HLA-DQ polymorphisms modify the risk of thyroid autoimmunity in children with type 1 diabetes mellitus

OBJECTIVE: Type 1 diabetes mellitus (DM1) is frequently accompanied by thyroid autoimmunity (TAI). The aims of the present study were to estimate the prevalence of TAI and to determine the contribution of HLA-DQA1 and -DQB1 polymorphisms to TAI susceptibility among children with DM1. PATIENTS AND METLHODS: Screening for TAI was performed in 285 children with DM1 by measuring autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). HLA-DQA1 and -DQB1 were genotyped using PCR-SSP. RESULTS: Repeated positivity of anti-TPO and/or anti-Tg was found in 45/285 children with DM1 (15.8%). The prevalence was significantly higher in girls than in boys (26.7% vs 6.7%; p<10(-5)). The HLA-DQB1*0302 allele conferred susceptibility to TAI in children with DM1 (OR 2.7, 95% CI 1.1-6.4), while the DQB1*05 alleles acted protectively (OR 0.2, CI 95% 0.08-0.7). CONCLUSIONS: HLA-DQ polymorphisms significantly modify the risk of TAI in children with DM1.     

Polymorphisms of the TNF-alpha gene and risk of celiac disease in T1DM children

BACKGROUND: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) frequently occur together. Previous reports suggested that the (-308)A variant of the tumor necrosis factor-alpha (TNF-alpha) gene is associated either with T1DM or with CD. The aim of our study was to determine whether (-308)A and (-238)A allelic variants of the TNF-alpha gene might have any impact on the risk of CD in T1DM children. METHODS: Three hundred and one T1DM children were enrolled to the study. The presence of CD was screened with IgA endomysial antibodies (EMA) test. Jejunal biopsy was performed to confirm CD. TNF-alpha-308 and -238 genetic variants were tested using the method of restriction fragment length polymorphism. RESULTS: The prevalence of CD in the enrolled diabetic children was 6.3% (19 out of 301 children). The frequency of the (-308)A TNF-alpha variant was similar in the CD and the non-CD groups, exceeding the Hungarian healthy reference value. The number of (-238)A allele carriers was higher in the CD (4/19) than in the non-CD group (17/277) (p < 0.05). CONCLUSIONS: Our study is limited by the small number of CD patients. On the basis of our findings, carriers of TNF (-308)A allele do not seem to have an increased risk for CD in T1DM. The association between TNF-alpha(-238)A allele carrier state and CD requires further investigation.     

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.     

Anti-CD38 autoimmunity in children with newly diagnosed type 1 diabetes mellitus

AIMS: To test for anti-CD38 autoimmunity in children with newly-diagnosed type 1 diabetes mellitus (DM1). METHODS: Serum anti-CD38 autoantibodies were detected by Western blot in 270 children (130 girls, 140 boys, mean age 8 +/- 4 years) with newly-diagnosed DM1 and 179 gender- and age-matched non-diabetic children. In 126 diabetic children, another blood sample was obtained 15 +/- 4 months after the diagnosis. RESULTS: Anti-CD38 autoantibody titers at least 3 SD above the mean value for the control group were found in 4.4% of children with DM1 vs 0.6% of controls (chi2 = 5.8, p <0.016). No statistical differences were observed between anti-CD38 positive and negative patients in terms of phenotype. At follow-up, of six diabetic children who were positive for anti-CD38 antibodies, two were new cases. A positive correlation was found between the antibody titer of diabetic sera at diagnosis and follow up (r = 0.46, p <0.0001). CONCLUSION: An autoimmune reaction against CD38, a protein expressed in human islets, is associated with newly-diagnosed DM1. In children with DM1, CD38 autoimmunity increases with time and persists.     

