| 1. |
- Henricsson, Marianne, et al.
(författare)
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The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:2, s. 349-354
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden. RESEARCH DESIGN AND METHODS—The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15–34 years in Sweden. In 1987–1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8–10 years later. The assessment was based on retinal photographs in most cases (86%). RESULTS—Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA1c 8.1 ± 1.5% and 6.8 ± 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA1c (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001). CONCLUSIONS—Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.
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| 2. |
- Torffvit, Ole, et al.
(författare)
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Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden.
- 2007
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 21:4, s. 246-251
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the relationship between early-onset retinopathy and urinary markers of renal dysfunction. Research Design and Methods: The Diabetes Incidence Study in Sweden (DISS) aims to register all new cases of diabetes in young adults (15-34 years). In 1987-1988, 806 patients were reported and later invited to participate in a follow-up study focusing on microvascular complications after similar to 10 years of diabetes. In the present study, 149 patients with type I diabetes, completed eye examination, and urine sampling were included. Results: The patients with retinopathy (n=58, 39%) had higher HbA(1c), (P<.001) and urinary IgG2/creatinine (P<.05) and IgG2/IgG4 ratios (P<.05). Patients with maculopathy had the highest levels. No significant differences in urinary albumin/creatinine, glycosaminoglycans (GAGs)/creatinine, Tamm-Horsfall protein (THP)/creatinine, and IgG4/creatinine ratios were found. Women had higher urinary albumin/ creatinine (P<.01) and urinary IgG2/creatinine ratios (P<.01) than men. Conclusions: Young adults with type I diabetes and early-onset retinopathy had higher IgG2/creatinine and IgG2/IgG4 ratios than patients without retinopathy indicating that retinopathy is associated with a change in glomerular size selectivity. This was found in association with normal urinary albumin and THP excretion and may be suspected to reflect early general vascular changes. (C) 2007 Elsevier Inc. All rights reserved.
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| 3. |
- Axmon, Anna, et al.
(författare)
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CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure
- 2000
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 21:4, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Certain human biotransformation enzymes have been implicated in the formation and scavenging of the ultimate reactive metabolites, the diolepoxides, from polycyclic aromatic hydrocarbons (PAHs). In the present study, performed on aluminum smelter workers, we have analyzed airborne PAH, the pyrene metabolite 1-hydroxypyrene (1-OHP) in urine, and genotypes for biotransformation enzymes involved in PAH metabolism. The aim was to evaluate the correlation between external exposure and biomarkers of exposure and to investigate to what extent genetic polymorphism in metabolic enzymes can explain interindividual variation in urinary 1-OHP levels. DNA was prepared from blood samples from 98 potroom workers and 55 controls and altogether eight polymorphisms in the CYP1A1, mEH, GSTM1, GSTP1 and GSTT1 genes were analyzed. The 1-OHP excretion was found to correlate significantly (P 100-fold) and univariate and multivariate regression analyses were used to find the variables that could determine differences in excretion. The variation could, to some degree, be explained by differences in exposure to airborne particulate-associated PAHs, the use of personal respiratory protection devices, smoking habits and genetic polymorphisms in the cytochrome P450 1A1, GSTM1 and GSTT1 enzymes. The part of the variance that could be explained by differences in biotransformation genotypes seemed to be of the same order of magnitude as the variance explained by differences in exposure. In the control group as well as in the occupationally exposed group, the highest 1-OHP levels were observed in individuals carrying the CYP1A1 Ile/Val genotype who were also of the GSTM1 null genotype. The results show that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that it may also to some extent reflect the interindividual variation in susceptibility to PAHs.
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| 4. |
- Littorin, Bengt, et al.
(författare)
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Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment : A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes
- 1999
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 22:3, s. 409-412
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes.RESEARCH DESIGN AND METHODS:The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay.RESULTS:Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone.CONCLUSIONS:Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.
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| 5. |
- Lundström, Jan O, et al.
(författare)
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Sindbis virus polyarthritis outbreak signalled by virus prevalence in the mosquito vectors
- 2019
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Polyarthritis and rash caused by Sindbis virus (SINV), was first recognised in northern Europe about 50 years ago and is known as Ockelbo disease in Sweden and Pogosta disease in Finland. This mosquito-borne virus occurs mainly in tropical and sub-tropical countries, and in northern Europe it is suggested to cause regularly reoccurring outbreaks. Here a seven-year cycle of SINV outbreaks has been referred to in scientific papers, although the hypothesis is based solely on reported human cases. In the search for a more objective outbreak signal, we evaluated mosquito abundance and SINV prevalence in vector mosquitoes from an endemic area in central Sweden. Vector mosquitoes collected in the River Dalalven floodplains during the years before, during, and after the hypothesised 2002 outbreak year were assayed for virus on cell culture. Obtained isolates were partially sequenced, and the nucleotide sequences analysed using Bayesian maximum clade credibility and median joining network analysis. Only one SINV strain was recovered in 2001, and 4 strains in 2003, while 15 strains were recovered in 2002 with significantly increased infection rates in both the enzootic and the bridge-vectors. In 2002, the Maximum Likelihood Estimated infection rates were 10.0/1000 in the enzootic vectors Culex torrentium/pipiens, and 0.62/1000 in the bridge-vector Aedes cinereus, compared to 4.9/1000 and 0.0/1000 in 2001 and 0.0/1000 and 0.32/1000 in 2003 Sequence analysis showed that all isolates belonged to the SINV genotype I (SINV-I). The genetic analysis revealed local maintenance of four SINV-I clades in the River Dalalven floodplains over the years. Our findings suggest that increased SINV-I prevalence in vector mosquitoes constitutes the most valuable outbreak marker for further scrutinising the hypothesized seven-year cycle of SINV-I outbreaks and the mechanisms behind.
