| 1. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 2. |
- Uusitupa, M., et al.
(författare)
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Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome : a randomized study (SYSDIET)
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:1, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.
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| 3. |
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| 4. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 5. |
- Hillman, M., et al.
(författare)
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Skim milk powder with high content of Maillard reaction products affect weight gain, organ development and intestinal inflammation in early life in rats
- 2019
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 125, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- Background: The intestinal tract is important for development of immune tolerance and disturbances are suggested to trigger autoimmune disorders. The aim of this study was to explore the effect of Maillard products in skim milk powder obtained after long storage, compared to fresh skim milk powder. Methods: Young rats were weaned onto a diet based on skim milk powder with high concentration of Maillard products (HM-SM, n = 18) or low (C-SM, n = 18) for one week or four weeks. Weekly body weight and feed consumption were noted. At the end, organ weights, intestinal histology, permeability and inflammatory cytokines were evaluated. Results: Rats fed with HM-SM had after one week, 15% less weight gain than controls, despite equal feed intake. After one week thymus and spleen were smaller, intestinal mucosa thickness was increased and acute inflammatory cytokines (IL-17, IL-1β, MCP-1) were elevated. After four weeks, cytokines associated with chronic intestinal inflammation (fractalkine, IP-10, leptin, LIX, MIP-2, RANTES and VEGF) were increased in rats fed with HM-SM compared to C-SM. Conclusion: High content of Maillard products in stored milk powder caused an intestinal inflammation. Whether this is relevant for tolerance development and future autoimmune diseases remains to be explored.
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| 6. |
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| 7. |
- Christie, M., et al.
(författare)
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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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Ingår i: Diabetologia. - 0012-186X. ; 31:8, s. 597-602
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Tidskriftsartikel (refereegranskat)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. |
- Dereke, J., et al.
(författare)
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Pregnancy-associated plasma protein-A2 levels are increased in early-pregnancy gestational diabetes : a novel biomarker for early risk estimation
- 2020
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 37:1, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To determine whether pregnancy-associated plasma protein-A2 levels are increased in early pregnancies complicated by gestational diabetes and whether gestation age influences levels. The possible use of pregnancy-associated plasma protein-A2 as a pre-screening biomarker to reduce the need for performing oral glucose tolerance tests in pregnant women was also investigated. Methods: Pregnant women were diagnosed with gestational diabetes in early pregnancy after a 2-hour 75 g oral glucose tolerance test in the catchment area of Skåne University Hospital, Lund, Sweden during 2011–2015 (n = 99). Age- and BMI-matched pregnant women without diabetes were recruited at similar gestational ages from maternal healthcare centres in the same geographical area during 2014–2015 to act as controls (n = 100). Circulating pregnancy-associated plasma protein-A2 was analysed in participant serum using commercially available enzyme-linked immunosorbent assay kits. Results: Circulating pregnancy-associated plasma protein-A2 was increased in women diagnosed with gestational diabetes [13.5 (9.58–18.8) ng/ml] compared with controls [8.11 (5.74–11.3) ng/ml; P < 0.001]. Pregnancy-associated plasma protein-A2 was associated with gestational diabetes independent of age, BMI, C-peptide and adiponectin (P < 0.001). Pregnancy-associated plasma protein-A2 as a pre-screening biomarker to identify women at a decreased risk of gestational diabetes resulted in a negative predictive value of 99.7%, with a sensitivity of 96% and a specificity of 30% at a cut-off level of 6 ng/ml. Conclusions: This is the first study to show increased pregnancy-associated plasma protein-A2 levels in gestational diabetes. Pregnancy-associated plasma protein-A2 also shows promise as a pre-screening biomarker with the potential to reduce the need for performing oral glucose tolerance tests in early pregnancy. Future prospective cohort studies in a larger group of both high- and low-risk women are, however, needed to further confirm this observation.
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| 9. |
- Dereke, J., et al.
