High prevalence of coeliac disease in Danish children with type I diabetes mellitus

The purpose of this population-based study was to determine the prevalence of coeliac disease (CD) in 106 Danish children (age 2-18 y) with type I diabetes mellitus compared with 106 ageand sex-matched healthy controls. Serum samples were analysed for immunoglobulin A (IgA) and IgG gliadin antibodies by enzyme-linked immunosorbent assay (ELISA), for IgA endomysium antibodies (EMA) by immunofluorescence and for IgA tissue transglutaminase antibodies (tTGA) by ELISA. None of the controls had EMA or tTGA. Two diabetics previously diagnosed with CD were antibody negative on a gluten-free diet. Ten diabetics had both EMA and tTGA. Intestinal biopsy was performed in nine of them. All biopsies showed a histological picture of partial or total villous atrophy confirming the diagnosis of CD. Diabetics with CD were significantly younger ( p = 0.026), had an earlier onset of diabetes ( p = 0.005), had a lower height standard deviation score ( p = 0.019) and more often had thyroid antibodies ( p = 0.040) compared with diabetics without CD.

Conclusion: A high prevalence of CD of 10.4% (95% confidence interval 4.6-16.2%) was found in young Danish diabetics. Early onset of diabetes may predispose to CD. Routine serological screening for CD may be valuable in patients with type I diabetes mellitus.     

The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

Objective:  To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM)
Research design and methods:  Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10–18 yr, puberty (≥Tanner breast stage 2 or testicular volume >4 mL), insulin dose ≥1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests.
Results:  Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (−0.3 vs. −0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone.
Conclusion:  The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM.     

Anticholinergic treatment improves glycaemic control in adolescent girls with insulin-dependent diabetes mellitus

Metabolic control often deteriorates during puberty in girls with insulin-dependent diabetes. It is well accepted that there is an abnormality in the growth hormone (GH)-insulin-like growth factor-I (lGF-I) axis in these girls, resulting in reduced IGF-I levels and elevated GH. As GH antagonizes insulin, attempts have previously been made to reduce excess GH secretion through anticholinergic treatment. However, most of these studies have been performed on adult patients. The aim of the present study was to evaluate the effects of 12 wk of oral anticholinergic treatment with Pirenzepine, 100 mg twice daily, in 16 adolescent girls with diabetes. Serum samples of IGF-I, glycated haemoglobin and fasting IGF-binding protein 1 were analysed at initiation and after 3, 8 and 12 wk of Pirenzepine therapy. Nocturnal urinary GH excretion was also examined. Glycated haemoglobin declined significantly after 3 wk of Pirenzepine therapy (9.8 +/- 0.18 vs 9.2 +/- 0.17; p < 0.001) and was still improved at the end of the study. Unexpectedly, nocturnal urinary GH excretion did not change. Serum IGF-I continuously increased during the study, while IGF-binding protein 1 levels were not significantly altered. Conclusion: Anticholinergic treatment with Pirenzepine improves glycaemic control in adolescent girls with diabetes. Although nocturnal urinary GH excretion was unchanged there may still be changes in pituitary GH secretion to explain the improvement. Effects of Pirenzepine on gastrointestinal motility can represent other possible mechanisms behind the improved metabolic control.     

High prevalence of coeliac disease in siblings of children with type 1 diabetes

Coeliac disease has been shown to occur more frequently among first-degree relatives of diabetic patients than in the general population. Our objective was to assess the prevalence of endomysium antibodies (EMA) in non-diabetic siblings of Czech diabetic children and to evaluate the effects of HLA-DQ polymorphisms in determining the genetic susceptibility to coeliac disease (CD) in these subjects. We investigated 240 siblings of diabetic children from 213 families (125 males and 115 females, aged 12.6±4.9 years, mean ± SD). All subjects were tested for the total IgA level to exclude IgA deficiency, and for endomysium IgA to disclose CD. In five IgA-deficient subjects, anti-gliadin IgG was used instead. Small bowel biopsy was offered to subjects with confirmed positive EMA. The HLA-DQA1, -DQB1 genotypes were determined using PCR-SSP. Positive EMA were found in 9/240 (3.8%) subjects (three males, six females). The biopsy confirmed CD in six children, two had a normal mucosal finding and one refused the biopsy. The HLA-DQ2 polymorphism was more frequent among siblings with EMA (seven of nine) than in siblings without EMA (33%), corrected P =0.031. Conclusion:The 3.8% frequency of coeliac disease found in siblings of diabetic children is close to the 4.3% found previously in Czech children with type 1 diabetes mellitus and is substantially higher than the rate in the healthy children population.     

