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 BMI-SDS (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 BMISDS, 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.
COBISS.SI-ID: 3331557
Background: Individuals with familial hypercholesterolemia (FH) who are untreated have up to 100-fold elevated risk for cardiovascular complications compared with those who are unaffected. Data for identification of FH with a universal screening for hypercholesterolemia in children are lacking. Objectives: This study sought genetic identification of FH from a cohort of children with elevated serum total cholesterol (TC) concentration, detected in a national universal screening for hypercholesterolemia. Methods: Slovenian children born between 1989 and 2009 (n = 272) with TC )6 mmol/l (231.7 mg/dl) or )5 mmol/l (193.1 mg/dl) plus a family history positive for premature cardiovascular complications, identified in a national universal screening for hypercholesterolemia at 5 years of age were genotyped for variants in LDLR, PCSK9, APOB, and APOE. Results: Of the referred children, 57.0% carried disease-causing variants for FH: 38.6% in LDLR, 18.4% in APOB, and none in PCSK9. Nine novel disease-causing variants were identified, 8 in LDLR, and 1 in APOB. Of the remaining participants, 43.6% carried the APOE E4 isoform. Estimated detection rate of FH in the universal screening program from 2009 to 2013 was 53.6% (95% confidence interval [CI]: 34.5% to 72.8%), peaking in 2013 with an upper estimated detection rate of 96.3%. Variants in LDLR, APOB, or the APOE E4 isoform occurred in 48.6%, 60.0%, and 76.5%, respectively, of patients with a family history negative for cardiovascular complications. Conclusions: Most participants who were referred from a national database of universal screening results for hypercholesterolemia had genetically confirmed FH. Data for family history may not suffice for reliable identification of patients through selective and cascade screening.
COBISS.SI-ID: 32206809
Using NMR and CD spectroscopy, gel electrophoresis and differential scanning calorimetry (DSC) we have characterized a new intermediate in the folding pathway of the telomeric Oxy-1.5 G-quadruplex. The intermediate exhibits two stable bipolar forms where all guanine residues are involved in GG N1-carbonyl symmetric base pairs. Kinetic analysis in the presence of K+ ions showed an increased folding rate with less intermediate states compared to single strand folding. A new pathway of folding of G-quadruplexes in the presence of cations like potassium is presented.
COBISS.SI-ID: 1701423
Inversion of strand directionality of G-rich DNA from 5'-3' to 3'-5' has a profound effect on the number of folded structures. The resulting topology of G-quadruplexes depends on the presence of K+ or Na+ cations. The melting temperature of G-quadruplexes with 5’-3’ strand directionality is higher compared to 3’-5’ oriented DNA regardless of K+ or Na+. CD, UV and NMR spectroscopy reveal the importance of primary structure in the structural polymorphism of G-quadruplexes. The changes which are the result solely of strand directionality have an effect on the polymorphic nature of G-quadruplexes and their physiological role.
COBISS.SI-ID: 5780506
AIMS/HYPOTHESIS: Hypoglycaemia during and after exercise remains a challenge. The present study evaluated the safety and efficacy of closed-loop insulin delivery during unannounced (to the closed-loop algorithm) afternoon physical activity and during the following night in young people with type 1 diabetes. METHODS:A randomised, two-arm, open-label, in-hospital, crossover clinical trial was performed at a single site in Slovenia. The order was randomly determined using an automated web-based programme with randomly permuted blocks of four. Allocation assignment was not masked. Children and adolescents with type 1 diabetes who were experienced insulin pump users were eligible for the trial. During four separate in-hospital visits, the participants performed two unannounced exercise protocols: moderate intensity (55% of [Formula: see text]) and moderate intensity with integrated high-intensity sprints (55/80% of [Formula: see text]), using the same study device either for closed-loop or open-loop insulin delivery. We investigated glycaemic control during the exercise period and the following night. The closed-loop insulin delivery was applied from 15:00 h on the day of the exercise to 13:00 h on the following day. RESULTS: Between 20 January and 16 June 2016, 20 eligible participants (9 female, mean age 14.2 ± 2.0 years, HbA1c 7.7 ± 0.6% [60.0 ± 6.6 mmol/mol]) were included in the trial and performed all trial-mandated activities. The median proportion of time spent in hypoglycaemia below 3.3 mmol/l was 0.00% for both treatment modalities (p = 0.7910). Use of the closed-loop insulin delivery system increased the proportion of time spent within the target glucose range of 3.9-10 mmol/l when compared with open-loop delivery: 84.1% (interquartile range 70.0-85.5) vs 68.7% (59.0-77.7), respectively (p = 0.0057), over the entire study period. This was achieved with significantly less insulin delivered via the closed-loop (p = 0.0123). CONCLUSIONS/INTERPRETATION: Closed-loop insulin delivery was safe both during and after unannounced exercise protocols in the in-hospital environment, maintaining glucose values mostly within the target range without an increased risk of hypoglycaemia. TRIAL REGISTRATION:Clinicaltrials.gov NCT02657083 FUNDING: University Medical Centre Ljubljana, Slovenian National Research Agency, and ISPAD Research Fellowship.
COBISS.SI-ID: 4633772