(författare)
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Structural and immunoendocrine remodeling in gut, pancreas and thymus in weaning rats fed powdered milk diets rich in Maillard reactants
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Western diet is extending worldwide and suspected to be associated with various metabolic diseases. Many food products have skim milk powder added to it and, during processing, lactose reacts with milk proteins and Maillard reaction products (MRPs) are formed. Dietary MRPs are suggested risk factors for metabolic dysregulation, but the mechanisms behind are still enigmatic. Here we describe that weaning rats fed diets rich in MRPs are affected in both their immune and endocrine systems. Marked structural changes in pancreas, intestine and thymus are noted already after 1 week of exposure. The pancreatic islets become sparser, the intestinal mucosa is thinner, and thymus displays increased apoptosis and atrophy. Glucagon- like peptide-1 (GLP-1) seems to play a key role in that the number of GLP-1 expressing cells is up-regulated in endocrine pancreas but down-regulated in the intestinal mucosa. Further, intestinal GLP-1-immunoreactive cells are juxta positioned not only to nerve fibres and tuft cells, as previously described, but also to intraepithelial CD3 positive T cells, rendering them a strategic location in metabolic regulation. Our results suggest dietary MRPs to cause metabolic disorders, dysregulation of intestinal GLP-1- immunoreactive cells, arrest in pancreas development and thymus atrophy.
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| 10. |
- Graham, J, et al.
(författare)
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Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:5, s. 1346-1355
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Tidskriftsartikel (refereegranskat)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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| 11. |
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| 12. |
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| 13. |
- Lernmark, Å, et al.
(författare)
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Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus
- 1995
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Ingår i: Virchows Archiv. - 0945-6317. ; 425:6, s. 631-640
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.
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| 14. |
- Lindqvist, P. G., et al.
(författare)
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Avoidance of sun exposure as a risk factor for major causes of death : A competing risk analysis of the Melanoma in Southern Sweden cohort
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 375-387
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. Methods: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. Results: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. Conclusion: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.
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| 15. |
- Lindqvist, P. G., et al.
(författare)
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Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- Background. Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels. Methods. We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data. Results. There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%. Conclusion. The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.
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| 16. |
- Lindqvist, Pelle G., et al.
(författare)
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Women with fair phenotypes seem to confer a survival advantage in a low UV milieu. A nested matched case control study
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Sun exposure in combination with skin pigmentation is the main determinant for vitamin D status. Human skin color seems to be adapted and optimized for regional sun ultraviolet (UV) intensity. However, we do not know if fair, UV-sensitive skin is a survival advantage in regions with low UV radiation. Methods A population-based nested case-control study of 29,518 Caucasian women, ages 25 to 64 years from Southern Sweden who responded to a questionnaire regarding risk-factors for malignant melanoma in 1990 and followed for 25 years. For each fair woman, defined as having red hair or freckles (n = 11,993), a control was randomly selected from all non-fair women from within the cohort of similar age, smoking habits, education, marital status, income, and comorbidity, i.e., 11,993 pairs. The main outcome was the difference in allcause mortality between fair and non-fair women in a low UV milieu, defined as living in Sweden and having low-to-moderate sun exposure habits. Secondary outcomes were mortality by sun exposure, and among those non-overweight. Results In a low UV milieu, fair women were at a significantly lower all-cause mortality risk as compared to non-fair women (log rank test p = 0.04) with an 8% lower all-cause mortality rate (hazard ratio [HR] = 0.92, 95% CI 0.84-1.0), including a 59% greater risk of dying from skin cancer among fair women (HR 1.59, 95% CI 1.26-2.0). Thus, it seem that the beneficial health effect from low skin coloration outweigh the risk of skin cancer at high latitudes. Conclusion In a region with low UV milieu, evolution seems to improve all-cause survival by selecting a fair skin phenotype, i.e., comprising fair women with a survival advantage.
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| 17. |
- Lindqvist, PG, et al.
