Thyroid autoimmunity in children with features of both type 1 and type 2 diabetes

Aim/hypothesis:  To assess the prevalence of autoimmune thyroid disease (ATD) in insulin-treated youth with clinical features of type 2 diabetes mellitus (T2DM).
Methods:  We evaluated prevalence of thyroid peroxidase (TPO) and thyroglobulin (TGA) antibodies at onset of insulin-treated diabetes and follow-up in 183 White and Black children. Of these, 136 had a body mass index (BMI) <85th percentile with 122 (89%) positive for β-cell autoimmunity [type 1 diabetes mellitus (T1DM)/group I], 25 were overweight (BMI ≥85thpercentile) with or without acanthosis nigricans with β-cell autoimmunity ['double' diabetes (DD)/group II], and 22 were overweight with no conventional β-cell autoantibodies (group III).
Results:  The prevalence of TPO and/or TGA was 39 and 29% (p = 0.19) in White and Black children and 39, 32, and 0% (p = 0.007) in groups I, II, and III, respectively. After a median follow-up of 60 months, 3.7, 4.3, and 0% developed hypothyroidism (increased thyroid-stimulating hormone with or without decreased free T4) in groups I, II, and III, respectively (p = 0.6). In subjects with TPO and/or TGA, hypothyroidism developed in 10 and 14% of groups I and II, respectively (p = 0.7). No child without thyroid antibodies developed hypothyroidism.
Conclusions:  In patients with clinical features of T2DM who have evidence of β-cell autoimmunity (DD), the frequency of thyroid antibodies and ATD is similar to that in classical T1DM. This suggests that TIDM comorbidities may be common in clinical T2DM patients who have β-cell autoimmunity. Despite their obesity, youth with insulin-requiring diabetes should be screened for thyroid and possibly other T1DM-associated autoimmune diseases.     

Prevalence of 20S proteasome, anti-nuclear and thyroid antibodies in young patients at onset of type 1 diabetes mellitus and the risk of autoimmune thyroiditis

Patients with type 1 diabetes mellitus (DM1) are at high risk to develop further autoimmune disorders, which are mostly characterized by the presence of organ-specific antibodies in serum and a subclinical disease course. Diabetes-related (glutamic acid decarboxylase, tyrosine phosphatase, IA-2) and thyroid-specific (thyroperoxidase, thyroglobulin) as well as antibodies to 20S proteasome, and anti-nuclear antibodies, were measured at DM1 onset in 147 children and adolescents. Patients were followed prospectively for the development of autoimmune thyroiditis (TSH elevation and/or sonographic thyroid gland enlargement in the presence of thyroid antibodies) up to 12 years, median observation time 4.4 years. Eight of 147 (5.4%) patients developed autoimmune thyroiditis. The cumulative incidence (+/-SE) at 5 years was 0.08+/-0.03. The prevalence of thyroid antibodies was 16.7%, of DM-related 88.4%, 20S proteasome 21.9%, and anti-nuclear antibodies 20.0%. There was a positive correlation between thyroid and anti-nuclear antibodies (p <0.001). Clinical course of DM1 and remission duration were not influenced by the presence of autoantibodies. However, in contrast to patients without antibodies, those with positive antibodies had significantly (p <0.001) elevated cumulative incidence of autoimmune thyroiditis at 5 years: thyroperoxidase 0.40+/-0.13, thyroglobulin 0.38+/-0.15, and anti-nuclear antibodies 0.29+/-0.12, respectively. These data underline that autoimmunity in patients with DM1 is not only restricted to beta-cell antigens at the onset of disease. In particular, patients with positive thyroid and anti-nuclear antibodies are at high risk to develop autoimmune thyroiditis during the first 5 years of DM1.     

