Ten Years of Improving Glycemic Control in Pediatric Diabetes Care: Data From the Norwegian Childhood Diabetes Registry.

OBJECTIVE: To evaluate, from 2013 to 2022, how HbA1c, the incidence of acute complications, and use of diabetes technology changed at the national level in Norway and how glycemic control was associated with use of diabetes technology, carbohydrate counting, or participation in a quality improvement project. RESEARCH DESIGN AND METHODS: This longitudinal observational study was based on 27,214 annual registrations of 6,775 children from the Norwegian Childhood Diabetes Registry from 2013 to 2022. Individuals aged >18 years, those with diabetes other than type 1, and those without HbA1c measurements were excluded. The outcome measure was HbA1c. The predictor variables in the adjusted linear mixed-effects model were 1) the use of diabetes technology, 2) the use of carbohydrate counting for meal bolusing, and 3) whether the patient's diabetes team participated in a quality improvement project. RESULTS: Mean HbA1c decreased from 8.2% (2013) to 7.2% (2021), and the proportion of youth reaching an HbA1c <7.0% increased from 13% (2013) to 43% (2022). Insulin pump use increased from 65% (2013) to 91% (2022). Continuous glucose monitoring (CGM) use increased from 34% (first recorded in 2016) to 97% (2022). Insulin pump, CGM, and carbohydrate counting were associated with lower HbA1c and higher achievement of glycemic targets. Girls had a higher mean HbA1c than boys. Mean HbA1c levels were lower in clinics that participated in a quality improvement project for the following 4 years after the project. CONCLUSIONS: Diabetes technology, carbohydrate counting, and systematic quality improvement in pediatric departments led to improved glycemic control.

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.

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.

Retinal venular oxygen saturation is associated with non-proliferative diabetic retinopathy in young patients with type 1 diabetes.

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.

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.

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. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04201171.

Associations between Macular OCT Angiography and Nonproliferative Diabetic Retinopathy in Young Patients with Type 1 Diabetes Mellitus.

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.

Venular oxygen saturation is increased in young patients with type 1 diabetes and mild nonproliferative diabetic retinopathy.

PURPOSE: To clarify how early in the development of diabetic retinopathy (DR) can oxygen (O2 ) saturation changes be detected. METHODS: Retinal oximetry was performed in a cross-sectional study, involving 14- to 30-year-old individuals: 185 with type 1 diabetes (T1D) and 94 controls. The subjects were divided into four groups according to the grade of DR. One-way ANOVA and post hoc tests were used to test for differences in the mean O2 saturations between the groups. RESULTS: Fifty-eight (31 %) of the T1D patients had nonproliferative DR. There was no significant difference in O2 saturations between controls and T1D patients with no DR. Arteriolar and venular O2 saturations in T1D patients were significantly higher in moderate/severe DR than in no DR (p = 0.009 and p > 0.001), while venular O2 saturation was significantly higher in mild DR than in no DR (p = 0.013). CONCLUSION: Increase in venular O2 saturation could not be detected before mild retinopathy had developed, and the retinal O2 saturation increase was measurable on the venular side first. Our results suggest that the increase in O2 saturation is likely a consequence of DR.

Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study.

BACKGROUND: Type 1 diabetes is a chronic disease including hyperglycemia and accelerated atherosclerosis, with high risk of micro- and macrovascular complications. Circulating microvesicles (cMVs) are procoagulant cell fragments shed during activation/apoptosis and discussed to be markers of vascular dysfunction and hypercoagulability. Limited knowledge exists on hypercoagulability in young diabetics. We aimed to investigate cMVs over a five-year period in children/adolescents with type 1 diabetes compared with controls and any associations with glycemic control and cardiovascular risk factors. We hypothesized increased shedding of cMVs in 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 Childhood Diabetes (ACD) study. Citrated plasma was prepared and stored at -80°C until cMV analysis by flow cytometry. RESULTS: Comparable levels of Annexin V (AV+) cMVs were observed at inclusion. At five-year follow-up, total AV+ cMVs were significantly lower in subjects with type 1 diabetes compared with controls; however, no significant differences were observed after adjusting for covariates. In the type 1 diabetes group, the total AV+, tissue factor-expressing AV+/CD142+, neutrophil-derived AV+/CD15+ and AV+/CD45+/CD15+, and endothelial-derived AV+/CD309+ and CD309+/CD34+ cMVs were inversely correlated with HbA1c (r = -0.437, r = -0.515, r = -0.575, r = -0.529, r = -0.416, and r = -0.445, respectively; all p ≤ 0.01), however, only at inclusion. No significant correlations with cardiovascular risk factors were observed. CONCLUSIONS: Children/adolescents with type 1 diabetes show similar levels of AV+ cMVs as healthy controls and limited associations with glucose control. This indicates that our young diabetics on intensive insulin treatment have preserved vascular homeostasis and absence of procoagulant cMVs.

