Hanna Dis Margeirsdottir

• Simeunovic, Aida; Brunborg, Cathrine; Heier, Martin; Berg, Tore Julsrud; Dahl-Jørgensen, Knut & MARGEIRSDOTTIR, HANNA DIS (2025). Early increase in carotid intima-media thickness in women with childhood-onset type 1 diabetes compared with healthy peers: the Norwegian Atherosclerosis and Childhood Diabetes study. BMJ Open Diabetes Research & Care. 13(1). doi: 10.1136/bmjdrc-2024-004505. Fulltekst i vitenarkiv Vis sammendrag

  Introduction The risk of cardiovascular disease is increased in individuals with type 1 diabetes, despite good glycemic control. This study aims to evaluate early signs of atherosclerosis and predisposing factors in individuals with childhood-onset type 1 diabetes compared with healthy controls. Research design and methods The Atherosclerosis and Childhood Diabetes study is a prospective population-based cohort study with follow-up every fifth year. The cohort consists of 329 subjects with type 1 diabetes and 173 controls. Carotid intima-media thickness (cIMT) was measured at baseline and 5 and 10 years of follow-up. Data from the Norwegian Childhood Diabetes Registry were used in assessment of traditional risk factors. Results Mean cIMT in young women with type 1 diabetes increased significantly over a 10-year period compared with healthy controls (∆0.019 mm (0.001–0.035), p=0.035). At the 10-year follow-up the group with type 1 diabetes had a mean age of 24.2±2.9 years (13.7±2.8 years at baseline), diabetes duration of 15.6±3.4 years (5.4±3.3 years at baseline) and HbA1c of 8.2±3.6% (66±16 mmol/mol) (8.4±3.4% (68±13 mmol/mol) at baseline). Women with type 1 diabetes had significantly higher mean weight, body mass index, waist circumference, diastolic blood pressure (DBP), serum low-density lipoprotein (LDL)-cholesterol and apolipoprotein B, while men with type 1 diabetes had significantly higher mean DBP and urinary albumin-creatinine ratio compared with the control group. Mean cIMT change over time was not associated with long-term HbA1c or LDL-cholesterol burden in childhood and adolescence. Conclusion Young women with childhood-onset type 1 diabetes of relatively short diabetes duration had a higher mean cIMT over a 10-year period compared with their healthy female controls, with values similar to males.

• Bratke, Heiko Holger Karl-Ernst; Biringer, Eva Aaker; Ushakova, Anastasia; MARGEIRSDOTTIR, HANNA DIS; Kummernes, Siv Janne & Njølstad, Pål Rasmus [Vis alle 7 forfattere av denne artikkelen] (2024). Ten Years of Improving Glycemic Control in Pediatric Diabetes Care: Data From the Norwegian Childhood Diabetes Registry. Diabetes Care. ISSN 0149-5992. 47(7), s. 1122–1130. doi: 10.2337/dc24-0086. Fulltekst i vitenarkiv
• Simeunovic, Aida; Brunborg, Cathrine; Heier, Martin; Seljeflot, Ingebjørg; Dahl-Jørgensen, Knut & MARGEIRSDOTTIR, HANNA DIS (2023). Sustained low-grade inflammation in young participants with childhood onset type 1 diabetes: The Norwegian atherosclerosis and childhood diabetes (ACD) study. Atherosclerosis. ISSN 0021-9150. 379. doi: 10.1016/j.atherosclerosis.2023.05.020. Fulltekst i vitenarkiv
• Bratke, Heiko; Biringer, Eva; Margeirsdottir, Hanna Dis; Njølstad, Pål Rasmus & Skrivarhaug, Torild (2022). Relation of health-related quality of life with glycemic control and use of diabetes technology in children and adolescents with type 1 diabetes: Results from a national population based study. Journal of Diabetes Research. ISSN 2314-6745. 2022:8401328, s. 1–14. doi: 10.1155/2022/8401328. Fulltekst i vitenarkiv Vis sammendrag

  Objective: The primary aim was to analyse the association between diabetes-specific health-related quality of life (HRQOL) and HbA1c in children and adolescents with type 1 diabetes. The secondary aims were to evaluate the associations between diabetes-specific HRQOL and age, sex, diabetes duration, and the use of diabetes technology in diabetes treatment. Research Design and Methods: Children with type 1 diabetes (10-17 years, N =1,019) and parents (children <10 years, N =371; 10-17 years, N =1,070) completed the DISABKIDS diabetes-specific questionnaire (DDM-10) as part of the 2017 data collection for the Norwegian Childhood Diabetes Registry. The DDM-10 consists of two subscales—‘impact’ and ‘treatment’—with six and four items, respectively. In the linear regression models, the items and subscales were outcome variables, while HbA1c, age, sex, diabetes duration, insulin pump use, and continuous glucose monitoring (CGM) system use were predictor variables. Results: Lower HbA1c measurements and male sex were associated with higher HRQOL scores on both DDM-10 scales in the age group 10-17 years, but not in children under 10 years. Parents gave lower HRQOL scores than children in the 10-17 age group. Insulin pump and CGM use were not significantly associated with HRQOL on the impact and treatment scale. Conclusions: Low HbA1c and male sex are significantly associated with high HRQOL in children aged 10-17 with type 1 diabetes, but the use of diabetes technology is not positively associated with HRQOL. Differences in child- and parent-reported scores imply that parents might both over- and underestimate their child’s HRQOL.

