| 1. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 2. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 3. |
- Lind, Mikael, et al.
(författare)
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Sea Traffic Management - Beneficial for all Maritime Stakeholders
- 2016
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Ingår i: Transportation Research Procedia. - : Elsevier BV. ; 14, s. 183-192
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Konferensbidrag (refereegranskat)abstract
- Sea Traffic Management is the idea of sharing information and collaborating to optimise the maritime transport chain while increasing safety and sustainability. The digital information on-board and on shore is abundant; however, the interconnection today is point-to-point and proprietary and stops the industry becoming more efficient. We will discuss how Sea Traffic Management will help the industry achieve improved predictability by introducing standards for key information and supplying an infrastructure for information exchange. This enables all actors involved in the transport to plan better and utilise their resources more efficiently. Shorter routes, just-in-time arrivals, shorter port calls are factors that will strengthen the competitiveness of the maritime sector. Improved situational awareness on the bridge and knowledge of planned routes will help optimised planning as well as reducing the number of incidents and accidents. The standard route exchange format submitted by the EU-financed MONALISA 2.0 project partners in 2014 is included in the current edition of the IEC standard, which was launched in August 2015. Solutions using that standard will start realising the benefits already next year. We will describe an infrastructure, which could work in a centralised manner but also has the flexibility to be organised in a more federative manner, similar to how the maritime world works in many aspects. Some key components are: a unique identifier for each voyage; that the information publisher controls who can access the data; that updated information should be made available in real-time; and that subscription to updated data will be the main trigger for many systems and processes. We will also describe the outcomes of the test beds in the MONALISA 2.0 project - The Sound: how shore and vessel can interact better in order improve safety in dense traffic areas; Port of Gothenburg and Port of Valencia - how collaborative decision making can improve operations for all involved actors; European Maritime Simulator Network - how new solutions can be tested in complex traffic situations and areas with real people on a large number of bridges, without risk. How large of an impact will all this have on the maritime transport industry? Based on a study from Linköping University, we believe that the number €1 billion/year in Europe due to shorter routes is only the tip of the benefit iceberg. In the study ship operators and society split the benefit 50/50. Ship operators save on fuel and other cost, society saves on reduced emissions, and other actors associated to maritime operations benefit from a higher degree of infrastructural use. We will also present results from other business cases developed during 2015, in which the benefits of Sea Traffic Management are elaborated on main stakeholders.
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| 4. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 5. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 6. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 7. |
- Ahlén, Elsa, 1990, et al.
(författare)
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Glycemic control, renal complications, and current smoking in relation to excess risk of mortality in persons with type 1 diabetes
- 2016
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Ingår i: Journal of Diabetes Science and Technology. - : SAGE Publications. - 1932-2968. ; 10:5, s. 1006-1014
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: A substantial excess risk of mortality still exists in persons with type 1 diabetes. The aim of this study was to evaluate the excess risk of mortality in persons with type 1 diabetes without renal complications who target goals for glycemic control and are nonsmokers. Furthermore, we evaluated risk factors of death due to hypoglycemia or ketoacidosis in young adults with type 1 diabetes. Methods: We evaluated a cohort based on 33 915 persons with type 1 diabetes and 169 249 randomly selected controls from the general population matched on age, sex, and county followed over a mean of 8.0 and 8.3 years, respectively. Hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality for persons with type 1 diabetes versus controls were estimated. Results: The adjusted HRs for all-cause and CVD mortality for persons with type 1 diabetes without renal complications (normoalbuminuria and eGFR ≥ 60 ml/min) and HbA1c ≤ 6.9% (52 mmol/mol) compared to controls were 1.22 (95% CI 0.98-1.52) and 1.03 (95% CI 0.66-1.60), respectively. The HRs increased with higher updated mean HbA1c. For nonsmokers in this group, the HRs for all-cause and CVD mortality were somewhat lower: 1.11 (95% CI 0.87-1.42) and 0.89 (95% CI 0.53-1.48) at updated mean HbA1c ≤ 6.9% (52 mmol/mol). HRs for significant predictors for deaths due to hypoglycemia or ketoacidosis in persons < 50 years were male sex 2.40 (95% CI 1.27-4.52), smoking 2.86 (95% CI 1.57-5.22), lower educational level 3.01 (95% CI 1.26-7.22), albuminuria or advanced kidney disease 2.83 (95% CI 1.63-4.93), earlier hospital diagnosis of hypoglycemia or ketoacidosis 2.30 (95% CI 1.20-4.42), and earlier diagnosis of intoxication 2.53 (95% CI 1.06-6.04). Conclusions: If currently recommended HbA1c targets can be reached, renal complications and smoking avoided in persons with type 1 diabetes, the excess risk of mortality will likely converge substantially to that of the general population.
