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| 5. |
- Patterson, Cc, et al.
(author)
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Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008 : little short-term influence of sunshine hours or average temperature
- 2015
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In: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 16:8, s. 573-580
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Journal article (peer-reviewed)abstract
- BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation.OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008.METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends.RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ±11 to ±38% (median ±17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours.CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.
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| 6. |
- Sanjeevi, Carani B., et al.
(author)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Journal article (peer-reviewed)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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| 7. |
- Christie, M., et al.
(author)
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Antibodies to a Mr-64000 islet cell protein in Swedish children with newly diagnosed Type 1 (insulin-dependent) diabetes
- 1988
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In: Diabetologia. - 0012-186X. ; 31:8, s. 597-602
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Journal article (peer-reviewed)abstract
- Sera from 40 Swedish children diagnosed as having Type 1 (insulin-dependent) diabetes mellitus during a one year period along with 40 age and geographically matched control subjects were tested for antibodies to a Mr-64000 islet protein by immunoprecipitation of 35S-methionine-labelled rat islet amphiphilic proteins. Of the 40 diabetic patients, 29 (73%) were found to be positive whereas all 40 control subjects were negative. Samples were also tested for titres of islet cell cytoplasmic antibodies by indirect immunofluorescence on frozen sections of human pancreas. In the diabetic group, 30 of the 40 patients (75%) were positive for islet cell cytoplasmic antibodies compared with 2 of the 40 control subjects (5%). A comparison of levels of antibodies to the Mr-64000 protein with islet cell cytoplasmic antibodies revealed a weak (rs=0.46), but significant (p<0.01) correlation between the two tests. There was no effect of age or sex on levels of antibodies to the Mr-64000 protein. These results in population-based diabetic children and control subjects demonstrate a high frequency of antibodies to the Mr-64000 protein at the time of clinical onset.
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| 8. |
- Dahlquist, G G, et al.
(author)
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Birthweight and risk of type 1 diabetes in children and young adults : a population-based register study.
- 2005
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In: Diabetologia. - 0012-186X. ; 48:6, s. 1114-7
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: We investigated the association between type 1 diabetes and birthweight by age at disease onset. METHODS: This population-based case-referent study used data from two nationwide case registers that are linked to the Swedish Medical Birth Registry and cover incident cases of type 1 diabetes in the 0- to 14-year (since 1 July 1977) and 15- to 34-year age groups (since 1 January 1983). Of the cases linked to the Medical Birth Registry, a total of 9,283 cases with onset before 15 years of age was recorded before 1 January 2003, and 1,610 cases were recorded with onset before 30 years of age and born after 1973 (together 95% of eligible cases). Multiple births and babies of diabetic mothers were excluded. Sex-specific birthweight by gestational week is expressed as multiples of the standard deviation (SDS) and adjusted for year of birth, maternal age and parity. RESULTS: Cases with onset before 10 years of age (n = 5,792) showed a significant linear trend in odds ratio (OR) by SDS of adjusted birthweight (OR by SDS: 0.062; 95% CI: 0.037-0.086; p < 0.0001), while cases with onset at the age of 10-29 years showed no significant trend (OR by SDS: 0.004; 95% CI: -0.007 to 0.0014; p = 0.22). CONCLUSIONS/INTERPRETATION: The association between type 1 diabetes risk and birthweight seems to be limited to cases with disease onset in younger years.
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| 9. |
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| 10. |
- Dahlquist, G G
(author)
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Primary and secondary prevention strategies of pre-type 1 diabetes. Potentials and pitfalls.
- 1999
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In: Diabetes Care. - 0149-5992 .- 1935-5548. ; 22 Suppl 2, s. B4-6
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Journal article (peer-reviewed)abstract
- Over the past decade, a large part of type 1 diabetes research has focused on the possibility of preventing the disease. The objective of this article is to analyze which potential and pitfalls different preventive strategies may involve from the individual, epidemiological, and ethical perspectives. Two potential prevention strategies are considered: l) to try to arrest or delay an already ongoing immune destruction of the beta-cells, and 2) to try to intervene with exposures that may initiate this process. In addition to the potential effects of immune modulation, this prevention strategy depends on screening for risk markers. There are inherent ethical problems with screening because of the introduction of awareness of risk in healthy individuals and also because false positivity, the rate of which differs tremendously in high- and low-risk groups. Because of these latter circumstances, the most promising low-risk preventive treatments presently used in trials, i.e., nicotinamide and insulin, will probably only be feasible in high-risk groups, such as family members, though this group covers only 10-15% of potential cases. The second strategy aiming at eradicating environmental initiators of the beta-cell destruction will avoid the problem of screening and approach a total population at risk. Potential risk factors, such as food components (cow's milk proteins, gliadin or nitroso products) or different viruses, are indicated by animal and epidemiological studies. So far, however, no single environmental risk factor has been proven to be necessary and certainly not sufficient for the disease causation, and the etiological fractions estimated in population-based studies are low. It is concluded that more basic research is warranted before effective and safe prevention can be introduced for type 1 diabetes. Most probably, different preventive strategies must be applied to different groups and populations and in different phases of the beta-cell destruction.
