Rare Antagonistic Leptin Variants and Severe, Early-Onset Obesity.

Hormone absence or inactivity is common in congenital disease, but hormone antagonism remains controversial. Here, we characterize two novel homozygous leptin variants that yielded antagonistic proteins in two unrelated children with intense hyperphagia, severe obesity, and high circulating levels of leptin. Both variants bind to the leptin receptor but trigger marginal, if any, signaling. In the presence of nonvariant leptin, the variants act as competitive antagonists. Thus, treatment with recombinant leptin was initiated at high doses, which were gradually lowered. Both patients eventually attained near-normal weight. Antidrug antibodies developed in the patients, although they had no apparent effect on efficacy. No severe adverse events were observed. (Funded by the German Research Foundation and others.).

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.).

Impact of a 4-week intensive track and field training intervention on glycaemia in adolescents with type 1 diabetes: The ChilDFiT1 study.

AIM: To investigate the safety and efficacy of track and field training compared with intensification of insulin treatment only in adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: Eighteen adolescents (seven females) with T1D were included (age 15.1 ± 1.1 years, HbA1c 7.3% ± 1.0% [56.3 ± 10.9 mmol/mol]). After a 4-week observational control phase, participants were randomized to either stand-alone intensive glycaemic management (IT; telemedicine or on-site visits, three times/week) or additionally performed track and field exercise (EX; three 60-minute sessions/week) for 4 weeks. Glycaemia was assessed via continuous glucose monitoring during observational control and intervention phases. RESULTS: Time in range (70-180 mg/dL; 3.9-10.0 mmol/L) significantly improved from the observational control phase to the exercise intervention phase in EX (69% ± 13% vs. 72% ± 11%, P = .049), but not in IT (59% ± 22% vs. 62% ± 16%, P = .399). Time below range 1 (54-69 mg/dL; < 3.9 mmol/L) improved in IT (3.1% ± 1.9% vs. 2.0% ± 0.8%, P = .017) and remained stable in EX (2.0% ± 1.7 vs. 1.9% ± 1.1%, P = .999). The EX group's HbA1c ameliorated preintervention to postintervention (mean difference: ΔHbA1c -0.19% ± 0.17%, P = .042), which was not seen within the IT group (ΔHbA1c -0.16% ± 0.37%, P = .40). Glucose standard deviation was reduced significantly in EX (55 ± 11 vs. 51 ± 10 mg/dL [3.1 ± 0.6 vs. 2.8 ± 0.6 mmol/L], P = .011), but not in IT (70 ± 24 vs. 63 ± 18 mg/dL [3.9 ± 1.3 vs. 3.5 ± 1.0 mmol/L], P = .186). CONCLUSION: Track and field training combined with intensive glycaemic management improved glycaemia in adolescents with T1D, which was not observed in the non-exercise group.

Early vs late histological confirmation of coeliac disease in children with new-onset type 1 diabetes.

AIM: Screening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed. METHODS: This was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis. RESULTS: Of 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, p<0.001) and more often female (53.1% vs 44.4%, p<0.001). A total of 533 participants (22.8% of those who screened positive) had a documented biopsy, of whom 444 had documented histological confirmation of coeliac disease. Of 411 participants with biopsy-proven coeliac disease within the first 36 months of diabetes and follow-up data, histological confirmation was performed in 264 (64.2%) within the first 6 months and in 147 (35.8%) between 6 and 36 months after diabetes onset. At follow-up (median diabetes duration 5.3 years and 5.1 years, respectively), estimated median HbA1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period. CONCLUSIONS: Our study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed.

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'.

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.

Less ready for adulthood?-Turner syndrome has an impact on transition readiness.

OBJECTIVE: Young women with Turner syndrome (TS) are known to be at risk for loss to medical follow-up. Recent literature indicates that there are disparities regarding transition readiness between different chronic conditions. So far, studies in young women with TS investigating their transition readiness compared to youths with other chronic conditions with no or minor neurocognitive challenges have not been reported. METHODS: Patients (n = 52), 26 patients with Turner syndrome (mean age 17.24 ± 2.10) and 26 controls with type 1 diabetes or a rheumatic disease (mean age 17.41 ± 2.44), were recruited from specialized paediatric endocrine outpatient clinics. The Transition Readiness Assessment Questionnaire TRAQ-GV-15 was used to compare transition readiness scores between TS and controls. In addition, information on individual handling of the questionnaire was obtained. Descriptive statistics and nonparametric methods were used to analyse the data. RESULTS: Significant differences for transition readiness scores were found between the two study groups. The global TRAQ-GV-15 score was significantly lower for females with TS. In particular, subscale 1 'autonomy' of the TRAQ-GV-15 showed lower scores in patients with TS. Patients with TS needed significantly more help and more time to complete the questionnaire. CONCLUSION: Special attention should be given to young women with Turner syndrome in the preparation for the transitional phase. By incorporating the assessment of transition readiness specialists will find it easier to identify underdeveloped skills and knowledge gaps in their patients. Unless a multidisciplinary young adult clinic is established, an older age than 18 years at transfer to adult endocrine care might be beneficial.

