Diabetes Mellitus and Autoimmune Hepatitis: Demographical and Clinical Description of a Relatively Rare Phenotype.

We studied demographic, metabolic, and clinical characteristics of patients with diabetes and autoimmune hepatitis (AIH) from the German/Austrian DPV registry. A total of 139 patients with diabetes and AIH were analyzed and compared to 437 728 patients with diabetes without AIH. The prevalence of AIH in patients with T1DM (44.8/100 000) seems higher than in the general population, the prevalence of AIH in patients with T2DM (23.6/100 000) does not seem to be increased. Patients with T2DM and AIH had a shorter duration of diabetes (p=0.007) and a higher proportion of females (p<0.001) compared to T2DM without AIH. Patients with diabetes (T1DM or T2DM) and AIH required higher insulin doses (p<0.001 and p=0.03, respectively) and showed increased liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyltransferase) compared to diabetes patients without (all p<0.001). We detected a lower percentage of patients treated with oral antidiabetic drugs (p=0.01) and a higher percentage of patients treated by insulin in patients with T2DM and AIH (p<0.001) compared to patients with T2DM alone. We observed a higher incidence of autoimmune thyroid disease (AIT) in patients with diabetes (T1DM or T2DM) and AIH (p<0.001) compared to diabetes patients without AIH. AIH seems more frequent in patients with T1DM. Patients with diabetes and AIH require intensification of antidiabetic therapy and seem to have a higher prevalence of AIT.

Needle detachment in a slim and physically active child with insulin pump treatment.

Insulin pump therapy (CSII) is well established in pediatric patients with type 1 diabetes. In childhood diabetes, insulin pump treatment shows considerable advantages such as fewer injections, increased flexibility, fewer hypoglycemic events and lower HbA1c levels. Side effects such as catheter obstruction, technical pump failure, and dermatological complications have been observed, but are rarely reported. The reported patient is a physically very active and slim 10-year-old boy with reduced subcutaneous fatty tissue. After strong muscular activity an accidental rupture of the infusion set and needle detachment occurred in October 2013. X-ray and ultrasound imaging localized the needle in the musculus rectus femoris dexter. The needle was kept in situ and oral antibiotic treatment to prevent inflammatory reaction was prescribed. Repeated ultrasound measurements documented that the needles position had remained unchanged. Steel needle catheters (Sure-T infusion set, 6 mm) positioned in a thin layer of subcutaneous fat tissue of the thigh, combined with intense sports activity can result in a needle rupture and penetration into the muscle. Careful monitoring provides an alternative to surgery and lowers the risk of muscular necrosis. Because of differences in the distribution of subcutaneous fat tissue, an individualized catheter selection is necessary in pump treatment for children and adolescents, requiring a variety of different catheter sets.

Use of Continuous Glucose Monitoring in Pump Therapy Sensor Augmented Pump or Automated Insulin Delivery in Different Age Groups (0.5 to <26 Years) With Type 1 Diabetes From 2018 to 2021: Analysis of the German/Austrian/Swiss/Luxemburg DPV Registry.

AIM: Insulin pump, continuous glucose monitoring (CGM), and sensor augmented pump (SAP) technology have evolved continuously leading to the development of automated insulin delivery (AID) systems. Evaluation of the use of diabetes technologies in people with T1D from January 2018 to December 2021. METHODS: A patient registry (Diabetes Prospective Follow-up Database [DPV]) was analyzed for use of SAP (insulin pump + CGM ≥90 days, no automated dose adjustment) and AID (HCL or LGS/PLGS). In total 46,043 people with T1D aged 0.5 to <26 years treated in 416 diabetes centers (Germany, Austria, Luxemburg, and Switzerland) were included and stratified into 4 groups A-D according to age. Additionally, TiR and HbA1c were analyzed. RESULTS: From 2018 to 2021, there was a significant increase from 28.7% to 32.9% (sensor augmented pump [SAP]) and 3.5% to 16.6% (AID) across all age groups, with the most frequent use in group A (<7 years, 38.8%-40.2% and 10.3%-28.5%). A similar increase in SAP and AID use was observed in groups B (7 to <11 years) and C (11 to <16 years): B: +15.8 PP, C: +15.9 PP. HbA1c improved significantly in groups C and D (16 to <26 years) (both P < .01). Time in range (TiR) increased in all groups (A: +3 PP; B: +5 PP; C: +5 PP; D: +5 PP; P < 0.01 for each group). Insulin pumps (61.0% versus 53.4% male) and SAP (33.5% versus 28.9% male) are used more frequently in females. CONCLUSION: In recent years, we found an increasing use of new diabetes technologies and an improvement in metabolic control (TiR) across all age groups.

Alarming Increase of Ketoacidosis Prevalence at Type 1 Diabetes-Onset in Austria-Results From a Nationwide Registry.

OBJECTIVE: We analyzed the annual prevalence of onset-DKA (diabetic ketoacidosis) from 2012 to 2020 with a sub-analysis for lockdown-periods during the COVID-19 pandemic in 2020. DESIGN: All newly diagnosed children with type 1 diabetes (T1D) aged <15 years are prospectively registered in the population-based Austrian Diabetes Incidence Study in Austria. MAIN OUTCOME MEASURES: The annual DKA prevalence was analyzed using Joinpoint regression. Definition of DKA: pH <7.3, mild DKA: pH 7.3 to ≤ 7.1, severe DKA: pH <7.1. DKA prevalence during the lockdown periods in 2020 and the corresponding periods in 2015-2019 were examined using Fisher's exact test. RESULTS: In the years 2012-2020 the mean prevalence for onset-DKA in Austria was 43.6% [95%CI (confidence interval): 41.6, 45.7] and thus above the mean prevalence of previous decades (1989-2011) of 37,1 % (95%CI: 35.6, 38.6). A particularly high prevalence was found among children <2 years of age (72.0% DKA, 32.8% severe DKA). No significant gender difference was found. Prevalence of severe DKA at T1D-onset increased significantly since 2015 (p = 0.023). During the lockdown in 2020, 59.3% of children were diagnosed with DKA at T1D-onset, compared to 42.1% during the previous 5 years (p = 0.022). Moreover, 20% of children had severe DKA at T1D diagnosis, compared to 14% during the comparison period. CONCLUSIONS: The previously already high prevalence of DKA at T1D-onset has further increased over time. The COVID-19 pandemic has exacerbated the problem of a late or delayed diagnosis of diabetes in children resulting in onset-DKA. The alarmingly increased prevalence of DKA in Austrian children with T1D calls for urgent action.

Incidence of neonatal diabetes in Austria-calculation based on the Austrian Diabetes Register.

BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes which is diagnosed in the first 6 months of life. Several studies in the last few years provide information on genetic causes for NDM. OBJECTIVE: The aim of this study was to identify all patients with diabetes in the first 6 months of life through the Austrian Diabetes Register, which is available since 1989. A retrospective data analyses was performed to calculate the current incidence of NDM. SUBJECTS AND METHODS: Ten patients were registered with diabetes onset within the first 6 months of life in the Austrian Diabetes Register. Evaluation of detailed clinical data was performed by sending a questionnaire to all diabetes centers. RESULTS: Ten patients from nine different families with NDM were diagnosed in Austria from 1989 until September 2007. Seven patients (one male, six females) had transient NDM (TNDM), three (two males, one female) showed a permanent course [permanent neonatal diabetes mellitus (PNDM)]. One had immunodeficiency, polyendocrinopathy and enteropathy X-linked (IPEX) syndrome and another showed aplasia of the pancreas; no genetic etiology was found in the third case. In three out of seven patients with a transient course of NDM a genetic diagnosis was possible. Two female siblings had activating point mutations in the ABCC8 gene, although one patient had paternal uniparental isodisomy of chromosome 6q24. One patient's family did not consent to genetic testing. CONCLUSIONS: The incidence of NDM in Austria is 1/160 949, with an incidence of 1/ 536 499 for PNDM and 1/229 928 for TNDM.

Former Very Preterm Infants Show Alterations in Thyroid Function at a Preschool Age.