(författare)
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Low sun exposure habits is associated with a dose-dependent increased risk of hypertension: a report from the large MISS cohort
- 2021
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Ingår i: Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology. - : Springer Science and Business Media LLC. - 1474-9092. ; 20:2, s. 285-292
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Tidskriftsartikel (refereegranskat)abstract
- In prospective observational cohort studies, increasing sun exposure habits have been associated with reduced risk of cardiovascular mortality. Our aim was to assess possible observational mechanisms for this phenomenon. A written questionnaire was answered by 23,593 women in the year 2000 regarding risk factors for melanoma, including factors of possible interest for hypertension, such as detailed sun exposure habits, hypertension, marital status, education, smoking, alcohol consumption, BMI, exercise, and chronic high stress. Hypertension was measured by the proxy “use of hypertension medication” 2005–2007, and high stress by “need of anti-depressive medication”. Sun exposure habits was assessed by the number of `yes’ to the following questions; Do you sunbath during summer?, During winter vacation?, Do you travel south to sunbath?, Or do you use sun bed? Women answering ‘yes’ on one or two questions had moderate and those answering ‘yes’ on three or four as having greatest sun exposure. The main outcome was the risk of hypertension by sun exposure habits adjusted for confounding. As compared to those women with the greatest sun exposure, women with low and moderate sun exposure were at 41% and 15% higher odds of hypertension (OR 1.41, 95% CI 1.3‒1.6, p < 0.001 and OR 1.15, 95% CI 1.1‒1.2, p < 0.001), respectively. There was a strong age-related increased risk of hypertension. Other risk factors for hypertension were lack of exercise (OR 1.36), a non-fair phenotype (OR 1.08), chronic high stress level (OR 1.8), and lack of university education (OR 1.3). We conclude that in our observational design sun exposure was associated with a dose-dependent reduced risk of hypertension, which might partly explain the fewer deaths of cardiovascular disease with increasing sun exposure.
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| 18. |
- Magnusdottir, O. K., et al.
(författare)
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Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity : a randomized study
- 2014
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 68:4, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS: Participants were 30-65 years of age, with body mass index 27-40 kg/m(2) and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND + control) regression analyses at 18/24 weeks. RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS.
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| 19. |
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| 20. |
- Olsson, H., et al.
(författare)
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Relation between tumour size and plasma prolactin levels in premenopausal patients with breast carcinoma : A preliminary report
- 1985
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Ingår i: Acta Radiologica: Oncology. - : Informa UK Limited. - 0349-652X. ; 24:1, s. 57-59
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Tidskriftsartikel (refereegranskat)abstract
- In thirty-one premenopausal patients with carcinoma of the breast the plasma prolactin was measured after mastectomy. A highly significant correlation between tumour size and plasma prolactin levels (p<0.002) was observed after adjustment for age at diagnosis and parity. At the time of the prolactin determination no clinical signs of metastatic disease were evident, suggesting that the prolactinc levels were unrelated to the tumour burden.
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| 21. |
- Olsson, H., et al.
(författare)
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Retrospective assessment of menstrual cycle length in patients with breast cancer, in patients with benign breast disease, and in women without breast disease
- 1983
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 70:1, s. 17-20
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Tidskriftsartikel (refereegranskat)abstract
- The length of the menstrual cycle was compared in women with breast cancer, women with benign breast disease, and controls. Older women in general tended to report shorter menstrual cycles (P < 0.05). After correction for the age difference, breast cancer patients still reported a shorter average menstrual cycle length than benign breast disease patients and controls (P < 0.006). Very short cycles (≤21 days) were present in 20% of the breast cancer patients compared to 8% of the patients with benign breast disease and 4% of the controls (P < 0.0001). Long cycles (≥30 days) were not a feature of breast cancer patients (2%), whereas 20% of the patients with benign breast disease and 28% of the controls reported such long cycles (P < 0.0001). Irregular menstrual cycles were more common in benign breast disease patients (20%) than in cancer patients (10%) and controls (8%) (P < 0.001).