Increased tissue factor activity promotes thrombin generation at type 1 diabetes onset in children.

OBJECTIVE: In type 1 diabetes (T1D), a prothrombotic status due to elevated coagulation factors coincides with metabolic derailment. In a previous study, we discovered altered thrombin generation profiles in children with T1D. These alterations are potentially most pronounced at T1D onset and ameliorated after insulin treatment. We tested this hypothesis in a longitudinal study, measuring thrombin generation together with coagulation parameters in children at T1D onset and during follow-up. MATERIALS AND METHODS: Twenty-three children (12 female, age: 9.4 [2.7-17.3] years; median [range]) were tested at T1D onset and after long-term insulin treatment. Thrombin generation was measured using calibrated automated thrombography. Tissue factor (TF) activity and tissue factor pathway inhibitor (TFPI) activity were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: A procoagulant shift was observed in thrombin generation traces at T1D onset compared to follow-up (time to peak: 5.67 [4.11-7.67] min vs 6.39 [4.89-10.44] min, P < .001). These alterations at T1D onset coincided with increased TF activity (5.18 [0.01-12.97] pmol/L vs 2.67 [0.04-10.41] pmol/L, P < .05) and increased TFPI activity (0.051 [0.038-0.074] U/mL vs 0.035 [0.026-0.056] U/mL, P < .05). CONCLUSION: The procoagulant shift in thrombin generation at T1D onset is a result of increased TF activity, but this effect is partially counterbalanced by increased TFPI levels. Elevated TF and TFPI levels hint to a fragile hemostatic balance at the endothelial lining of blood vessels. Additional prothrombotic stimuli may tip over this balance explaining the increased thrombotic risk of children with T1D.

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.

Lower HbA1c in patients with type 1 diabetes and celiac disease who reached celiac-specific antibody-negativity-A multicenter DPV analysis.

OBJECTIVES: To study celiac-specific antibody status over 3 years in patients with type 1 diabetes and biopsy-proven celiac disease (T1D + CD). Furthermore, to determine clinical differences after diagnosis between patients reaching constant antibody-negativity (Ab-neg) and staying antibody-positive (Ab-pos). METHODS: A total of 608 pediatric T1D + CD patients from the multicenter DPV registry were studied longitudinally regarding their CD specific antibody-status. Differences between Ab-neg (n = 218) and Ab-pos (n = 158) patients 3 years after biopsy were assessed and compared with 26 833 T1D patients without CD by linear and logistic regression adjusted for age, gender, diabetes duration and migration background. RESULTS: Thirty-six percent of T1D + CD patients reached and sustained antibody-negativity 3 years after CD diagnosis. The median time until patients returned to Ab-neg was 0.86 (0.51;1.16) years. Three years after diagnosis, HbA1c was lowest in Ab-neg and highest in Ab-pos patients compared to T1D-only patients (adjusted mean (95%CI): 7.72 (7.51-7.92) % vs 8.44 (8.20-8.68) % vs 8.19 (8.17-8.21) %, adjusted P < 0.001, respectively). Total cholesterol, LDL-cholesterol and frequency of dyslipidemia were significantly lower in Ab-neg compared to T1D-only patients (167 (161-173) mg/dl vs 179 (178-179) mg/dl, P < .001; 90 (84-96) mg/dl vs 99 (98-99) mg/dl, P = .005; 15.7 (10.5-22.9) % vs 25.9 (25.2-26.6) %, P = .017). In longitudinal analyses over 6 years after diagnosis, a constantly higher HbA1c (P < .001) and a lower height-SDS (P = .044) was observed in Ab-pos compared to Ab-neg patients. CONCLUSION: Only one third of T1D + CD patients reached constant Ab-negativity after CD diagnosis. Achieving Ab-negativity after diagnosis seems to be associated with better metabolic control and growth, supposedly due to a higher adherence to therapy in general.

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.

Early childhood BMI trajectories in monogenic obesity due to leptin, leptin receptor, and melanocortin 4 receptor deficiency.

