Dietary components in the pathogenesis and prevention of type 1 diabetes in children.

BACKGROUND: Type 1 diabetes (T1D) is a disease closely linked to nutrition and modifications in various dietary components have been part of the effort to prevent or slow the progression of the disease even before the discovery of insulin. SUMMARY: The scientific focus in the prevention or progression modification of T1D is mostly centered on four dietary compounds and their modifications - gluten and its omission, vitamin D supplementation, omega-3 fatty acids supplementation and decreasing of the amount of ingested carbohydrates. The aim of this narrative review is to provide an overview of nutritional interventions studied in children either as preventive methods or as modifiers in the early stages of T1D from autoantibody positive individuals to persons with newly diagnosed T1D. KEY MESSAGES: Our review shows that dietary modifications in various dietary components might be useful but none of them seems to provide universal effects in T1D prevention or progression modification. More research is therefore needed with focus on promising modes of action of individual dietary components.

ISPAD ANNUAL CONFERENCE HIGHLIGHTS 2023.

The 49th Annual Conference of the International Society of Pediatric and Adolescent Diabetes (ISPAD), held from October 18 to 21, 2023, in Rotterdam, Netherlands, showcased significant advancements and diversity in paediatric and adolescent diabetes research and clinical innovations. The conference, renowned for its global impact, brought together experts to discuss cutting-edge developments in the field. Highlights from the plenary sessions included ground-breaking research on immunotherapies and diabetes technologies and offering new insights into personalised treatment approaches. Keynote speakers emphasised the importance of early diagnosis, prevention and the potential of novel biomarkers in predicting disease progression. The symposia covered a broad spectrum of topics, from advancements in continuous glucose monitoring technologies to the latest in hybrid closed loop systems which promise to revolutionise diabetes management for young patients.

Telemedicine maintains good glucose control in children with type 1 diabetes but is not time saving for healthcare professionals: KITES randomized study.

AIMS: To evaluate glucose control non-inferiority and time benefits of telemedicine follow-up in children with type 1 diabetes (CwD). METHODS: In a single-center 9-month-long randomized controlled study (clinicaltrials.gov NCT05484427), 50 children were randomized to either telemedicine group (TG) followed-up distantly by e-mail, or to face-to-face group (FFG) attending standard personal visits. The primary endpoint was non-inferiority of HbA1c at final visit (level of non-inferiority was set at 5 mmol/mol). The secondary endpoints were subcutaneous glucose monitoring parameters and time consumption from both study subjects' and the physicians' point of view. RESULTS: Non-inferiority of HbA1c in the TG was proven (mean HbA1C 45.8 ± 7.3 [TG] vs. 50.0 ± 12.6 [FFG] mmol/mol, 6.3 vs. 6.7 % DCCT, p = 0.17; between groups HbA1C difference 95 % CI -10.2 to 1.9 mmol/mol). Telemedicine saved time for participants (mean visit duration [MVD] 50 [TG] vs. 247 min [FFG], p < 0.001). There were no other differences between groups neither in CGM parameters nor physician's time consumption (MVD 19 [TG] vs. 20 min [FFG], p = 0.58). CONCLUSIONS: Nine-month telemedicine follow-up of the children with well-controlled T1D is not inferior to standard face-to-face visits. Telemedicine visits saved time for the participants but not for their diabetologists.

Genetic testing of children with familial tall stature: is it worth doing?