Preterm birth is frequently associated with altered thyroid hormone levels in the newborn period. Recent data suggest a role of prematurity independent of birth size also in childhood thyroid dysfunction. Whether the high-risk population of former very preterm infants (VPI) is particularly susceptible to thyroid hormone alterations is currently unknown. The aim of the present study was to assess whether former VPI display changes in thyroid hormone status in comparison to term-born controls at a preschool age. Free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) concentrations were determined in former VPI and same-aged children born at term at five to seven years of age. 31 former term infants and 82 former VPI were included in the study. In comparison to children born at term, former VPI had lower fT4 (16.1 ± 1.8 versus 17.0 ± 2.1 pmol/l), higher fT3 (6.8 ± 0.7 versus 6.5 pmol/l), and higher TSH levels (3.0 ± 1.4 versus 2.3 ± 1.0 µU/l), independent of major neonatal morbidities. As subclinical changes in thyroid hormone status are potentially associated with adverse health profiles, close follow-up of these children is warranted.

Genotyping of coeliac-specific human leucocyte antigen in children with type 1 diabetes: does this screening method make sense?

OBJECTIVES: Due to a high linkage disequilibrium of diabetes and coeliac-specific human leucocyte antigen (HLA) genotypes, the prevalence of coeliac disease (CD) in children and adolescents with diabetes mellitus type 1 (T1D) is much higher than in the general population. Recently, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) revised new screening guidelines in which genotyping for coeliac-specific HLA alleles is recommended for high-risk patients as patients with T1D. The aim of our study was to investigate the frequency and distribution of coeliac-specific HLA genotypes in paediatric patients with T1D. STUDY DESIGN: HLA genotyping was performed on paediatric patients with T1D, recruited at the Medical University Hospital of Innsbruck and Graz. The test was done by PCR. Statistical analysis was performed with IBM-SPSS V.20. RESULTS: In 121 paediatric patients with T1D (52% male), mean age 13.3 (SD 3.9) years, mean age at diabetes diagnosis 7.4 (SD 3.8) and mean diabetes duration of 5.9 (SD 3.3) years, HLA genotyping was conducted. Ninety-two per cent showed positive HLA DQ2 and/or HLA DQ8 genotypes. Thirty-four per cent carried HLA DQ2, 33% were HLA DQ2+DQ8 positive and 25% of the patients showed positive results for HLA DQ8 alone. Only 8% had no coeliac-specific HLA markers. Four (3%) patients were diagnosed with CD. CONCLUSIONS: The majority of paediatric patients with T1D has positive coeliac-specific HLA genotypes DQ2 and/or DQ8. Therefore, genotyping for coeliac-specific HLA alleles as a first-line test in patients with T1D as recommended in the ESPGHAN guidelines does not seem reasonable. Screening for coeliac-specific antibodies needs to be performed on a regular basis for patients with T1D.

Neonatal characteristics and risk of atopic asthma in schoolchildren: results from a large prospective birth-cohort study.

AIM: Asthma is among the most common chronic diseases in childhood and steadily increasing in prevalence. Identification of risk predictors for a hospitalization for atopic asthma in childhood may help design prevention programmes and improve our understanding of disease pathobiology. METHODS: An ongoing birth-cohort study prospectively enrolled all liveborn infants in Tyrol. Between 1994 and 1999 baseline data were collected for 33,808 infants. From 2000 to 2005, all children hospitalized for atopic asthma at an age of 6 years or over (n = 305) were identified in a careful search of hospital databases. Disease status was ascertained from the typical medical history, a thorough examination and proof of atopy. RESULTS: Male sex (relative risk 2.11, 95% CI 1.65-2.70), urban living environment (vs. rural) (1.93, 1.47-2.54), neonatal admission to hospital (1.70, 1.20-2.40), lack of breastfeeding (1.32, 1.02-1.70), postnatal smoking (1.31, 1.00-1.72) and low birth weight (1.45, 0.94-2.23) all emerged as adverse risk predictors for hospitalization for atopic asthma whereas a low risk was found among children living on a farm (0.22, 0.05-0.87) and children with two to three siblings (vs. no or one sibling) (0.71, 0.51-0.97). CONCLUSION: In this study a number of neonatal characteristics and environmental exposures were associated with hospitalization for atopic asthma in childhood, suggesting that early life is crucial for disease determination and lending further indirect support to the hygiene hypothesis.