Autoimmune thyroid dysfunction in children with type 1 diabetes mellitus: screening guidelines based on a retrospective analysis

Individuals with type 1 diabetes mellitus (DM1) have an increased risk of developing autoimmune thyroid dysfunction (AITD). We measured the prevalence of AITD in a pediatric DM1 population in order to examine the best combination of markers for predicting the development of AITD. A database of 1,254 patients with DM1 under 21 years of age was retrospectively screened for abnormalities in antithyroglobulin antibody (ATA), thyroid peroxidase antibody (TPO) and thyroid stimulating hormone (TSH). Charts on all 134 who had any of these serologic abnormalities were reviewed. 4.2% of the DM1 population was clinically diagnosed with AITD. Thirty-nine percent of the AITD diagnoses came within 1 year of DM1 diagnosis. Based upon evidence-based medicine statistics, TPO and TSH measurements are the most efficient and cost-effective combination of screening tests for AITD prediction and detection. The positive predictive value (of TPO and TSH) is 90%, with a positive likelihood ratio of 131.     

Autoimmune thyroid disease in Indian children with type 1 diabetes mellitus

The objective of the present study was to determine the prevalence of autoimmune thyroid disease in Indian children with type 1 diabetes mellitus by the assay of antibodies to thyroid peroxidase and thyroglobulin. The study population consisted of 35 children with type 1 diabetes mellitus and 32 healthy age- and sex-matched control children. Thyroid peroxidase antibodies (TPO) were determined by ELISA and thyroglobulin antibodies (TGA) by passive hemagglutination. Thyroid function tests and tests of glycemic control were also performed. These assays were repeated after six months and one year. TPO were observed in 19 (54.3%) patients compared to three (10%) controls, and TGA in 11 (31.4%) patients and none of the controls. Both these observations were statistically significant with p=0.0002 for TPO and 0.0016 for TGA. The prevalence of these antibodies was not different in boys and girls and did not change with the duration of diabetes. All patients who were positive for TGA were also positive for TPO. Thyroid function tests were abnormal in one patient who was found to have Hashimoto's thyroiditis. There is a definite need to screen all diabetic children for thyroid antibodies and carefully follow up those patients in whom these antibodies are positive.     

Delayed menarche in young German women with type 1 diabetes mellitus: recent results from the DPV diabetes documentation and quality management system

Background  Findings have been inconsistent regarding the effect of T1DM (type 1 diabetes) on age at menarche. Objective  The purpose was to investigate in young German women with T1DM menarcheal age and factors potentially affecting menarche, including glycemic control, BMI (body mass index), relative T1DM duration (proportion of life with diabetes), insulin dose, and insulin therapy intensity. Initiated in 1990, the DPV program is an ongoing, prospective long-term longitudinal follow-up study to benchmark the quality of care provided to pediatric and, more recently, adult diabetes patients. Two hundered two German diabetes centers participated in nationwide data collection. Based on ethnicity and the availability of menarche and T1DM onset data as the main inclusion criteria, 643 young German women were selected from 11,629 female T1DM patients aged <20 years, recruited by referral, clinic or hospital ascertainment, or self report. Mean age at menarche (±SD) was 13.22 ± 1.31 years, representing a delay of 0.52 years (p < 0.001) relative to the general population. Significant delay (p < 0.05) was also found for relative T1DM duration, BMI SD score, insulin dose, and HbA1c level, with a 1% increase in HbA1c resulting in a delay in menarche by 0.07 years. Conclusions  Age at menarche is delayed in type 1 diabetes mellitus. The delay increases with relative T1DM duration and poor quality of glycemic control.     

Prevalence of thyroid antibodies (TPO and ATG) at the onset of type 1 diabetes mellitus in children treated in two diabetes centres in Łódź and Kielce

Patients with autoimmune type 1 diabetes mellitus have often, besides immune diabetes markers, also other organ-specific antibodies, particularly thyroid autoantibodies (antithyreoglobulin antibodies - ATG and/or thyroid peroxidase antibodies - TPO). In many of these patients autoimmune thyroid diseases, i.e. Hashimoto thyroiditis and Grave's disease, with silent clinical course can be diagnosed. The aim of this study was to evaluate the prevalence of TPO and ATG antibodies in children with newly diagnosed type 1 diabetes treated in two diabetes centres, in Lodz and in Kielce. Elevated ATG and/or TPO antibodies were found in 17,8% (15/84) of children: in 19,2% (11/57) in Lodz centre and in 14,8% (4/27) in Kielce centre. Children with elevated thyroid autoantibodies were significantly older than those without thyroid autoantibodies. Daily insulin requirement did not differ between both groups.     

