Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes.

BACKGROUND: The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear. METHODS: In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level, <70 mg per deciliter). Safety was assessed. RESULTS: A total of 74 participants underwent randomization. The mean (±SD) age of the participants was 5.6±1.6 years, and the baseline glycated hemoglobin level was 7.3±0.7%. The percentage of time with the glucose level in the target range was 8.7 percentage points (95% confidence interval [CI], 7.4 to 9.9) higher during the closed-loop period than during the control period (P<0.001). The mean adjusted difference (closed-loop minus control) in the percentage of time spent in a hyperglycemic state was -8.5 percentage points (95% CI, -9.9 to -7.1), the difference in the glycated hemoglobin level was -0.4 percentage points (95% CI, -0.5 to -0.3), and the difference in the mean sensor glucose level was -12.3 mg per deciliter (95% CI, -14.8 to -9.8) (P<0.001 for all comparisons). The time spent in a hypoglycemic state was similar with the two treatments (P = 0.74). The median time spent in the closed-loop mode was 95% (interquartile range, 92 to 97) over the 16-week closed-loop period. One serious adverse event of severe hypoglycemia occurred during the closed-loop period. One serious adverse event that was deemed to be unrelated to treatment occurred. CONCLUSIONS: A hybrid closed-loop system significantly improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in hypoglycemia. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT03784027.).

Parents' experiences of using remote monitoring technology to manage type 1 diabetes in very young children during a clinical trial: Qualitative study.

AIMS: To explore parents' experiences of using remote monitoring technology when caring for a very young child with type 1 diabetes during a clinical trial. METHODS: Interviews were conducted with parents of 30 children (aged 1-7 years) participating in a trial (the KidsAP02 study) comparing hybrid closed-loop insulin delivery with sensor-augmented pump therapy. In both arms, parents had access to remote monitoring technology. Data analysis focused on identification of descriptive themes. RESULTS: Remote monitoring technology gave parents improved access to data which helped them pre-empt and manage glucose excursions. Parents observed how, when children were in their own care, they could be more absent while present, as their attention could shift to non-diabetes-related activities. Conversely, when children were others' care, remote monitoring enabled parents to be present while absent, by facilitating oversight and collaboration with caregivers. Parents described how remote monitoring made them feel more confident allowing others to care for their children. Parents' confidence increased when using a hybrid closed-loop system, as less work was required to keep glucose in range. Benefits to children were also highlighted, including being able to play and sleep uninterrupted and attend parties and sleepovers without their parents. While most parents welcomed the increased sense of control remote monitoring offered, some noted downsides, such as lack of respite from caregiving responsibilities. CONCLUSIONS: Remote monitoring can offer manifold benefits to both parents and very young children with type 1 diabetes. Some parents, however, may profit from opportunities to take 'time out'.

Clinical presentation and long-term outcome of patients with KCNJ11/ABCC8 variants: Neonatal diabetes or MODY in the DPV registry from Germany and Austria.

OBJECTIVE: To describe clinical presentation/longterm outcomes of patients with ABCC8/KCNJ11 variants in a large cohort of patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed patients in the Diabetes Prospective Follow-up (DPV) registry with diabetes and pathogenic variants in the ABCC8/KCNJ11 genes. For patients with available data at three specific time-points-classification as K+ -channel variant, 2-year follow-up and most recent visit-the longitudinal course was evaluated in addition to the cross-sectional examination. RESULTS: We identified 93 cases with ABCC8 (n = 54)/KCNJ11 (n = 39) variants, 63 of them with neonatal diabetes. For 22 patients, follow-up data were available. Of these, 19 were treated with insulin at diagnosis, and the majority of patients was switched to sulfonylurea thereafter. However, insulin was still administered in six patients at the most recent visit. Patients were in good metabolic control with a median (IQR) A1c level of 6.0% (5.5-6.7), that is, 42.1 (36.6-49.7) mmol/mol after 2 years and 6.7% (6.0-8.0), that is, 49.7 (42.1-63.9) mmol/mol at the most recent visit. Five patients were temporarily without medication for a median (IQR) time of 4.0 (3.5-4.4) years, while two other patients continue to be off medication at the last follow-up. CONCLUSIONS: ABCC8/KCNJ11 variants should be suspected in children diagnosed with diabetes below the age of 6 months, as a high percentage can be switched from insulin to oral antidiabetic drugs. Thirty patients with diabetes due to pathogenic variants of ABCC8 or KCNJ11 were diagnosed beyond the neonatal period. Patients maintain good metabolic control even after a diabetes duration of up to 11 years.

