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Skrivarhaug T.,University of Oslo | Skrivarhaug T.,Oslo Diabetes Research Center | Stene L.C.,Oslo Diabetes Research Center | Stene L.C.,Norwegian Institute of Public Health | And 5 more authors.
Diabetologia | Year: 2014

Aims/hypothesis: Our study aimed to describe the incidence of type 1 diabetes in children below 15 years of age in Norway during the period 1989-2012 and to assess the regional variation during 2004-2012. We further set out to estimate the completeness of ascertainment in the Norwegian Childhood Diabetes Registry (NCDR). Methods: Incident cases of type 1 diabetes were registered in the NCDR and incidence rates were modelled using Poisson regression. Ascertainment for 2005-2008 was estimated using capture-recapture methodology by using data from the Norwegian Prescription Database (NorPD), a nationwide register established in 2004, which included insulin prescribed and dispensed at pharmacies to individual patients. Population data were obtained from Statistics Norway. Results: Observed incidence rates for 1989-2012 suggested three distinct time segments: in 1989-1996, the average incidence rate was 22.6 per 100,000 person-years (95% CI 21.4, 23.7); in 1996-2004, the average incidence rate was 28.4 per 100,000 person-years (95% CI 27.3, 29.6); and from 2004 to 2012, the average incidence rate per 100,000 person-years was 32.7 (95% CI 31.5, 34.0). After adjustment for age and sex, the estimated change per year was 1.8% for 1989-1996 (95% CI -0.07, 3.6; p = 0.059), 3.4% for 1996-2004 (95% CI 2.2, 4.7; p < 0.0001) and 0.3% for 2004-2012 (95% CI -0.9, 1.6; p = 0.64). The highest incidence was in the age group 10-14 years for both sexes. A significant regional variation in incidence was observed (p < 0.001). Completeness of ascertainment in the NCDR was estimated to be 91%. Conclusions/interpretation: The previously observed increase in incidence of type 1 diabetes has levelled off and remained essentially constant at 32.7 per 100,000 person-years during 2004-2012. There is a significant variation in type 1 diabetes incidence within Norway. © 2013 Springer-Verlag Berlin Heidelberg.


Heier M.,University of Oslo | Heier M.,Oslo Diabetes Research Center | Margeirsdottir H.D.,University of Oslo | Margeirsdottir H.D.,Oslo Diabetes Research Center | And 10 more authors.
Diabetes and Vascular Disease Research | Year: 2015

Background: Advanced protein glycation is an important mechanism for the development of late diabetic complications including atherosclerosis. Methylglyoxal-derived hydroimidazolone-1 is the most abundant advanced glycation end product in human plasma. Aim: To investigate the relationship between methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in children and adolescents with type 1 diabetes and healthy controls. Methods: A total of 314 diabetes patients aged 818 years were compared with 120 healthy controls. Serum methylglyoxalderived hydroimidazolone-1 was measured by immunoassay. Atherosclerosis was evaluated by assessing carotid intimamedia thickness by ultrasound, arterial stiffness by Youngs modulus and inflammation by C-reactive protein. Results: Methylglyoxal-derived hydroimidazolone-1 was significantly increased in the diabetes group compared with controls, 155.3 (standard deviation (SD) = 41.0) versus 143.0 (SD = 35.1) U/mL, ρ = 0.003, as was C-reactive protein, median 0.51 (0.27, 1.83) versus 0.31 (0.19, 0.67) mg/L, ρ < 0.001. There was no significant difference between the groups regarding carotid intima-media thickness or Youngs modulus. Multiple regression analysis showed a significant positive association between methylglyoxal-derived hydroimidazolone-1 and C-reactive protein in the diabetes group. Conclusion: Serum levels of methylglyoxal-derived hydroimidazolone-1 in diabetes patients are increased and associated with low-grade inflammation, but not yet arterial stiffness or wall thickness. This indicates that methylglyoxal-derived hydroimidazolone-1 may be important in the early phase of the accelerated atherosclerotic process in diabetes.