OBJECTIVE: To evaluate whether early childhood body mass index (BMI) is an appropriate indicator for monogenic obesity. METHODS: A cohort of n = 21 children living in Germany or Austria with monogenic obesity due to congenital leptin deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed. A control group (CTRL) was defined that consisted of n = 22 obese adolescents with no mutation in the above mentioned genes. Early childhood (0-5 years) BMI trajectories were compared between the groups at selected time points. RESULTS: The LEP and LEPR group showed a tremendous increase in BMI during the first 2 years of life with all patients displaying a BMI >27 kg/m2 (27.2-38.4 kg/m2) and %BMIP95 (percentage of the 95th percentile BMI for age and sex) >140% (144.8-198.6%) at the age of 2 years and a BMI > 33 kg/m2 (33.3-45.9 kg/m2) and %BMIP95 > 184% (184.1-212.6%) at the age of 5 years. The MC4R and CTRL groups had a later onset of obesity with significantly lower BMI values at both time points (p < 0.01). CONCLUSION: As result of the investigation of early childhood BMI trajectories in this pediatric cohort with monogenic obesity we suggest that BMI values >27.0 kg/m2 or %BMIP95 > 140% at the age of 2 years and BMI values >33.0 kg/m2 or %BMIP95 > 184% at the age of 5 years may be useful cut points to identify children who should undergo genetic screening for monogenic obesity due to functionally relevant mutations in the leptin gene or leptin receptor gene.

Type 1 diabetes during adolescence: International comparison between Germany, Austria, and Sweden.

OBJECTIVES: By using pediatric diabetes quality registries in Austria, Germany, and Sweden treatment of type 1 diabetes and the outcome of care during the vulnerable adolescence period were compared. METHODS: Data in DPV, broadly used in Austria and Germany, and Swediabkids used in Sweden, from clinical visits in the year 2013 on 14 383 patients aged 11 to 16 years regarding hemoglobin A1c (HbA1c), insulin regimen, body mass index (BMI)-SD score (SDS), blood pressure, hypoglycemia, ketoacidosis, and smoking habits were analyzed. RESULTS: Patients in Sweden had fewer clinical visits per year (P < .05), lower insulin dose per kg (P < .001), and lower proportion of fast acting insulin compared with Germany and Austria (P < .001). The proportion of pump users was higher in Sweden (P < .001). Patients in Sweden had lower mean HbA1c levels (Austria: 64 mmol/mol, Germany: 63 mmol/mol, and Sweden: 61 mmol/mol [8.0%, 7.9%, and 7.7%, respectively]; P < .001). The frequency of severe hypoglycemia was higher in Sweden while it was lower for ketoacidosis (3.3% and 1.1%, respectively) than in Austria (1.1% and 5.3%) and Germany (2.0% and 4.4%) (P < .001). Girls in all 3 countries had higher HbA1c and BMI-SDS than boys. CONCLUSIONS: Sharing data between diabetes registries and nations enables us to better understand differences in diabetes outcome between countries. In this particular comparison, pediatric patients with diabetes in Sweden were more often treated with insulin pump, had lower HbA1c levels and a higher rate of severe hypoglycemia. Patients in Austria and Germany used rapid acting insulin analogs more often and had a lower rate of ketoacidosis.

Asthma in children and adolescents with type 1 diabetes in Germany and Austria: Frequency and metabolic control.

OBJECTIVE: To investigate the prevalence of asthma in young patients with type 1 diabetes mellitus (T1D) from Austria and Germany and its influence on their metabolic control. METHODS: This prospective, multicenter observational cohort study was based on the DPV-registry (German/Austrian DPV initiative) including 51 926 patients with T1D (<20 years). All clinical data were documented prospectively. To identify patients with additional asthma, the entry of the diagnosis asthma as well as asthma medication was used for classification. RESULTS: 1755 patients (3.4%) of the cohort had the diagnosis asthma or received asthma-specific drugs. Patients with asthma needed higher insulin doses (0.88 ± 0.3 vs 0.84 ± 0.3 U/kg, P < .01) and had decreased height-standard deviation score (SDS) (-0.002 ± 1.04 vs 0.085 ± 1.02, P < .01); they were more often males (61% vs 52%, P < .01), had an increased body mass index (BMI)-SDS (0.31 ± 0.89 vs 0.28 ± 0.89, P = .04) and experienced more severe hypoglycemia (4.5 [4.2; 4.8] vs 3.2 [3.2; 3.3] events/100 pts. years, P < .01). Glycated hemoglobin A1c (HbA1c) did not differ between patients with and without asthma overall, only sub groups (corticosteroids vs leukotriene antagonist and corticosteroids vs sympatomimetics) revealed differences. No influence of asthma medication on metabolic control or BMI-SDS could be found. CONCLUSION: In our DPV-database, frequency of asthma and T1D seems similar to the prevalence of asthma in the healthy German background population. The concomitant diagnosis of asthma and T1D had minor influence on metabolic control and diabetes complication rate, although there was no difference in HbA1c overall. Patients with both diseases seem to be slightly growth restricted and require slightly higher insulin doses.