Coeliac disease is associated with intrauterine growth and neonatal infections

To investigate whether factors in the fetal or neonatal period influence the risk of later development of coeliac disease we conducted a population-based register study. The Swedish Medical Birth Register was linked with the Hospital Discharge Register and identified 3392 singleton infants born in the period 1987-97 who developed coeliac disease. Perinatal data for these children were compared with all children born in these years. Exposure variables: Maternal age, parity and smoking habits in early pregnancy, preeclampsia, pregnancy duration and birthweight, birthweight by gestational week, Apgar score, neonatal icterus, neonatal infections, maternal-fetal blood group incompatibility, exchange transfusion, phototherapy. Odds ratios and test-based confidence intervals were calculated. Analyses were made with stratification for year of birth and other risk factors. The risk of developing coeliac disease decreased with maternal age and was lower in first-born than in second-born children. Maternal smoking in early pregnancy was a weak risk factor, as was low birthweight. The most evident risk factors were being exposed to neonatal infections (OR = 1.52, confidence limits 1.19; 1.95) and being small for gestational age (OR = 1.45, confidence limits 1.20; 1.75). These risk factors were independent of each other.

Conclusions: We have demonstrated that the intrauterine environment, mainly as mirrored by a low birthweight for gestational age and, independently, neonatal infection diagnosis, is associated with the risk of developing coeliac disease, supporting the idea of a multifactorial aetiology of the disease.     

Coeliac disease in children in Christchurch,New Zealand:Presentation and patterns from 2000-2010

AIM: To evaluate the presentation patterns of a cohort of children diagnosed with coeliac disease(CD) at Christchurch Hospital, New Zealand.METHODS: Children aged 16 years or less diagnosed with CD at Christchurch Hospital, Christchurch, New Zealand, over the 11 year period between 2000 and 2010 were identified retrospectively. Diagnosis of CD was based upon standard histological criteria of endoscopically-obtained duodenal biopsies. Overlapping search methods were used to identify all relevant diagnoses within the time period. Endoscopy reports and histology findings were reviewed to confirm diagnosis. The numbers of diagnoses per year were calculated and changes in annual rates over the study period were delineated. Available records were reviewed to ascertain presenting symptoms, baseline anthropometry and the indication for referral for each child. In addition, the results of relevant investigations prior to diagnosis were accessed and reviewed. These key investigations included the results of coeliac serology testing(including tissue transglutaminase and endomysial antibodies) as well as the results of tests measuring levels of micronutrients, such as iron. In addition, the histological findings of concurrent biopsies in the oesophagus and stomach were reviewed. RESULTS: Over the 11 year study period, 263 children were diagnosed with CD at this New Zealand paediatric facility. Children were diagnosed from late infancy to 16.9 years: the largest subgroup of children(n = 111) were diagnosed between 5 and 12 years of age. The numbers of children diagnosed each year increased from 13 per year to 31 per year over the 11 years(P = 0.0095).Preschool children(aged less than 5 years) were more likely to have low weight, and to have diarrhoea and abdominal pain prior to diagnosis. Older children(over 5 years of age) most commonly presented with abdominal pain. Fifty-six(21.6%) of the 263 children were diagnosed following screening in high risk groups, with 38 of these children having no symptoms at diagnosis. Mean weight Z scores were lower in children aged less than five years than children aged 5-12 years or older children(-0.4096 ± 1.24, vs 0.1196 ± 0.966 vs 0.0901 ± 1.14 respectively: P = 0.0033). CONCLUSION: Increasing numbers of children were diagnosed with CD in this New Zealand centre over this time, with varied presentations and symptoms.     