• Veiby, Nina; Simeunovic, Aida; Heier, Martin; Brunborg, Cathrine; Saddique, Naila & Moe, Morten C. [Vis alle 9 forfattere av denne artikkelen] (2021). Retinal venular oxygen saturation is associated with non-proliferative diabetic retinopathy in young patients with type 1 diabetes. Acta Ophthalmologica. ISSN 1755-375X. doi: 10.1111/aos.15018. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To determine the contribution of retinal vessel density (VD), central retinal vessel diameter and retinal oxygen (O2) saturation independently of other known risk factors in the development of non-proliferative diabetic retinopathy (NPDR). Methods Macular optical coherence tomography angiography (OCTA), central retinal artery/vein equivalent diameter (CRAE/CRVE) measurements and retinal oximetry were performed in a cross-sectional study of 166 eyes from 166 individuals with type 1 diabetes (T1D) aged 14–30 years. Multiple logistic regression analysis was used to investigate whether O2 saturation, retinal vessel diameters and vessel density in the deep capillary plexus (VD-DCP) were associated with NPDR, when adjusting for known risk factors. The individuals were allocated to one group without and one group with NPDR. Results Multiple logistic regression analysis showed that age (OR = 1.25, 95% CI: 1.04–1.49) and AV-difference in O2 saturation (OR = 0.85, 95% CI 0.77–0.93) were significantly associated with NPDR. Conclusion Our findings suggest that age and lower AV-O2 saturation difference contribute to explaining the grade of NPDR independently of other well-known risk factors. Reduced delivery of O2 to the retinal tissue is associated with the development of NPDR in young patients with T1D and should be given appropriate weight in the risk stratification at early stages of the disease.

• Bratke, Heiko; Margeirsdottir, Hanna D.; Assmus, Jörg; Njølstad, Pål Rasmus & Skrivarhaug, Torild (2021). Does Current Diabetes Technology Improve Metabolic Control? A Cross-Sectional Study on the Use of Insulin Pumps and Continuous Glucose Monitoring Devices in a Nationwide Pediatric Population. Diabetes Therapy. 12, s. 2571–2583. doi: 10.1007/s13300-021-01127-6. Fulltekst i vitenarkiv Vis sammendrag

  Objective To examine the use of multiple daily injections (MDI), insulin pumps, self-measured blood glucose (SMBG), and continuous glucose monitoring (CGM) systems, and their association with glycated hemoglobin (HbA1c), diabetic ketoacidosis (DKA), and severe hypoglycemia. Methods In a pediatric population-based nationwide cross-sectional study, we analyzed data from 2623 participants up to 18 years of age with type 1 diabetes, using 2017 annual data from the Norwegian Childhood Diabetes Registry. HbA1c was adjusted for age, gender, and diabetes duration. Using a linear mixed-effects model, we assessed HbA1c and the incidence of DKA and severe hypoglycemia according to the use of MDI, insulin pumps, SMBG, and CGM. Results We observed that 74.7% of participants were using an insulin pump and 52.6% were using a CGM system. Mean HbA1c was 7.8% (62 mmol/mol). The HbA1c of pump users was 0.14 percentage points (pp) higher than that of MDI users. Fewer pump users than MDI users achieved an HbA1c of < 7.5% (38.3 vs. 41.6%). CGM users had a 0.18 pp lower HbA1c than SMBG users, with 40.5 and 38.0%, respectively, achieving an HbA1c of < 7.5%. The incidence of severe hypoglycemia or hospitalization due to DKA was not different in pump and CGM users compared with nonusers. Compared with other insulin pumps, patch pump use was associated with a significantly lower odds ratio for DKA. Conclusions Despite the broad use of diabetes technology, as many as 61% of our pediatric cohort did not reach the HbA1c target recommended by the International Society for Pediatric and Adolescent Diabetes (ISPAD). Lower HbA1c was associated with CGM use but not with insulin pump use. Acute complications were not less frequent in the groups using insulin pumps or CGM compared with those using MDI and SMBG. Further research is required to explore the lower incidence of DKA among patch pump users.