Screening frequency for celiac disease and autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus--data from a German/Austrian multicentre survey

Objective: Type 1 diabetes mellitus (T1DM) is associated with other autoimmune diseases such as celiac disease (CD) and Hashimoto thyroiditis. The aim of this study was to evaluate the screening frequency for CD and thyroid antibodies in a multicentre survey. Methods: The Diabetes Patienten Verlaufsdokumentationssystem (DPV) initiative is based on standardized, prospective, multicentre documentation in children and adolescents with diabetes. Data from 31 104 patients <18 yr of age (52% males, mean age 13.1 yr) with T1DM from 177 paediatric centres in Germany and Austria from 1995 until 2007 were analysed. Results: Of 31 104 patients, 16 994 patients (55%) were screened at least once for CD. In 1995, 44% of the patients were screened for CD compared with 68.6% in 2006. Annual screening for CD has also increased (11.9% in 1995 compared with 43.6% in 2006). Eleven per cent of the patients had positive antibodies for CD. Patients with positive antibodies were significantly younger at diabetes onset and had a significantly longer duration of diabetes (p < 0.001). Compared with screening for CD, screening for thyroid antibodies was performed more frequently (at least once in 62% of the patients). Fifteen per cent of the patients had positive thyroid antibodies. Screening for thyroid antibodies also increased from 62.6 to 72.9%, and annual screening frequency increased from 15.9 to 48.9%. Conclusion: Screening for associated autoimmune diseases in children with T1DM has increased during the past decade. Eleven per cent of the patients had positive CD‐specific antibodies, and 15% had positive thyroid antibodies. Screening for thyroid antibodies is performed more frequently than screening for CD.     

Cardiovascular impairment in children,adolescents, and young adults with type 1 diabetes mellitus (T1DM)

Left ventricular (LV) function was assessed in 42 patients (mean age ± SD, 18.45 ± 3.76 years; 17 males) with type I diabetes mellitus (T1DM; mean duration 9.89 years) and in 43 healthy controls (mean age ± SD, 18.27 ± 3.36 years; 18 males). Systolic, diastolic cardiac function and LV dimensions were assessed using M-mode and Doppler echocardiography. Neural autonomic function was assessed by measuring RR variation during deep breathing, Valsava maneuver, 30/15 ratio, and blood pressure response to standing. Fractional shortening, peak velocity of early ventricular filling (E wave), peak velocity of LV filling (A wave), E/A ratio, deceleration time, isovolumic relaxation time, LV dimensions (interventricular septum, posterior wall thickness, end diastolic diameter [EDD] and systolic diameter [ESD]) were all comparable between patients with T1DM and controls. However, in 11 T1DM patients with microalbuminuria and/or retinopathy, EDD, ESD, E/A ratio, and E wave were all lower (p = 0.0011, p = 0.019, p = 0.0011, and p = 0.030, respectively) while, A wave, heart rate, and diastolic blood pressure were all higher (p = 0.008, p = 0.0024 and p = 0.004, respectively) compared to matched for age and sex controls. Furthermore, in six of the 11 T1DM patients with microangiopathy who had E/A <1.12 (<2 SD of the control mean), significant and marginally significant correlations were found between E/A ratio and the duration of the disease as well as the mean HbA1c of the last year (r = –0.38, p = 0.011 and r =  –0.287, p = 0.064, respectively). In conclusion, it has been found that impairment of diastolic, but not systolic, LV function can be detected early in young patients with T1DM and microangiopathy.     

Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus: prevalence and risk factors

Studies show great variation in prevalence of anti-thyroid antibodies in children with type 1 diabetes mellitus (DM1). There still is no consensus regarding screening of autoimmune thyroiditis in patients with DM1, especially in asymptomatic patients. AIM: To investigate the natural history and prevalence of autoimmune thyroiditis in pediatric patients with DM1 and relate it to potential risk factors. PATIENTS AND METHODS: This study is a historical cohort, through research of the records of 474 patients with DM1 from 9 months to 25 years of age, between 1980 and 2005 - 222 boys (46.8%) and 252 girls (53.2%), with an average duration of DM1 of 9.3 +/- 5.8 years. The sample was selected by having at least one measurement of TSH and anti-thyroid autoantibodies (antithyroperoxidase or anti-microssomal and/or anti-thyroglobulin) at any time from diagnosis of DM1. A questionnaire was answered in order to study the variables of interest for the study. Thyroid function disorder was defined as altered levels of TSH, with or without altered free T4 levels. RESULTS: A total of 383 patients (9 months to 25 years of age) were studied, 199 girls (52%) and 184 boys (48%). Sixty-four (16.7%) had positive anti-thyroid antibodies, predominantly girls (p = 0.064). Average duration of DM1 was 9.3 +/- 5.8 years and those above this age had a higher incidence of thyroiditis (p = 0.01). The prevalence of thyroid function disorder in patients with DM1 was 7.3% (n = 28), mostly with thyroiditis (32.8% vs 2.2% with negative antibodies, p < 0.001). There was a positive association between thyroiditis, as well as thyroid function disorders, and other autoimmune disorders (p < 0.001 and p < 0.02, respectively). CONCLUSIONS: Prevalence of thyroiditis in the diabetic population is considerably higher than in the general population. Annual laboratory determinations of anti-TPO antibodies and dosage of TSH should be part of routine tests in the diabetic population, especially in girls, children with DM1 for > 9 years, patients above 12 years of age, and those in whom DM1 is associated with another autoimmune disease. Anti-thyroid antibody positivity may indicate the necessity for thyroid function testing at shorter intervals.     

Early atherosclerosis in childhood type 1 diabetes: role of raised systolic blood pressure in the absence of dyslipidaemia

The intentions of our investigation were (1) to search for atherogenic risk factors and signs of incipient atherosclerosis in children and adolescents with type 1 diabetes (T1DM) in comparison to well-matched control subjects, (2) to evaluate risk factor associations with carotid intima media thickness (cIMT) in diabetic patients and control subjects, and (3) to acquire a better knowledge of early atherogenesis in children and adolescents with and without T1DM. 94 diabetic children (age median 12.3 years, HbA_1c median 7.7%) and 40 non-diabetic controls (age median 12.3 years) were investigated. Mean cIMT was determined using high-resolution B-mode ultrasound with an automated contour identification procedure. Compared to controls, subjects with diabetes had significantly elevated cIMT (p = 0.041) and systolic BP (p = 0.007) but showed a less atherogenic lipid profile. Most markers of inflammation, endothelial function and fibrinolytic activity were higher in diabetic subjects than in controls. Multiple linear regression analysis revealed a significant relationship (r = 0.53, p = 0.036) between bilateral mean cIMT and diverse risk factors in patients with T1DM. Spearman rank correlation showed that diabetes duration (rho = 0.32, p = 0.029), systolic BP (rho = 0.32, p = 0.004), weight (rho = 0.257, p = 0.022), and height (rho = 0.265, p = 0.018) significantly correlated with bilateral mean cIMT in the 94 diabetic patients. In conclusion, in well-controlled type 1 diabetic children systolic BP may be of greater importance than dyslipidaemia in early atherogenesis. BMI, markers of sustained inflammation, endothelial dysfunction and fibrinolytic activity are increased in diabetic versus non-diabetic children but none of them correlates significantly with cIMT. Their prognostic value remains to be determined.     