Coexistent coeliac disease,Graves' disease and diabetes mellitus type 1 in a patient with Down syndrome

A 17-year-old girl with Down syndrome is presented who developed coeliac disease, Graves' disease and diabetes type 1. Her HLA type was A3, A9, B8, B15, DR3, DR5.     

Coeliac disease in children: a social epidemiological study in Sweden

Aim: Little is known on the possible existence of socioeconomic and geographical differences in early coeliac disease (CD) risk. Therefore, we investigated these aspects in children before age two. Methods: Linking the Swedish Medical Birth Registry to several other national registries, we identified all singletons born in Sweden from 1987 to 1993 (n = 792 401) and followed them until 2 years of age to identify cases of CD. Applying multilevel logistic regression analysis, we investigated the association between socioeconomic position (SEP) and CD in children and also whether a possible geographical variation in CD risk was explained by individual characteristics. Results: Low SEP was associated with CD in boys OR 1.37 (95% CI 1.03–1.82), but not in girls OR 0.87 (95% CI 0.68–1.12). We found a considerable geographical variation in disease risk (i.e. intra‐municipality correlation ≈ 10%) that was not explained by individual characteristics. Conclusions: Low SEP is associated with CD in boys but not in girls. Also, CD appears to be conditioned by geographical area of residence. While our study represents an innovative contribution to the epidemiology of CD in children, the reasons for the observed geographical and socioeconomic differences could be speculated but are still unknown.     

Relationship between bullying and type 1 diabetes mellitus in children and adolescents: a systematic review

ObjectiveTo carry out a systematic review on the relationship of bullying with type 1 diabetes in children and adolescents.MethodsSystematic review, according to the PRISMA methodology, in which the databases PubMed, Web of Science, Scopus, Thomson Reuters, Eighteenth Century Collections Online, Begell House Digital Library, LILACS, and SciELO were searched using the terms “bullied”, “aggression”, “peer victimization”, “victimization”, “school violence”, “diabetes mellitus”, “type 1 diabetes mellitus”, “autoimmune diabetes”, “children” and “adolescents.” The authors included original studies, involving bullying associated with type 1 diabetes, with children and adolescents, without language restriction and publication period, with texts available in full.ResultsOf the 32 articles found, four studies met the selection criteria. Of these studies 85.7% identified occurrence of victimization in diabetics or found a higher frequency in diabetic children and adolescents when compared with young people with other chronic conditions or with healthy peers. Association between bullying and worse glycemic control was observed in two studies, and all the studies mention the fact that type 1 diabetes is a limiting factor for socialization related to diabetes, with less social support and difficulties for the management of the disease in public environments, such as school. The type of bullying suffered varied, including physical, verbal, social, psychological, and sexual.ConclusionMost of the studies showed an association between bullying and type 1 diabetes when compared to individuals with no such condition. Knowledge of this association has become essential for the follow-up of these patients and the implementation of preventive programs.     

Electrogastrography in children and adolescents with type 1 diabetes: weak correlation with metabolic control parameters

AIM: To evaluate gastric myoelectrical activity with respect to duration and metabolic control of type 1 diabetes mellitus (T1DM). METHODS: 172 children and adolescents with T1DM (mean 14.4+/-3.7 y), divided into subgroups depending on diabetes duration (< 5 and > 5 y), and 35 healthy controls (mean 13.93+/-3.59 y) were examined. All subjects underwent electrogastrography (EGG) performed after overnight fasting. In subjects with T1DM, haemoglobin A1c (HbA1c) and blood glucose levels during EGG records were measured. RESULTS: 15.69% of T1DM patients and 91.42% of the controls fulfilled normal EGG criteria (p < 0.001). T1DM subjects had a lower percentage of fasting normogastria (34.56+/-27.35% vs 69.84+/-18.16%, p = 0.0001) and higher bradygastria (51.97+/-30.24% vs 19.11+/-15.01%, p = 0.0001) compared to controls. In diabetic patients, an increase in postprandial normogastria (60.37+/-23.96% vs 76.68+/-12.38, p < 0.05) and a decrease in bradygastria percentage (25.67+/-21.01% vs 9.58+/-7.13%, p < 0.05) was observed. In children with disease < 5 y, diabetes duration correlated with power ratio (r = - 0.27, p = 0.01), postprandial normogastria (r = - 0.24, p = 0.03) and tachygastria (r = 0.25, p = 0.02). Weak correlations between EGG parameters and glucose (preprandial dominant frequency r = - 0.19, p < 0.05; postprandial normogastria r = 0.23, p < 0.01) and HbA1c levels (preprandial bradygastria r = 0.19, postprandial dominant power r = 0.23; p < 0.05) were observed. CONCLUSION: Gastric myoelectrical rhythm derangement is present in a large proportion of young diabetic patients. Bradygastria is the most prominent EGG abnormality. Weak correlation was found between EGG parameters and diabetes metabolic control.     