CONTEXT: Familial tall stature (FTS) is considered to be a benign variant of growth with a presumed polygenic etiology. However, monogenic disorders with possible associated pathological features could also be hidden under the FTS phenotype. OBJECTIVES: To elucidate the genetic etiology in families with FTS and to describe their phenotype in detail. DESIGN, SETTINGS AND PATIENTS: Children with FTS (height in both the child and his/her taller parent >2 SD) referred to the Endocrinology center of Motol University Hospital were enrolled to the study. Their DNA was examined cytogenetically and via next-generation sequencing panel of 786 genes associated with growth. The genetic results were evaluated by the American College of Molecular Genetics and Genomics guidelines. All of the participants underwent standard endocrinological examination followed by specialized anthropometric evaluation. RESULTS: In total, 34 children (19 girls) with FTS were enrolled in the study. Their median height and their taller parent's height were 3.1 SD and 2.5 SD, respectively. The genetic cause of FTS was elucidated in 11/34 (32.4%) children (47, XXX and 47, XYY karyotypes, SHOX duplication, and causative variants in NSD1 [in 2], SUZ12 [in 2], FGFR3, CHD8, GPC3, and PPP2R5D genes). Ten children had absent syndromic sings and 24 had dysmorphic features. CONCLUSION: Monogenic (and cytogenetic) etiology of FTS can be found among children with FTS. Genetic examination should be considered in all children with FTS regardless of the presence of dysmorphic features.

Glycemic Control by Treatment Modalities: National Registry-Based Population Data in Children and Adolescents with Type 1 Diabetes.

INTRODUCTION: The aim of the study was 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 CENDA. 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 3,251 children (mean age 13.4 ± 3.8 years) were analyzed. 2,187 (67.3%) were treated with MDI, 1,064 (32.7%) with insulin pump, 585/1,064 (55%) with HCL. The HCL users achieved the highest median TIR 75.4% (IQR 6.3) and lowest 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 (nonsignificant 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. CONCLUSION: 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.

Are all HCL systems the same? long term outcomes of three HCL systems in children with type 1 diabetes: real-life registry-based study.

Objective: To compare parameters of glycemic control among three types of hybrid closed loop (HCL) systems in children with T1D (CwD) using population-wide data from the national pediatric diabetes registry CENDA. Methods: CwD aged <19 years treated with Medtronic MiniMed 780G (780G), Tandem t:slim X2 (Control-IQ) or do-it-yourself AndroidAPS (AAPS) systems for >12 months and monitored by CGM >70% of the time were included. HbA1c, times in glycemic ranges, and Glycemia Risk Index (GRI) were used for cross-sectional comparison between the HCL systems. Results: Data from 512 CwD were analyzed. 780G, Control-IQ and AAPS were used by 217 (42.4%), 211 (41.2%), and 84 (16.4%) CwD, respectively. The lowest HbA1c value was observed in the AAPS group (44 mmol/mol; IQR 8.0, p<0.0001 vs any other group), followed by Control-IQ and 780G groups (48 (IQR 11) and 52 (IQR 10) mmol/mol, respectively). All of the systems met the recommended criteria for time in range (78% in AAPS, 76% in 780G, and 75% in Control-IQ users). CwD using AAPS spent significantly more time in hypoglycemia (5% vs 2% in 780G and 3% in Control-IQ) and scored the highest GRI (32, IQR 17). The lowest GRI (27, IQR 15) was seen in 780G users. Conclusion: Although all HCL systems proved effective in maintaining recommended long-term glycemic control, we observed differences that illustrate strengths and weaknesses of particular systems. Our findings could help in individualizing the choice of HCL systems.

Analysis of children with familial short stature: who should be indicated for genetic testing?

Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤-2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader-Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth plate, 4 (11%) a variant affecting GH-insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent's height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent's heights ≤-2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent's height and BA are clinical predictors of monogenic FSS.

First Use of Open-Source Automated Insulin Delivery AndroidAPS in Full Closed-Loop Scenario: Pancreas4ALL Randomized Pilot Study.