Parents' views about healthcare professionals having real-time remote access to their young child's diabetes data: Qualitative study.

OBJECTIVES: We explored parents' views about healthcare professionals having remote access to their young child's insulin and glucose data during a clinical trial to inform use of data sharing in routine pediatric diabetes care. RESEARCH DESIGN AND METHODS: Interviews with 33 parents of 30 children (aged 1-7 years) with type 1 diabetes participating in a randomized trial (KidsAP02) comparing hybrid closed-loop system use with sensor-augmented pump therapy. Data were analyzed using a qualitative descriptive approach. RESULTS: Parents reported multiple benefits to healthcare professionals being able to remotely access their child's glucose and insulin data during the trial, despite some initial concerns regarding the insights offered into everyday family life. Key benefits included: less work uploading/sharing data; improved consultations; and, better clinical input and support from healthcare professionals between consultations. Parents noted how healthcare professionals' real-time data access facilitated remote delivery of consultations during the COVID-19 pandemic, and how these were more suitable for young children than face-to-face appointments. Parents endorsed use of real-time data sharing in routine clinical care, subject to caveats regarding data access, security, and privacy. They also proposed that, if data sharing were used, consultations for closed-loop system users in routine clinical care could be replaced with needs-driven, ad-hoc contact. CONCLUSIONS: Real-time data sharing can offer clinical, logistical, and quality-of-life benefits and enhance opportunities for remote consultations, which may be more appropriate for young children. Wider rollout would require consideration of ethical and cybersecurity issues and, given the heightened intrusion on families' privacy, a non-judgmental, collaborative approach by healthcare professionals.

Differences in retinopathy prevalence and associated risk factors across 11 countries in three continents: A cross-sectional study of 156,090 children and adolescents with type 1 diabetes.

OBJECTIVE: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales). SUBJECTS AND METHODS: Data on individuals aged 10-21 years with T1D for >1 year during the period 2000-2020 were analyzed. We used a cross-sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR. RESULTS: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aORper-1-year-increase  = 1.04, 95% CI: 1.03-1.04, p < 0.0001), and decreased over time (aORper-1-year-increase  = 0.99, 95% CI: 0.98-1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aORper-1-mmol/mol-increase-in-HbA1c  = 1.03, 95% CI: 1.03-1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11-1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17-1.44, p < 0.0001). CONCLUSIONS: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking.

Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents.

AIMS/HYPOTHESIS: The aim of this work was to evaluate geographical variability and trends in the prevalence of diabetic ketoacidosis (DKA), between 2006 and 2016, at the diagnosis of childhood-onset type 1 diabetes in 13 countries over three continents. METHODS: An international retrospective study on DKA at diagnosis of diabetes was conducted. Data on age, sex, date of diabetes diagnosis, ethnic minority status and presence of DKA at diabetes onset were obtained from Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA and the UK (Wales). Mean prevalence was estimated for the entire period, both overall and by country, adjusted for sex and age group. Temporal trends in annual prevalence of DKA were estimated using logistic regression analysis for each country, before and after adjustment for sex, age group and ethnic minority status. RESULTS: During the study period, new-onset type 1 diabetes was diagnosed in 59,000 children (median age [interquartile range], 9.0 years [5.5-11.7]; male sex, 52.9%). The overall adjusted DKA prevalence was 29.9%, with the lowest prevalence in Sweden and Denmark and the highest in Luxembourg and Italy. The adjusted DKA prevalence significantly increased over time in Australia, Germany and the USA while it decreased in Italy. Preschool children, adolescents and children from ethnic minority groups were at highest risk of DKA at diabetes diagnosis in most countries. A significantly higher risk was also found for females in Denmark, Germany and Slovenia. CONCLUSIONS/INTERPRETATION: DKA prevalence at type 1 diabetes diagnosis varied considerably across countries, albeit it was generally high and showed a slight increase between 2006 and 2016. Increased awareness of symptoms to prevent delay in diagnosis is warranted, especially in preschool children, adolescents and children from ethnic minority groups.