Prevalence of celiac disease in Brazilian children and adolescents with type 1 diabetes mellitus

OBJECTIVE: A previously unrecognized high prevalence of celiac disease (CD) has been found by screening among European and North American patients with type 1 diabetes mellitus (DM 1). The prevalence of CD among Brazilian children with DM1 is not known. This study was conducted to determine the prevalence of CD in Brazilian children and adolescents with DM 1. METHODS: One hundred and four children and adolescents with DM 1 (52 males and 52 females; age range 22 months - 19 years) and 105 age and gender-matched control participants were screened for CD using the IgA anti-endomysial antibody test (IgA-EmA) and total serum IgA. A small bowel biopsy was performed in all patients with positive IgA-EmA. RESULTS: Nine of 104 diabetic patients (8.7%) had a positive IgA-EmA. Biopsies were normal in four patients, two had partial or subtotal villous atrophy with elevated intraepithelial lymphocyte (IEL) counts, and three showed partial villous atrophy but with IEL counts under the maximum limit adopted (40 IEL/100 enterocytes). EmA-IgA positive patients had mild, non-specific gastrointestinal complaints including dyspepsia, abdominal pain, flatulence and constipation. All control participants had negative results for IgA-EmA. CONCLUSION: The prevalence of CD in a group of Brazilian pediatric DM 1 patients was at least 4.8%, a prevalence comparable to European and North American studies. The high prevalence of CD among DM 1 emphasizes the need for routine screening in all countries including Brazil.     

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。     

Usefulness of a double immunofluorescence technique for detection of intestinal tTG-IgA deposits in diabetic and non-diabetic children with celiac disease

BackgroundCeliac disease (CD) is frequently associated with type I diabetes mellitus (T1D), where its diagnosis may be a challenging task. This study aims to test the usefulness of the double staining immunofluorescence (dsIF) technique for the detection of intestinal anti-tissue transglutaminase specific IgA antibody (tTG-IgA) deposits in CD and T1D children with coexisting CD.MethodsA total of 46 patients (30 cases of CD and 16 cases of T1D with CD) and 16 non-diabetic, non-celiac children were recruited. Endoscopic biopsies were taken and analyzed by light microscopy, quantitative histology (QH), and a dsIF technique.ResultsHistologically, villous atrophy was most severe in CD, followed by T1D with CD, while all control biopsies except 1 were normal. QH showed a statistically significant difference in villous height (Vh), crypt depth (CrD), and Vh:CrD ratio between diabetic and non-diabetic patients with CD. dsIF technique could detect tTG-IgA deposits in 85.7% of cases of CD alone and 93.8% of biopsies from diabetic children. Surprisingly, deposits were more extensive in biopsies with minimal villous shortening. Also, all 5 biopsies from T1D patients with normal histology were dsIF positive.ConclusionIn-situ analysis of tTG-IgA immune deposits facilitates the detection of positive serology early-onset CD. Quantitative analysis may be used as an ancillary tool to increase the reliability of histological findings in these patients.     

Screening of coeliac disease in north Italian children with type 1 diabetes: limited usefulness of HLA-DQ typing

Aim: To determine the contribution of HLA-DQA1* and HLA-DQB1* genes to the risk of coeliac disease (CD) in a cohort of children with type 1 diabetes mellitus (T1DM) from northern Italy. Methods: Three hundred and fifty-seven children with T1DM, attending the Childhood Diabetes Unit of the University of Verona, have been regularly tested for serum IgA endomysial antibodies (EMA). All patients with positive EMA underwent small bowel biopsy to confirm the diagnosis of CD. HLA typing was performed in subjects with T1DM and CD, and in a control group of 79 EMA-negative patients with T1DM. Results: Of the 357 patients tested, 25 (7%) had CD. The frequency of HLA- DQA1*0501-DQB1*0201 (T1DM + CD 68% vs T1DM 62%) and of DQA1*0301-DQB1*0302 (T1DM + CD 40% vs T1DM 35%) haplotypes, between T1DM patients with and without CD, was statistically comparable. A trend towards a reduction of the risk of CD (p = 0.055, OR: 0.22, CI 0.05: 1.04) was observed in patients with T1DM (28% vs T1DM + CD 2%) who did not carry either the HLA-DQA1*0501-DQB1*0201 or the DQA1*0301-DQB1*0302 haplotype.