Type 1 diabetes in children and adolescents is not associated with a reduced prevalence of atopy and allergic diseases.

BACKGROUND: Type 1 diabetes mellitus (T1D) as well as allergies in childhood have increased worldwide during the last 2 decades. The reasons for this increase are still unknown but early life origins are being discussed, such as dietary and hygiene factors that may play a role in the development of both diseases. The aim of this study was to compare the prevalence of allergies in children with and without T1D and to define potential influencing factors. MATERIALS AND METHODS: Data were collected from 104 patients with T1D (n = 104; mean age 11.4 ± 4.4 years; m/f: 77/27) and 104 healthy controls (CG) (n = 104; mean age 11.4 ± 4.3 years; m/f: 77/27). A questionnaire on allergic symptoms was obtained from each individual. In parallel, ImmunoCAP tests to detect specific allergen sensitization were performed. RESULTS: Allergen sensitization rates were not significantly different between both groups (T1D: 42% vs CG 38%; P = 0.625). In both groups, a comparable number of patients reported allergic symptoms in the questionnaire (T1D: 20% vs CG 26%; P = 0.43). Allergen sensitization and allergic symptoms were independent of breastfeeding, pets at home or diabetes duration. However, in T1D, fewer family members smoked (T1D: 10% vs CG 56%; P < 0.001). CONCLUSIONS: The present cohort study shows the same prevalence of allergy and atopy in a pediatric diabetes population compared to healthy controls. Diabetes per se does not seem to influence the development of allergies.

Vascular risk factors in children, adolescents, and young adults with type 1 diabetes complicated by celiac disease: results from the DPV initiative.

OBJECTIVE: Celiac disease (CD) is a common comorbidity of type 1 diabetes (T1D). Long-term consequences of CD are not completely understood, and adhering to a gluten-free diet is a burden for many patients. We investigated the effect of CD on vascular risk factors in a large cohort of T1D patients aged <20 yr. RESEARCH DESIGN AND METHODS: Within the longitudinal Diabetes Patienten Verlaufsdokumentation (DPV)-diabetes registry, data were analyzed from 59,909 < 20-yr-old T1D patients treated at 392 centers in Germany and Austria. A total of 974 patients with biopsy-proven celiac disease (BPCD) were compared with 28,398 patients without CD with respect to blood pressure (BP), lipids, glycohemoglobin (HbA1c ), body mass index (BMI), and reported smoking behavior. RESULTS: Patients with T1D and BPCD showed significantly lower high-density lipoprotein (HDL) cholesterol levels [median (interquartile range): 53.0 (43.0-62.6) mg/dL] than patients without CD [55.0 (45.0-66.0) mg/dL; p < 0.01; p < 0.001 after adjustment for confounding variables]. Systolic BP was lower in patients with CD [105.5 (100.0-112.5) mmHg] than in patients without CD [110.0 (102.0-117.0) mmHg; p < 0.0001; p < 0.001 after adjustment]. There were no significant differences regarding smoking behavior, BMI, or HbA1c . In a subgroup of 335 patients with BPCD, HDL cholesterol was measured 1 yr after diagnosis of CD:HDL increased by 8% (p < 0.01). CONCLUSION: Young people with T1D and CD have lower HDL cholesterol values than patients without CD. As low HDL cholesterol is associated with vascular risk, our findings support screening for CD and monitoring of HDL cholesterol in young people with T1D.

Cholecalciferol supplementation improves suppressive capacity of regulatory T-cells in young patients with new-onset type 1 diabetes mellitus - A randomized clinical trial.

It is unknown if cholecalciferol is able to modify defects in regulatory T cells (Tregs) in type 1 diabetes (T1D). In this randomized, double-blind, placebo controlled trial 30 young patients with new-onset T1D were assigned to cholecalciferol (70IU/kgbodyweight/day) or placebo for 12months. Tregs were determined by FACS-analysis and functional tests were assessed with ex vivo suppression co-cultures at months 0, 3, 6 and 12. Suppressive capacity of Tregs increased (p<0.001) with cholecalciferol from baseline (-1.59±25.6%) to 3 (30.5±39.4%), 6 (44.6±23.8%) and 12months (37.2±25.0%) and change of suppression capacity from baseline to 12months was significantly higher (p<0.05) with cholecalciferol (22.2±47.2%) than placebo (-16.6±21.1%). Serum calcium and parathormone stayed within normal range. This is the first study, which showed that cholecalciferol improved suppressor function of Tregs in patients with T1D and vitamin D could serve as one possible agent in the development of immunomodulatory combination therapies for 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.