• Bratset, Vibeke; MARGEIRSDOTTIR, HANNA DIS; Heier, Martin; Solheim, Svein; Arnesen, Harald & Dahl-Jørgensen, Knut [Vis alle 7 forfattere av denne artikkelen] (2020). Procoagulant activity in children and adolescents on intensive insulin therapy. Pediatric Diabetes. ISSN 1399-543X. 21(3), s. 496–504. doi: 10.1111/pedi.12978. Fulltekst i vitenarkiv Vis sammendrag

  Background Type 1 diabetes is associated with atherothrombosis, but limited data exist on procoagulant activity in the young. We investigated procoagulant activity in children/adolescents with type 1 diabetes using intensified insulin treatment compared with controls in a 5‐year follow‐up study, and further any associations with cardiovascular risk factors. Methods The study included 314 diabetes children/adolescents and 120 healthy controls. Prothrombin fragment 1+2 (F1+2), D‐dimer, tissue‐factor‐procoagulant‐activity (TF‐PCA), and tissue‐factor‐pathway‐inhibitor (TFPI) were analyzed with ELISAs. Results F1+2, D‐dimer, and TF‐PCA did not differ between the groups or correlate to HbA1c in the diabetes group at either time points. TFPI was significantly higher in the diabetes group compared with controls both at inclusion and follow‐up (both P < .001). In the diabetes group, TFPI correlated significantly to HbA1c at both time points (r = 0.221 and 0.304, both P < .001). At follow‐up, females using oral contraceptives had significantly elevated F1+2, D‐dimer, and TF‐PCA and lower TFPI compared to no‐users (all P < .005), and females had lower TFPI (P = .017) and higher F1+2 compared with males (P = .052), also after adjusting for the use of oral contraceptives. Conclusions The current results show similar procoagulant activity in children/adolescents with type 1 diabetes compared with controls over a 5‐year period, indicating that these children using modern intensified insulin treatment are not at high thrombotic risk at younger age. The elevated levels of TFPI in the diabetes group, related to hyperglycaemia, are probably reflecting increased endothelial activation. These findings highlight the significance of optimal blood glucose control in children/adolescents with type 1 diabetes, to maintain a healthy endothelium.

• Veiby, Nina; Simeunovic, Aida; Heier, Martin; Brunborg, Cathrine; Saddique, Naila & Moe, Morten Carsten [Vis alle 9 forfattere av denne artikkelen] (2020). Venular oxygen saturation is increased in young patients with type 1 diabetes and mild nonproliferative diabetic retinopathy. Acta Ophthalmologica. ISSN 1755-375X. 98(8), s. 800–807. doi: 10.1111/aos.14462. Fulltekst i vitenarkiv
• Bratset, Vibeke; MARGEIRSDOTTIR, HANNA DIS; Chiva-Blanch, Gemma; Heier, Martin; Solheim, Svein & Arnesen, Harald [Vis alle 8 forfattere av denne artikkelen] (2020). Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study. Journal of Diabetes Research. ISSN 2314-6745. 2020, s. 1–8. doi: 10.1155/2020/7216863. Fulltekst i vitenarkiv Vis sammendrag

  Background. Type 1 diabetes is a chronic disease including hyperglycemia and accelerated atherosclerosis, with high risk of micro- andmacrovascular complications. Circulating microvesicles (cMVs) are procoagulant cell fragments shed during activation/apoptosis anddiscussed to be markers of vascular dysfunction and hypercoagulability. Limited knowledge exists on hypercoagulability in youngdiabetics. We aimed to investigate cMVs over afive-year period in children/adolescents with type 1 diabetes compared withcontrols and any associations with glycemic control and cardiovascular risk factors. We hypothesized increased shedding of cMVsin type 1 diabetes in response to vascular activation.Methods. The cohort included type 1 diabetics (n=40) and healthy controls(n=40), mean age 14 years (range 11) at inclusion, randomly selected from the Norwegian Atherosclerosis and ChildhoodDiabetes (ACD) study. Citrated plasma was prepared and stored at -80°C until cMV analysis byflow cytometry.Results.Comparable levels of Annexin V (AV+) cMVs were observed at inclusion. Atfive-year follow-up, total AV+cMVs weresignificantly lower in subjects with type 1 diabetes compared with controls; however, no significant differences were observed afteradjusting for covariates. In the type 1 diabetes group, the total AV+, tissue factor-expressing AV+/CD142+, neutrophil-derivedAV+/CD15+and AV+/CD45+/CD15+, and endothelial-derived AV+/CD309+and CD309+/CD34+cMVs were inversely correlatedwith HbA1c (r=‐0:437,r=‐0:515,r=‐0:575,r=‐0:529,r=‐0:416,andr=‐0:445, respectively; allp≤0:01), however, only atinclusion. No significant correlations with cardiovascular risk factors were observed.Conclusions. Children/adolescents with type1 diabetes show similar levels of AV+cMVs as healthy controls and limited associations with glucose control. This indicatesthat our young diabetics on intensive insulin treatment have preserved vascular homeostasis and absence of procoagulant cMVs.