Conclusion: A high prevalence of HLA-DQA1* and -DQB1* susceptibility haplotypes for CD was observed both in EMA-negative diabetics and in those with associated CD. The implementation of screening programmes of CD in a T1DM population, based on the identification of HLA susceptibility haplotypes, seems to be of limited usefulness. Serial serologic screening of diabetic patients remains the advisable strategy.     

Changes in lymphocyte subsets in children with newly diagnosed type 1 diabetes mellitus

The aim of this study was to assess changes in selected peripheral blood lymphocyte subsets in children and adolescents with newly diagnosed type 1 diabetes mellitus (DM) and determine the correlation between these changes and other immunological markers. The study involved a group of 39 patients aged 2-14 years and a control group. The number of T- and B-lymphocytes and the number of CD4, CD8, CD4/HLA-DR, CD8/HLA-DR, CD5/CD20 subsets were measured by flow-cytometry using monoclonal antibodies. Islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GADA) were assessed. In both the diabetic and control groups the number of T-and B-lymphocytes were within normal limits. In patients with DM, the percentage of CD5+/CD20+ cells was significantly increased compared with the control group (p < 0.0001). ICA were positive in 80% of patients and GADA in nearly 65%. A positive correlation between the CD5/CD20 subset and ICA and GADA was found. In patients with a high percentage of CD5+/CD20+ lymphocytes, a higher percentage of activated subsets (CD4/HLA DR and CD8/ HLA DR) was detected. In conclusion: CD5/ CD20 lymphocyte subsets are a good additional marker of autoimmunological processes in DM.     

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.     

The role of diabetes duration, pubertal development and metabolic control in growth in children with type 1 diabetes mellitus

OBJECTIVE: To investigate whether pubertal development, duration of type 1 diabetes mellitus (DM1), or metabolic control play some role in the anomalies in growth observed in diabetic children. PATIENTS: We conducted a prospective evaluation of 83 patients (37 female, 46 male) who were followed from the onset of DM1 at the prepubertal stage until they reached final height. All patients were treated with a conventional regimen of insulin. METHODS: Height SDS, weight SDS, BMI SDS, duration of DM1 in years, and values of HbA1c were the study variables. RESULTS: In prepubertal (P1) girls (data for the initial vs the intermediate evaluations): weight SDS was -0.14 +/- 0.19 vs 0.11 +/- 0.20, p = ns; BMI SDS -0.25 +/- 0.15 vs 0.01 +/- 0.13, p = ns. In postpubertal (P3) girls, weight SDS was 0.49 +/- 0.2 vs 1.2 +/- 0.32, p <0.01; BMI SDS 0.09 +/- 0.16 vs 1.03 +/- 0.24, p <0.01, whereas in P1 boys, height SDS was 0.16 +/- 0.30 vs -0.20 +/- 0.27, p <0.05; and in P3 boys: 0.09 +/- 0.21 vs -0.28 +/- 0.26, p <0.05. Thus pubertal development influenced changes observed in girls with DM1, but did not do so in boys. The anomalies described in children with DM1 were observed from the third year of DM1 duration in both girls and boys. We did not observe any correlation between HbA1c values with height SDS, weight SDS or BMI SDS. CONCLUSIONS: The anomalies in growth observed in girls with DM1 are related to pubertal development, but this is not the case in boys. Alterations in children with DM1 were found from the third year of DM1 duration. Furthermore, the present data also indicate that the degree of metabolic control observed in our patients treated with modern but conventional regimen did not play a major role in the anomalies observed.     