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| 11. |
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| 12. |
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| 13. |
- Graham, J, et al.
(author)
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Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes
- 2002
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:5, s. 1346-1355
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Journal article (peer-reviewed)abstract
- Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0–34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3′ end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.
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| 14. |
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| 15. |
- Landin-Olsson, M, et al.
(author)
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Epidemiological and genetic aspects on islet autoimmunity in childhood insulin-dependent diabetes.
- 1988
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In: Genetic susceptibility to environmental factors : a challenge for public intervention : [First International Ernhold Lundström Symposium, Malmö, Sweden, May 14-16, 1987] - [First International Ernhold Lundström Symposium, Malmö, Sweden, May 14-16, 1987]. - 9122012621 ; , s. 87-93
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Book chapter (peer-reviewed)
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| 16. |
- Landin-Olsson, M., et al.
(author)
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Islet cell and other organ-specific autoantibodies in all children developing Type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children
- 1989
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In: Diabetologia. - 0012-186X. ; 32:6, s. 387-395
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Journal article (peer-reviewed)abstract
- The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p<0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+- ATPase (3%) were all increased in the patients compared with the control children, being 2% (p<0.001), 2% (p<0.01), and 0.3% (p<0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.
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| 17. |
- Landin-Olsson, M, et al.
(author)
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Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children
- 1992
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In: Diabetologia. - 0012-186X. ; 35:11, s. 73-1068
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Journal article (peer-reviewed)abstract
- Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10% of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99% of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0-14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986-1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96%) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84% (415 of 494), insulin autoantibodies 43% (145 of 334); 40% (135 of 334) were positive for both and 88% (294 of 334) were positive for one or both. Among control children, 3% (14 of 420) had islet cell antibodies, 1% (4 of 390) insulin autoantibodies, and 4% (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4% of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38%. None of the autoantibody-positive (n = 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.
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| 18. |
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| 19. |
- Lowe, Michael R., et al.
(author)
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The length of the CTLA-4 microsatellite (AT)(N)-repeat affects the risk for type 1 diabetes
- 2000
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In: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 32:3, s. 173-180
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Journal article (peer-reviewed)abstract
- CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)(n) microsatellite in the 3' untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping to determine the length of the 3'-end (AT)(n)repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). This study suggests that the 3'-end (AT)(n) repeat region of the CTLA-4 gene represents a recessive risk factor for type 1 diabetes.
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| 20. |
- Madsen, O D, et al.
(author)
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A two-colour immunofluorescence test with a monoclonal human proinsulin antibody improves the assay for islet cell antibodies
- 1986
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In: Diabetologia. - : Springer-Verlag New York. - 0012-186X .- 1432-0428. ; 29:2, s. 8-115
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Journal article (peer-reviewed)abstract
- The conventional indirect immunofluorescence assay for islet cell antibodies was compared with a two-colour immunofluorescent assay to detect both islet cell antibodies with fluorescein isothiocyanate-labeled rabbit anti-human IgG and pancreatic B cells with a monoclonal human proinsulin antibody and Texas red-labeled sheep anti-mouse IgG. Determinations of end-point titres showed a correlation between the new two-colour immunofluorescent assay and the conventional indirect immunofluorescent assay in 1) selected sera positive for islet cell antibodies and insulin autoantibodies rs = 0.93 (p less than 0.01) or for islet cell antibodies alone rs = 0.99 (p less than 0.005) and 2) sera from children or young adults with newly diagnosed Type 1 (insulin-dependent) diabetes rs = 0.95 (p less than 0.0001). No interference between the monoclonal human proinsulin antibodies and islet cell antibodies with or without insulin autoantibodies or between the two second fluorescent antibodies was detected. It is concluded that the two-colour immunofluorescence assay is advantageous since it is possible to mix the reagents to avoid a more time-consuming and technically complicated assay, the presence of B cells can be confirmed in each section to permit detection of B cell cytoplasmic antibodies and microscopic evaluation is easier and more accurate, particularly in islet cell antibody negative samples.