Prevalence of coeliac disease in diabetic children and adolescents

Screening for coeliac disease (CD) with serum antigliadin antibodies (AGA) was performed in 1032 diabetic children and adolescents. In 8 children CD had been diagnosed before study entry. Of the remaining 1024 children, 33 had an elevated AGA titre in the first serum sample. On follow-up an elevated AGA titre was confirmed in only 17 of 31 patients. Nine of the repeatedly positive patients underwent jejunal biopsy, and CD was diagnosed in two asymptomatic patients; both were positive for IgG- and IgA-AGA. Among 10 AGA-positive patients in whom biopsies could not be performed, only 1 showed IgA-AGA and thus carried a high risk for CD. From our results we estimate a prevalence of CD in Swiss and German diabetic children between 1.1% and 1.3%. Falsepositive AGA titres occurred significantly more often in patients with diabetes duration of less than 1 year. AGA testing teached a specificity of 99% if performed at least 1 year after the onset of diabetes. Children suffering from both diabetes and CD showed a diabetes manifestation at a significantly younger age than non-coeliac patients, whereas CD tended to be diagnosed at a remarkably late age.Abbreviations AGA antigliadin antibodies - CD coeliac disease - FIST fluorescent immunosorbent test - IDDM insulindependent diabetes mellitus     

Longitudinal growth in children and adolescents with type 1 diabetes

Objective

To study longitudinal growth in children with type 1 diabetes mellitus.

Methods

Anthropometry, disease duration, insulin regimens and HbA1C recorded from patients with diabetes enrolled in a specialty clinic.

Results

160 children (75 boys; mean (SD) age 9.4 (3.3) y) were enrolled. 35% children had low (<25^th centile) height velocity. Disease duration and HbA1C affected height velocity (adjusted for puberty). Children on basal-bolus had higher height velocity Z scores than those on a split mix regimen [(0.5(1.6) vs. -0.3(1.4), P<0.05)]. Children diagnosed before 5 years of age had lowest height velocity. Of the children who reached final height, 53% remained below target height.

Conclusion

Children with type 1 diabetes mellitus have lower height velocity compared to healthy children; those diagnosed at younger age were at higher risk for growth failure.

     

HLA-DQA1*05-DQB1*0201 positivity predisposes to coeliac disease in Czech diabetic children

The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLADQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMApositive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%). Conclusion: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity.     

Psychological issues in the care of children and adolescents with type 1 diabetes

The present article highlights some of the psychological issues in children and adolescents with type 1 diabetes and provides health professionals with some strategies for addressing them.     

Microvascular complications in children and adolescents with type 1 diabetes mellitus in Assiut governorate,Egypt

Background

Type 1 diabetes mellitus (T1DM) carries a long-term burden of increased microvascular complications in the form of nephropathy, retinopathy, and neuropathy. As the incidence of T1DM continues to rise, the burden of microvascular complications will also increase and negatively influence the prognosis of young patients. Microalbuminuria (MA) represents the earliest clinical indication of diabetic nephropathy and is a predictor of increased cardiovascular morbidity and mortality. Our study’s aim was to determine the prevalence of microvascular complications among type 1 diabetic patients in Assiut University Children Hospital, Upper Egypt and to find out its correlation with various risk factors.