Time trends in incidence of diabetes mellitus in Austrian children and adolescents <15 years (1989-2017).

OBJECTIVE: To analyze the time trends of nationwide diabetes incidence <15 years of age from 1989 until 2017 in Austria. METHODS: The Austrian Diabetes Incidence Study Group registers all newly diagnosed patients with diabetes mellitus <15 years of age in a prospective population-based study. The diabetes type was classified on the basis of clinical and laboratory findings according to American Diabetes Association criteria. Time trends were estimated by Joinpoint analysis. RESULTS: 1311 patients were diagnosed with type 1 diabetes (T1D) between 1989 and 1999 and 4624 patients with any type of diabetes (1999-2017). T1D accounted for the majority of cases (94.2%), 1.8% were classified as type 2 (T2D) and 4.0% as other specific types of diabetes (1999-2017). In the total cohort (age 0 to <15 years), a constant increase until 2012 (annual percent change [APC] 4.5, 95% confidence interval [CI]: 3.94, 5.06) was observed, followed by a leveling off with a corresponding drop (APC 0.28, 95%CI: -3.94, 4.69). This observation was mainly driven by the dynamic in the youngest age group (0-4 years) with a steep increase until 2007 (APC 7.1, 95%CI: 5.05, 9.19) and a decrease from 2007 to 2017 (APC -0.86, 95%CI: 4.41, 2.82). No significant increase of T2D <15 years was detected. Over the observed time period (APC = 3.7, 95%CI: -0.30, 7.78). CONCLUSIONS: The incidence of T1D is declining in young children aged 0 to 4 years, but is still rising in children 5 to 14 years in Austria. Incidence of T2D did not increase significantly and other specific types of diabetes occur twice as often compared to T2D.

International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study.

OBJECTIVES: To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. SUBJECTS: 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. METHODS: Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. RESULTS: Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. CONCLUSIONS: In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.

Reduced burden of diabetes and improved quality of life: Experiences from unrestricted day-and-night hybrid closed-loop use in very young children with type 1 diabetes.

OBJECTIVE: To evaluate the experiences of families with very young children aged 1 to 7 years (inclusive) with type 1 diabetes using day-and-night hybrid closed-loop insulin delivery. METHODS: Parents/caregivers of 20 children aged 1 to 7 years with type 1 diabetes completed a closed-loop experience survey following two 3-week periods of unrestricted day-and-night hybrid closed-loop insulin therapy using Cambridge FlorenceM system at home. Benefits, limitations, and improvements of closed-loop technology were explored. RESULTS: Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed-loop. Ninety percent of the responders felt less worried about their child's glucose control using closed-loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets. CONCLUSIONS: Parents/caregivers of very young children reported important quality of life benefits associated with using closed-loop, supporting adoption of this technology in this population.