• Veiby, Nina; Simeunovic, Aida; Heier, Martin; Brunborg, Cathrine; Saddique, Naila & Moe, Morten Carsten [Vis alle 9 forfattere av denne artikkelen] (2020). Associations between macular OCT angiography and nonproliferative diabetic retinopathy in young patients with type 1 diabetes mellitus. Journal of Diabetes Research. ISSN 2314-6745. 2020, s. 1–12. doi: 10.1155/2020/8849116. Fulltekst i vitenarkiv Vis sammendrag

  Background/Objective. Optical coherence tomography angiography (OCTA) is increasingly used to supplement ophthalmoscopy in the diagnosis and follow-up of diabetic retinopathy. Our objective was to confirm if OCTA parameters can predict the development of nonproliferative diabetic retinopathy (NPDR) and to clarify if any single OCTA parameter is associated with NPDR independently of well-known risk factors in young type 1 diabetes (T1D) patients. Methods. OCTA of both eyes was performed in a cross-sectional study of 14 to 30-year-old individuals with at least 10-year duration of T1D and controls recruited from the Norwegian Atherosclerosis and Childhood Diabetes (ACD) study. Vessel density (VD) and foveal avascular zone (FAZ) area in the superficial and deep capillary plexus (SCP and DCP), total retinal volume (TRV), and central macular thickness (CMT) were calculated using automated software. Univariate and multivariate ordered logistic regression (OLR) models were used accordingly. Results. We included 168 control eyes and 315 T1D eyes. Lower VD in DCP (OR 0.65, 95% CI 0.51–0.83), longer diabetes duration (OR 1.51, 95% CI 1.22–1.87), and higher waist circumference (OR 1.08, 95% CI 1.02–1.14) were significantly associated with progression of NPDR. VD in SCP and DCP were significantly lower in T1D patients without diabetic retinopathy than in controls. Conclusions. Sparser VD in DCP is significantly associated with severity of NPDR, supporting that OCTA might detect the earliest signs of NPDR before it is visible by ophthalmoscopy.

• Heier, Martin; Stensæth, Knut Haakon; Brunborg, Cathrine; Seljeflot, Ingebjørg; Margeirsdottir, Hanna Dis & Hanssen, Kristian Folkvord [Vis alle 7 forfattere av denne artikkelen] (2018). Increased arterial stiffness in childhood onset diabetes: A cardiovascular magnetic resonance study. European Heart Journal-Cardiovascular Imaging. ISSN 2047-2404. 19(6), s. 694–700. doi: 10.1093/ehjci/jex178. Fulltekst i vitenarkiv
• Heier, Martin; Nygaard, Cathrine Skorpen; Brunborg, Cathrine; Seljeflot, Ingebjørg; MARGEIRSDOTTIR, HANNA DIS & Hanssen, Kristian Folkvord [Vis alle 8 forfattere av denne artikkelen] (2018). Preserved endothelial function in young adults with type 1 diabetes. PLOS ONE. 13:e0206523(10), s. 1–8. doi: 10.1371/journal.pone.0206523. Fulltekst i vitenarkiv Vis sammendrag

  Background and aim Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and is typically present in older adults with type 1 diabetes (T1D). In young adults, we aimed to assess the impact of T1D on endothelial function as detected by digital peripheral arterial tonometry (PAT) and its relationship with cardiovascular risk factors and long term glycemic control. Materials and methods Reactive hyperemia index (RHI) as a measure of endothelial function was assessed by PAT in 46 T1D patients and 32 healthy controls. All were participants in the "Atherosclerosis and Childhood Diabetes" study, with baseline values registered five years previously. Annual measurements of HbA1c for assessment of glycemic burden were provided by the Norwegian Childhood Diabetes Registry. Results The diabetes patients had a mean age of 20.8 years, a median duration of diabetes of 10.0 years and a mean HbA1c of 8.7%. RHI was not significantly decreased in the diabetes group, mean 2.00 (SD = 0.59) vs. 2.21 (SD = 0.56), p = .116. There was no gender difference or any associations with traditional risk factors. Furthermore, there was no significant association between RHI and either HbA1c or long term glycemic burden. Conclusions RHI as a measure of endothelial function was preserved in young adults with T1D compared with healthy controls.

• Heier, Martin; Borja, Mark S.; Brunborg, Cathrine; Seljeflot, Ingebjørg; MARGEIRSDOTTIR, HANNA DIS & Hanssen, Kristian Folkvord [Vis alle 8 forfattere av denne artikkelen] (2017). Reduced HDL function in children and young adults with type 1 diabetes. Cardiovascular Diabetology. 16:85, s. 1–8. doi: 10.1186/s12933-017-0570-2. Fulltekst i vitenarkiv Vis sammendrag

  Background Patients with type 1 diabetes (T1D) are at increased risk of cardiovascular disease (CVD). Measures of high-density lipoprotein (HDL) function provide a better risk estimate for future CVD events than serum levels of HDL cholesterol. The objective of this study was to evaluate HDL function in T1D patients shortly after disease onset compared with healthy control subjects. Methods Participants in the atherosclerosis and childhood diabetes study were examined at baseline and after 5 years. At baseline, the cohort included 293 T1D patients with a mean age of 13.7 years and mean HbA1c of 8.4%, along with 111 healthy control subjects. Their HDL function, quantified by HDL-apoA-I exchange (HAE), was assessed at both time points. HAE is a measure of HDL’s dynamic property, specifically its ability to release lipid-poor apolipoprotein A-I (apoA-I), an essential step in reverse cholesterol transport. Results The HAE-apoA-I ratio, reflecting the HDL function per concentration unit apoA-I, was significantly lower in the diabetes group both at baseline, 0.33 (SD = 0.06) versus 0.36 (SD = 0.06) %HAE/mg/dL, p < 0.001 and at follow-up, 0.34 (SD = 0.06) versus 0.36 (SD = 0.06)  %HAE/mg/dL, p = 0.003. HAE-apoA-I ratio was significantly and inversely correlated with HbA1c in the diabetes group. Over the 5 years of the study, the mean HAE-apoA-I ratio remained consistent in both groups. Individual changes were less than 15% for half of the study participants. Conclusions This study shows reduced HDL function, quantified as HAE-apoA-I ratio, in children and young adults with T1D compared with healthy control subjects. The differences in HDL function appeared shortly after disease onset and persisted over time.

