| 1. |
- Andersen, Marie Louise M., et al.
(författare)
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Association between autoantibodies to the Arginine variant of the Zinc transporter 8 (ZnT8) and stimulated C-peptide levels in Danish children and adolescents with newly diagnosed type 1 diabetes
- 2012
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 13:6, s. 454-462
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Tidskriftsartikel (refereegranskat)abstract
- Background The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D. Objectives The main aims were to determine whether ZnT8Ab vary during follow-up 1 year after diagnosis, and to relate the reactivity of three types of ZnT8Ab to the residual stimulated C-peptide levels during the first year after diagnosis. Subjects A total of 129 newly diagnosed T1D patients <15 years was followed prospectively 1, 3, 6, and 12 months after diagnosis. Methods Hemoglobin A1c, meal-stimulated C-peptide, ZnT8Ab, and other pancreatic autoantibodies were measured at each visit. Patients were genotyped for the rs13266634 variant at the SLC30A8 gene and HLA-DQ alleles. Results The levels of all ZnT8Ab [ZnT8Arg (arginine), ZnT8Trp (tryptophan), ZnT8Gln (glutamine)] tended to decrease during disease progression. A twofold higher level of ZnT8Arg and ZnT8Gln was associated with 4.6%/5.2% (p = 0.02), 5.3%/8.2% (p = 0.02) and 8.9%/9.7% (p = 0.004) higher concentrations of stimulated C-peptide 3, 6, and 12 months after diagnosis. The TT genotype carriers of the SLC30A8 gene had 45.8% (p = 0.01) and 60.1% (p = 0.002) lower stimulated C-peptide 6 and 12 months after diagnosis compared to the CC and the CT genotype carriers in a recessive model. Conclusions The levels of the Arg variant of the ZnT8 autoantibodies are associated with higher levels of stimulated C-peptide after diagnosis of T1D and during follow-up. Carriers of the TT genotype of the SLC30A8 gene predict lower stimulated C-peptide levels 12 months after diagnosis.
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| 2. |
- Andersen, Paul Krüger, et al.
(författare)
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Response to the Proposal for a Directive on Corporate Sustainability Due Diligence by Nordic and Baltic Company Law Scholars
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- On February 23, 2022, The EU Commission published its Proposal for a Directive of the European Parliament and of the Council on Corporate Sustainability Due Diligence and amending Directive (EU) 2019/1937 (“CSDDD” or “the Proposal”). The purpose of the Proposal, to further the “Union’s transition to a climate-neutral and green economy in line with the European Green Deal and in delivering on the UN Sustainable Development Goals”, is of great importance, and the Commission’s initiative is therefore commendable. However, it is our firm opinion that the Proposal should not be enacted in its present form, and that if it were to be, it would not only damage European businesses but also run the risk of having an adverse effect on both the transition to a climate-neutral economy as well as the goal of delivering on the UN Sustainable Development Goals. This is to a large extent because many of the Proposal’s provisions are excessive, unfounded and disproportionate and as such in violation of the fundamental principles of subsidiarity and proportionality safeguarded by Art. 5 TEU as well as having a questionable basis in Art. 50 TFEU. Furthermore and in regard of procedure, we find that the presentation of the Proposal by the Commission represents a disregard for the principles of better regulation that should not pass unnoticed and must be observed in the future to maintain trust in the legislative process of the Union.In this response to the consultation, we have presented an analysis of the key issues of the Proposal from a corporate governance perspective. We have divided the response into two parts: one on the pure corporate governance parts of the Proposal (article 15, 25 and 26) and one of the due diligence parts of the Proposal. With regards to the corporate governance parts of the Proposal, our conclusion is that they, by and large, should not be included in the proposed directive at all. Including them would in several ways be in breach of the EU principles on subsidiarity and proportionality, but perhaps more importantly, they are not only unsubstantiated by available empirical evidence on corporate behaviour, but also refuted by what we know. There is also good reason to believe that the proposed rules on director’s duties and environmental remuneration would risk decreasing the effectiveness of the stock markets within the EU contrary to the goal of a Capital Market Union, which also risk slowing down the necessary transition to a green economy and the goals of the EU Green Deal. The regulation necessary for the Capital Market Union and the EU Green Deal should complement each other, not collide as would be the outcome if the Proposal is adopted in its present form.With regards to the due diligence parts of the Proposal, our criticism is limited to corporate governance aspects and far less fundamental. We primarily believe that