Screening for Type 1 Diabetes Risk in Newborns: The Freder1k Pilot Study in Saxony.

An increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB1*03 (DR3), HLA DRB1*04 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.

Why is insulin pump treatment rarely used in adolescents and young adults with cystic fibrosis-related diabetes?

BACKGROUND: In type 1 diabetes (T1D), the use of continuous subcutaneous insulin infusion (CSII) has increased steadily in the last years. Compared with conventional insulin injection regimes, major advantages might be a nearly physiological insulin secretion, lower rates of hypoglycemia, higher flexibility in daily life, and increased quality of life. Data on CSII in cystic fibrosis-related diabetes (CFRD) are scarce. OBJECTIVE: To analyze current use of insulin pumps in CFRD and compare demographics of pump-treated patients between CFRD and T1D. METHODS: Data from the prospective German/Austrian diabetes patient registry on insulin-treated patients with either CFRD (n = 515) or T1D (n = 43 165) aged >10 yr at manifestation of diabetes were analyzed. RESULTS: A total of 4.1% (n = 21) of CFRD and 17.7% (n = 7647) of T1D patients received insulin pump treatment within the recent year of care (p < 0.001). Pump-treated patients with CFRD had a significantly shorter duration of diabetes [median (Q1 ; Q3 ): 5.8 (2.9; 9.5) vs. 7.8 (4.3; 20.4) yr, p = 0.026] and tended to be younger [22.0 (18.2; 30.1) vs. 24.9 (17.3; 45.9) yr] than pump-treated T1D patients. Age at initiation of CSII seemed to be lower in CFRD [19.2 (16.5; 29.2) vs. 23.3 (14.8; 43.5) yr]. Insulin pump therapy was used slightly more often in male CFRD patients than females (4.7 vs. 3.6%), whereas in T1D the opposite was observed (14.9 vs. 21.2%, p < 0.001). Discontinuation rate of CSII was higher in CFRD than T1D (30.0 vs. 12.7%, p = 0.005). CONCLUSIONS: Despite potential advantages, insulin pump therapy was rarely used among adolescent and young adult CFRD patients.

Temporal Changes in Hemoglobin A1c and Diabetes Technology Use in DPV, NPDA, and T1DX Pediatric Cohorts from 2010 to 2018.

Objective: The German/Austrian Diabetes Patient Follow-up Registry (Diabetes-Patienten-Verlaufsdokumentation or DPV), England/Wales National Pediatric Diabetes Audit (NPDA), and Type 1 Diabetes Exchange (T1DX) in the United States investigated changes in hemoglobin A1c (HbA1c) and diabetes technology use from 2010 to 2018. Methods: Registry/audit data from 2010 to 2018 were analyzed in annual cohorts using linear regression for those <18 years of age with type 1 diabetes diagnosed at age >6 months. Time trends in HbA1c, pump, and continuous glucose monitoring (CGM) use were studied using repeated measurements linear and logistic regression models with an autoregressive covariance structure and with year and data source as independent variables. Results: A total of 1,172,980 visits among 114,264 (54,119 DPV, 43,550 NPDA, 16,595 T1DX) patients were identified. HbA1c remained clinically stable in DPV (7.7% [61 mmol/mol] to 7.6% [60 mmol/mol]), decreased in the NPDA (8.7% [72 mmol/mol] to 7.9% [63 mmol/mol]), and increased in T1DX (8.0% [64 mmol/mol] to 8.5% [69 mmol/mol] from 2010 to 2018). In all registries/audits, insulin pump and CGM use increased over time with greatest pump use in T1DX and lowest uptake reported in NPDA. Conclusions: These data reveal three different longitudinal patterns of change in registry/audit HbA1c from 2010 to 2018. Diabetes technology use increased throughout, at different rates. Quality improvement (QI) programs in DPV have been ongoing for 25 years, began in NPDA in 2009 and T1DX in 2016. We speculate that in England/Wales, development of networks, peer review, and implementation of QI measures contributed to reductions in population HbA1c. Many of these interventions had been implemented in DPV before 2010. Further efforts to understand this improvement, including the role of QI, and continued success within standardized documentation and benchmarking could inform T1DX programs to reduce HbA1c.

Smoking and metabolic control in adolescents with type 1 diabetes.