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| 22. |
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| 23. |
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| 24. |
- Rosenstock, J, et al.
(författare)
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Effects of the DPP-4 Inhibitor Vildagliptin on Incretin Hormones, Islet Function, and Postprandial Glycemia in Subjects with Impaired Glucose Tolerance
- 2008
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 31:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). Research Design and Methods: A 12-week double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 179 subjects with IGT (2-h glucose= 9.1 mmol/l, A1C= 5.9%). Plasma levels of intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and Week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to endpoint in the total and incremental (Delta) AUC(0-2h) for these analytes were assessed by ANCOVA; glucose AUC(0-2h) was the primary outcome variable. Results: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0+/-1.2 pmol/l*h, P<0.001) and GIP (DeltaAUC, +46.8+/-5.4 pmol/l*h, P<0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol/l*h, P=0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8+/-35.7 pmol/l*h, P=0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0+/-0.3 mmol/l*h, P<0.001), representing approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2h)/glucose AUC(0-2h) was significantly increased (+6.4 +/- 2.0 pmol*min(-1)*m(-2)*mM(-1), P=0.002). Adverse event profiles were similar in the two treatment groups and no hypoglycemia was reported. Conclusions: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.
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| 25. |
- Sairenji, T., et al.
(författare)
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Relating homology between the Epstein-Barr virus BOLF1 molecule and HLA-DQw8 β chain to recent onset Type 1 (insulin-dependent) diabetes mellitus
- 1991
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Ingår i: Diabetologia. - 0012-186X. ; 34:1, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1(497-513) AVTPL RIFIVP PAAEY has an 11 amino acid identity with HLA-DQw8 β (49-60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496-515) peptide crossreacted with the homologous DQw8 β (44-63) peptide but not with the related DQw7 β(44-63) peptide, which differed from the DQw8 peptide only in an ALA to ASP substitution in position 57. Antisera to DQw8 β(49-60) reacted with the DQw8 β(44-63) peptide and BOLF1 (496-515), but not with DQw7 β (44-63). The antiserum to the BOLF1 peptide bound to denatured class II major histocompatibility complex β chains from Epstein-Barr virus-transformed DQw8-positive lymphocytes in an immunoblotting analysis. Epstein-Barr virus antibodies were detected at equal frequencies and similar titres in sera of 30 patients with Type 1 diabetes (16 of 30;63%) and in sera of 20 non-diabetic control subjects (13 of 20;65%). Sera from diabetic patients did not bind to DQw8 β (44-63) or BOLF1(496-515) peptides. From these data we conclude that there is no simple relationship between serological evidence of Epstein-Barr virus infection and crossreactions between homologous Epstein-Barr virus and class II major histocompatibility complex peptides.
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| 26. |
- Sanjeevi, Carani B., et al.
(författare)
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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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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Tidskriftsartikel (refereegranskat)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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| 27. |
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| 28. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 29. |
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| 30. |
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| 31. |
- Sun, Chengjun, et al.
(författare)
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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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Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)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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| 32. |
- Svensson, MK, et al.
(författare)
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The risk for diabetic nephropathy is low in young adults in a 17-year follow-up of the Diabetes Incidence Study in Sweden (DISS) : Higher age and BMI at diabetes onset can be important risk factors
- 2015
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 31:2, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To estimate the occurrence of diabetic nephropathy (DN) in a population-based cohort of patients diagnosed with diabetes as young adults (15-34 years). Methods: All 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19 years after diagnosis and 468 (58%) participated. Islet cell antibodies were used to classify type of diabetes.RESULTS: After median 17 years of diabetes 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with DN. 91% had micro- 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 1 kg/m(2) ) a near-significant predictor of development of DN. Age at onset of diabetes (p = 0.041), BMI (p = 0.012) and HbA1c (p < 0.001) were significant predictors of developing DN between 9 and 17 years of diabetes. At 17 years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1 mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.05-1.12 per 1 mmHg increase) were associated with DN.CONCLUSIONS: Patients with T2DM diagnosed as young adults seem to have an increased risk to develop DN compared to those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers of development of DN. In addition, poor glycaemic control but not systolic blood pressure at 9 years of follow up were risk markers for later development of DN.