Objective: We evaluated the safety and feasibility of open-source automated insulin delivery AndroidAPS in adolescents and young adults with type 1 diabetes (T1D) and compared its efficacy in three different scenarios: hybrid closed loop (HCL) with meal boluses, meal announcement only (MA), and full closed loop (FCL). Research Design and Methods: In an open-label, prospective, randomized crossover trial (clinicaltrials.gov NCT04835350), 16 adolescents with T1D (10 females) with mean age of 17 years (range 15-20), glycated hemoglobin 56 mmol/mol (range 43-75), and mean duration of diabetes 5.9 years (9-15) underwent three distinct 3-day periods of camp living, comparing the above-mentioned scenarios of AndroidAPS. We used modified and locked version of AndroidAPS 3.1.03, which was called Pancreas4ALL for study purposes. The order of MA and FCL periods was assigned randomly. The primary endpoints were feasibility and safety of the system represented by percentage of time of glucose control by the system and time in hypoglycemia below 3 mmol/L. Results: The glycemia was controlled by the system 95% time of the study and the proportion of time below 3 mmol/L did not exceed 1% over the whole study period (0.72%). The HCL scenario reached significantly higher percentage of time below 3 mmol/L (HCL 1.05% vs. MA 0.0% vs. FCL 0.0%; P = 0.05) compared to other scenarios. No difference was observed among the scenarios in the percentage of time between 3.9 and 10 mmol/L (HCL 83.3% vs. MA 79.85% vs. FCL 81.03%, P = 0.58) corresponding to mean glycemia (HCL 6.65 mmol/L vs. MA 7.34 mmol/L vs. FCL 7.05 mmol/L, P = 0.28). No difference was observed in the mean daily dose of insulin or in the daily carbohydrate intake. No serious adverse event occurred during the study period. Conclusions: Our pilot study showed that FCL might be a realistic mode of treatment for people with T1D.

Changes in the gut bacteriome upon gluten-free diet intervention do not mediate beta cell preservation.

AIMS/HYPOTHESIS: We previously detected indications that beta cell function is protected by gluten-free diet (GFD) introduced shortly after the onset of childhood type 1 diabetes. The present aim was to assess whether GFD was associated with changes in the gut bacteriome composition and in its functional capacity, and whether such changes mediated the observed effects of GFD on beta cell function. METHODS: Forty-five children (aged 10.2 ± 3.3 years) were recruited into a self-selected intervention trial primarily focused on determining the role of GFD on beta cell preservation ( ClinicalTrials.gov NCT02867436). Stool samples were collected prior to the dietary intervention and then at 3-month intervals. A total of 128 samples from the GFD group and 112 from the control group were analysed for bacteriome 16S rDNA community profiles, the bacteriome functional capacity was predicted using PICRUSt2 and actual gut metabolome profiles measured using NMR. Intestinal permeability was assessed using serum zonulin concentrations at 1, 6 and 12 months and lactulose/mannitol tests at the end of intervention. Dietary questionnaires were used to ensure that the dietary intervention did not result in differences in energy or nutrient intake. RESULTS: The bacteriome community composition changed during the intervention with GFD: of abundant genera, a 3.3-fold decrease was noted for Bifidobacterium genus (adjusted p=1.4 × 10-4 in a DESeq2 model, p=0.026 in generalised estimating equations model), whereas a 2.4-fold increase was observed in Roseburia (adjusted p=0.02 in DESeq2 model, p=0.002 in generalised estimating equations model). The within-sample (alpha) diversity did not change, and there was no statistically significant clustering of GFD samples in the ordination graphs of beta diversity. Neither of the genera changes upon GFD intervention showed any association with the pace of beta cell loss (p>0.50), but of the remaining taxa, several genera of Bacteroidaceae family yielded suggestive signals. The faecal metabolome profile ordination correlated with that of bacteriomes but did not associate with GFD or categories of beta cell preservation. There was no indication of changes in gut permeability. CONCLUSIONS/INTERPRETATION: The bacteriome reacted to GFD, but the changes were unrelated to the pace of beta cell capacity loss. The previously observed moderately protective effect of GFD is therefore mediated through other pathways.

Isolated growth hormone deficiency in children with vertically transmitted short stature: What do the genes tell us?