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| 21. |
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| 22. |
- Pundziute-Lycka, A, et al.
(author)
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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 to 1998
- 2002
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 45:6, s. 783-791
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Journal article (peer-reviewed)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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| 23. |
- Pundziute-Lyckå, A, et al.
(author)
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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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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 45:6, s. 783-91
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Journal article (peer-reviewed)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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| 24. |
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| 25. |
- Sanjeevi, C. B., et al.
(author)
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Polymorphic amino acid variations in HLA-DQ are associated with systematic physical property changes and occurrence of IDDM
- 1995
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 44:1, s. 125-131
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Journal article (peer-reviewed)abstract
- The association between human leukocyte antigen (HLA) insulin-dependent diabetes was studied in a large population-based investigation using genotyping of 425 new-onset patients, 0-14 years of age, and 367 matched control subjects. As many as 97% of patients compared with 75% of control subjects were positive for one or several of DQA1*0301, DQA1*0501, DQB1*0302, or DQB1*0201. Asp-57 DQB was present among 28% of patients, indicating that this residue alone does not confer protection. Combining Asp- 57 DQB1 with either Arg-52 DQA1 or Leu-69 DQA1 did not explain susceptibility or protection either. DQA1*0301-DQB1*0302 (DQS) and DQA1*0301-DQB1*0301 (DQ7) are identical except for four amino acid substitutions in the β- chain, but DQ8 was positively (odds ratio 8.07; P < 0.001) and DQ7 negatively (odds ratio 0.38; P < 0.001) associated with the disease. Molecular modeling was used to determine whether physicochemical properties such as steric factors and surface electrostatic potentials also differ in a systematic way for various DQ molecules. Amino acids were substituted systematically at the four polymorphic sites, and the solvent-accessible surfaces and electrostatic potentials were computed for each molecule. Dramatic alterations in electrostatic potential were seen for double substitutions at position 45 (G45E) and 57 (A57D) of DQB1. The variation of physicochemical properties due to polymorphic substitutions may be significant to the mechanism of HLA-DQ association with insulin-dependent diabetes, via the effect these property variations have on peptide antigen binding selectivity and subsequent interactions with specific T-cell receptors.
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| 26. |
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| 27. |
- Soltesz, G, et al.
(author)
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Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology?
- 2007
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In: Pediatr Diabetes. - 1399-543X. ; 8 Suppl 6, s. 6-14
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Journal article (peer-reviewed)abstract
- Type 1 diabetes is the most common form of diabetes in most part of the world, although reliable data are still unavailable in several countries. Wide variations exist between the incidence rates of different populations, incidence is lowest in China and Venezuela (0.1 per 100,000 per year) and highest in Finland and Sardinia (37 per 100,000 per year). In most populations girls and boys are equally affected. In general, the incidence increases with age, the incidence peak is at puberty. After the pubertal years, the incidence rate significantly drops in young women, but remains relatively high in young adult males up to the age 29-35 years. Prospective national and large international registries (DIAMOND and EURODIAB) demonstrated an increasing trend in incidence in most regions of the world over the last few decades and increases seem to be the highest in the youngest age group. Analytical epidemiological studies have identified environmental risk factors operating early in life which might have contributed to the increasing trend in incidence. These include enteroviral infections in pregnant women, older maternal age (39-42 years), preeclampsia, cesarean section delivery, increased birthweight, early introduction of cow's milk proteins and an increased rate of postnatal growth (weight and height). Optimal vitamin D supplementation during early life has been shown to be protective. Some of these environmental risk factors such as viruses may initiate autoimmunity toward the beta cell, other exposures may put on overload on the already affected beta cell and thus accelerate the disease process.
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| 28. |
- Sun, Chengjun, et al.
(author)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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In: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Journal article (peer-reviewed)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Chen, Hao, et al.
(author)
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Profitability Analysis of Integrating Fast Pyrolysis into Existing Combined Heat and Power Plants for Biofuel Production
- 2024
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In: Energy Proceedings. - : Scanditale AB.