grounds for harmonisation needs further consideration in the present very challenging times, that Article 22 on Civil Liability might in several ways be counter-productive to the goals of the Proposal, that the effects on SMEs as well as for the financial companies included covered by the Proposal warrants further analysis, that the choice to focus the Proposal on individual companies instead of company groups needs to be reviewed, and that a risk based approach should be taken rather than an approach were companies are unable to focus their efforts to where they can be most effective. Overall, these issues can be worked out, but if they are not, then the proposed directive would not only have a severe adverse impact on EU companies and possibly capital markets, but might actually hinder EU companies from acting in the way that the Proposal aims for them to do.This joint response to the public consultation is made by a group of Nordic and Baltic company law scholars who, although we may not agree on every detail, do share the main arguments and grave concerns expressed here.
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| 3. |
- Christensen, Diana Hedevang, et al.
(författare)
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Type 2 diabetes classification : a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
- 2022
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort. Research design and methods In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes. Results Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m 2 vs 36 kg/m 2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype. Conclusion Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.
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| 4. |
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| 5. |
- Gedebjerg, Anne, et al.
(författare)
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CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes : A Danish Cohort Study
- 2023
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:5, s. 1037-1045
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the relationship between hs-CRP, a marker of low-grade inflam-mation, alone or in combination with C-peptide, a marker of hyperinsulinemia/ insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes cohort study. Patients with no prior CVE (n = 6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n = 7,301) were followed for all-cause mortality. We com-puted adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide. RESULTS During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP was associated with increased CVE risk (aHR 1.45 [95% CI 1.07–1.96]) and with even greater risk of all-cause mortality (2.47 [1.88–3.25]). Compared with patients with low hs-CRP (£3 mg/L) and low C-peptide (<1,470 pmol/L), those with high lev-els of both biomarkers had the highest CVE (1.61 [1.10–2.34]) and all-cause mortality risk (2.36 [1.73–3.21]). Among patients with high C-peptide, risk of CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did. CONCLUSIONS The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker sup-ports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.
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| 6. |
- Goyette, Philippe, et al.
(författare)
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High-density mapping of the MHC identifies a shared role for HLA-DRB1*01 : 03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis
- 2015
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Ingår i: Nature Genetics. - New York, USA : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:2, s. 172-179
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
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| 10. |
- Haugbølle, Troels, et al.
(författare)
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The Velocity Field of the Local Universe from Measurements of Type Ia Supernovae
- 2007
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Ingår i: The Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 661:2, s. 650-659
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the velocity flow of the local universe relative to the CMB rest frame, based on the recent Jha et al. sample of 133 low-redshift Type Ia supernovae. At a depth of 4500 km s-1 we find a dipole amplitude of 279+/-68 km s-1 in the direction l=285°+/-18°, b=-10°+/-15°, consistent with earlier measurements and with the assumption that the local velocity field is dominated by the Great Attractor region. At a greater depth of 5900 km s-1, we find a shift in the dipole direction toward the Shapley Concentration. We also present the first measurement of the quadrupole term in the local velocity flow at these depths. Finally, we have performed detailed studies based on N-body simulations of the expected precision with which the lowest multipoles in the velocity field can be measured out to redshifts of order 0.1. Our mock catalogs are in good agreement with current observations and demonstrate that our results are robust with respect to assumptions about the influence of local environment on the Type Ia supernova rate.
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