Gagnum V.,University of Oslo | Gagnum V.,Oslo Diabetes Research Center | Stene L.C.,Oslo Diabetes Research Center | Stene L.C.,Norwegian Institute of Public Health | And 7 more authors.
Diabetologia | Year: 2015

Aims/hypothesis: The aim of this study was to assess the association between all-cause mortality and sex, age at diagnosis and year of diagnosis in Norwegian patients with childhood-onset diabetes. Methods: The study was based on the nationwide, population-based Norwegian Childhood Diabetes Registry, which includes all newly diagnosed cases of childhood-onset diabetes at age 0–14 years in 1973–1982 and 1989–2012 (n = 7,884). Patients were followed until date of death, emigration or 30 September 2013. Results: Among the 7,884 patients, representing 132,420 person-years, 249 (3.2%) died during a mean follow-up of 16.8 (range 0.0–40.7) years. The standardised mortality ratio (SMR) for the total cohort was 3.6 (95% CI 3.1, 4.0), increasing by attained age. Absolute mortality was significantly lower in females than in males (HR 0.50 [95% CI 0.38, 0.65]), although the SMRs were similar. Cox regression analysis showed a significant decrease in mortality of 49% (HR 0.51 [95% CI 0.28, 0.93]) for those diagnosed in 1999–2012 compared with those diagnosed in 1973–1982 (p = 0.03). Conclusions/interpretation: In spite of improved diabetes care, mortality is still three to four times higher in those with childhood-onset diabetes compared with the general population in Norway. However, absolute mortality has declined among children diagnosed most recently (1999–2012) compared with those diagnosed in the earliest period (1973–1982). © 2015, Springer-Verlag Berlin Heidelberg.


Heier M.,University of Oslo | Heier M.,Oslo Diabetes Research Center | Margeirsdottir H.D.,University of Oslo | Margeirsdottir H.D.,Oslo Diabetes Research Center | And 7 more authors.
Atherosclerosis | Year: 2015

Objective: Patients with type 1 diabetes have increased mortality from cardiovascular disease, and inflammation is important in the development of atherosclerosis. Our aim was to evaluate the extent of inflammation and the influence of glycemic control in the early phases of atherosclerosis in childhood type 1 diabetes. Materials and methods: A population based cohort representative of all children with type 1 diabetes in Norway was studied. Diabetes patients (. n=314) were compared to healthy controls (. n=120), aged 8-18 years. Circulating levels of VCAM-1, ICAM-1, E-selectin, P-selectin, TNFα, IL-6, CRP, MCP-1, IL-18, MMP-9 and TIMP-1 were measured by immunoassays. Results: The diabetes patients had a mean age of 13.7 (SD=2.8) years, disease duration of 5.5 (SD=3.4) years and HbA1c of 8.4 (SD=1.2) % (68mmol/mol, SD=13.1). The levels of most of the measured markers were significantly increased in the diabetes group compared to controls. In the diabetes group, all except MCP-1 and MMP-9 were significantly correlated to HbA1c, albeit the relation to VCAM-1 was inverse. There were no significant correlations in the control group. The measured markers were only to a limited degree associated with traditional risk factors. CRP showed the most pronounced difference between diabetes patients and controls and the strongest correlation with HbA1c. The use of oral contraceptives profoundly increased CRP levels, independent of the presence of diabetes. Conclusions: Our results indicate that inflammation may play an important role in the accelerated atherosclerosis in early type 1 diabetes, and that this process seems primarily driven by hyperglycemia. © 2014 Elsevier Ireland Ltd.


Dzidzonu D.K.,University of Oslo | Skrivarhaug T.,University of Oslo | Skrivarhaug T.,Oslo Diabetes Research Center | Joner G.,University of Oslo | Moger T.A.,University of Oslo
Pediatric Diabetes | Year: 2016

Background: Few studies have looked at variation in type 1 diabetes incidence between immigrant groups within a country. Objective: To investigate differences in incidence rates of childhood-onset type 1 diabetes between immigrant groups and ethnic Norwegians, and their contribution to the number of incident cases of type 1 diabetes in Norway. Subjects: The study includes 2221 individuals with newly onset type 1 diabetes diagnosed during 2002–2009 in children of 0–14 yr in Norway registered in the nationwide and population-based Norwegian Childhood Diabetes Registry. Methods: Incident cases were classified in seven groups based on country of maternal birth and three age groups. Statistics Norway provided the corresponding population sizes. Incidence rates were compared by Poisson regression. Results: The overall incidence rate was 34.0 cases per 100,000 person-years (95% CI: 32.6, 35.5). There were large variations in incidence across the immigrant groups (p < 0.001), ranging from 6.8 per 100,000 person-years (95% CI: 1.9–17.5) for South/East Asians to 26.0 cases per 100,000 person-years (95% CI: 11.9–49.3) for sub-Saharan Africans. The differences remained significant after adjusting for age and gender. Conclusions: There are large variations in the rate of incidence of type 1 diabetes across the ethnic groups, and several immigrant groups have significantly lower incidence than ethnic Norwegians. Immigrant groups contributed ca. 5% of the total cases of type 1 diabetes and influence the overall incidence in Norway only to a small extent. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