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| 8. |
- Ahmadi, Shilan Seyed, et al.
(författare)
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Effect of liraglutide on anthropometric measurements, sagittal abdominal diameter and adiponectin levels in people with type 2 diabetes treated with multiple daily insulin injections: evaluations from a randomized trial (MDI-liraglutide study 5)
- 2019
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Ingår i: Obesity Science and Practice. - : Wiley. - 2055-2238. ; 5:2, s. 130-140
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Tidskriftsartikel (refereegranskat)abstract
- Aim Use of the glucagon-like peptide 1 receptor agonist liraglutide has been shown to reduce weight. Different types of anthropometric measurements can be used to measure adiposity. This study evaluated the effect of liraglutide on sagittal abdominal diameter, waist circumference, waist-to-hip ratio and adiponectin levels in people with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDI). Materials and methods In the multicentre, double-blind, placebo-controlled MDI-liraglutide trial, 124 individuals with T2D treated with MDI were randomized to either liraglutide or placebo. Basal values of weight, waist circumference, waist-to-hip ratio, sagittal abdominal diameter and adiponectin were compared with measurements at 12 and 24 weeks after randomization. Results Baseline-adjusted mean weight loss was 3.8 +/- 2.9 kg greater in liraglutide than placebo-treated individuals (p < 0.0001). Waist circumference was reduced by 2.9 +/- 4.3 cm and 0.2 +/- 3.6 cm in the liraglutide and placebo groups, respectively, after 24 weeks (baseline-adjusted mean difference: 2.6 +/- 4.0 cm, p = 0.0005). Corresponding reductions in sagittal abdominal diameter were 1.1 +/- 1.7 cm and 0.0 +/- 1.8 cm (baseline-adjusted mean difference: 1.1 +/- 1.7 cm, p = 0.0008). Hip circumference was reduced in patients randomized to liraglutide (baseline-adjusted mean difference between treatment groups: 2.8 +/- 3.8 cm, p = 0.0001), but there was no significant difference between the groups in either waist-to-hip ratio (baseline-adjusted mean difference: 0.0 +/- 0.04 cm, p = 0.51) or adiponectin levels (baseline-adjusted mean difference: 0.8 +/- 3.3 mg L-1, p = 0.17). Lower HbA1c and mean glucose levels measured by masked continuous glucose monitoring at baseline were associated with greater effects of liraglutide on reductions in waist circumference and sagittal abdominal diameter. Conclusions In patients with T2D, adding liraglutide to MDI may reduce abdominal and hip obesity to a similar extent, suggesting an effect on both visceral and subcutaneous fat. Liraglutide had greater effects on reducing abdominal obesity in patients with less pronounced long-term hyperglycaemia but did not affect adiponectin levels.
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| 9. |
- Andelin, M., et al.
(författare)
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Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.
- 2016
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Ingår i: Journal of Diabetes Science and Technology. - : Diabetes Technology Society. - 1932-2968. ; 10:4, s. 876-884
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Tidskriftsartikel (refereegranskat)abstract
- Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM.less thanbr /greater thanMethods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples.less thanbr /greater thanResults: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P less than .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P less than .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P less than .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82.less thanbr /greater thanConclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.less thanbr /greater than (© 2016 Diabetes Technology Society.)
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| 10. |
- Arnold, S. V., et al.