Introduction: The growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that children diagnosed with GHD form a heterogeneous group with growth disorder frequently independent on GH function. No study evaluating the complex etiology of growth failure in children with diagnosed GHD has been performed thus far. Aims: To discover genetic etiology of short stature in children with diagnosed GHD from families with short stature. Methods: Fifty-two children diagnosed with primary GHD and vertically transmitted short stature (height SDS in the child and his/her shorter parent <-2 SD) were included to our study. The GHD diagnosis was based on growth data suggestive of GHD, absence of substantial disproportionality (sitting height to total height ratio <-2 SD or >+2 SD), IGF-1 levels <0 for age and sex specific SD and peak GH concentration <10 ug/L in two stimulation tests. All children were examined using next-generation sequencing methods, and the genetic variants were subsequently evaluated by American College of Medical Genetics standards and guidelines. Results: The age of children at enrollment into the study was 11 years (median, IQR 9-14 years), their height prior to GH treatment was -3.0 SD (-3.6 to -2.8 SD), IGF-1 concentration -1.4 SD (-2.0 to -1.1 SD), and maximal stimulated GH 6.3 ug/L (4.8-7.6 ug/L). No child had multiple pituitary hormone deficiency or a midbrain region pathology. Causative variant in a gene that affects growth was discovered in 15/52 (29%) children. Of them, only 2 (13%) had a genetic variant affecting GH secretion or function (GHSR and OTX2). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (ACAN, COL1A2, COL11A1, COL2A1, EXT2, FGFR3, NF1, NPR2, PTPN11 [2x]), in one (7%) a genetic variant impairing IGF-1 action (IGFALS) and in two (12%) a variant in miscellaneous genes (SALL4, MBTPS2). Conclusions: In children with vertically transmitted short stature, genetic results frequently did not correspond with the clinical diagnosis of GH deficiency. These results underline the doubtful reliability of methods standardly used to diagnose GH deficiency.

Low-Carbohydrate Diet among Children with Type 1 Diabetes: A Multi-Center Study.

AIMS/HYPOTHESIS: The proportion of children with type 1 diabetes (T1D) who have experience with low-carbohydrate diet (LCD) is unknown. Our goal was to map the frequency of LCD among children with T1D and to describe their clinical and laboratory data. METHODS: Caregivers of 1040 children with T1D from three centers were addressed with a structured questionnaire regarding the children's carbohydrate intake and experience with LCD (daily energy intake from carbohydrates below 26% of age-recommended values). The subjects currently on LCD were compared to a group of non-LCD respondents matched to age, T1D duration, sex, type and center of treatment. RESULTS: A total of 624/1040 (60%) of the subjects completed the survey. A total of 242/624 (39%) subjects reported experience with voluntary carbohydrate restriction with 36/624 (5.8%) subjects currently following the LCD. The LCD group had similar HbA1c (45 vs. 49.5, p = 0.11), lower average glycemia (7.0 vs. 7.9, p = 0.02), higher time in range (74 vs. 67%, p = 0.02), lower time in hyperglycemia >10 mmol/L (17 vs. 20%, p = 0.04), tendency to more time in hypoglycemia <3.9 mmol/L(8 vs. 5%, p = 0.05) and lower systolic blood pressure percentile (43 vs. 74, p = 0.03). The groups did not differ in their lipid profile nor in current body height, weight or BMI. The LCD was mostly initiated by the parents or the subjects themselves and only 39% of the families consulted their decision with the diabetologist. CONCLUSIONS/INTERPRETATION: Low carbohydrate diet is not scarce in children with T1D and is associated with modestly better disease control. At the same time, caution should be applied as it showed a tendency toward more frequent hypoglycemia.

Pre-school and school-aged children benefit from the switch from a sensor-augmented pump to an AndroidAPS hybrid closed loop: A retrospective analysis.

