Positive correlation of thyroid hormones and serum copper in children with congenital hypothyroidism.

Thyroid hormones are of central relevance for growth and development. However, the underlying molecular mechanisms are still not fully understood. Recent studies in humans and mice have demonstrated that serum levels of selenium (Se) and copper (Cu) are positively affected by thyroid hormones. Given the importance of these trace elements for many biochemical processes, we tested whether this interaction is found in children at risk for hypothyroidism, potentially providing a novel factor contributing to the disturbed development observed in congenital hypothyroidism (CH). We conducted a cross-sectional analysis of 84 children diagnosed with CH displaying a wide range of thyroid hormone concentrations. Serum Se and Cu concentrations were measured by total reflection X-ray fluorescence. Data for thyrotropin (TSH) were available in all, thyroxine (T4) and free thyroxine (fT4) in the majority and triiodothyronine (T3) in 29 of the children. Spearman rank analyzes were performed. Cu and thyroid hormones showed a strong positive correlation (Cu/T4, rho=0.5241, P=0.0003; Cu/T3, rho=0.6003, P=0.0006). Unlike in adults, no associations were found between Se and any of the thyroid hormones. Our data highlight that serum Cu and thyroid hormones are strongly associated already in early postnatal life. Severely hypothyroid children are thus at risk of developing a Cu deficiency if not adequately nourished or supplemented. This finding needs to be verified in larger groups of children in order not to miss an easily-avoidable risk factor for poor development.

Pharmacokinetic and prandial pharmacodynamic properties of insulin degludec/insulin aspart in children, adolescents, and adults with type 1 diabetes.

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of long-acting insulin degludec and short-acting insulin aspart. This open-label, Phase 1 study aimed to determine the pharmacodynamic and pharmacokinetic properties of IDegAsp in children (6-11 yr), adolescents (12-17 yr), and adults (18-65 yr) with type 1 diabetes mellitus (T1DM). Thirty-eight subjects received single subcutaneous IDegAsp dosing (0.5 U/kg) immediately before a standardized liquid meal (17.3 g carbohydrates/100 mL; adjusted for body weight) followed by plasma glucose (PG) and pharmacokinetic blood sampling for 36 and 57 h, respectively. There were no apparent differences between age groups in PG lowering effect (AUCPG baseline,0-6 h,meal,SD ), maximum PG excursion (ΔPGmax,meal,SD ), or maximum PG concentration (PGmax,meal,SD ) after the standardized meal. Estimated ratios (ERs) for total exposure (AUCIAsp,0-12 h,SD ) and maximum concentration (Cmax,IAsp,SD ) of IAsp in IDegAsp were children/adults, 1.69 (95% confidence interval, CI: 1.02; 2.80) and 1.66 (95% CI: 1.10; 2.51); adolescents/adults, 1.14 (95% CI: 0.76; 1.69) and 1.16 (95% CI: 0.84; 1.61). ERs for total exposure (AUCIDeg,0-∞,SD ) and maximum concentration (Cmax,IDeg,SD ) of IDeg in IDegAsp were children/adults, 1.42 (95% CI: 0.94; 2.16) and 1.38 (95% CI: 1.09; 1.76); adolescents/adults, 1.23 (95% CI: 0.96; 1.58) and 1.16 (95% CI: 0.95; 1.42). IDegAsp was well tolerated across age groups. The fast onset of prandial coverage of IAsp in IDegAsp and the ultra-long pharmacokinetic properties of IDeg in IDegAsp were preserved in children and adolescents. Exposure to IAsp and IDeg seemed to be higher in children vs. adults, but no differences were observed in PG lowering effect. IDegAsp could be an alternative treatment option in children and adolescents with T1DM.

Reduced Worries of Hypoglycaemia, High Satisfaction, and Increased Perceived Ease of Use after Experiencing Four Nights of MD-Logic Artificial Pancreas at Home (DREAM4).

AIMS: This study assesses the impact of using an AP-system at home on fear of hypoglycaemia. In addition, satisfaction and acceptance of the new technology are evaluated. METHODS: In a multicentre, multinational study of 75 patients using the MD-Logic AP during four consecutive nights in home setting 59 of them (aged 10-54 years, 54% male, HbA1c 7.89 ± 0.69% [62.72 ± 7.51 mmol/mol], diabetes duration 11.6 ± 8.4 yrs) answered standardized questionnaires (HFS, adapted TAM, and AP satisfaction) before and after using the AP. RESULTS: After experiencing the AP in home setting worries of hypoglycaemia were significantly reduced (before 1.04 ± 0.53 versus after 0.90 ± 0.63; P = 0.017). Perceived ease of use as a measure of acceptance with the AP significantly increased after personal experience (before 4.64 ± 0.94 versus after 5.06 ± 1.09; P = 0.002). The overall satisfaction mean score after using the AP was 3.02 ± 0.54 (range 0-4), demonstrating a high level of satisfaction with this technology. CONCLUSIONS: The four-night home-based experience of using MD Logic AP was associated with reduced worries of hypoglycaemia, high level of satisfaction, and increased perceived ease of use of the new technology in children, adolescents, and adults.

Benefit of supplementary fat plus protein counting as compared with conventional carbohydrate counting for insulin bolus calculation in children with pump therapy.

OBJECTIVE: To investigate carbohydrate (CARB) and supplementary fat/protein (CFP) counting using normal and dual-wave bolus in pump therapy of children and young people with type 1 diabetes (T1D). STUDY DESIGN AND METHODS: A randomized clinical trial was conducted in 42 patients (age 6-21 yr) with T1D for at least 1 yr (5.2 ± 3.1 yr, mean ± SD) and pump therapy for at least 3 months (3.3 ± 1.8 yr). Standardized test meals (pizza-salami; 50% carbohydrate, 34% fat, 16% protein; corresponding to 33% of age-adjusted daily energy requirement) were given at lunch time on four different days with normal and dual-wave bolus using CARB and CFP counting in a randomized sequence. Sensor-augmented pumps were used for continuous glucose monitoring of 6-h postprandial glucose profiles. Intra-individual comparisons of glucose parameters [area under the curve (AUC) mg/dL × 6 h; average glucose, AV mg/dL] were performed. RESULTS: Using CFP counting, 6-h postprandial glucose AUC (805 ± 261) and AV (137.8 ± 46.2) were significantly lower than AUC (926 ± 285) and AV (160.5 ± 51.9) by CARB counting (p < 0.001, each). CFP counting led to significantly lower postprandial glucose parameters independently from the kind of bolus (normal bolus: ΔAUC 169, p < 0.001; ΔAV 30.6, p < 0.001/dual-wave bolus: ΔAUC 73, p = 0.045, ΔAV 14.8, p = 0.033). Postprandial hypoglycemia episodes (<70 mg/dL) occurred more frequently in CFP than in CARB counting (35.7% vs. 9.5%, p < 0.001). No severe hypoglycemia was reported. CONCLUSION: In patients with long-term T1D, meal-related insulin dosing based on carbohydrate plus fat/protein counting reduces the postprandial glucose levels (ClinicalTrials.gov NCT01400659).