0.07) and 2.30 (+/- 2.61) before EC and 0.28 (+/- 0.17) and 1.67 (+/- 1.82) after EC. Levels of ß-TG were 110.11 ng/ml (+/- 3.78) before and 110.51 ng/ml (+/- 2.56) after EC, levels of PF4 were 35.64 ng/ml (+/- 12.94) before and 32.40 ng/ml (+/- 4.95) after EC. Platelet aggregation triggered with adenosine diphosphate (ADP), arachidonic acid, collagen, Ristocetin, or thrombin receptor activating peptide (TRAP) revealed results within the normally expected ranges without significant changes before and after EC. DISCUSSION: Electric cardioversion has no influence on platelet activation markers which is in agreement with other studies reporting electrical cardioversion to be safe.

The influence of physical activity on ghrelin and IGF-1/IGFBP-3 levels in children and adolescents with type 1 diabetes mellitus.

OBJECTIVES: The aim of the study was to determine the influence of regular physical activity on ghrelin and IGF-1/IGFBP-3 levels during a diabetes camp. METHODS: Twenty-eight children and adolescents (14 boys; mean age 12.1 yr) with type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2-wk diabetes camp that features increased regular physical activities have been studied. Serum levels of ghrelin (total and acylated), growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-bindng protein-3 (IGFBP-3) and insulin were measured in fasting state on day 1 and day 14. Improvement of metabolic control was documented by haemoglobin A1c (HbA1c). Glucose levels and insulin doses were determined daily. RESULTS: Mean insulin dosage decreased from 0.87 to 0.78 U/kg/d, mean HbA1c levels decreased from 8.6 to 8.3%, but the changes were not statistical. There was a significant decline in total ghrelin. IGFBP-3 and IGF-1 decreased also significantly. Total basal ghrelin was inversely related to the change in IGFBP-3. CONCLUSIONS: We hypothesize an association between ghrelin and metabolic control in T1DM. Higher ghrelin levels might be associated with poor metabolic control. The dynamic of IGFBP-3 levels appears to be under the influence of basal ghrelin concentrations in T1DM.

Only minor changes in thrombin generation of children and adolescents with type 1 diabetes mellitus - A case-control study.

BACKGROUND: Micro- and macrovascular diseases are frequent complications in patients with diabetes. Hypercoagulability may contribute to microvascular alterations. OBJECTIVE: In this study, we investigated whether type 1 diabetes in children is associated with a hypercoagulable state by performing a global function test of coagulation - the thrombin generation assay. SUBJECTS: 75 patients with type 1 diabetes aged between 2 and 19years were compared to an age-matched healthy control group. Diabetes patients were divided into high-dose and low-dose insulin cohorts with a cut-off at 0.8Ukg-1d-1. METHODS: Measurements were performed with platelet poor plasma using Calibrated Automated Thrombography and 1 pM or 5 pM tissue factor. Additionally, we quantified prothrombin fragments F1+2, thrombin-antithrombin complex, prothrombin, tissue factor pathway inhibitor, and antithrombin. RESULTS: Patients with type 1 diabetes exhibited a significantly shorter of lag time as well as decreased thrombin peak and endogenous thrombin potential compared to control subjects with 5 pM but not with 1 pM tissue factor. In high-dose insulin patients peak thrombin generation was higher and time to peak shorter than in low-dose patients. Thrombin-antithrombin complex was decreased in patients with type 1 diabetes, whereas prothrombin fragments F1+2 was comparable in both groups. Thrombin generation parameters did not correlate with parameters of metabolic control and the duration of diabetes. CONCLUSIONS: Taken together, we found only minor changes of thrombin generation in children and adolescents with type 1 diabetes which - in contrast to type 2 diabetes - do not argue for a hypercoagulable state.