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| 33. |
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| 34. |
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| 35. |
- Tyrberg, M., et al.
(författare)
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Overweight, hyperglycemia and tobacco use are modifiable risk factors for onset of retinopathy 9 and 17 years after the diagnosis of diabetes – A retrospective observational nation-wide cohort study
- 2017
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 133, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Background The aims of this study were to estimate the risk for diabetic retinopathy (DR) and to identify risk factors. We investigated a nationwide population-based cohort with diabetes diagnosed at age 15–34 years. Patients and methods Of 794 patients registered 1987–1988 in the Diabetes Incidence Study in Sweden (DISS) 444 (56%) patients with retinal photos available for classification of retinopathy participated in a follow-up study 15–19 (median 17) years after diagnosis. Mean age was 42.3 ± 5.7 years, BMI 26.1 ± 4.1 kg/m2, 62% were male and 91% had type 1 diabetes. A sub-study was performed in 367 patients with retinal photos from both the 9 and 17 year follow up and the risk for development of retinopathy between 9 and 17 years of follow up was calculated. Results After median 17 years 324/444 (73%, 67% of T1D and 71% of T2D), had developed any DR but only 5.4% proliferative DR. Male sex increased the risk of developing retinopathy (OR 1.9, 95% CI 1.2–2.9). In the sub-study obesity (OR 1.2, 95% CI 1.04–1.4), hyperglycemia (OR 2.5, 95% CI 1.6–3.8) and tobacco use (OR 2.9, 95% CI 1.1–7.3) predicted onset of retinopathy between 9 and 17 years after diagnosis of diabetes. Conclusion The number of patients with severe retinopathy after 17 years of diabetes disease was small. The risk of developing retinopathy with onset between 9 and 17 years after diagnosis of diabetes was strongly associated to modifiable risk factors such as glycemic control, obesity and tobacco use.
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| 36. |
- Borg, H., et al.
(författare)
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High levels of antigen-specific islet antibodies predict future β-cell failure in patients with onset of diabetes in adult age
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X. ; 86:7, s. 3032-3038
-
Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict β-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete β-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with β-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without β-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with β-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete β-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete β-cell failure, whereas low GADA levels predict slowly progressive β-cell insufficiency.
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| 37. |
- Fawwaz, S., et al.
(författare)
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No evidence of association of the PDCD1 gene with Type 1 diabetes
- 2007
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 24:12, s. 1473-1477
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To test the association between the immunoreceptor PD-1 (PDCD1) gene and Type 1 diabetes mellitus (T1DM). This gene has been reported to be associated with other autoimmune diseases such as systemic lupus erythematosus (SLE) as well as T1DM. Methods: Genotyping of single nucleotide polymorphisms (SNPs) in the PDCD1 gene was performed using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), pyrosequencing and TaqMan in two separate cohorts of Swedish patients and control subjects: a family study consisting of 184 multiplex and eight simplex families and a case-control study consisting of 586 patients and 836 control subjects. Three SNPs were genotyped: PD-1 7146, PD-1 7785 and PD-1 8738. Results: We did not detect any association or linkage between SNPs in PDCD1 and T1DM. We further performed a meta-analysis for association of PD-1 7146, PD-1 7785 and PD-1 8738 to T1DM. We detected heterogeneity in association with weak evidence for overall association. Conclusions: We conclude that PDCD1 is unlikely to be a major susceptibility gene for T1DM.
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| 38. |
- Gottsater, A., et al.