OBJECTIVE: Data on closed loop systems in young children with type 1 diabetes (T1D) are limited. We tested the efficacy and safety of an open-source, do-it-yourself automated insulin delivery system AndroidAPS in preschool and school-aged children. RESEARCH DESIGN AND METHODS: This retrospective study analyzed diabetes control in 18 preschool (3-7 years) and 18 school-aged children (8-14 years) with T1D who switched from a sensor-augmented pump (SAP) to AndroidAPS. We compared the CGM parameters and HbA1c levels 3 months before and 6 months after the initiation of AndroidAPS therapy and evaluated frequency of severe adverse events during AndroidAPS use, the most frequent reasons for its interruption, and the experience and psychosocial benefits of AndroidAPS use. RESULTS: General glycemic control was significantly improved after the switch from SAP to AndroidAPS. Time in range (TIR) increased in both preschool (70.8%-78.6%, p = 0.004) and school-aged children (77.2%-82.9%, p < 0.001), whereas HbA1c levels decreased (preschool children 53.8-48.5 mmol/mol, p < 0.001; school-aged children 52.6-45.1 mmol/mol, p = 0.001). Time spent in range of 3.0-3.8 mmol/L increased slightly in school children (2.6%-3.8%, p = 0.040), but not in preschool children (3.0%-3.0%, p = 0.913). Time spent at <3 mmol/L remained unchanged in both preschool (0.95%-0.67%, p = 0.432) and school-aged children (0.8%-0.8%, p = 1.000). No episodes of severe hypoglycemia or DKA and significant improvement of quality of life were reported by AndroidAPS users. CONCLUSIONS: AndroidAPS seems effective for T1D control both in preschool and school-age children but further validation by prospective studies is necessary.

Gluten-free diet in children with recent-onset type 1 diabetes: A 12-month intervention trial.

AIM: To test whether a gluten-free diet (GFD) is associated with the deceleration of the decline in beta-cell capacity in non-coeliac children with recently diagnosed type 1 diabetes. METHODS: Forty-five children (aged 10.2 ± 3.3 years) were recruited into a self-selected intervention trial: 26 started with a GFD within a median of 38 days postonset, whereas 19 remained on a standard diet. The main outcomes were the decline in C-peptide area under the curve (AUC) in mixed-meal tolerance tests (MMTTs) at 6 and 12 months relative to 1 month after diabetes onset and the difference in insulin dose, insulin dose-adjusted A1c (IDAA1c) and HbA1c assessed every 3 months. The adherence to the GFD was verified by immunoreactive gluten in the stool and by food questionnaires at every visit. Quality of life (QoL) questionnaires were administered to the participants at the end of the intervention at 12 months. The data were analysed as per protocol (in 39 subjects who duly completed the whole follow-up: 20 in the GFD group, 19 in the control group) by linear and longitudinal regression models adjusted for sex, age and baseline variables. RESULTS: At 12 months, the difference in C-peptide AUC between subjects in the GFD group and controls was 205 pmol/L (95% CI -223 to 633; P = 0.34) in a model adjusted for age, sex and body weight, and for baseline insulin dose, MMTT C-peptide AUC and HbA1c assessed at 1 month after diagnosis. In a longitudinal analysis of all three time points adjusted for age, sex and body weight, C-peptide declined more slowly in the GFD group than in controls, with the difference in trends being 409 pmol/L/year (P = 0.04). The GFD group had a marginally lower insulin dose (by 0.15 U/kg/day; P = 0.07), a lower IDAA1c (by 1.37; P = 0.01) and a lower mean HbA1c (by 0.7% [7.8 mmol/mol]; P = 0.02) than those of the controls at 12 months. There was no appreciable difference between the groups in daily carbohydrate intake (P = 0.49) or in the QoL reported by the patients (P = 0.70) and their parents/caregivers (P = 0.59). CONCLUSIONS: A GFD maintained over the first year after type 1 diabetes diagnosis was associated with better HbA1c and a prolonged partial remission period. There was a hint of slower C-peptide decline but the association was not strong enough to make definite conclusions.

Human gut microbiota transferred to germ-free NOD mice modulate the progression towards type 1 diabetes regardless of the pace of beta cell function loss in the donor.