OBJECTIVE: To relate self-reported smoking frequency to metabolic control and other cardiovascular risk factors in adolescents with type 1 diabetes. STUDY DESIGN: In the multicenter Diabetes Patienten Verlaufsdokumentationssystem database from Germany and Austria, anonymized records on 27 561 patients < 20 years of age with documented smoking status were available for analysis. RESULTS: Self-reported smoking was negligible in patients younger than 11 years (0.1%), increasing to 5% in 11- to 15-year-old patients, and 28.4% in the 15- to 20-year-old age group. Multivariate analysis with adjustment for age, diabetes duration, sex, insulin therapy, and center differences, revealed that smokers had higher HbA1c-levels compared with non-smokers (9.1% vs 8.0%, P < .0001). Diastolic blood pressure was higher (68.2 vs 67.6 mm Hg, P < .0001), and the lipid profile was unfavorable in patients who smoke: Triglycerides and total cholesterol were higher and high-density lipoprotein-cholesterol was lower (all P < .0001). CONCLUSIONS: Smokers display significantly worse metabolic control and a higher cardiovascular risk profile. Although not attested in trials, we state that education about smoking, smoking prevention, and psychological help for smoking cessation should be an integral part of comprehensive pediatric care for adolescent patients with type 1 diabetes.

Influence of food intake, age, gender, HbA1c, and BMI levels on plasma cholesterol in 29,979 children and adolescents with type 1 diabetes--reference data from the German diabetes documentation and quality management system (DPV).

OBJECTIVE: We investigated influences of a 12-h fast, age, gender, body mass index (BMI), hemoglobin A1c (HbA1c) on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) to provide reference percentiles for TC, LDL-C, and HDL-C of patients with good diabetes control (HbA1c < 7.5%) and normal weight (BMI < 90th percentile). METHOD: A cross-sectional analysis of the diabetes documentation and quality management system using the diabetes data acquisition system for prospective surveillance (DPV) software included 29 979 patients with type 1 diabetes mellitus (T1DM) aged 1-20 yr (52.4% male) from 253 diabetes centers in Germany and Austria. RESULTS: Fasting had no relevant influence on TC, LDL-C, and HDL-C. Multivariate regression analysis revealed strongest dependences of cholesterol on gender and HbA1c followed by BMI and age. Reference cholesterol percentiles of well-controlled and normal weight patients showed TC >or=4.40 mmol/L (170 mg/dL) corresponding to the 50th percentile in females and the 75th percentile in males. LDL-C >or=2.59 mmol/L (100 mg/dL) corresponded to the 50th-75th percentile in females and the 75th percentile in males. CONCLUSIONS: (i) Fasting is no precondition for the determination of TC, LDL-C, and HDL-C; (ii) TC, LDL-C, and HDL-C are strongest associated with gender and HbA1c followed by BMI and age; (iii) Gender- and age-adjusted cholesterol percentiles of well-controlled and normal weight patients with T1DM may serve as reference values and are similar to healthy German children; and (iv) Single target values for TC, LDL-C, and HDL-C based on healthy individuals' data do not sufficiently characterize abnormal cholesterol levels in young patients with T1DM.

Arterial hypertension determined by ambulatory blood pressure profiles: contribution to microalbuminuria risk in a multicenter investigation in 2,105 children and adolescents with type 1 diabetes.

OBJECTIVE: Arterial hypertension is a key player in the development of diabetes complications. We used a nationwide database to study risk factors for abnormal 24-h blood pressure regulation and microalbuminuria in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ambulatory blood pressure monitoring was performed in 2,105 children and adolescents from 195 pediatric diabetes centers in Germany and Austria. Individual least median squares (LMS)-SD scores were calculated for diurnal and nocturnal systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure according to normalized values of a reference population of 949 healthy German children. The nocturnal blood pressure reduction (dipping) was calculated for SBP as well as DBP. RESULTS: In diabetic children, nocturnal blood pressure in particular was significantly elevated (SBP +0.51, DBP +0.58, MAP +0.80 LMS-SD) and dipping of SBP DBP, and MAP was significantly reduced (P < 0.0001). Age, diabetes duration, sex BMI, A1C, and insulin dose were related to altered blood pressure profiles; dipping, however, was only affected by age, female sex, and A1C. The presence of microalbuminuria was associated with nocturnal DBP (P < 0.0001) and diastolic dipping (P < 0.01). CONCLUSIONS: Our observations revealed a clear link between the quality of metabolic control and altered blood pressure regulation even in pediatric patients with short diabetes duration. Nocturnal blood pressure in particular seems to mainly contribute to diabetes complications such as microalbuminuria.