Reduced physical activity level and cardiorespiratory fitness in children with chronic diseases

We aimed to compare physical activity level and cardiorespiratory fitness in children with different chronic diseases, such as type 1 diabetes mellitus (T1DM), obesity (OB) and juvenile idiopathic arthritis (JIA), with healthy controls (HC). We performed a cross-sectional study including 209 children: OB: n = 45, T1DM: n = 48, JIA: n = 31, and HC: n = 85. Physical activity level was assessed by accelerometer and cardiorespiratory fitness by a treadmill test. ANOVA, linear regressions and Pearson correlations were used. Children with chronic diseases had reduced total daily physical activity counts (T1DM 497 ± 54 cpm, p = 0.003; JIA 518 ± 28, p < 0.001, OB 590 ± 25, p = 0.003) and cardiorespiratory fitness (JIA 39.3 ± 1.7, p = 0.001, OB 41.7 ± 1.2, p = 0.020) compared to HC (668 ± 35 cpm; 45.3 ± 0.9 ml kg⁻¹ min⁻¹, respectively). Only 60.4% of HC, 51.6% of OB, 38.1% of JIA and 38.5% of T1DM children met the recommended daily 60 min of moderate-to-vigorous physical activity. Low cardiorespiratory fitness was associated with female gender and low daily PA. Conclusion: Children with chronic diseases had reduced physical activity and cardiorespiratory fitness. As the benefits of PA on health have been well demonstrated during growth, it should be encouraged in those children to prevent a reduction of cardiorespiratory fitness and the development of comorbidities.     

GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis

Kordonouri O, Charpentier N, Hartmann R. GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis. Aim: To evaluate whether the presence of diabetes‐specific autoantibodies may predict the development of autoimmune thyroiditis (AIT) in children with type 1 diabetes (T1D). Methods: Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase IA2 antibodies (IA2A), and insulin autoantibodies (IAA) were determined at T1D onset in 341 children and adolescents. Thyroid antibodies (anti‐TG, anti‐TPO), thyroid stimulating hormone (TSH), T₃ and T₄ were measured in 335 patients at T1D onset and thereafter annually with a follow‐up time of 1–15 yr. In case of thyroid antibody positivity and/or TSH elevation, thyroid gland sonography was performed. Treatment with l ‐thyroxine was started if persistent elevation of TSH and/or thyroid volume was present. Results: The majority of patients (92.1%) had at least one T1D antibody (71.6% GADA, 73.0% IA2A, and 44.9% IAA). GADA positive patients were older than those without GADA (p < 0.001). Thyroid autoimmunity was found in 15 of 335 patients (4.5%) at T1D onset with female preponderance (p = 0.013). At the end of follow‐up, 70 patients (20.9%) had developed thyroid autoantibodies [cumulative incidence (CI) 0.36 ± 0.06 at 10 yr of T1D]. In 30 patients (9.0%), AIT was diagnosed up to 9.4 yr after T1D onset (CI 0.24 ± 0.06 at 10 yr). AIT incidence was not influenced by IAA or IA2A positivity. In multivariate analysis, GADA positive patients were estimated to have a 3.5‐fold increased risk of AIT (CI 0.31 ± 0.11 at 10 yr) compared to those without GADA (p = 0.024). Conclusion: Based on the present results, a special focus should be given to GADA positive patients concerning screening for AIT as they are at increased risk to develop autoimmune thyroiditis.     

Overweight children with type 1 diabetes have a more favourable lipid profile than overweight non-diabetic children

In the present article, we aimed to compare the cardiometabolic risk between overweight children with and without type 1 diabetes (T1DM). Therefore, data with regard to cardiometabolic risk parameters of 44 overweight Caucasian children (3–18 years) with T1DM were matched with 44 overweight peers without T1DM for sex, ethnicity, age and standard deviation score of BMI (Z-BMI). Detailed history was taken, information regarding anthropometrics and family history were collected and blood pressure was measured. Blood samples were collected for evaluation of lipid profiles (fasting in controls, non-fasting in T1DM children), alanine aminotransferase and HbA1c (in children with T1DM). It was found that overweight children with T1DM had lower median standard deviation score of waist circumference (Z-WC) as compared to the overweight control group [median, 2.0 (interquartile range, IQR, 1.5–2.3) vs. 2.6 (IQR, 2.0–2.9), P < 0.001]. After adjustment for Z-WC, in children with T1DM, median high-density lipoprotein cholesterol levels were significantly higher and median low-density lipoprotein cholesterol lower in T1DM children, as compared to their peers without T1DM [1.40 (IQR, 1.2–1.5) vs. 1.2 (IQR, 1.0–1.3) and 2.7 (IQR, 2.5–3.2) vs. 3.0 (IQR, 2.5–3.4), respectively, all P < 0.01]. When dividing children according to glycaemic status, children with suboptimal glycaemic control had higher values of triglycerides as compared to well-controlled children [1.3 (IQR, 1.0–1.8) vs. 0.96 (IQR, 0.80–1.2), P = 0.036]. In conclusion, overweight children with T1DM have a more favourable lipid profile, as compared to non-diabetic overweight controls, in spite of a higher frequency of a positive family history of CVD, T2DM and hypertension. Still, paediatricians should give extra attention to cardiometabolic risk factors within this vulnerable group, taking into account the already high cardiometabolic risk.     