Intraepithelial lymphocytes in duodenum from Brazilian adolescents with type 1 diabetes. Influence of Helicobacter pylori

Background: An increased number of intraepithelial lymphocytes (IELs) can be the only histological feature in early stages of celiac disease (CD). This is also presented in duodenum of patients with Helicobacter pylori -associated gastritis and in autoimmune diseases. Because CD is frequently associated with type 1 diabetes mellitus, we analyzed the density of IELs in the distal duodenum of non-celiac diabetic patients associated or not with H. pylori infection.
Methods: IEL density and the presence of H. pylori were determined in biopsies of the distal duodenum and gastric antrum and body obtained from Brazilian diabetic adolescents who were negative for anti-human tissue transglutaminase and anti-endomysial. The results were compared with the histological findings of gastric and duodenal biopsies obtained from non-diabetic older children and adolescents.
Results: H. pylori was detected in 33.3% of diabetic patients and in 56.7% of the control group. No association was observed between the presence of H. pylori and an increased lymphocyte density in the distal duodenum in either group. Diabetic patients presented a duodenal IEL density similar to that of the control group. Lymphocytic gastritis was not identified in any of the biopsies analyzed.
Conclusions: The density of IELs in the distal duodenum of diabetic adolescents did not differ from that observed in older children and adolescents without this autoimmune disease. H. pylori infection, which is frequent among adolescents from developing countries, did not modify lymphocyte density in the distal duodenum in the absence of lymphocytic gastritis.     

Thyroid Disorders in Children and Adolescents with Type 1 Diabetes Mellitus in Isfahan,Iran

Objective

Studies in different populations have shown great variation in the prevalence of thyroid diseases in patients with type 1 diabetes mellitus (T1DM). Our aim was to study the prevalence of thyroid disorders such as autoimmunity of thyroid (AIT), thyroid dysfunction, and goiter in children and adolescents with T1DM, compared with age- and sex-matched healthy controls in Isfahan.

Methods

One hundred patients with T1DM who were referred to Isfahan Endocrine and Metabolism Research Center and 184 healthy schoolchildren matched for age and sex were included. They were examined for goiter by two endocrinologists. Thyroid function test and serum thyroid antibodies (anti-TPO Ab and anti-Tg Ab) were measured.

Findings

The prevalence of subclinical hypothyroidism was high in both groups (18%). T1DM patients had lower frequency of goiter (21% vs. 38%, P=0.001), and higher prevalence of positive AIT (22% vs. 8%, P=0.001), anti-TPO Ab positivity (19.3% vs. 5.3%, P=0.000), and anti-Tg Ab (11.1% vs. 6.4%, P=0.1) in comparison with the control group. Being positive for AIT in diabetic patients meant an odds ratio of 5 (CI 95%: 1.5-15.6) for thyroid dysfunction. There was no association between age, sex, duration of diabetes and HbA_1C with serum anti-TPO Ab and anti-Tg Ab concentrations in this group.

Conclusion

Our results demonstrated the high prevalence of AIT and thyroid dysfunction in patients with T1DM. We suggest regular thyroid function and antibody testing in these patients.     

Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus

El‐Karaksy HM, Anwar G, Esmat G, Mansour S, Sabry M, Helmy H, El‐Hennawy A, Fouad H. Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus. Background and aim: Children with type 1 diabetes mellitus (T1DM) are frequently investigated for hepatic abnormalities. This study was carried out to report on the prevalence of hepatic abnormalities in diabetic children and adolescents and to highlight the possible etiology and appropriate management. Methods: The study included 692 children (333 were males) with T1DM attending the Diabetes Unit at Cairo University Pediatric Hospital. Their mean age was 9.65 ± 4.18 yr. All children were subjected to clinical examination for hepatomegaly, determination of alanine aminotransferase (ALT) and antibodies to hepatitis C virus (anti‐HCV), and abdominal ultrasonography. All children with clinical, laboratory or ultrasound abnormality were counseled about proper glycemic control and followed up. If abnormalities persisted, more detailed investigations were carried out. HCV RNA was done for anti‐HCV positive children. Results: Sixty (8.7%) were found to have one or more abnormalities: clinical hepatomegaly in 13 (1.9%), elevated ALT in 27 (3.9%), anti‐HCV in 25 (3.6%) and abnormal hepatic ultrasound in 31 (4.5%). Forty percent of anti‐HCV positive children were HCV‐RNA positive. Glycogenic hepatopathy was diagnosed in three cases by liver biopsy. Abnormalities were reversible in 37/60 after proper glycemic control. Conclusion: Although diabetic children are at risk of acquisition of HCV, poor glycemic control is the key factor that predisposes to hepatomegaly, elevated ALT and abnormal ultrasound findings. A 4 to 8‐wk therapeutic trial of proper glycemic control is recommended prior to more invasive diagnostic procedures.     