• Brunvand, Leif; Heier, Martin; Brunborg, Cathrine; Hanssen, Kristian Folkvord; Fugelseth, Drude & STENSÆTH, KNUT HAAKON [Vis alle 8 forfattere av denne artikkelen] (2017). Advanced glycation end products in children with type 1 diabetes and early reduced diastolic heart function. BMC Cardiovascular Disorders. 17(133). doi: 10.1186/s12872-017-0551-0. Fulltekst i vitenarkiv Vis sammendrag

  Background Reduced diastolic function is an early sign of diabetes cardiomyopathy in adults and is associated with elevated levels of HbA1c and advanced glycation end products (AGEs). Objective To assess the associations between early reduced diastolic function and elevated levels of HbA1c and AGEs in children and adolescents with type 1 diabetes (T1D). Methods One hundred fourty six T1D patients (age 8–18 years) without known diabetic complications were examined with tissue Doppler imaging and stratified into two groups according to diastolic function. A clinical examination and ultrasound of the common carotid arteries were performed. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured by immunoassay. Results At inclusion, 36 (25%) participants were stratified into a low diastolic function group (E’/A’-ratio < 2.0). Compared to the rest of the T1D children, these participants had higher body mass index (BMI), 22.8 (SD = 4.0) vs. 20.1 (SD = 3.4) kg/m2, p < 0.001, higher systolic blood pressure 104.2 (SD = 8.7) vs. 99.7 (SD = 9.3) mmHg, p = 0.010, and higher diastolic blood pressure, 63.6 (SD = 8.3) vs. 59.9 (SD = 7.9) mmHg, p = 0.016. The distensibility coefficient was lower, 0.035 (SD = 0.010) vs. 0.042 (SD = 0.02) kPa−1, p = 0.013, Young’s modulus higher, 429 (SD = 106) vs. 365 (SD = 143), p = 0.009, and MG-H1 higher, 163.9 (SD = 39.2) vs. 150.3 (SD = 33.4) U/ml, p = 0.046. There was no difference in carotid intima-media thickness between the groups. There were no associations between reduced diastolic function and years from diagnosis, HBA1c, mean HBA1c, CRP or calculated glycemic burden. Logistic regression analysis showed that BMI was an independent risk factor for E’/A’-ratio as well as a non-significant, but relatively large effect size for MG-H1, indicating a possible role for AGEs. Conclusions Early signs of reduced diastolic function in children and adolescents with T1D had higher BMI, but not higher HbA1c. They also had elevated serum levels of the advanced glycation end product MG-H1, higher blood pressure and increased stiffness of the common carotid artery, but these associations did not reach statistical significance when tested in a logistic regression model.

• Brunvand, Leif; Fugelseth, Drude; STENSÆTH, KNUT-HAAKON; Dahl-Jørgensen, Knut & MARGEIRSDOTTIR, HANNA DIS (2016). Early reduced myocardial diastolic function in children and adolescents with type 1 diabetes mellitus a population-based study. BMC Cardiovascular Disorders. 16(103). doi: 10.1186/s12872-016-0288-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Reduced diastolic myocardial function is an early sign of diabetic cardiomyopathy. The aim of this study was to test the hypothesis that children and adolescents with type 1 diabetes mellitus (T1D), but without other known complications, have early reduced diastolic myocardial function diagnosed with echocardiographic color tissue Doppler imaging (cTDI). Methods cTDI examination was carried out in 173 T1D patients and 62 age-matched controls. The T1D-patients were 8–18 years old with (mean (SD)) diabetes duration of 5.6 (3.4) years and HbA1c of 8.4 (1.3). All were treated with either insulin pumps or 4–6 daily insulin injections. cTDI early (E’) and late (A’) peak diastolic velocities and systolic peak velocity were measured from the lateral, septal, anterior and posterior mitral annulus and from the lateral tricuspidal annulus. Results Myocardial diastolic function was reduced in the T1D-patients with higher peak A’-velocity and lower E’/A’-ratio in all registrations. Overall mean (SD) mitral E’/A’-ratio was 2.3 (0.5) in T1D and 2.7 (0.6) in the controls (p < 0001). The overall mitral E’/A’-ratio was negative associated with blood pressure (BP) and body mass index (BMI). Stratifying all participants into three groups according to BMI (<25, 25–75, >75 centile, respectively), the T1D had lower E’/A’-values in all stratified groups, except for in the highest BMI-group where both T1D and controls had the lowest E’/A’-ratio. Systolic function did not differ in any of the measurements. There were no associations with sex, diabetes duration, carotid artery intima-media-thickness, vessel elasticity or HbA1c. Conclusion Diabetic children and adolescents using modern intensive insulin treatment had echocardiographic signs of reduced diastolic myocardial function despite short duration of disease. The reduced function was associated with higher BP and higher BMI.