(författare)
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β-cell function in relation to islet cell antibodies during the first 3 yr after clinical diagnosis of diabetes in type II diabetic patients
- 1993
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 16:6, s. 902-910
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To determine the effects of islet cell antibodies on β-cell function during the first 3 yr after diagnosis in type II diabetic patients. RESEARCH DESIGN AND METHODS - β-cell function in type II diabetic patients with (n = 11, 50 ± 5 yr of age) and without (n = 10, 52 ± 4 yr of age) ICA was followed prospectively and compared with β-cell function in type I adult diabetic patients (n = 17, 37 ± 5 yr of age) and in healthy control subjects (n = 34, age 45 ± 3 yr). β-cell function was evaluated as fasting C- peptide, 1 + 3 min C-peptide after intravenous glucose, and Δ C-peptide after glucagon. RESULTS - Fasting C-peptide was equal in type II diabetic patients with ICA (0.30 ± 0.03 nM) and type I diabetic patients (0.24 ± 0.03 nM) at diagnosis, and decreased (P < 0.05) during 3 yr in these groups but not in type II diabetic patients without ICA. At diagnosis, type II diabetic patients with ICA showed a 1 + 3 min C-peptide (0.92 ± 0.17 nM) lower (P < 0.001) than control subjects but higher (P < 0.05) than type I diabetic patients (0.53 ± 0.11 nM). After 1 yr, 1 + 3 min C-peptide in type II diabetic patients with ICA had decreased (P < 0.05) to 0.18 ± 0.11 nM and was equal to type I diabetic patients (0.38 ± 0.10 nM). Δ C-peptide after glucagon was equally impaired in type II diabetic patients with ICA (0.38 ± 0.06 nM) and type I diabetic patients (0.35 ± 0.11 nM) at diagnosis. After 3 yr, type II diabetic patients with ICA had fasting C-peptide of 0.09 ± 0.04 nM, 1 + 3 min C-peptide of 0.18 ± 0.10 nM, and Δ C-peptide after glucagon of 0.20 ± 0.09 nM, values equal to type I diabetic patients but lower (P < 0.01) than in type II diabetic patients without ICA, whose values remained unchanged; fasting C-peptide of 0.97 ± 0.17 nM, 1 + 3 min C-peptide of 2.31 ± 0.50 nM, and Δ C-peptide after glucagon of 1.76 ± 0.28 nM. CONCLUSIONS - In patients considered type II diabetic with ICA, β-cell function progressively decreased after diagnosis, and after 3 yr was similar to type I diabetic patients, whereas β-cell function in type II diabetic patients without ICA was unchanged.
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| 39. |
- Gottsäter, A., et al.
(författare)
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Glutamate decarboxylase antibody levels predict rate of β-cell decline in adult-onset diabetes
- 1995
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Ingår i: Diabetes Research and Clinical Practice. - 0168-8227. ; 27:2, s. 133-140
-
Tidskriftsartikel (refereegranskat)abstract
- Glutamate decarboxylase autoantibodies (GAD65Ab) and β-cell function were evaluated at and 3 years after diabetes onset in consecutive subjects over 15 years of age. At onset, 21 32 (66%) insulin-treated patients (mean age 43, range 16-79 years) had GAD65Ab; all GAD65Ab persisted 3 years later. At onset, 20 82 (24%) non-insulin-treated patients (mean age 56, range 20-79 years) had GAD65Ab. Of those with persistent GAD65Ab, 8 non-insulin-treated and 11 insulin-treated patients consented to follow-up glucose and glucagon stimulation tests. For non-insulin-treated patients, quantitative GAD65Ab index at onset correlated inversely with 1+3 min C-peptide response to glucose (r = -0.68, P < 0.05) and to glucagon (r = -0.79, P < 0.05) 3 years later. Those with high (> 0.50) initial GAD65Ab index had lower C-peptide (fasting, 1+3 min after glucose and after glucagon) 3 years later, versus those with low (<0.50) initial GAD65Ab index (P < 0.05). In conclusion, not only did GAD65Ab presence predict future insulin dependence, but higher GAD65Ab levels may mark more rapid decline in β-cell function in apparent non-insulin-dependent diabetes.