Young children (<5 yr) and adolescents (>12 yr) with type 1 diabetes mellitus have low rate of partial remission: diabetic ketoacidosis is an important risk factor

Objective:  To determine whether there are different rates of partial remission in preschool, school-age children, and adolescents with type 1 diabetes mellitus (T1DM) and to identify clinical characteristics that are associated with increased rate of partial remission.
Design/methods:  A total of 152 consecutive patients with newly diagnosed T1DM in 2004 were studied. Clinical characteristics at diagnosis, hemoglobin A1C (HbA1C), and total daily insulin dose (TDD) at 3-month interval follow-up for 1 yr were analyzed in each age-group (group 1, aged <5 yr; group 2, aged 5–12 yr; and group 3, aged >12 yr). Partial remission was defined as TDD <0.5 units/kg/d with HbA1C <8% assessed at 6 months after diagnosis.
Results:  Young children (group 1, 26.8%) and adolescents (group 3, 29%) had low rates of partial remission compared with school-age children (group 2, 56%, p = 0.002). There were no differences in the rates of diabetic ketoacidosis (DKA), autoantibody frequency, and HbA1C at diagnosis between age-groups. DKA at diagnosis was associated with less likelihood of having partial remission (p < 0.001). There were no associations between gender, autoantibodies, and HbA1C at diagnosis and the rate of partial remission.
Conclusions:  Young children and adolescent children with T1DM had a low rate of partial remission. Metabolic control was poorest in young children, whereas higher dose insulin in adolescents because of insulin resistance contributes to less likelihood of having partial remission. DKA at diagnosis was associated with low rate of partial remission. It is possible that the low frequency of honeymoon phase in young children reflects more aggressive beta-cell destruction in young children.     

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.     

Sustained IL-1alpha, IL-4, and IL-6 elevations following correction of hyperglycemia in children with type 1 diabetes mellitus.

OBJECTIVE: An imbalance of pro-/anti-inflammatory cytokines may accelerate diabetic vascular complications and interfere with proper wound healing. Currently, limited available literature suggests that plasma concentrations of certain pro- and anti-inflammatory cytokines may be altered during hyperglycemia/diabetes mellitus. It is still unclear, however, whether these concepts also apply to children with diabetes, and whether alterations in circulating cytokine levels are a permanent feature of diabetes or an acute effect of fluctuating glucose concentrations. METHODS: Twenty-two children with type 1 diabetes mellitus (T1DM) were studied. In 13 children, postprandial morning plasma glucose was >11.1 mmol/L at least once (hyperglycemic group, or HyG group); in 9 subjects, plasma glucose never exceeded 10.6 mmol/L (non-hyperglycemic group, or non-HyG group). After admission, intensive euglycemia (5.0-6.1 mmol/L) was achieved in all participants via intravenous insulin and dextrose for at least 90 min. Blood samples were drawn every 30 min to determine plasma levels of 14 cytokines and chemokines. RESULTS: Interleukin IL-1alpha, IL-4, and IL-6 were elevated in HyG group compared with non-HyG not only when plasma glucose was elevated but also during the first 2 h following return to euglycemia. The levels of the other 11 cytokines were not significantly different. CONCLUSIONS: Specific cytokines (IL-1alpha, IL-4, and IL-6) are acutely elevated during hyperglycemia in children with T1DM, and these elevations persist for hours after hyperglycemia has been corrected. Therefore, aside from glycemic control, additional therapeutic measures against elevated proinflammatory signals may be necessary for preventing vascular complications in children with hyperglycemic diabetes.     