(författare)
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Recognition of Incident Diabetes Mellitus During an Acute Myocardial Infarction
- 2015
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Ingår i: Circulation-Cardiovascular Quality and Outcomes. - : Ovid Technologies (Wolters Kluwer Health). - 1941-7705 .- 1941-7713. ; 8:3, s. 260-267
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Tidskriftsartikel (refereegranskat)abstract
- Background-Diabetes mellitus (DM) is common in patients hospitalized with an acute myocardial infarction (AMI), representing in some cases the first opportunity to recognize and treat DM. We report the incidence of new DM and its recognition among patients with AMI. Methods and Results-Patients in a 24-site US AMI registry (2005-08) had glycosylated hemoglobin assessed at a core laboratory, with results blinded to clinicians and local clinical measurements left to the discretion of the treating providers. Among 2854 AMI patients without known DM on admission, 287 patients (10%) met criteria for previously unknown DM, defined by a core laboratory glycosylated hemoglobin of >= 6.5%. Among these, 186 (65%) were unrecognized by treating clinicians, receiving neither DM education, glucose-lowering medications at discharge, nor documentation of DM in the chart (median glycosylated hemoglobin of unrecognized patients, 6.7%; range, 6.5-12.3%). Six months after discharge, only 5% of those not recognized as having DM during hospitalization had been initiated on glucose-lowering medications versus 66% of those recognized (P< 0.001). Conclusions-Underlying DM that has not been previously diagnosed is common among AMI patients, affecting 1 in 10 patients, yet is recognized by the care team only one third of the time. Given its frequency and therapeutic implications, including but extending beyond the initiation of glucose-lowering treatment, consideration should be given to screening all AMI patients for DM during hospitalization. Inexpensive, ubiquitous, and endorsed as an acceptable screen for DM, glycosylated hemoglobin testing should be considered for this purpose.
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| 11. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 12. |
- Ciuculete, Diana-Maria, et al.
(författare)
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A genetic risk score is significantly associated with statin therapy response in the elderly population
- 2017
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 91:3, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- The ability of statins to strongly reduce low-density lipoprotein cholesterol (LDL-C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population-based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL-C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population-based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL-C reduction to a considerable extent in the older population.
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| 13. |
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| 14. |
- Dahlqvist, S., et al.
(författare)
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Risk of atrial fibrillation in people with type 1 diabetes compared with matched controls from the general population: a prospective case-control study
- 2017
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 5:10, s. 799-807
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Tidskriftsartikel (refereegranskat)abstract
- Background Type 1 diabetes is associated with an increased risk of developing several cardiovascular complications. To our knowledge, the independent association between type 1 diabetes and atrial fibrillation has not been studied. Methods We did a prospective case-control study of individuals with type 1 diabetes in the Swedish National Diabetes Registry who were each matched with five controls for age, sex, and county of residence who were randomly selected from the Swedish Population Register. Cases of atrial fibrillation were obtained from the Swedish National Patient Registry. Findings We followed up 36 258 patients with type 1 diabetes and 179 980 controls between Jan 1, 2001, and Dec 31, 2013. Median follow-up was 9.7 years (IQR 5.2-13.0) for patients and 10.2 years (5.7-13.0) for controls. 749 (2%) individuals with type 1 diabetes and 2882 (2%) controls were diagnosed with atrial fibrillation, with an adjusted hazard ratio (HR) of 1.13 (95% CI 1.01-1.25; p = 0.029) in men and 1.50 (1.30-1.72; p < 0.0001) in women (p = 0.0019 for interaction). The excess risk of atrial fibrillation in individuals with type 1 diabetes increased with worsening glycaemic control and renal complications. Among individuals with normoalbuminuria, no excess risk of atrial fibrillation was noted in men with type 1 diabetes who had HbA(1c) lower than 9.7% (< 83 mmol/mol) or in women with type 1 diabetes who had HbA(1c) lower than 8.8% (< 73 mmol/mol). Interpretation Compared with the general population, the risk of atrial fibrillation in men with type 1 diabetes was slightly raised, whereas for female patients it was 50% higher. The risk of atrial fibrillation in people with type 1 diabetes increased with renal complications and poor glycaemic control.