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| 40. |
- Gottsäter, A., et al.
(författare)
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Islet cell antibodies are associated with β-cell failure also in obese adult onset diabetic patients
- 1994
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Ingår i: Acta Diabetologica. - 0940-5429. ; 31:4, s. 226-231
-
Tidskriftsartikel (refereegranskat)abstract
- To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data Group, NDDG criteria). Among the 233 patients, 31 were nonobese ICA-positive (mean age at diagnosis 43±3 years), 55 nonobese ICA-negative (mean age at diagnosis 58±2 years), 7 obese ICA-positive (mean age at diagnosis 57±5 years), and 139 obese ICA-negative (mean age at diagnosis 58±1 years). Fasting C-peptide decreased (P<0.05) in nonobese ICA-positive patients who after 3 years showed lower BMI (22.6±0.6 versus 24.5±0.4;P<0.05), lower fasting C-peptide (0.14±0.06 nmol/l versus 0.71±0.07 nmol/l;P<0.001), and higher frequency of insulin treatment [28/31 (90%) versus 6/45 (13%);P<0.001] than nonobese ICA-negative patients. In obese ICA-positive patients, fasting C-peptide also decreased (Δ C-peptide 0.17±0.04 nmol/l;P<0.05) after diagnosis, and 3 years after diagnosis, obese ICA-positive patients showed lower BMI (25.7±1.2 versus 29.8±0.4;P<0.01) and fasting C-peptide (0.08±0.04 nmol/l versus 1.06±0.05 nmol/l;P<0.001) and higher HbA1c values (9.92%±0.68% versus 7.39%±0.21%;P<0.01) and a higher frequency of insulin treatment [7/7 (100%) versus 5/121 (4%);P<0.001] than obese ICA-negative patients. Therefore, ICA detected at diagnosis of diabetes in both obese and nonobese adult patients indicate β-cell dysfunction, high HbA1c levels, and progression to insulin dependency.
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| 41. |
- Gottsäter, A., et al.
(författare)
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Pancreatic beta-cell function evaluated by intravenous glucose and glucagon stimulation. A comparison between insulin and c-peptide to measure insulin secretion
- 1992
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 52:7, s. 631-639
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Tidskriftsartikel (refereegranskat)abstract
- Insulin and C-peptide responses to 0.5 g kg-1 intravenous glucose and 1.0 mg glucagon were studied in 34 healthy subjects (age 19-78 years, mean 45). Fasting blood glucose (r=0.59; p<0.001) and glycosylated haemoglobin (r=0.61; p<0.001) increased with age, but not the initial C-peptide and insulin responses to the glucose infusion. However, the C-peptide response at 70 min (r=0.36; p<0.05), 80 min (r=0.41; p<0.05), and 90 min (r=0.46; p<0.01) after the glucose infusion correlated with age as well as both insulin (r=0.42; p<0.05) and C-peptide (r=0.45; p<0.05) responses to the glucagon injection. Reproducibility of insulin and C-peptide responses was evaluated by duplicate tests, separated 2-143 days in time, in 10 healthy subjects (age 19-48 years, mean 32 years) showing no significant differences in median within-subject variation between the initial (1+3 min) or overall (0-90 min area under curve) insulin (24% and 17% respectively) and C-peptide (15% and 14% respectively) responses to glucose, while the within-subject variation for the fasting values and the response to glucagon was higher (p<0.05) for insulin (47% and 32% respectively) than C-peptide (13% and 14% respectively). Between-subject variation was also lower (p<0.001) for C-peptide than for insulin. Thus, C-peptide measurements in healthy subjects are more reproducible than insulin measurements in determination of beta-cell function.
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| 42. |
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| 43. |
- Grubin, C. E., et al.