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Conference paper (peer-reviewed)abstract
- Existing combined heat and power plants are seeking additional heat sinks to address challenges arising from the declining district heating demand and the increasing share of renewable energy in primary energy use in the coming decades. In the meantime, the world’s demand for sustainable fuel production keeps increasing due to the need to reduce carbon emissions and mitigate the effects of climate change. Fast pyrolysis, as a thermochemical conversion process based on widely available feedstocks such as lignocellulosic biomass, is promising to provide a long‐term supply of sustainable fuels, and could be integrated into existing combined heat and power plants due to the scalability and maturity of this method. This work focuses on techno‐economic analysis of integrating fast pyrolysis into existing combined heat and power plants for biofuel production. A process model of fast pyrolysis and bio‐oil upgrading is established in Aspen Plus to simulate the integration process. In this work, particular attention is given to the profitability analysis based on different final fuel products(crude pyrolysis oil and upgraded bio‐oil). Different hydrogen generation solutions (electrolysis, and gasification) for onsite bio‐oil upgrading are also examined. This study also performs an analysis of several economic indicators, such as payback period, net present value, and internal rate of return to provide insights for the future business model development for such systems. Sensitivity analysis is also carried out to further reveal the impacts of key variables in the economic evaluation process on the system’s profitability.
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| 34. |
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| 35. |
- Dahlquist, G
(author)
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Can we slow the rising incidence of childhood-onset autoimmune diabetes? The overload hypothesis.
- 2006
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In: Diabetologia. - 0012-186X. ; 49:1, s. 20-4
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Journal article (other academic/artistic)abstract
- Overload of the beta cell, mediated by a variety of mechanisms, may sensitise it to immune damage and apoptosis, and thus accelerate ongoing autoimmune processes leading to its destruction. Environmental risk determinants that may exert such overload effects include insulin resistance due to excess fat cell accumulation, and increased insulin requirement due to a high growth rate, physical stress (infection, inflammation) or psychological stress. The increasing incidence of childhood diabetes, and the shift to younger age at onset, is unlikely to be driven by environmental risk factors that have been associated with initiation of autoimmunity, e.g. virus infections or early infant feeding. Risk factors that may accelerate beta cell destruction have shown a steady increase in the population, and are more plausible causes of such a pattern of change. Child growth, weight and birthweight are well-established estimates of community wealth and increase in most countries of Europe. Overfeeding of children early in life leads to both accelerated growth and weight, and even a moderate excess of child growth, not necessarily associated with obesity, is associated with risk of type 1 diabetes. New, safe and effective immune-modulating drugs for possible arrest of the autoimmune process may become available in time, but in the interim these accelerating factors may be targeted. Public health programmes for pregnant mothers and young families, aiming at changing overfeeding and the sedentary lifestyle of the children would be preferable to other alternatives. Interventions such as these would be safe and could potentially influence future risks of type 1 and type 2 diabetes and other major threats to adult health.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Dahlquist, G, et al.
(author)
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Mortality in childhood-onset type 1 diabetes
- 2005
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In: Diabetes Care. - 1935-5548. ; 28:10, s. 2384-2387
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Journal article (peer-reviewed)abstract
- OBJECTIVE - To describe the age- and sex-specific mortality in a cohort of young type 1 diabetic patients and to analyze the causes of death with special focus on suicide, accidents, and unexplained deaths. RESEARCH DESIGN AND METHODS - A population-based incident childhood diabetes register, covering onset cases since 1 July 1977, was linked to the Swedish Cause of Death Register up to 31 December 2000. The official Swedish population register was used to calculate age- and sex-standardized mortality rates (SMRs), excluding neonatal deaths. To analyze excess risks for specific diagnoses, case subjects were compared with five nondiabetic control subjects, matched by age, sex, and year of death. Death certificates were collected for all case and control subjects. For case subjects with an unclear diagnosis, hospital records and/or forensic autopsy reports were obtained. RESULTS - Mean age- and sex-SMR was 2.15 (95% CI 1.70-2.68) and tended to be higher among females (2.65 vs. 1.93, P = 0.045). Mean age at death was 15.2 years (range 1.2-27.3) and mean duration 8.2 years (0-20.7). Twenty-three deaths were clearly related to diabetes; 20 died of diabetic ketoacidosis. Only two case subjects died with late diabetes complications (acute coronary infarction). Thirty-three case subjects died with a diagnosis not directly related to diabetes; 7 of them committed suicide, and 14 died from accidents. There was no significant difference in traffic accidents (odds ratio 1.02 [95% CI 0.40-2.37]). Obvious suicide tended to be increased but not statistically significantly so (1.55 [0.54-3.89]). Seventeen diabetic case subjects were found deceased in bed without any cause of death found at forensic autopsy. Only two of the control subjects died of similar unexplained deaths. CONCLUSIONS - in a well-developed health care system, there is still a significant excess mortality in young type 1 diabetic patients. We confirm a very large proportion of unexplained deaths in bed, which should be further studied. There is no clear excess death rate caused by suicide or traffic accidents among young diabetic subjects.