Wisting L.,University of Oslo | Froisland D.H.,Lillehammer University College | Froisland D.H.,Innlandet Hospital Trust | Skrivarhaug T.,University of Oslo | And 4 more authors.
Diabetes Care | Year: 2013

OBJECTIVE-To establish the prevalence of disturbed eating behavior (DEB) and insulin omission among adolescents with type 1 diabetes using intensive insulin treatment in a nationwide population-based study. RESEARCH DESIGN ANDMETHODSdThe Diabetes Eating Problem Survey-Revised (DEPS-R) is a diabetes-specific screening tool for DEB. Clinical data and HbA1c were obtained from the Norwegian Childhood Diabetes Registry. RESULTS-A total of 770 children and adolescents 11-19 years of age with type 1 diabetes completed the DEPS-R. A total of 27.7% of the females and 8.6% of the males scored above the DEPS-R cutoff. Participants scoring above the cutoff had significantly higher HbA1c (9.2% [77 mmol/mol]; SD, 1.6) than participants scoring below the cutoff (8.4% [68 mmol/mol]; SD, 1.3; P<0.001). The prevalence of DEB increased significantly with age and weight, from7.2%in the underweight group to 32.7% in the obese group, and from 8.1% in the youngest age-group (11- 13 years) to 38.1% in the oldest age-group (17-19 years). A total of 31.6% of the participants reported insulin restriction and 6.9% reported insulin omission after overeating. Patients reporting insulin restriction had significantly higher HbA1c (9.0% [75 mmol/mol]; SD, 1.7) than nonrestrictors (8.3% [67 mmol/mol]; SD, 1.2; P < 0.001). CONCLUSIONS-One-fourth of girls with type 1 diabetes scored above the cutoff for DEB and one-third reported skipping their insulin dose entirely at least occasionally after overeating. Both DEB and insulin restriction were associated with poorer metabolic control, which may increase the risk of serious late diabetes complications. © 2013 by the American Diabetes Association.


Froisland D.H.,Lillehammer University College | Froisland D.H.,Innlandet Hospital Trust | Graue M.,University of Bergen | Graue M.,Bergen University College | And 8 more authors.
Acta Paediatrica, International Journal of Paediatrics | Year: 2013

Aim To examine health-related quality of life (HRQOL) in children and adolescents with type 1 diabetes on intensive insulin treatment. Methods All children and adolescents with type 1 diabetes above 8 years of age scheduled for follow-up at 21 paediatric departments in Norway, and one of their parents was invited to describe HRQOL by completing DISABKIDS questionnaires. HRQOL was related to sociodemographic factors (i.e. parental economy, education, marital status and to level of physical activity and disease characteristics, obtained from the Norwegian Childhood Diabetes Registry). Results Nine hundred and thirty seven (48%) and one of their parents responded. Mean duration of diabetes was 4.9 years (SD 3.3), 51% were girls, 56% used insulin pumps, and 44% used multiple insulin injections, predominantly of long-acting and rapid insulin analogues. Mean HbA1c was 8.5% (SD 1.3). Lower HRQOL scores were significantly associated with higher HbA1c, being a girl and experience of diabetes ketoacidosis. Mothers scored lower than fathers on total score and most subscales. No significant differences in scores were found between users of an insulin pump and multi-injection treatment. Conclusions Health-related quality of life was related to metabolic control and gender, but not to mode of intensified insulin treatment. © 2013 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd.