• Heier, Martin; MARGEIRSDOTTIR, HANNA DIS; Torjesen, Peter A; Seljeflot, Ingebjørg; STENSÆTH, KNUT-HAAKON & Gaarder, Mario [Vis alle 9 forfattere av denne artikkelen] (2015). The advanced glycation end product methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in childhood diabetes. Diabetes & vascular disease research. ISSN 1479-1641. 12(2), s. 139–145. doi: 10.1177/1479164114560910. Fulltekst i vitenarkiv
• Heier, Martin; MARGEIRSDOTTIR, HANNA DIS; Brunborg, Cathrine; Hanssen, Kristian Folkvord; Dahl-Jørgensen, Knut & Seljeflot, Ingebjørg (2015). Inflammation in childhood type-1 diabetes; influence of glycemic control. Atherosclerosis. ISSN 0021-9150. 238, s. 33–37. doi: 10.1016/j.atherosclerosis.2014.11.018. Fulltekst i vitenarkiv
• Heier, Martin; MARGEIRSDOTTIR, HANNA DIS; Gaarder, Mario; STENSÆTH, KNUT-HAAKON; Brunborg, Cathrine & Torjesen, Peter A [Vis alle 9 forfattere av denne artikkelen] (2015). Soluble RAGE and atherosclerosis in youth with type 1 diabetes: A 5-year follow-up study. Cardiovascular Diabetology. 14(126). doi: 10.1186/s12933-015-0292-2. Fulltekst i vitenarkiv Vis sammendrag

  Background: Advanced glycation end products (AGEs) play a role in the development of late complications and ath‑ erosclerosis in diabetes by engaging the receptor for advanced glycation end products, RAGE. Receptor binding leads to activation of the vascular endothelium and increased inflammation in the vessel wall. The soluble variants of the receptor, endogenous secretory RAGE (esRAGE) and the cleaved cell ‑ surface part of RAGE, which together comprise soluble RAGE (sRAGE), are suggested to have a protective effect acting as decoys for RAGE. We aimed to test whether high levels of soluble variants of RAGE could be protective against atherosclerosis development. Methods: Participants in the prospective atherosclerosis and childhood diabetes study were examined at baseline (aged 8–18) and at follow ‑ up after 5 years. Both sRAGE and esRAGE were measured by immunoassay in 299 patients with type 1 diabetes and 112 healthy controls at baseline and 241 patients and 128 controls at follow ‑ up. The AGEs methylglyoxal ‑ derived hydroimidazolone ‑ 1 (MG ‑ H1) and carboxymethyllysine (CML) were measured by immunoas‑ say. The surrogate markers of atherosclerosis assessed were carotid intima ‑ media thickness (cIMT ), C ‑ reactive protein (CRP) and Young’s modulus, measures of arterial wall thickness, inflammation and arterial stiffness, respectively. Results: Levels of sRAGE and esRAGE correlated strongly both at baseline and at follow ‑ up in both diabetes patients and controls. With increasing age, mean values of both variants declined, independent of gender, diabetes or pubertal stage. In the diabetes group, multiple regression analysis showed a positive association between both variants of solu ‑ ble RAGE and cIMT. There was no significant relationship with Young’s modulus, but a negative association between sRAGE at baseline and CRP at follow ‑ up. The ratios between the AGEs and the variants of soluble RAGE were increased in diabetes patients compared to controls. Conclusions: The results show a possible protective effect of high levels of sRAGE at baseline against inflammation 5 years later, but not on arterial stiffness or wall thickness, in this cohort of adolescents and young adults with T1D. Keywords: Advanced glycation end products, Receptor for advanced glycation end products, sRAGE, esRAGE, Atherosclerosis, Type 1 diabetes, CRP.