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- Dahlquist, G, et al.
(author)
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School marks for Swedish children whose mothers had diabetes during pregnancy: a population-based study
- 2007
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:9, s. 1826-1831
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Journal article (peer-reviewed)abstract
- Aims/hypothesis To study, at a population level, school performance when leaving compulsory school of Swedish children whose mothers had diabetes during pregnancy compared with a reference population. Mehtohds We linked the Swedish Medical Birth Register with the Swedish School Mark Register, which contains school marks for all children in Sweden when leaving compulsory school. A total of 6,397 children were identified whose mothers had a diagnosis of diabetes during pregnancy in the years 1973 to 1986. Data on these children were compared with 1,300,683 children whose mothers had no diagnosis of diabetes during pregnancy. Risks were estimated as odd ratios (ORs) after adjustment for year of birth, maternal age, parity and educational level of the mother. Results The children's average numerical school marks (for children leaving school between 1988 and 1997) were statistically significantly lower among children born to mothers with diabetes in pregnancy compared with reference children (3.13 +/- 0.01 vs 3.23, p < 0.001). The effect was similar among boys and girls. There was also an effect of maternal diabetes during pregnancy on the risk of the child not completing compulsory school (OR 1.25; 95% CI 1.10-1.43, and after exclusion of infants with certain perinatal characteristics an OR of 1.25; 95% CI 1.02-1.53). When sports and the core subjects mathematics, English and Swedish were studied, there were increased risks of having scores below pass level and decreased probabilities of having scores above pass level for children of mothers with diabetes during pregnancy. Conclusions/interpretation Children of mothers with diabetes during pregnancy performed slightly but significantly less well than reference children when leaving compulsory school at about 16 years old; this was also seen after adjustment for some putative perinatal and social confounders.
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- Hartling, Svend G, et al.
(author)
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Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity
- 1989
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 38:10, s. 1271-1274
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Journal article (peer-reviewed)abstract
- Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered β-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for >6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes. Median (range) fasting proinsulin in siblings was 8.9 pM (1.7–58 pM) vs. 3.8 pM (<1.2–28 pM) in control subjects (P < .00001). There was no difference between the groups in fasting blood glucose concentrations. Both groups had fasting insulin concentrations within the normal range with a tendency toward lower values in the siblings: 108 pM (60–237 pM) vs. 118 pM (71–175 pM) (P = .07). The 99 siblings were subdivided into groups according to HLA sharing with their diabetic proband. The concentration of proinsulin, insulin, and blood glucose among the groups of 33 HLA-identical, 40 HLA-haploidentical, and 26 nonidentical siblings did not differ significantly. The fasting proinsulin level did not correlate with fasting levels of insulin, blood glucose, age, or body weight. We conclude that fasting proinsulin is elevated in healthy siblings of IDDM patients, whereas fasting insulin is normal or slightly decreased independent of HLA identity with their diabetic sibling. Elevated proinsulin levels could represent a family trait, perhaps mirroring a β-cell more vulnerable to destruction, or it could reflect previous β-cell damage that does not lead to IDDM.
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| 45. |
- Heurlin, N, et al.
(author)
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Fatal outcome of disseminated Mycobacterium avium infection in childhood. A case of primary incompetent monocyte/macrophage function?
- 1996
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In: Acta Paediatrica. - Oslo : Scandinavian University Press. - 0803-5253 .- 1651-2227. ; 85:12, s. 1511-1513
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Journal article (peer-reviewed)abstract
- Disseminated BCG infection rarely heals, and disseminated disease caused by the Mycobacterium avium complex usually has a poor prognosis with a short time to death. The case of a boy who died after 9 years of diagnosed disseminated M. avium complex infection is described. He showed no signs of previously known immunodeficiency except an incompetent primary monocyte/macrophage function. This case has been commented on in Acta Paediatrica Scandinavia (1982) as "the first infant to survive a generalized BCG infection".
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