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| 15. |
- Dahlqvist, S., et al.
(författare)
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Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3)
- 2018
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Ingår i: BMC Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate variables associated with hemoglobin A1c (HbA1c) and weight reduction when adding liraglutide to persons with type 2 diabetes treated with multiple daily insulin injections (MDI). Research design and methods This was a reanalysis of a previous trial where 124 patients were enrolled in a double-blind, placebo-controlled, multicenter randomized trial carried out over 24 weeks. Predictors for effect on change in HbA1c and weight were analyzed within the treatment group and with concurrent interaction analyses. Correlation analyses for change in HbA1c and weight from baseline to week 24 were made. Results The mean age at baseline was 63.7 years, 64.8% were men, the mean number of insulin injections was 4.4 per day, the mean daily insulin dose was 105 units and the mean HbA1c was 74.5 mmol/mol (9.0%). The mean HbA1c and weight reductions were 12.3 mmol/mol (1.13%; P<0.001) and 3.8 kg (P<0.001) greater in liraglutide than placebo-Treated persons. There was no significant predictor for greater effect on HbA1c that existed in all analyses (univariate, multivariate and interaction analyses against controls). For a greater weight reduction when adding liraglutide, a lower HbA1c level at baseline was a predictor (liraglutide group P=0.002, P=0.020 for liraglutide group vs placebo). During follow-up in the liraglutide group, no significant correlation was found between change in weight and change in HbA1c (r=0.09, P=0.46), whereas a correlation existed between weight and insulin dose reduction (r=0.44, P<0.001). Conclusion Weight reduction becomes greater when adding liraglutide in patients with type 2 diabetes treated with MDI who had a lower HbA1c level compared with those with a higher HbA1c level. There was no correlation between reductions in HbA1c and weight when liraglutide was added, that is, different patient groups responded with HbA1c and weight reductions. Trial registration number EudraCT nr: 2012-001941-42. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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| 16. |
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| 17. |
- Edqvist, Jon, 1988, et al.
(författare)
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BMI and Mortality in Patients With New-Onset Type 2 Diabetes: A Comparison With Age- and Sex-Matched Control Subjects From the General Population
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:3, s. 485-493
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Type 2 diabetes is strongly associated with obesity, but the mortality risk related to elevated body weight in people with type 2 diabetes compared with people without diabetes has not been established. RESEARCH DESIGN AND METHODS: We prospectively assessed short- and long-term mortality in people with type 2 diabetes with a recorded diabetes duration /=40 kg/m(2) compared with control subjects after multiple adjustments. Long-term, all weight categories showed increased mortality, with a nadir at BMI 25 to <30 kg/m(2) and a stepwise increase up to HR 2.00 (95% CI 1.58-2.54) among patients with BMI >/=40 kg/m(2), that was more pronounced in patients <65 years old. CONCLUSIONS: Our findings suggest that the apparent paradoxical findings in other studies in this area may have been affected by reverse causality. Long-term, overweight (BMI 25 to <30 kg/m(2)) patients with type 2 diabetes had low excess mortality risk compared with control subjects, whereas risk in those with BMI >/=40 kg/m(2) was substantially increased.
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| 18. |
- Edqvist, Jon, 1988, et al.
(författare)
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BMI, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes: Findings Against an Obesity Paradox
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:7, s. 1297-1304
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Low weight has been associated with increased mortality risks in type 1 diabetes. We aimed to investigate the importance of weight and weight gain/loss in the Swedish population diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (n = 26,125; mean age 33.3 years; 45% women) registered in the Swedish National Diabetes Registry from 1998 to 2012 were followed from the first day of study entry. Cox regression was used to calculate risk of death from cardiovascular disease (CVD), major CVD events, hospitalizations for heart failure (HF), and total deaths. RESULTS Population mean BMI in patients with type 1 diabetes increased from 24.7 to 25.7 kg/m(2) from 1998 to 2012. Over a median follow-up of 10.9 years, there were 1,031 deaths (33.2% from CVD), 1,460 major CVD events, and 580 hospitalizations for HF. After exclusion of smokers, patients with poor metabolic control, and patients with a short follow-up time, there was no increased risk for mortality in those with BMI <25 kg/m(2), while BMI >25 kg/m(2) was associated with a minor increase in risk of mortality, major CVD, and HF. In women, associations with BMI were largely absent. Weight gain implied an increased risk of mortality and HF, while weight loss was not associated with higher risk. CONCLUSIONS Risk of major CVD, HF, CVD death, and mortality increased with increasing BMI, with associations more apparent in men than in women. After exclusion of factors associated with reverse causality, there was no evidence of an obesity paradox.