• MARGEIRSDOTTIR, HANNA DIS; Larsen, Jakob; Kummernes, Siv Janne; Brunborg, Cathrine & Dahl-Jørgensen, Knut (2010). The establishment of a new national network leads to quality improvement in childhood diabetes: Implementation of the ISPAD Guidelines. Pediatric Diabetes. ISSN 1399-543X. 11(2), s. 88–95. doi: 10.1111/j.1399-5448.2009.00542.x. Fulltekst i vitenarkiv
• MARGEIRSDOTTIR, HANNA DIS; STENSÆTH, KNUT-HAAKON; Larsen, Jacob Roald; Brunborg, Cathrine & Dahl-Jørgensen, Knut (2010). Early Signs of Atherosclerosis in Diabetic Children on Intensive Insulin Treatment A population-based study. Diabetes Care. ISSN 0149-5992. 33(9), s. 2043–2048. doi: 10.2337/dc10-0505. Fulltekst i vitenarkiv
• MARGEIRSDOTTIR, HANNA DIS; Larsen, JR; Kummernes, Siv Janne; Brunborg, Cathrine & Dahl-Jørgensen, Knut (2009). The establishment of a new national network leads to quality improvement in childhood diabetes: Implementation of the ISPAD Guidelines. Pediatric Diabetes. ISSN 1399-543X. doi: 10.1111/j.1399-5448.2009.00542.x. Fulltekst i vitenarkiv
• Øverby, Nina Cecilie; MARGEIRSDOTTIR, HANNA DIS; Brunborg, Cathrine; Anderssen, Sigmund; Andersen, Lene Frost & Dahl-Jørgensen, Knut (2009). Physical activity and overweight in children and adolescents using intensified insulin treatment. Pediatric Diabetes. ISSN 1399-543X. 10(2), s. 135–141. doi: 10.1111/j.1399-5448.2008.00454.x. Fulltekst i vitenarkiv
• Øverby, Nina Cecilie; MARGEIRSDOTTIR, HANNA DIS; Brunborg, Cathrine; Anderssen, SA; Andersen, Lene Frost & Dahl-Jørgensen, Knut (2008). Physical activity and overweight in children and adolescents using intensified insulin treatment. Pediatric Diabetes. ISSN 1399-543X. doi: 10.1111/j.1399-5448.2008.00454.x. Fulltekst i vitenarkiv
• Øverby, Nina Cecilie; MARGEIRSDOTTIR, HANNA DIS; Brunborg, C; Dahl-Jørgensen, Knut & Andersen, Lene Frost (2008). Sweets, snacking habits, and skipping meals in children and adolescents on intensive insulin treatment. Pediatric Diabetes. ISSN 1399-543X. 9, s. 393–400. doi: 10.1111/j.1399-5448.2008.00381.x. Fulltekst i vitenarkiv
• MARGEIRSDOTTIR, HANNA DIS; Larsen, Jakob; Brunborg, C; Øverby, Nina Cecilie & Dahl-Jørgensen, Knut (2008). High prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes: a population-based study. Diabetologia. ISSN 0012-186X. 51. doi: 10.1007/s00125-007-0921-8. Fulltekst i vitenarkiv
• Øverby, Nina Cecilie; MARGEIRSDOTTIR, HANNA DIS; Brunborg, Cathrine; Andersen, Lene Frost & Dahl-Jørgensen, Knut (2007). The influence of dietary intake and meal pattern on blood glucose control in children and adolescents using intensive insulin treatment. Diabetologia. ISSN 0012-186X. 50(10), s. 2044–2051. doi: 10.1007/s00125-007-0775-0. Fulltekst i vitenarkiv
• Øverby, Nina Cecilie; Flaaten, V.; Veierød, Marit Bragelien; Bergstad, Ingunn; MARGEIRSDOTTIR, HANNA DIS & Dahl-Jørgensen, Knut [Vis alle 7 forfattere av denne artikkelen] (2007). Children and adolescents with type 1 diabetes eat a more atherosclerosis-prone diet than healthy control subjects. Diabetologia. ISSN 0012-186X. 50, s. 307–316. doi: 10.1007/s00125-006-0540-9. Fulltekst i vitenarkiv
• MARGEIRSDOTTIR, HANNA DIS; Larsen, Jakob; Brunborg, C; Sandvik, Leiv & Dahl-Jørgensen, Knut (2007). Strong association between time watching television and blood glucose control in children and adolescents with type 1 diabetes. Diabetes Care. ISSN 0149-5992. 30, s. 1567–1570. doi: 10.2337/dc06-2112. Fulltekst i vitenarkiv

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• MARGEIRSDOTTIR, HANNA DIS; STENSÆTH, KNUT-HAAKON; Larsen, Jacob Roald; Brunborg, Cathrine & Dahl-Jørgensen, Knut (2010). Early signs of atherosclerosis in diabetic children on intensive insulin treatment: a population based study. Diabetologia. ISSN 0012-186X. 53, s. S13–S13. Fulltekst i vitenarkiv
• dahl, thomas marinius; Gaarder, Mario; MARGEIRSDOTTIR, HANNA DIS & Stensæth, Knut-Haakon (2008). Ultralyd-målinger av IMT og elastisitet i a.carotis hos barn/ungdom med diabetes. Fulltekst i vitenarkiv
• Bratke, Heiko; Skrivarhaug, Torild; Margeirsdottir, Hanna Dis; Biringer, Eva & Njølstad, Pål Rasmus (2025). Pediatric Diabetes Care in Norway : Glycemic Results and Health-Related Quality of Life. Universitetet i Bergen. ISSN 9788230860380. Fulltekst i vitenarkiv Vis sammendrag