1型糖尿病儿童甲状腺抗体的检测

目的：明确1型糖尿病（T1DM）儿童甲状腺抗体阳性的发生率及其相关因素。方法：回顾性分析我院2005年5月至2011年4月T1DM病例的临床资料,分析甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)与细胞因子IL-2、IL-4、IL-6、IL-10、TNF、IFN-γ和CD3+、CD4+、CD8+淋巴细胞的关系。结果：经筛选后共获得甲状腺双抗体资料完整的T1DM患儿186例,其中甲状腺双抗体正常143例,甲状腺抗体阳性43例（23.1％）,其中双抗体阳性21例。诊断为自身免疫性多腺体综合征3型变异型患儿18例（9.7%）。甲状腺抗体阳性组有糖尿病家族史的比例显著高于甲状腺抗体正常组（27.9% vs 14.7%,P＜0.05）。甲状腺抗体阳性组患儿年龄大于甲状腺抗体正常组（10.1±3.2岁vs 8.1±4.0岁,P＜0.05）。甲状腺抗体阳性组IL-2水平显著高于甲状腺抗体正常组（4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL,P＜0.05）,而其CD3+细胞比例低于甲状腺抗体正常组［（61±11)% vs (66±11）%, P＜0.05）］。结论：儿童T1DM甲状腺抗体阳性率增高可能与遗传背景和T细胞免疫功能紊乱,尤其是IL-2异常升高有关。     

Falciparum Malaria in Children—A Brief Report of 305 Patients from Rourkela,Eastern India

Most of the studies on malaria in children are reported from Africa, but only a few are from India. A retrospective study of 305 children with slide positive malaria was conducted at Rourkela, Orissa. 5.2% children were below 1 year of age. 34.1% were between 1 and 5 years and 60.7% were above 5 years. 63.9% were boys. The presenting symptoms were fever (98.4%), vomiting (52%), and headache (22%). 121 patients had one or more complications viz., cerebral malaria (n = 56), severe anemia (39), jaundice (31), convulsions (20), hypoglycemia (10) and only one with acute renal failure. 22 patients died.     

The influence of growth hormone monotherapy and growth hormone in combination with oxandrolone or testosterone on thyroxid hormone parameters and thyrxine binding globulin in patients with Ullrich- Turner syndrome

