A Description of Clinician Reported Diagnosis of Type 2 Diabetes and Other Non-Type 1 Diabetes Included in a Large International Multicentered Pediatric Diabetes Registry (SWEET)

Although type 1 diabetes (T1D) remains the most frequent form of diabetes in individuals aged less than 20 years at onset, other forms of diabetes are being increasingly recognized.info:eu-repo/semantics/publishedVersio

In Silico Trials of an Open-Source Android-Based Artificial Pancreas: A New Paradigm to Test Safety and Efficacy of Do-It-Yourself Systems

Objective: Safety data on Do-It-Yourself Artificial Pancreas Systems are missing. The most widespread in Europe is the AndroidAPS implementation of the OpenAPS algorithm. We used the UVA/Padova Type 1 Diabetes Simulator to in silico test safety and efficacy of this algorithm in different scenarios. Methods: We tested five configurations of the AndroidAPS algorithm differing in aggressiveness and patient's interaction with the system. All configurations were tested with insulin sensitivity variation of ±30%. The most promising configurations were tested in real-life scenarios: over- and underestimated bolus by 50%, bolus delivered 15 min before meal, and late bolus delivered 15 min after meal. Continuous Glucose Monitoring (CGM) time in ranges (TIRs) metrics were used to assess the glycemic control. Results: In silico testing showed that open-source closed-loop system AndroidAPS works effectively and safely. The best results were reached if AndroidAPS algorithm worked with microboluses and when half of calculated bolus was issued (mean glycemia 131 mg/dL, SD 27 mg/dL, TIR 91%, time between 54 and 70 mg/dL <1%, and low blood glucose index even <1). The meal bolus over- and underestimation as well as late bolus did not affect the TIR and, importantly, the time between 54 and 70 mg/dL. Conclusion: In silico testing proved that AndroidAPS implementation of the OpenAPS algorithm is safe and effective, and it showed a great potential to be tested in prospective home setting study

Anti-zinc transporter protein 8 autoantibodies significantly improve the diagnostic approach to type 1 diabetes: an Italian multicentre study on paediatric patients

BACKGROUND AND AIM: Anti-ZnT8 antibodies (ZnT8A) were recently proposed as a new independent serological marker in Type 1 diabetes (T1D), leading to a significant improvement of the positive predictive value of autoantibody measurement in this setting. The aim of this retrospective multicentre study was to investigate ZnT8A as a complement to the current T1D autoantibody assays in a large cohort of paediatric Italian patients. METHODS: ZnT8A were assessed by ELISA in 213 T1DM paediatric patients referred to six different centres in North-East Italy. Fifty-four were analysed at disease onset, 79 within 4 years from diagnosis and 80 after 5 or more years from diagnosis. Retrospective data about islet cell autoantibodies (ICA), anti-insulin (IAA), anti-glutamate decarboxylase (GADA) and anti-protein tyrosine phosphatase IA-2 (IA-2A) antibodies were collected and compared. RESULTS: Overall, ZnT8A showed positive results in 106/213 (49.8 %) T1D patients and were found in 10 (4.7 %) subjects previously classified as autoantibody negative based on the existing markers (GADA, IA-2A, IAA and ICA), increasing the overall diagnostic sensitivity from 85.9 to 90.6 %. ZnT8A disclosed the same sensitivity (61.1 %) at disease onset as GADA (61.1 %) and higher than IA-2A (53.7 %), with only GADA showing much persistence in the long-term follow-up. Focusing on patients at disease onset, all the ICA positive were associated with at least one positive autoantibody among GADA, IA-2A and ZnT8A, 16.7 % of whom presenting only anti-ZnT8-positive antibodies. CONCLUSION: This study confirms ZnT8A as an important additional and independent diagnostic marker of T1D and supports its introduction in the routine diagnostic process to replace less sensitive methods and improve the overall autoantibody sensitivity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13317-015-0068-4) contains supplementary material, which is available to authorized users

Supplementary Material for: Glycemic control by treatment modalities: national registry-based population data in children and adolescents with type 1 diabetes

AIMS To assess the differences in key parameters of type 1 diabetes (T1D) control associated with treatment and monitoring modalities including newly introduced hybrid closed-loop (HCL) algorithm in children and adolescents with T1D (CwD) using the data from the population-wide pediatric diabetes registry ČENDA. MATERIALS AND METHODS CwD younger than 19 years with T1D duration > 1 year were included and divided according to the treatment modality and type of CGM used: multiple daily injection (MDI), insulin pump without (CSII) and with HCL function, intermittently scanned continuous glucose monitoring (isCGM), real-time CGM (rtCGM), and intermittent or no CGM (noCGM). HbA1c, times in glycemic ranges, and glucose risk index (GRI) were compared between the groups. RESULTS Data of a total of 3251 children (mean age 13.4± years) were analyzed. 2187 (67.3%) were treated with MDI, 1064 (32.7%) with insulin pump, 585/1064 (55%) with HCL. The HCL users achieved the highest median TIR 75.4% (IQR 6.3), and GRI 29.1 (7.8), both p<0.001 compared to other groups, followed by MDI rtCGM and CSII groups with TIR 68.8% (IQR 9.0) and 69.0% (7.5), GRI 38.8 (12.5) and 40.1 (8.5), respectively (non-significant to each other). These three groups did not significantly differ in their HbA1c medians (51.8 (IQR 4.5), 50.7 (4.5), and 52.7 (5.7) mmol/mol, respectively). NoCGM groups had the highest HbA1c and GRI and lowest TIR regardless of the treatment modality. CONCLUSIONS This population-based study shows that the HCL technology is superior to other treatment modalities in CGM-derived parameters and should be considered as a treatment of choice in all CwD fulfilling the indication criteria

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects

Item does not contain fulltextBACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. OBJECTIVE: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. METHODS: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. RESULTS: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. CONCLUSIONS: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials