Background: This study estimated temporal trends of metabolic control over 12 years in a national cohort of childhood-onset type 1 diabetes. Subjects and Methods: Data from the prospective childhood-onset diabetes register, which included 886 case subjects from 0 to 17.99 years of age at diagnosis and at least 1 year of follow-up until the age of 22.99 years, were analyzed using multivariable linear and logistic regression models in the observational period between 2000 and 2011. Results: Hemoglobin A1c (HbA1c) significantly decreased over 12 years, from 78mmol/mol (interquartile range [IQR], 68-88mmol/mol) (9.26% [IQR, 8.41-10.24%]) in the year 2000 to 61mmol/mol (IQR, 55-67mmol/mol) (7.75% [IQR, 7.20-8.30%]) in the year 2011 (P(0.001). HbA1c was significantly associated with age, treatment modality, and duration of diabetes (P(0.001), with females having on average 1.02% higher HbA1c (P=0.01; 95% confidence interval [CI] 1.005-1.035). The overall use of insulin pumps was 74%. The incidence rate of severe acute complications was low: 1.07 per 100 patient-years for severe diabetic ketoacidosis (95% CI 0.81-1.40) and 1.21 per 100 patient-years for severe (requiring intravenous or intramuscular therapy) hypoglycemia (95% CI 0.81-1.40). Conclusions: The metabolic control of the entire nationwide pediatric type 1 diabetes population significantly improved during the 12-year observational period with a low rate of severe acute complications events. The improvement was associated with the treatment modality. Additional efforts and solutions are necessary to further improve metabolic control and the quality of life of young people with type 1 diabetes.
COBISS.SI-ID: 31060185
A new folding intermediate of Oxytricha nova telomeric Oxy-1.5 G-quadruplex was characterized in aqueous solution using NMR spectroscopy, native gel electrophoresis, thermal differential spectra (TDS), CD spectroscopy, and differential scanning calorimetry (DSC). NMR experiments have revealed that this intermediate (i-Oxy-1.5) exists in two symmetric bimolecular forms in which all guanine bases are involved in GG N1-carbonyl symmetric base pairs. Kinetic analysis of K+-induced structural transitions shows that folding of Oxy-1.5 G-quadruplex from i-Oxy-1.5 is much faster and proceeds through less intermediates than folding from single strands. Therefore, a new folding pathway of Oxy-1.5 G- quadruplex is proposed. This study provides evidence that G- rich DNA sequences can self-assemble into specific pre- organized DNA structures that are predisposed to fold into G-quadruplex when interacting with cations such as potassiumions.
COBISS.SI-ID: 1701423
Background: Type 1 diabetes (T1D) is an autoimmune chronic disease where hyperglycemia, increased risk of oxidative stress, advanced glycation end-products and other genetic and environmental factors lead to T1D complications. Shorter telomeres are associated with hyperglycemic levels and lower serum vitamin D levels. Methods: Average telomere length (ATL) in whole blood DNA samples was assessed with qPCR method in 53 Slovenian T1D children/adolescents (median age 8.7 years, 1:1.3 male/female ratio). Body mass index standard deviation score (BMI-SDS), glycated haemoglobin and serum level of vitamin D metabolite (25-(OH)-D3) and the age at the onset of T1D were collected from the available medical documentation. Results: Results indicate shorter ATL in subjects with higher BMI-SDS when compared to those with longer ATL (0.455 ± 0.438, -0.63 ± 0.295; p=0.049). Subjects with higher BMI-SDS had lower serum vitamin D levels when compared to those with lower BMISDS (40.66 ± 3.07 vs. 52.86 ± 4.85 nmol/L; p=0.045). Vitamin D serum levels did not significantly differ between subjects with longer/shorter ATL. Conclusion: T1D children/adolescents with shorter ATL tend to have higher BMI-SDS. Lower serum vitamin D levels were associated with higher BMI-SDS, while associations between vitamin D serum levels, age at the onset of T1D, glycated haemoglobin and ATL were not observed. Additional studies with more participants are required to clarify the role of the telomere dynamics in T1D aetiology and development of complications.