  Background In Norway, a variety of efforts have been made to improve pediatric diabetes care and to support children with diabetes in the best possible way. Aside from the early adoption of new diabetes technology, Norwegian pediatric diabetes care has also focused on standardized patient education starting from the onset of diabetes, precise insulin dose calculation, systematic quality improvement and clearly defined treatment targets. Children and adolescents with type 1 diabetes in Norway routinely receive diabetes care from diagnosis and until the age of 18 years solely at the pediatric departments within the Norwegian public health care system. Thus, the pediatric departments annually deliver comprehensive data, including relevant treatment outcomes, of the children and adolescents with diabetes under follow-up to the Norwegian Childhood Diabetes Registry (NCDR), with a data completeness of ≥98%. Aims The overall aims of this thesis were to study the glycemic status, characterized by glycated hemoglobin A1c (HbA1c), and the incidence of diabetic ketoacidosis (DKA) and severe hypoglycemia (SH), and the diabetes-specific health-related quality of life (HRQOL) of children and adolescents with type 1 diabetes in Norway. We also aimed to identify factors associated with better glycemic control and diabetes-specific HRQOL in the last decade. Material and methods This thesis is based on data collected for the NCDR from 2013 to 2022, including 27,214 annual registrations of 6,775 children and adolescents (0-17 years) with type 1 diabetes and HbA1c levels analyzed at the same DCCT reference laboratory. In addition, we used the results of a survey on diabetes-specific HRQOL conducted as part of the 2017 annual NCDR data collection. In Paper I, we included the 2017 NCDR cohort (N=2,623) in a cross-sectional study and used linear mixed-effects regression analysis to assess the association of diabetes technology use and HbA1c. Logistic regression analysis was used to assess the association between diabetes technology use and the incidence of DKA and SH. Paper II was a cross-sectional study based on the DISABKIDS diabetes-specific module (DDM 10). Children 10 years and older, and parents of all children regardless their age were invited to complete the questionnaire as part of the NCDR’s 2017 annual data collection. Of 2,059 children 10 years or older, 1,059 children (50%) completed the questionnaire. Of the 2,725 parents, 1,441 (53%) participated. We analyzed potential associations between diabetes-specific HRQOL and HbA1c, age, sex, diabetes duration and the use of diabetes technology. For Paper III, we analyzed longitudinal registry data from 2013 to 2022. Using linear mixed-effects regression analysis, we assessed longitudinal associations of glycemic outcomes (HbA1c, DKA and SH), and the use of diabetes technology and carbohydrate counting for meal bolus calculation, separately for boys and girls. Further, we compared the glycemic outcomes of the 9 pediatric departments in the NCDR that participated in a national quality improvement project (IQ Norway) from 2017 to 2019 with the glycemic outcomes of the 17 nonparticipating departments. Results In 2017, 75% of children in the NCDR used an insulin pump, and 53% used continuous glucose monitoring (CGM). Cross-sectional analyses of the 2017 annual NCDR cohort showed that insulin pump use was associated with a higher HbA1c compared to insulin pen use, whereas CGM use was associated with a lower HbA1c compared to not using CGM. DKA and SH were not associated with insulin pump or CGM use. However, the use of patch pumps was associated with a notably lower odds ratio for DKA compared to other pump types. Diabetes-specific HRQOL in children with type 1 diabetes was generally high. Parents assessed diabetes specific HRQOL as lower than the children themselves. There was no cross-sectional association between diabetes-specific HRQOL and the use of diabetes technology. Higher diabetes-specific HRQOL was associated with lower HbA1c and male sex in children 10 years and older, but not in younger children. From 2013 to 2022, mean HbA1c in children and adolescents with type 1 diabetes in Norway decreased steadily from 66.6 mmol/mol to 55.4 mmol/mol. The proportion of children reaching an HbA1c of under 53.0 mmol/mol increased from 13% to 43%. The incidence of acute complications declined from 4.8% to 1.0% (DKA) and 4.9% to 2.1% (SH). The use of diabetes technology increased continuously over the study period, resulting in 91% of children using an insulin pump and 97% using CGM in 2022. Insulin pump and CGM use as well as carbohydrate counting were associated with better glycemic results in this longitudinal study. The 9 pediatric departments that participated in the quality improvement project enhanced their average institutional HbA1c more than the 17 nonparticipating departments. This difference in HbA1c remained stable over the following three years after the completion of ‘IQ Norway’. At all annual registrations, female sex was associated with higher HbA1c during this 10-year period. We found unexpected differences between boys and girls regarding HbA1c, the use of diabetes technology and carbohydrate counting. Conclusions and consequences This thesis identified important factors that likely contributed to the considerably improving glycemic outcomes seen in the Norwegian pediatric population from 2013 to 2022. We showed sex specific differences regarding HbA1c and diabetes-specific HRQOL that advocate for a more personalized approach for boys and girls in diabetes care. Diabetes technology use was not associated with better diabetes-specific HRQOL in 2017, but due to the enormous development in diabetes technology since 2017, the potential association of such technology with HRQOL may be more positive in future assessments. As shown in the present thesis, the NCDR was very useful in the identification of factors contributing to improved diabetes care and monitoring of glycemic outcomes over time at a national level. The results of this thesis can be inspiring and relevant for the future development of pediatric diabetes care in Norway and guide health care efforts in other populations, aiming for better glycemic results and HRQOL. For this purpose, the establishment of a diabetes registry to monitor treatment outcome measures and HRQOL, benchmark the pediatric departments, and identify factors that contribute to the improvement of diabetes care at a national or local level, in combination with universal access to diabetes technology and specialized diabetes care, might be important cornerstones.

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