| 1. |
- Nilsson, Anna-Lena, et al.
(författare)
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Relationship between Ljungan virus antibodies, HLA-DQ8, and insulin autoantibodies in newly diagnosed type 1 diabetes children
- 2013
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Ingår i: Viral immunology. - : Mary Ann Liebert, Inc.. - 0882-8245 .- 1557-8976. ; 26:3, s. 207-215
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n = 676) and controls (n = 309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75th percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4th quartile LVAb were found in 25% (170/676) of which 64% were < 10 (n = 108, p < 0.0001), and 27% were < 5 (n = 45; p < 0.0001) years old. The 4th quartile LVAb in children < 10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p < 0.0001). Furthermore, in the group with 4th quartile LVAb, 55% were IAA positive (p = 0.01) and correlation was found between 4th quartile LVAb and IAA in children < 10 years of age (p = 0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4th quartile LVAb correlated with IAA; and 3) there was a correlation between 4th quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.
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| 2. |
- Andersson, C, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
- 2011
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Ingår i: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:5, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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| 3. |
- Carlsson, Björn, 1958, et al.
(författare)
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Obese (ob) gene defects are rare in human obesity
- 1997
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 5:1, s. 30-5
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
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| 4. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.
- 2023
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Ingår i: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Tidskriftsartikel (refereegranskat)abstract
- To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study.The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n=265), banding (n=376), or vertical banded gastroplasty (n=1369). The control group (n=2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n=392 surgery patients/n=305 controls) or non-T2D (n=1609 surgery patients/n=1726 controls) during a median follow-up 26 years.In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p=0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p=0.516)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
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| 5. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study.
- 2017
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:4, s. 271-279
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery is associated with remission of diabetes and prevention of diabetic complications in patients with obesity and type 2 diabetes. Long-term effects of bariatric surgery on microvascular complications in patients with prediabetes are unknown. The aim of this study was to examine the effects of bariatric surgery on incidence of microvascular complications in patients with obesity stratified by baseline glycaemic status.Patients were recruited to the Swedish Obese Subjects (SOS) study between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years and BMI of 34 kg/m(2) or greater in men and 38 kg/m(2) or greater in women. Exclusion criteria were identical in surgery and control groups and designed to exclude patients not suitable for surgery. The surgery group (n=2010) underwent gastric bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty (1369 [68%]). Participants in the control group (n=2037) received usual care. Bodyweight was measured and questionnaires were completed at baseline and at 0·5 years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years. Biochemical variables were measured at baseline and at 2 years, 10 years, and 15 years. We categorised participants into subgroups on the basis of baseline glycaemic status (normal [fasting blood glucose concentration <5·0 mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at baseline visit without previous diagnosis], and established diabetes [diagnosis of diabetes before study inclusion]). We obtained data about first incidence of microvascular disease from nationwide registers and about diabetes incidence at study visits at 2 years, 10 years, and 15 years. We did the main analysis by intention to treat, and subgroup analyses after stratification by baseline glycaemic status and by diabetes status at the 15 year follow-up. The SOS study is registered with ClinicalTrials.gov, NCT01479452.4032 of the 4047 participants in the SOS study were included in this analysis. We excluded four patients with suspected type 1 diabetes, and 11 patients with unknown glycaemic status at baseline. At baseline, 2838 patients had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes, and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We identified 374 incident cases of microvascular disease in the control group and 224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001). Interaction between baseline glycaemic status and effect of treatment on incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was associated with reduced incidence of microvascular events in people with prediabetes regardless of whether they developed diabetes during follow-up.Bariatric surgery was associated with reduced risk of microvascular complications in all subgroups, but the greatest relative risk reduction was observed in patients with prediabetes at baseline. Our results suggest that prediabetes should be treated aggressively to prevent future microvascular events, and effective non-surgical treatments need to be developed for this purpose.US National Institutes of Health, Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and Swedish Diabetes Foundation.
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| 6. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
- 2019
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Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
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Tidskriftsartikel (refereegranskat)abstract
- Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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| 7. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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Molecular characterization of a local sulfonylurea system in human adipose tissue.
- 2004
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Ingår i: Molecular and cellular biochemistry. - 0300-8177 .- 1573-4919. ; 258:1-2, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- ATP-sensitive potassium (KATP) channels are present in many cell types and link cellular metabolism to the membrane potential. These channels are heterooctamers composed of two subunits. The sulfonylurea receptor (SUR) subunits are targets for drugs that are inhibitors or openers of the KATP channels, while the inwardly rectifying K+ (Kir) subunits form the ion channel. Two different SUR genes (SUR1 and SUR2) and two different Kir6.x genes (Kir6.1 and Kir6.2) have been identified. In addition, isoforms of SUR2, SUR2A and SUR2B, have been described. We have previously performed expression profiling on pooled human adipose tissue and found high expression of SUR2. Others have reported expression of SUR1 in human adipocytes. The aim of this study was to characterize the expression of the sulfonylurea receptor complex components in human adipose tissue. RT-PCR analysis, verified by restriction enzyme digestions and DNA sequencing, showed that SUR2B, Kir6.1 and alpha-endosulfine, but not SUR1, SUR2A or Kir6.2, are expressed in human adipose tissue. Real-time RT-PCR showed that SUR2B was expressed at higher levels in subcutaneous compared with omental adipose tissue in paired biopsies obtained from seven obese men (p < 0.05). Analysis of tissue distribution showed that SUR2B expression in adipose tissue was lower than that in muscle, similar to that in heart and liver, while the expression in pancreas was lower. The effect of caloric restriction was tested in obese men (n = 10) treated with very low calorie diet for 16 weeks, followed by a gradual reintroduction of ordinary food for 2 weeks. Biopsies were taken at week 0, 8 and 18. There was no consistent effect of weight reduction on SUR2B or Kir6.1 expression. We conclude that the necessary components for a local sulfonylurea system are expressed in human adipose tissue and that the sulfonylurea receptor complex in this tissue is composed of SUR2B and Kir6.1. The expression of SUR2B was higher in subcutaneous compared with omental adipose tissue and was not affected by weight loss.
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| 8. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 9. |
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| 10. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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