Lipoprotein-associated phospholipase A2 activity in obese adolescents with and without type 2 diabetes.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) was identified as a strong predictor for cardiovascular events. Furthermore, it is highly associated with obesity. The role of Lp-PLA2 in diabetes mellitus is controversial and analyses, especially in adolescents with type 2 diabetes (T2D), are missing. Therefore, we compared Lp-PLA2 activity between two obese age-, sex-, and BMI-matched cohorts of adolescents with and without T2D. Relationships between Lp-PLA2 activity and age, BMI, hemoglobin A1c, lipids, and adipokines were evaluated. Lp-PLA2 activity was analyzed in serum of 72 obese adolescents without T2D (mean age 15.2 ± 1.6 years) and in 65 obese adolescents with T2D (mean age 15.5 ± 1.8 years). Clinical data were obtained from the Diabetes-Patienten-Verlaufsdokumentation (DPV) registry. Surprisingly, obese adolescents with T2D had lower levels of Lp-PLA2 activity than obese children without T2D (160.2 ± 45.0 versus 180.9 ± 35.6 nmol/min/ml, p = 0.003), but this decrease could only be detected in male (158.8 ± 45.3 versus 190.8 ± 31.3 nmol/min/ml, p < 0.001) and not in female adolescents (162.1 ± 45.5 versus 167.7 ± 37.1 nmol/min/ml, p = 0.60). In multiple linear regression analysis, differences in Lp-PLA2 activity between cohorts remained large and significant (ß-coefficient: -31.60, 95% confidence interval [-49.27;-13.93], p < 0.001). Furthermore, Lp-PLA2 activity was positively associated with BMI (ß-coefficient: 2.04 [0.68;3.40], p = 0.004) and negatively associated with the adipokines leptin (ß-coefficient: -0.53 [-0.89;-0.17], p = 0.004) and adiponectin (ß-coefficient: -3.06, [-5.63;-0.48], p = 0.02). Elevated mean glucose concentrations in adolescents with T2D were not associated with an increase but with a decrease of Lp-PLA2 activity. Hence, in young patients with T2D the Lp-PLA2 activity as a risk predictor for cardiovascular events needs further investigation.

Adolescent type 2 diabetes: Comparing the Pediatric Diabetes Consortium and Germany/Austria/Luxemburg Pediatric Diabetes Prospective registries.

OBJECTIVE: To examine and compare the clinical characteristics and treatment of youth with type 2 diabetes (T2D) in two registries: one in Europe and one in the United States. METHODS: Youth with onset of T2D at 10 to 18 years of age with current age <20 years and an office visit after diabetes duration >1 year were identified in the European (Prospective Diabetes Follow-up, DPV) and the United States (Pediatric Diabetes Consortium, PDC) databases. Demographic, physical and clinical characteristics and treatment at diagnosis as well as physical characteristics, treatment, laboratory data, and diabetes adverse events at most recent visit were analyzed from both registries. RESULTS: At diagnosis, the majority were female and obese; 70% of DPV vs 34% of PDC youth were diagnosed by targeted diabetes testing. PDC youth were younger, 12 vs 13 years (P < 0.001), had a greater body mass index-SDS, 3.07 vs 2.74 (P < 0.001), a higher hemoglobin A1c (HbA1c), 9.9% vs 7.1% (P < 0.001), were more likely to present in DKA, 7.5% vs 1.3% (P < 0.001) and more likely to be treated with insulin, 62% vs 32% (P < 0.001); insulin treatment difference was not significant when adjusted for HbA1c. At follow-up, DPV youth had shorter diabetes duration, 2.1 vs 3.2 years (P < 0.001), lower HbA1c, 6.5% vs 7.8% (P < 0.001), were less likely to be treated with insulin, 36% vs 56%, (P < 0.001), and were more likely to have dyslipidemia and hypertension than PDC youth. PDC youth had a higher rate of microalbuminuria. CONCLUSIONS: Both DPV and PDC youth have multiple risks for diabetes complications. Understanding reasons for persistently higher HbA1c in PDC youth requires further study.

Continuous glucose monitoring and glycemic control among youth with type 1 diabetes: International comparison from the T1D Exchange and DPV Initiative.

BACKGROUND: To assess the change in rates of pediatric real-time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5 years, and how it impacts glycemic control, data from two registries were compared: the US-based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow-Up Registry). METHODS: Registry participants aged <18 years with T1D duration ≥1 year encompassed 29 007 individuals in 2011 and 29 150 participants in 2016. Demographic data, CGM use and hemoglobin A1c (HbA1c) were obtained from medical records. RESULTS: CGM use increased from 2011 to 2016 in both registries across all age groups, regardless of gender, ethnic minority status or insulin delivery method. The increase in CGM use was most pronounced in the youngest patients, and usage rates remain lowest for adolescent patients in 2016. For both registries in 2016, mean HbA1c was lower among CGM users regardless of insulin delivery method compared to pump only (P < 0.001) and injection only (P < 0.001), and CGM users were more likely to achieve glycemic target of HbA1c <7.5% (56% vs 43% for DPV and 30% vs 15% for T1DX, P < 0.001). T1DX participants had a higher mean HbA1c compared with DPV despite whether they were CGM users or non-users; however, the difference was less pronounced in CGM users (P < 0.001). CONCLUSIONS: Pediatric CGM use increased in both registries and was associated with lower mean HbA1c regardless of insulin delivery modality.

