The association between socio-economic status and diabetes care and outcome in children with diabetes type 1 in Germany: The DIAS study (diabetes and social disparities).

OBJECTIVE: To evaluate the association between socioeconomic status (SES) and diabetes outcomes in German children and adolescents. METHODS: A total of 1829 subjects <18 years old with type 1 diabetes mellitus from 13 German diabetes centers were included from June 2013 until June 2014. Data were collected within the multicenter DPV (Diabetes Prospective Follow-up) registry. SES was measured with a composite index. Multivariable regression models were applied to analyze the association of SES and outcomes adjusted for age, sex, diabetes duration, and migration status. RESULTS: Low SES was significantly associated with worse diabetes outcomes: higher hemoglobin A1C (HbA1c) (64.3 mmol/mol), lower proportion of insulin pump therapy (43.6%), fewer daily self-monitored blood glucose (SMBG) measurements (5.7), more inpatient days per patient-year (5.8) compared to patients with medium/high SES (HbA1c: 61.3 mmol/mol, P < 0.001/59.8 mmol/mol, P < 0.0001; proportion of pump therapy: 54.5%, P < 0.01/ 54.9%, P < 0.01; SMBG: 6.0, P < 0.01/ 6.1, P < 0.01; inpatient days: 4.5, P < 0.0001/3.4, P < 0.0001). The inclusion of migration status in the models resulted in only minor changes in the outcomes. CONCLUSION: Despite free health care, low SES is associated with unfavorable diabetes outcomes in Germany. The poorer diabetes outcomes of children with diabetes have been attributed to their migration status and may be partly explained by low SES. Both factors must become part of targeted diabetes care in children and adolescents with type 1 diabetes.

Clinical presentation and outcome in a series of 88 patients with the cblC defect.

UNLABELLED: The cblC defect is the most common inborn error of vitamin B12 metabolism. Despite therapeutic measures, the long-term outcome is often unsatisfactory. This retrospective multicentre study evaluates clinical, biochemical and genetic findings in 88 cblC patients. The questionnaire designed for the study evaluates clinical and biochemical features at both initial presentation and during follow up. Also the development of severity scores allows investigation of individual disease load, statistical evaluation of parameters between the different age of presentation groups, as well as a search for correlations between clinical endpoints and potential modifying factors. RESULTS: No major differences were found between neonatal and early onset patients so that these groups were combined as an infantile-onset group representing 88 % of all cases. Hypotonia, lethargy, feeding problems and developmental delay were predominant in this group, while late-onset patients frequently presented with psychiatric/behaviour problems and myelopathy. Plasma total homocysteine was higher and methionine lower in infantile-onset patients. Plasma methionine levels correlated with "overall impression" as judged by treating physicians. Physician's impression of patient's well-being correlated with assessed disease load. We confirmed the association between homozygosity for the c.271dupA mutation and infantile-onset but not between homozygosity for c.394C>T and late-onset. Patients were treated with parenteral hydroxocobalamin, betaine, folate/folinic acid and carnitine resulting in improvement of biochemical abnormalities, non-neurological signs and mortality. However the long-term neurological and ophthalmological outcome is not significantly influenced. In summary the survey points to the need for prospective studies in a large cohort using agreed treatment modalities and monitoring criteria.

2017 American Academy of Pediatrics Clinical Practice Guideline: Impact on Prevalence of Arterial Hypertension in Children and Adolescents With Type 1 Diabetes.

OBJECTIVE: In 2017, the American Academy of Pediatrics introduced a new guideline (2017 Clinical Practice Guideline of the American Academy of Pediatrics [AAP 2017]) to diagnose arterial hypertension (HTN) in children that included revised, lower normative blood pressure (BP) values and cut points for diagnosing high BP in adolescents. We studied the impact of the new AAP 2017 on prevalence of HTN in children with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: Up to September 2018, 1.4 million office BP measurements in 79,849 children and adolescents (aged 5-20 years) with T1DM were documented in the DPV (Diabetes Prospective Follow-up) registry. BP values of the most recent year were aggregated, and BP values of 74,677 patients without antihypertensive medication were analyzed (median age 16 years and diabetes duration 5.3 years, 52.8% boys). BP values were classified according to AAP 2017 and the references of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (2011) and the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (fourth report) (2004). RESULTS: Of the patients, 44.1%, 29.5%, and 26.5% were hypertensive according to AAP 2017, KiGGS, and fourth report, respectively. Differences in prevalence of HTN were strongly age dependent: <10 years, AAP 2017 31.4%, KiGGS 30.7%, fourth report 19.6%; 10 to <15 years, AAP 2017 30.9%, KiGGS 31.2%, fourth report 22.4%; and ≥15 years, AAP 2017 53.2%, KiGGS 28.4%, fourth report 30.0%. Among teenagers ≥15 years, 59.1% of boys and only 46.3% of girls were classified as hypertensive by AAP 2017 but only 21.1%/26% of boys and 36.7%/34.4% of girls by KiGGS/fourth report, respectively. CONCLUSIONS: Classification of BP as hypertension depends strongly on the normative data used. Use of AAP 2017 results in a significant increase in HTN in teenagers ≥15 years with T1DM, particularly in boys. AAP 2017 enhances the awareness of elevated BP in children, particularly in patients with increased risk for cardiovascular disease.

Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment.

New technology enables expansion of newborn screening (NBS) of inborn errors aimed to prevent adverse outcome. In conditions with a large share of asymptomatic phenotypes, the potential harm created by NBS must carefully be weighed against benefit. Policies vary throughout the United States, Australia, and Europe due to limited data on outcome and treatability of candidate screening conditions. We elaborated the rationale for decision making in 3-methylcrotonyl-coenzyme A (CoA) carboxylase deficiency (MCCD), which afflicts leucine catabolism, with reported outcomes ranging from asymptomatic to death. In Bavaria, we screened 677,852 neonates for 25 conditions, including MCCD, based on elevated concentrations of 3-hydroxyisovalerylcarnitine (3-HIVA-C). Genotypes of MCCA (MCCC1) and MCCB (MCCC2) were assessed in identified newborns, their relatives, and in individuals (n = 17) from other regions, and correlated to biochemical and clinical phenotypes. NBS revealed eight newborns and six relatives with MCCD, suggesting a higher frequency than previously assumed (1:84,700). We found a strikingly heterogeneous spectrum of 22 novel and eight reported mutations. Allelic variants were neither related to biochemical nor anamnestic data of our probands showing all asymptomatic or benign phenotypes. Comparative analysis of case reports with NBS data implied that only few individuals (< 10%) develop symptoms. In addition, none of the symptoms reported so far can clearly be attributed to MCCD. MCCD is a genetic condition with low clinical expressivity and penetrance. It largely represents as nondisease. So far, there are no genetic or biochemical markers that would identify the few individuals potentially at risk for harmful clinical expression. The low ratio of benefit to harm was pivotal to the decision to exclude MCCD from NBS in Germany. MCCD may be regarded as exemplary of the ongoing controversy arising from the inclusion of potentially asymptomatic conditions, which generates a psychological burden for afflicted families and a financial burden for health care systems.

Comorbidities related to BMI category in children and adolescents: German/Austrian/Swiss Obesity Register APV compared to the German KiGGS Study.

PURPOSE: To assess cardiovascular risk factors in overweight or obese children and adolescents in Germany, Austria and Switzerland and to investigate the relationship to BMI category. METHODS: Data of 63,025 overweight or obese patients (APV population) were compared to normal-weight subjects from a representative study on health status of 14,298 children and adolescents in Germany (KiGGS survey). The weight status was assessed by BMI, and BMI-SDS values were cal-culated using national reference data. RESULTS: In normal-weight KiGGS subjects, mean BMI was 17.3 ± 2.5 (BMI-SDS -0.1 ± 0.8). In the overweight or obese APV population, mean BMI was 30.2 ± 5.6 (BMI-SDS 2.5 ± 0.6). In normal-weight subjects blood pressure, total cholesterol, LDL-cholesterol, and triglycerides were elevated in 6.1, 8.6, 7.0 and 3.0%, respectively, and HDL-cholesterol was reduced in 3.0%, whereas in overweight/obese subjects the percentages of abnormal values were 35.3, 13.8, 14.5, 13.6, and 10.1%, respectively. CONCLUSIONS: Cardiovascular risk is increased in obese children and adolescents. There is a strong need to monitor blood pressure and serum lipids in this group of patients. Our results emphasize the importance of prevention of obesity in order to reduce cardiovascular risk.

Efficacy and outcome of expanded newborn screening for metabolic diseases--report of 10 years from South-West Germany.

BACKGROUND: National newborn screening programmes based on tandem-mass spectrometry (MS/MS) and other newborn screening (NBS) technologies show a substantial variation in number and types of disorders included in the screening panel. Once established, these methods offer the opportunity to extend newborn screening panels without significant investment and cost. However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome. METHODS: In a prospective single screening centre observational study 373 cases with confirmed diagnosis of a metabolic disorder from a total cohort of 1,084,195 neonates screened in one newborn screening laboratory between January 1, 1999, and June 30, 2009 and subsequently treated and monitored in five specialised centres for inborn errors of metabolism were examined. Process times for taking screening samples, obtaining results, initiating diagnostic confirmation and starting treatment as well as the outcome variables metabolic decompensations, clinical status, and intellectual development at a mean age of 3.3 years were evaluated. RESULTS: Optimal outcome is achieved especially for the large subgroup of patients with medium-chain acyl-CoA dehydrogenase deficiency. Kaplan-Meier-analysis revealed disorder related patterns of decompensation. Urea cycle disorders, organic acid disorders, and amino acid disorders show an early high and continuous risk, medium-chain acyl-CoA dehydrogenase deficiency a continuous but much lower risk for decompensation, other fatty acid oxidation disorders an intermediate risk increasing towards the end of the first year. Clinical symptoms seem inevitable in a small subgroup of patients with very early disease onset. Later decompensation can not be completely prevented despite pre-symptomatic start of treatment. Metabolic decompensation does not necessarily result in impairment of intellectual development, but there is a definite association between the two. CONCLUSIONS: Physical and cognitive outcome in patients with presymptomatic diagnosis of metabolic disorders included in the current German screening panel is equally good as in phenylketonuria, used as a gold standard for NBS. Extended NBS entails many different interrelated variables which need to be carefully evaluated and optimized. More reports from different parts of the world are needed to allow a comprehensive assessment of the likely benefits, harms and costs in different populations.