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| 6. |
- Mezheyeuski, Artur, et al.
(författare)
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Digitalized multiparametric analyses of tumor stroma for identification of low perivascular PDGFBR expression and low vessel density as independent prognosis markers for stage IV CRC
- 2014
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Ingår i: Journal of Clinical Oncology. - Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus. Akad Univ Hosp, Uppsala, Sweden. Odense Univ Hosp, Dept Oncol, DK-5000 Odense, Denmark. Oslo Univ Hosp, Dept Genet, Inst Canc Res, Oslo, Norway. Oslo Univ Hosp, Dept Oncol, Oslo, Norway. Univ Oslo, Oslo, Norway. Haukeland Hosp, N-5021 Bergen, Norway. Karolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, Stockholm, Sweden. Dept Surg, Uppsala, Sweden. Karolinska Inst, Dept Neurosci, Sci Life Lab, Stockholm, Sweden. : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:15
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Pundziute-Lyckå, A, et al.
(författare)
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The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998.
- 2002
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 45:6, s. 783-91
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998.METHODS: Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers.RESULTS: Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods ( p=0.63), but time changes among the 3-year age groups differed ( p<0.001). In females the incidence between the periods varied ( p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ ( p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 ( p<0.001) (15.0 and 12.5 years in males; 11.9 and 10.4 in females, respectively).CONCLUSION/INTERPRETATION: During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.
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| 8. |
- Sparring, Vibeke, et al.
(författare)
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Diabetes duration and health-related quality of life in individuals with onset of diabetes in the age group 15-34 years - a Swedish population-based study using EQ-5D
- 2013
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 13, s. 377-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes with onset in younger ages affects both length of life and health status due to debilitating and life-threatening long-term complications. In addition, episodes and fear of hypoglycaemia and of long-term consequences may have a substantial impact on health status. This study aims to describe and analyse health-related quality of life (HRQoL) in individuals with onset of diabetes at the age of 15-34 years and with a disease duration of 1, 8, 15 and 24 years compared with control individuals matched for age, sex and county of residence. Methods: Cross-sectional study of 839 individuals with diabetes and 1564 control individuals. Data on socioeconomic status and HRQoL using EQ-5D were collected by a postal questionnaire. Insulin treatment was self-reported by 94% of the patients, the majority most likely being type 1. Results: Individuals with diabetes reported lower HRQoL, with a significantly lower mean EQ VAS score in all cohorts of disease duration compared with control individuals for both men and women, and with a significantly lower EQ-5D(index) for women, but not for men, 15 years (0.76, p = 0.022) and 24 years (0.77, p = 0.016) after diagnosis compared with corresponding control individuals. Newly diagnosed individuals with diabetes reported significantly more problems compared with the control individuals in the dimension usual activities (women: 13.2% vs. 4.0%, p = 0.048; men: 11.4% vs. 4.1%, p = 0.033). In the other dimensions, differences between individuals with diabetes and control individuals were found 15 and 24 years after diagnosis: for women in the dimensions mobility, self-care, usual activities and pain/discomfort and for men in the dimension mobility. Multivariable regression analysis showed that diabetes duration, being a woman, having a lower education and not being married or cohabiting had a negative impact on HRQoL. Conclusions: Our study confirms the negative impact of diabetes on HRQoL and that the difference to control individuals increased by disease duration for women with diabetes. The small difference one year after diagnosis could imply a good management of diabetes care and a relatively quick adaptation. Our results also indicate that gender differences still exist in Sweden, despite modern diabetes treatment and management in Sweden.
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| 9. |
- Strell, Carina, et al.
(författare)
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Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:9, s. 983-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal-epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases. Methods: Stromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided. Results: PDGFR alpha((low))/PDGFR beta((high)) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype. Conclusions: A PDGFR alpha((low))/PDGFR beta((high)) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma-epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial-stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.
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| 10. |
- Svensson, M.K, 1965, et al.
(författare)
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The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors
- 2015
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Ingår i: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7560 .- 1520-7552. ; 31:2, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34years). MethodsAll 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. ResultsAfter median 17years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1kg/m(2)), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p=0.041), BMI (p=0.012) and HbA1c (p<0.001) were significant predictors of developing diabetic nephropathy between 9 and 17years of diabetes. At 17years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.051.12 per 1mmHg increase) were associated with DN. ConclusionsPatients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9years of follow-up was a risk marker for later development of diabetic nephropathy. Copyright (c) 2014 John Wiley & Sons, Ltd.
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