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| 19. |
- Edqvist, Jon, 1988, et al.
(författare)
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Contrasting Associations of Body Mass Index and Hemoglobin A1c on the Excess Risk of Acute Myocardial Infarction and Heart Failure in Type 2 Diabetes Mellitus.
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:24
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Tidskriftsartikel (refereegranskat)abstract
- Background Body mass index (BMI) may be a stronger risk factor for heart failure than for coronary heart disease in type 2 diabetes mellitus, but prior studies have not been powered to investigate the relative and absolute risks for acute myocardial infarction and heart failure in type 2 diabetes mellitus by BMI and glycemic level combined as compared with age- and sex-matched general population comparators. Methods and Results We identified 181045 patients from The Swedish National Diabetes Registry, registered during 1998 to 2012 and 1538434 general population comparators without diabetes mellitus, matched for age, sex, and county, all without prior major cardiovascular disease. Cases and comparators were followed with respect to the outcomes through linkage to the Swedish Inpatient Registry. Over a median follow-up time of 5.7years, there were 28855 acute myocardial infarction and 33060 heart failure cases among patients and comparators. Excess risk (above that of comparators in whom no data on hemoglobin A1c and BMI was available), incidence rates and hazard ratios for heart failure were substantially higher among the obese patients compared with those with low BMI, where very obese patients (BMI ≥40kg/m2) who also had poor glycemic control, suffered a 7-fold risk of heart failure versus comparators (reference level). By contrast, for acute myocardial infarction, the highest absolute and relative risks were found among patients with poor glycemic control, with no additional risk conferred by increasing BMI. Conclusions BMI is a strong independent risk factor for heart failure but not for acute myocardial infarction among patients with type 2 diabetes mellitus.
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| 20. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 21. |
- Evans, M., et al.
(författare)
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Use of fast-acting insulin aspart in insulin pump therapy in clinical practice
- 2019
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:9, s. 2039-2047
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Tidskriftsartikel (refereegranskat)abstract
- Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) containing the additional excipients niacinamide and L-arginine. The improved pharmacological profile and greater early glucose-lowering action of faster aspart compared with IAsp suggests that faster aspart may be advantageous for people with diabetes using continuous subcutaneous insulin infusion (CSII). The recent onset 5 trial was the first to evaluate the efficacy and safety of an ultra-fast-acting insulin in CSII therapy in a large number of participants with type 1 diabetes (T1D). Non-inferiority of faster aspart to IAsp in terms of change from baseline in HbA1c was confirmed, with an estimated treatment difference (ETD) of 0.09% (95% CI, 0.01; 0.17; P < 0.001 for non-inferiority [0.4% margin]). Faster aspart was superior to IAsp in terms of change from baseline in 1-hour post-prandial glucose (PPG) increment after a meal test (ETD [95% CI], −0.91 mmol/L [−1.43; −0.39]; P = 0.001), with statistically significant improvements also at 30 minutes and 2 hours. The overall rate of severe or blood glucose-confirmed hypoglycaemia was not statistically significantly different between treatments, with an estimated rate ratio of 1.00 (95% CI, 0.85; 1.16). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and the 4-week run-in periods (4 vs 0). Experience from clinical practice indicates that all pump settings should be reviewed when initiating faster aspart with CSII, and that the use of continuous glucose monitoring or flash glucose monitoring, along with a good understanding of meal content and bolus type, may also facilitate optimal use. This review summarizes the available clinical evidence for faster aspart administered via CSII and highlights practical considerations based on clinical experience that may help healthcare providers and individuals with T1D successfully initiate and adjust faster aspart with CSII. © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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| 22. |
- Forsberg, Lars A., 1974-, et al.