 Administration of human growth hormone (GH) has yielded conflicting results concerning its role on thyroid function in patients with Ullrich-Turner syndrome. Therefore, we investigated the course of thyroid hormone parameters and thyroxin binding globulin in relation to GH therapy, IGF-I and additional oxandrolone-(Ox) or testosterone (T) treatment in 20 patients with Ullrich-Turner syndrome. During the 1st year the patients received only GH. There was no change in T4, fT4, and TSH levels, T3 increased significantly (P <  0.01) after 6 and 12 months, resulting in a higher T3/T4 ratio. TBG (P < 0.05) and IGF-I (P < 0.01) increased after 6 months and remained elevated at 12 months. A significant positive correlation was found between the change of T4 and TBG after 6 months (r = 0.47, P < 0.05) and after 12 months (r = 0.69, P < 0.005). Thirteen patients were further investigated after addition of an anabolic compound; 7 received Ox (0.0625 mg/kg/day po) and 6 low dose T (5 mg i.m. every 14 days). Chronological age was comparable in these groups (10.7 ±  2.7 vs 10.7  ± 3.6 years). After 6 months of combination therapy with Ox, T4, T3 and TSH decreased. As T4 and T3 showed a parallel decrease the T3/T4 ratio remained elevated. TBG declined after 6 and 12 months (P < 0.05), while IGF-I showed a further increment (P < 0.05). There was no correlation between the changes in T4 and IGF-I, TSH and TBG, respectively. In the T-treated group only IGF-I increased (P < 0.05) to the same extent as in the Ox-treated patients, whereas the thyroid parameters did not change. Conclusion The observed changes in thyroid hormone and TBG levels in the Ox group were not mediated by GH or IGF-I. The Ox-induced TBG decrease might be linked to altered pancreatic functions regulating carbo-hydrate metabolism. Received: 22 April 1996 / Accepted: 1 August 1996     

Attitudes toward complementary and alternative medicine: a national survey among paediatricians in the Netherlands

The purpose of the present survey was to assess attitudes, beliefs, experience, referral patterns and desire for education regarding complementary and alternative medicine (CAM) therapies of paediatricians in the Netherlands. In 2009, the link to an anonymous, self-reporting, 30-item web-based questionnaire was mailed to all members of the Dutch Association of Paediatrics. The questionnaire included questions about demographics and practice characteristics, use of CAM by the paediatrician and/or his family, attitudes towards and knowledge of CAM, and inquiries about CAM use in their practice. A total of 343 (24%) paediatricians responded to the survey: 39% had used some kind of CAM therapy themselves during the past 2 years, of which supplements (64%) and herbal and/or homeopathic remedies (30%) were most frequently mentioned. The majority of the paediatricians (62%) seldom asked parents of patients about CAM use. Referrals to CAM doctors were made by approximately 30% of the paediatricians. In general, more than 50% of the surveyed paediatricians had little knowledge of CAM therapies. Predictors for a positive attitude towards CAM were own CAM use (p < 0.0001), age >45 years (p = 0.02) and perceived knowledge level of CAM (p < 0.005). In conclusion, a significant group of Dutch paediatricians has a positive attitude towards CAM and refers patients to CAM therapies. The majority of paediatricians, however, do not ask patients about CAM use and seem to lack sufficient knowledge on CAM.     

Antibody persistence for 3?years following two doses of tetravalent measles–mumps–rubella–varicella vaccine in healthy children

Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12–18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42–56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42–56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15–20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. Conclusion: Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).     

Celiac disease prevalence in children and adolescents with type 1 diabetes from Serbia

Background: The association between celiac disease (CD) and type 1 diabetes mellitus (T1DM) is well known. Up to now, CD prevalence in children and adolescents with T1DM in Serbia has not been reported. The aim of the present study was to determine CD prevalence and its clinical manifestations in patients with T1DM. Methods: One hundred and twenty‐one patients (70 girls, 51 boys; mean age, 10.8 years) with T1DM (mean duration of diabetes, 3.4 years) and 125 control group participants (75 girls, 50 boys; mean age, 10.4 years) were tested for CD on tissue transglutaminase antibodies (tTG). In seven serologically positive T1DM patients endoscopic small bowel biopsies were taken and examined on histopathology. In all patients with CD and T1DM age, duration of T1DM, height for age, body mass index, glycosylated hemoglobin and clinical symptoms were noted. Results: Nine patients with T1DM were positive on IgA tTG antibodies. In seven of them small bowel biopsy was performed, and all were proven to have CD on histopathology. The prevalence of biopsy‐proven CD in children and adolescents with T1DM was significantly higher in the study group compared to controls (5.79%. vs 0.8%, P < 0.05). Conclusion: The significantly higher prevalence of CD in children with type 1 diabetes, in accordance with the large volume of data published in the literature, underlines the need for yearly screening of CD in patients with diabetes in order to promptly start a gluten‐free diet when appropriate.