(författare)
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A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM
- 1994
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Ingår i: Diabetologia. - 0012-186X. ; 37:4, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p<0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14 year-old patients (n=105), and matched, healthy control subjects (n=157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77% and the specificity 92% compared with 8% and 98%, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD.
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| 44. |
- Gupta, M, et al.
(författare)
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Coxsackie virus B antibodies are increased in HLA DR3-MICA5.1 positive type 1 diabetes patients in the Linkoping region of Sweden
- 2003
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Ingår i: Human Immunology. - 0198-8859. ; 64:9, s. 874-879
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which genetics and environmental factors play a role. Among the environmental factors, viruses (especially Coxsackie virus B [CBV]), and among genetic markers, human leukocyte antigen (HLA) DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) and DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2), and major histocompatibility complex class I chain-related gene-A (MICA) alleles 5 and 5.1 have been reported to be associated with T1DM in Caucasians. Sweden ranks third in the world for T1DM incidence. In Sweden, the Linkoping region indicates the highest incidence for T1DM. In this study, we analyzed whether antibodies against CBV are increased in DR3, DR4, MICA5, or MICA5.1 positive patients from Linkoping (n = 46) and from Swedish population as a whole (n = 298) between the age of 0 and 15 years old. There was no difference in the frequency of antibodies to CBV in patients compared with controls in Linkoping (26% vs 23%) or in all of Sweden (26% vs 21%). However, CBV antibodies were increased in DR3, DR3-DR4 (heterozygous), DR3-MICA5.1, and DR3-DR4-MICA5.1 positive compared with DR3, DR3-DR4, DR3-MICA5.1, and DR3-DR4-MICA5.1 negative patients in Linkoping (p < 0.05 for all), but not in Swedish population as a whole. Thus, our study suggests that in addition to DR3, MICA5.1 has an influence on the immune response to CBV infection in patients from Linkoping. (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Inc.
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| 45. |
- Hallengren, B., et al.
(författare)
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Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients : At diagnosis and following treatment
- 1996
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 239:1, s. 63-68
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To study the frequency of islet cell (ICA) and glutamic acid decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different types at diagnosis before treatment and in the euthyroid state following treatment. Setting. Department of Endocrinology, Malmo University Hospital, Malmo, Sweden. Subjects and design. Blood samples were collected at diagnosis from 129 hyperthyroid patients, and about 6 months later, from 78 of the patients (euthyroid state). Ninety-two patients had Graves' disease (69 females and 23 males, median age 49 years, range 17-85 years), and 37 patients had toxic nodular goitre/solitary toxic adenoma (34 females and three males, median age 69 years, range 24-86 years). Interventions. Most patients were treated by radioactive iodine following the first blood sample. Main outcome measures. ICA and GAD-Ab in serum. Results. At diagnosis of Graves' disease, ICA were detected in two out of 92 (2.2%) patients, two out of 85 (2.4%) without diabetes mellitus and in the euthyroid state in one patient. None of the patients with toxic nodular goitre/solitary toxic adenoma had detectable ICA. At diagnosis of Graves' disease, GAD65-Ab as well as GAD67-Ab were detected in 11 out of 85 (13%) patients without diabetes. As many as six out of 11 GAD67-Ab-positive patients were GAD65-Ab negative. In the euthyroid state, GAD65-Ab were found in six out of 51 (12%) and GAD67-Ab in eight out of 51 (16%) of the non-diabetic Graves' disease patients. The frequencies of GAD65-Ab and GAD67-Ab in toxic nodular goitre/solitary toxic adenoma, diabetes excluded, were 3 and 0%, respectively, in the hyperthyroid state. Conclusion. The frequency of ICA in patients with hyperthyroidism is not increased as compared to the background population. GAD-Ab seems to be associated with Graves' disease and not with hyperthyroidism. The presence of GAD67-Ab in GAD65-Ab negative sera from patients with Graves' disease indicates autoreactivity against a specific GAD67 epitope.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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