Self-reported regular alcohol consumption in adolescents and emerging adults with type 1 diabetes: A neglected risk factor for diabetic ketoacidosis? Multicenter analysis of 29 630 patients from the DPV registry.

BACKGROUND: The risk of hypoglycemia increases after alcohol consumption in patients with type 1 diabetes. This study aimed to investigate the association between metabolic control and self-reported alcohol consumption in young patients with type 1 diabetes. MATERIALS AND METHODS: N = 29 630 patients with type 1 diabetes aged 12 to <30 years (median age 17.0 [14.9, 18.3] years, duration of diabetes 6.8 [3.3, 10.9] years, 53% male) from the German/Austrian DPV registry were analyzed. Patients were categorized into abstainers, low-risk drinkers, and at-risk drinkers. BMI, HbA1c, and rates of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) were compared between alcohol consumption groups using multivariable hierarchical regression models. The association between alcohol use and smoking status was assessed using χ 2 test. RESULTS: Overall, 10.8% of the patients reported regular alcohol consumption. Proportion of alcohol use as well as the amount of alcohol consumed increased with age and were higher in males than in females (all P < .05). Patients with Turkish migration background reported less alcohol consumption. HbA1c, SH rate, and DKA rate (adjusted for age, gender, duration of diabetes, therapy) were significantly lower in abstainers than in patients drinking alcohol (all P < .05). Smoking status was significantly associated with alcohol consumption (P < .001). CONCLUSION: Self-reported alcohol consumption is likely to be underreported when collected in face-to-face settings such as doctors' visits. Nevertheless, our data revealed a significant association between higher alcohol consumption and worse glycemic control, in particular higher DKA rates. Information about alcohol-induced complications is of great importance in diabetes education in young people with type 1 diabetes.

Severe hypoglycemia rates are not associated with HbA1c: a cross-sectional analysis of 3 contemporary pediatric diabetes registry databases.

OBJECTIVE: To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries. METHODS: Data for patients with type 1 diabetes, aged <18 years with a minimum duration of diabetes of 2 years, were extracted from each registry for a 12-month observation period between 2011 and 2012 (7,102 T1DX, 18,887 DPV, and 865 WACDD). Rates of severe hypoglycemia (self-reported loss of consciousness/convulsion) were estimated per 100 patient-years and analyzed by HbA1c, source registry, treatment regimen, and age group. RESULTS: Overall, the severe hypoglycemia rate per 100 patient years was 7.1, 3.3, and 6.7 in T1DX, DPV, and WACDD patients, respectively. Lower HbA1c was not associated with an increased rate of severe hypoglycemia when examined by source registry, treatment regimen, or age group. CONCLUSION: An inverse relationship between mean HbA1c and risk of severe hypoglycemia was not observed in this study of 3, independent cohorts of children and adolescents with type 1 diabetes. Investigation in other large, longitudinal cohorts is recommended to further characterize the contemporary relationship between glycemic control and risk of severe hypoglycemia rates in pediatric patients with type 1 diabetes.

Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large, transatlantic paediatric registries.

AIMS/HYPOTHESIS: While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries. METHODS: Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV; n = 26,198), T1D Exchange (T1DX; n = 13,755) and the National Paediatric Diabetes Audit (NPDA; n = 14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA1c levels were compared. RESULTS: The overall mean HbA1c level was higher in the NPDA (8.9 ± 1.6% [74 ± 17.5 mmol/mol]) than in the DPV (8.0 ± 1.6% [64 ± 17.0 mmol/mol], p < 0.001) and T1DX (8.3 ± 1.4% [68 ± 15.4 mmol/mol], p < 0.001). Conversely, pump use was much lower in the NPDA (14%) than in the DPV (41%, p < 0.001) and T1DX (47%, p < 0.001). In a pooled analysis, pump use was associated with a lower mean HbA1c (pump: 8.0 ± 1.2% [64 ± 13.3 mmol/mol] vs injection: 8.5 ± 1.7% [69 ± 18.7 mmol/mol], p < 0.001). In all three registries, those with an ethnic minority status were less likely to be treated with a pump (p < 0.001) and boys were treated with a pump less often compared with girls (p < 0.001). CONCLUSIONS/INTERPRETATION: Despite similar clinical characteristics and proportion of minority participants, substantial differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy.