Annual screening detects celiac disease in children with type 1 diabetes

Objective:  To investigate the prevalence of celiac disease (CD) in a cohort of type 1 diabetes mellitus (T1DM) children and adolescents at the time of clinical diagnosis and to evaluate the screening procedure and possible role of human leukocyte antigen (HLA)-DQ during a 5-yr follow-up.
Research design and methods:  The study group was a cohort of 300 newly diagnosed T1DM children and youths younger than 20 yr followed for 5 yr at six clinical centers for pediatric diabetes in the region Skåne in Sweden. Immunoglobulin A endomysium antibodies were used to screen the patients annually to be considered for an intestinal biopsy. All patients were analyzed for HLA-DQA1-B1 genotypes.
Results:  While 0.7% (2/300) already had a diagnosed symptomatic CD, an additional 3% (10/300) had silent CD at the diagnosis of T1DM. During follow-up, another 6% (17/300) developed CD as follows: 10 after 1 yr, 5 after 2 yr, 1 after 3 yr, and 1 after 5 yr. Therefore, the cumulative frequency of CD confirmed by intestinal biopsies was 10% (29/300). HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone.
Conclusions:  Our study confirmed the low prevalence (0.7%) of diagnosed symptomatic CD at the time of clinical diagnosis but document by screening an increasing prevalence of silent CD during a 5-yr follow-up to reach an overall prevalence of 10%. We suggest that children with T1DM should be screened for CD at the onset of T1DM and annually for a minimum of at least 2 yr. HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone.     

Sustained IL-1α, IL-4, and IL-6 elevations following correction of hyperglycemia in children with type 1 diabetes mellitus

Objective:  An imbalance of pro-/anti-inflammatory cytokines may accelerate diabetic vascular complications and interfere with proper wound healing. Currently, limited available literature suggests that plasma concentrations of certain pro- and anti-inflammatory cytokines may be altered during hyperglycemia/diabetes mellitus. It is still unclear, however, whether these concepts also apply to children with diabetes, and whether alterations in circulating cytokine levels are a permanent feature of diabetes or an acute effect of fluctuating glucose concentrations.
Methods:  Twenty-two children with type 1 diabetes mellitus (T1DM) were studied. In 13 children, postprandial morning plasma glucose was >11.1 mmol/L at least once (hyperglycemic group, or HyG group); in 9 subjects, plasma glucose never exceeded 10.6 mmol/L (non-hyperglycemic group, or non-HyG group). After admission, intensive euglycemia (5.0–6.1 mmol/L) was achieved in all participants via intravenous insulin and dextrose for at least 90 min. Blood samples were drawn every 30 min to determine plasma levels of 14 cytokines and chemokines.
Results:  Interleukin IL-1α, IL-4, and IL-6 were elevated in HyG group compared with non-HyG not only when plasma glucose was elevated but also during the first 2 h following return to euglycemia. The levels of the other 11 cytokines were not significantly different.
Conclusions:  Specific cytokines (IL-1α, IL-4, and IL-6) are acutely elevated during hyperglycemia in children with T1DM, and these elevations persist for hours after hyperglycemia has been corrected. Therefore, aside from glycemic control, additional therapeutic measures against elevated proinflammatory signals may be necessary for preventing vascular complications in children with hyperglycemic diabetes.     

Type 1 diabetes-associated autoimmune diseases: screening, diagnostic principles and management

Type 1 diabetes (T1DM) is often associated with autoimmune diseases such as: autoimmune thyroid disease (ATD), celiac disease (CD), autoimmune gastritis (AIG), pernicious anemia (PA) and vitiligo. Autoimmune thyroid disease is the most prevalent endocrinopathy among diabetic patients. Hypothyroidism, celiac disease or Addison's disease in patients with type 1 diabetes may deteriorate glycemic control and can lead to an increased rate of hypoglycemia. Autoimmune gastritis, pernicious anemia and celiac disease can cause malabsorption and anemia which additionally impair the quality of life in patients with T1DM. The presence of organ-specific autoantibodies can be used to screen patients who are at higher risk of developing autoimmune diseases. Such procedure can help to identify patients, who need to undergo treatment in order to decrease the rate of possible complications in the future. In this clinical review we present current opinions in terms of diagnosis, management and screening in the most common type 1 diabetes-associated autoimmune diseases.