Procoagulant activity in children and adolescents on intensive insulin therapy.

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.

The establishment of a new national network leads to quality improvement in childhood diabetes: implementation of the ISPAD Guidelines.

AIMS: To investigate whether implementation of International Society for Pediatric and Adolescent Diabetes (ISPAD) Guidelines and the establishment of a system for nationwide anonymous comparison, between treatment centres, of quality indicators for childhood diabetes could lead to improvement in diabetes care. METHODS: Children and adolescents with type-1 diabetes in Norway are treated at the public hospitals. Data were collected prospectively yearly according to standardized written instructions. Quality indicators were defined and benchmarked. HbA1c was measured at a central national Diabetes Control and Complications Trial (DCCT) standardized laboratory. RESULTS: The participation increased with 454 type-1 diabetes patients from eight clinics included in 2001 and 1658 patients from 25 clinics in 2005. The adherence rate in 2005 was 85% of all eligible patients from 25 of 26 pediatric clinics. The mean HbA1c of all clinics improved (8.6% in 2001 and 8.1% in 2005) and this was statistically significant (p < 0.01). The use of intensive insulin treatment increased from 56% to 78% (p < 0.01) and pumps from 8% to 37% (p < 0.01). The incidence of diabetes ketoacidosis (DKA) remained constant. The incidence of severe hypoglycemia declined insignificantly. The proportion of patients not screened yearly for microalbuminuria and retinopathy, according to ISPAD guidelines, decreased from 12% to 2% (p < 0.01) and from 42% to 27% (p < 0.01), respectively. All changes occurred gradually from 2001 to 2005. CONCLUSIONS: During the establishment of a system for benchmarking of diabetes treatment in Norway the outcomes showed significant improvements associated with changes in management and the quality of screening assessments. Benchmarking combined with organized quality meetings and discussions was effective to improve outcome on a national level.

Physical activity and overweight in children and adolescents using intensified insulin treatment.

AIM: To describe physical activity and inactivity and parameters associated with overweight in a population-based study of children and adolescents on intensive insulin treatment. METHODS: Physical activity and inactivity were evaluated in 723 type 1 diabetic subjects, 240 children aged 6-10 yr and 483 adolescents aged 11-19 yr, using a questionnaire that can estimate total amount of time spent on inactivity and light, moderate and vigorous activity. RESULTS: Overall, 54% of the participants do not fulfil the international recommendations of 60 min of moderate-to-vigorous activity per day. Girls are less active than boys in childhood (70 vs. 88 min/d, p = 0.01) and in adolescence (47 vs. 57 min/d, p = 0.02). Furthermore, this study shows that those who are more active are also those who seldom skip meals (p < 0.001). Forty-three percent of the participants watch TV for more than 2 h a day, and TV viewing was found to be related to overweight in children and adolescents with type 1 diabetes [OR: 2.5 (1.40-4.54), p = 0.002]. No statistical differences in physical activity were noted between the different intensified insulin regimens. Patients wearing insulin pumps were not less active. CONCLUSION: To increase physical activity to recommended level and limit TV viewing should be an important issue in education of all children and adolescents with type 1 diabetes, independent of insulin regimen.

Strong association between time watching television and blood glucose control in children and adolescents with type 1 diabetes.

OBJECTIVE: To examine the relationship between blood glucose control and the time spent watching television in Norwegian children and adolescents with type 1 diabetes in a population-based study. RESEARCH DESIGN AND METHODS: A total of 538 children and adolescents from 9 hospitals in the eastern part of Norway participated in the study; 70% of eligible subjects participated. The time spent watching television and time using a computer was recorded separately by interview together with clinical data. Mean (+/-SD) age was 13.1 +/- 3.7 years, mean diabetes duration was 5.4 +/- 3.4 years, and mean A1C was 8.6 +/- 1.3% (reference range 4.1-6.4). RESULTS: Sixty-two patients (11%) watched television <1 h daily (mean A1C 8.2 +/- 0.9%), 189 patients (35%) watched television between 1 and 2 h daily (8.4 +/- 1.2%), 166 patients (31%) watched television 2-3 h daily (8.7 +/- 1.4%), 75 patients (14%) watched television 3-4 h daily (8.8 +/- 1.2%), and 46 patients (9%) watched television > or =4 h daily (9.5 +/- 1.6%). This trend was highly significant (P < 0.001). The association between television viewing and A1C remained significant, even after adjusting for age and BMI and insulin dose. No correlation between A1C and the use of a personal computer was observed. CONCLUSIONS: Extensive television watching is associated with poor blood glucose control in children and adolescents with type 1 diabetes.