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.

Obesity in Youth with Type 1 Diabetes in Germany, Austria, and the United States.

OBJECTIVE: To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D). STUDY DESIGN: International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-<18 years and ≥ 1 year duration of T1D) enrolled in the T1D Exchange (n = 11,435) and the Diabetes Prospective Follow-up (n = 21,501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed. RESULTS: Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P < .001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P < .001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant. CONCLUSIONS: Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D.

Tracking of metabolic control from childhood to young adulthood in type 1 diabetes.

OBJECTIVE: This prospective longitudinal survey was designed to follow patients with diabetes from disease onset in childhood over an extended period of time including puberty until young adulthood with respect to metabolic control. STUDY DESIGN: An electronic diabetes patient documentation system used in diabetes centers in Austria and Germany was utilized for standardized data collection. Complete documentation of metabolic control for prepuberty (≤ 13 years), puberty (14-19 years), and adulthood (≥ 20 years) was available in 1146 patients. RESULTS: Median age at diabetes manifestation was 7.2 (IQR 4.7-9.4) years; 49% were male. In the prepubertal stage, median glycated hemoglobin A1c (HbA1c) was 7.5 (IQR 6.8-8.3), during puberty 8.0 (IQR 7.3-8.9), and after puberty 7.8 (IQR 7.1-9.0). A significant intra-individual correlation was found for prepuberty to puberty HbA1c levels (R = 0.55, P < .001), puberty to adulthood (R = 0.59, P < .001), as well as prepuberty to adulthood (R = 0.30, P < .001). When patients were divided into tertiles of prepubertal HbA1c, HbA1c increased in all 3 groups over time, however, significant group differences tracked into adulthood (P < .001 at all stages). A regression model identified pre-pubertal HbA1c as a significant and relevant predictor of metabolic control in young adulthood adjusted for confounders (P < .001). CONCLUSIONS: This survey provides evidence for long-term tracking of metabolic control from childhood until adulthood, suggesting an early focus on metabolic control.

Metabolic safety of growth hormone in type 1 diabetes and idiopathic growth hormone deficiency.

OBJECTIVE: To evaluate metabolic consequences of growth hormone (GH) treatment in children with type 1 diabetes. STUDY DESIGN: This study is an analysis of metabolic changes in 37 patients with childhood-onset GH deficiency and type 1 diabetes, documented in the Diabetes Patienten Verlaufsdocumentationsystem database. Main outcome measures were changes in hemoglobin A1c and daily insulin requirements during GH therapy in children with GH deficiency and type 1 diabetes compared with a large cohort of adolescents with type 1 diabetes. RESULTS: Thirty-seven patients with type 1 diabetes and a diagnosis of idiopathic GH deficiency after onset of diabetes were compared with 48856 patients with type 1 diabetes. After adjustment for age, sex, duration of diabetes, and migration background, a significant difference in mean daily insulin requirement was seen between the 2 groups (1.0 IU/kg/day in subjects with GH deficiency and type 1 diabetes vs 0.85 IU/kg/day in controls; P < .01) and height-SDS (-2.0 in subjects with GH deficiency and diabetes vs +0.03 in controls; P < .0001). There was no significant between-group difference in hemoglobin A1 concentration, however (8.1% ± 1.4% in patients with GH deficiency and type 1 diabetes vs 8.2% ± 1.7% in those with type 1 diabetes only; P > .05). CONCLUSION: An increased daily insulin requirement should be considered in patients with type 1 diabetes treated with GH. With adequate adaptation of insulin dosage, metabolic control is not impaired during GH treatment.