AIMS/HYPOTHESIS: This study aimed to assess the ability of human gut microbiota to delay the onset of type 1 diabetes when transferred into germ-free NOD mice. METHODS: Two children with rapid and three children with slow beta cell function loss (as assessed by C-peptide AUC change in the mixed-meal tolerance tests performed 1 and 12 months after type 1 diabetes onset), participating in an ongoing trial with gluten-free diet, donated faeces, which were transferred into germ-free NOD mice. The mice were subsequently followed for diabetes incidence. RESULTS: The bacterial profiles of bacteriome-humanised mice had significantly (p < 10-5) lower alpha diversity than the donor material, with marked shifts in ratios between the main phyla. Diabetes onset was significantly delayed in all bacteriome-humanised colonies vs germ-free NOD mice, but the pace of beta cell loss was not transferable to the mouse model. CONCLUSIONS/INTERPRETATION: Germ-free NOD mice colonised with human gut microbiome are able to adopt a large proportion of transferred bacterial content, although the ratios of main phyla are reproduced only suboptimally. The recipient mice did not replicate the phenotype of the stool donor in relation to the pace towards type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02867436.

Excellent Glycemic Control Maintained by Open-Source Hybrid Closed-Loop AndroidAPS During and After Sustained Physical Activity.

OBJECTIVE: Officially licensed hybrid closed-loop systems are not currently available worldwide; therefore, open-source systems have become increasingly popular. Our aim was to assess the safety, feasibility, and efficacy of an open-source hybrid closed-loop system (AndroidAPS) versus SmartGuard® technology for day-and-night glucose control in children under extreme sports conditions. RESEARCH DESIGN AND METHODS: Twenty-two children (16 girls, 6-15 years of age, median HbA1c 56 ± 9 mmol/mol) were enrolled in this pivotal winter sports camp study. The participants were divided into two groups using either the AndroidAPS or SmartGuard technology. Physical exertion was represented by all-day alpine skiing. The primary endpoints were mean glucose level, time below the threshold of 3.9 mmol/L, and time within the target range of 3.9 to 10 mmol/L. RESULTS: The children using the AndroidAPS had significantly lower mean glycemia levels (7.2 ± 2.7 vs. 7.7 ± 2.8 mmol/L; 129.6 ± 49 vs. 138.6 ± 50 mg/dL, P < 0.042) than the children using the SmartGuard. The proportion of time below the target (median 5.0% ± 2.5% vs. 3.0% ± 2.3%, P = 0.6) and in the target zone (63% ± 9.5% vs. 63% ± 18%, P = 0.5) did not significantly differ. The AndroidAPS group experienced more frequent malfunctions of the cannula set (median 0.8 ± 0.4 vs. 0.2 ± 0.4, P = 0.02), which could have affected the results. No significant difference was found in the amount of carbohydrates consumed for the prevention and treatment of hypoglycemia [median 40 ± 23 vs. 25 ± 29 g/(patient ·3 days)]. No episodes of severe hypoglycemia or other serious adverse events were noted. CONCLUSIONS: This pilot study showed that the AndroidAPS system was a safe and feasible alternative to the SmartGuard Technology.

For Debate: The Significance of Etiologic Diagnosis in Neonates with Overgrowth Syndromes. Lesson Learned from the Simpson-Golabi-Behmel Syndrome.

Overgrowth syndromes are rare genetic disorders characterized by excessive pre- and postnatal growth accompanied by dysmorphic features and developmental disorders. In addition to other health hazards, the life expectancy of affected children may be compromised due to an increased risk of developing tumors. To demonstrate the need for early recognition, correct diagnostic evaluation and adequate follow-up, we present a family with recurrent Simpson-Golabi-Behmel syndrome (SGBS). SGBS is a X-linked neonatal overgrowth syndrome caused by mutations in the GPC3 or GPC4 genes. All three affected males manifested with congenital diaphragmatic hernia. When fetal overgrowth and congenital diaphragmatic hernia co-occur, the choice for a possible cause is limited among SGBS, Marfan syndrome and Pallister-Killian syndrome. Their different phenotypes allow clinical assessment and correct diagnosis in most cases and should be followed by genetic testing. Regular oncologic screening aimed towards early recognition of malignant tumors may improve long-term outcomes in SGBS as well as in all other overgrowth syndromes.