Margeirsdottir H.D.,University of Oslo | Margeirsdottir H.D.,Oslo Diabetes Research Center | Stensaeth K.H.,University of Oslo | Larsen J.R.,Oslo Diabetes Research Center | And 3 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - To evaluate early stages of atherosclerosis and predisposing factors in type 1 diabetic children and adolescents compared with age- and sex-matched healthy control subjects. RESEARCH DESIGN AND METHODS - All children and adolescents with type 1 diabetes, aged 8-18 years in Health Region South-East in Norway were invited to participate in the study (n=800). A total of 40% (n=314) agreed to participate and were compared with 118 age-matched healthy control subjects. Carotid artery intima-media thickness (cIMT) and elasticity were measured using standardized methods. RESULTS - Mean age of the diabetic patients was 13.7 years, mean diabetes duration was 5.5 years, and mean A1C was 8.4%; 97% were using intensive insulin treatment, and 60% were using insulin pumps. Diabetic patients had more frequently elevated cIMT than healthy control subjects: 19.5% were above the 90th centile of healthy control subjects, and 13.1% were above the 95th centile (P < 0.001). Mean cIMT was higher in diabetic boys than in healthy control subjects (0.46±0.06 vs. 0.44±0.05 mm, P=0.04) but not significantly so in girls. There was no significant difference between the groups regarding carotid distensibility, compliance, or wall stress. None of the subjects had atherosclerotic plaque formation. Although within the normal range, the mean values of systolic blood pressure, total cholesterol, LDL cholesterol, and apolipoprotein B were significantly higher in the diabetic patients than in the healthy control subjects. CONCLUSIONS - Despite short disease duration, intensive insulin treatment, fair glycemic control, and no signs of microvascular complications, children and adolescents with type 1 diabetes had slightly increased cIMT compared with healthy control subjects, and the differences were more prominent in boys. © 2010 by the American Diabetes Association.


PubMed | Oslo Diabetes Research Center and University of Oslo
Type: | Journal: Diabetes care | Year: 2016

To study long-term mortality, causes of death, and end-stage renal disease (ESRD) in people diagnosed with type 1 diabetes at age 15-29 years.This nationwide, population-based cohort with type 1 diabetes diagnosed during 1978-1982 (n = 719) was followed from diagnosis until death, emigration, or September 2013. Linkages to the Norwegian Cause of Death Registry and the Norwegian Renal Registry provided information on causes of death and whether ESRD was present. A clinical committee reviewed the causes of death. We calculated standardized mortality ratios (SMRs) for comparison with the background population.During 30 years follow-up, 4.6% of participants developed ESRD and 20.6% (n = 148; 106 men and 42 women) died. Cumulative mortality by years since diagnosis was 6.0% (95% CI 4.5-8.0) at 10 years, 12.2% (10.0-14.8) at 20 years, and 18.4% (15.8-21.5) at 30 years. The SMR was 4.4 (95% CI 3.7-5.1). Mean time from diagnosis of diabetes to ESRD was 23.6 years (range 14.2-33.5). Death was caused by chronic complications (32.2%), acute complications (20.5%), violent death (19.9%), or any other cause (27.4%). Death was related to alcohol in 15% of cases. SMR for alcohol-related death was 6.8 (95% CI 4.5-10.3), for cardiovascular death was 7.3 (5.4-10.0), and for violent death was 3.6 (2.3-5.3).The cumulative incidence of ESRD was low in this cohort with type 1 diabetes followed for 30 years. Mortality was 4.4 times that of the general population, and more than 50% of all deaths were caused by acute or chronic complications. A relatively high proportion of deaths were related to alcohol.


PubMed | University of Bergen, Oslo Diabetes Research Center, University of Oslo and Norwegian Institute of Public Health
Type: | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2016

To assess the causes of death and cause-specific standardized mortality ratios in two nationwide, population-based cohorts diagnosed with Type 1 diabetes during the periods 1973-1982 and 1989-2012, and to evaluate changes in causes of death during the follow-up period.People with Type 1 diabetes who were aged <15 years at diagnosis were identified in the Norwegian Childhood Diabetes Registry and followed from diagnosis until death, emigration or September 2013 (n=7871). We assessed causes of death by linking data to the nationwide Cause of Death Registry and through a review committee that evaluated medical records, autopsy reports and death certificates.During a mean (range) follow-up of 16.8 (0-40.7) years, 241 individuals (3.1%) died, representing 132 143 person-years. The leading cause of death before the age of 30 years was acute complications (41/119, 34.5%). After the age of 30 years cardiovascular disease was predominant (41/122, 33.6%), although death attributable to acute complications was still important in this age group (22/122, 18.0%). A total of 5% of deaths were caused by dead-in-bed syndrome. The standardized mortality ratio was elevated for cardiovascular disease [11.9 (95% CI 8.6-16.4)] and violent death [1.7 (95% CI 1.3-2.1)] in both sexes combined, but was elevated for suicide only in women [2.5 (95% CI 1.2-5.3)]. The risk of death from acute complications was approximately half in women compared with men [hazard ratio 0.43 (95% CI 0.25-0.76)], and did not change with more recent year of diagnosis [hazard ratio 1.02 (0.98-1.05)].There was no change in mortality attributable to acute complications during the study period. To reduce premature mortality in people with childhood-onset diabetes focus should be on prevention of acute complications. Male gender implied increased risk. This article is protected by copyright. All rights reserved.

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