(författare)
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Mosaic loss of chromosome Y in leukocytes matters
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:1, s. 4-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 23. |
- Grodzinsky, A., et al.
(författare)
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Bleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy
- 2016
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 182, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention (PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown. Methods Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up. Results Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI(DMvs no DM: BARC = 1: 78.0% vs 87.7%, P <.001; BARC >= 2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC = 1 bleeding during follow-up (relative risk [RR] 0.89, 95% CI 0.83-0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition. Conclusions In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.
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| 24. |
- Hallström, Sara, et al.
(författare)
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Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:8, s. 1530-1538
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE This study identified variables associated with increased risk of atrial fibrillation in people with type 1 diabetes. RESEARCH DESIGN AND METHODS We performed a cohort study of people with type 1 diabetes from the Swedish National Diabetes Registry followed up between 1 January 2001 and 31 December 2013. Median follow-up was 9.7 years (interquartile range 5.2-13.0). The association between potential risk factors and incident atrial fibrillation was investigated using adjusted Cox regression. To compare the impact of each risk factor, the gradient of risk per 1 SD was estimated. RESULTS In this cohort of 36,258 patients with type 1 diabetes, 749 developed atrial fibrillation during follow-up. Older age, male sex, renal complications, increased BMI and HbA(1c), coronary artery disease, heart failure, and heart valve disease increased the risk of atrial fibrillation. Age, signs of renal dysfunction with macroalbuminuria, and decreasing estimated glomerular filtration rate were associated with the highest gradient of risk for atrial fibrillation. High blood pressure, severe obesity (BMI >35 kg/m(2)), and elevated levels of HbA(1c) (>9.6%) were associated with increased risk, but no associations were found with hyperlipidemia or smoking. CONCLUSIONS The most prominent risk factors for atrial fibrillation in people with type 1 diabetes were older age, cardiovascular comorbidities, and renal complications, while obesity, hypertension, and hyperglycemia had more modest affects.
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| 25. |
- Hedén Ståhl, Christina, 1972, et al.
(författare)
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Glycaemic control and excess risk of ischaemic and haemorrhagic stroke in patients with type 1 diabetes: a cohort study of 33 453 patients
- 2017
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 281:3, s. 261-272
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To estimate the excess risk of stroke in relation to glycaemic control in patients with type 1 diabetes. METHODS: In this prospective, matched cohort study, we identified patients with type 1 diabetes, aged >/=18 years, who were registered in the Swedish National Diabetes Register from 1998-2011 and five control subjects for each case from the general population, matched for age, sex and county of residence. The risks of all strokes, ischaemic stroke and haemorrhagic stroke were estimated using Cox hazard regression. RESULTS: Of 33 453 type 1 diabetes patients [mean age, 35.5 (SD 14.4) years; mean follow-up, 7.9 (SD 4.3) years; and mean diabetes duration, 20.2 years (SD 14.6)], 762 (2.3%) were diagnosed with stroke compared with 1122 (0.7%) of 159 924 control subjects [mean follow-up, 8.2 (SD 4.3) years]. The overall multiple-adjusted hazard ratios (HRs) for type 1 diabetes patients versus control subjects were 3.29 (95% CI: 2.96-3.66) and 2.49 (95% CI: 1.96-3.16) for ischaemic and haemorrhagic stroke, respectively. The risk of ischaemic and haemorrhagic stroke incrementally increased with increasing HbA1c; the risk of ischaemic stroke was significantly increased with HbA1c within target [/=9.7% (>/=83 mmol mol-1 ), there was a markedly increased risk of both ischaemic and haemorrhagic stroke, with multiple-adjusted HRs of 7.94 (95% CI: 6.29-10.03) and 8.17 (95% CI 5.00-13.35), respectively. CONCLUSIONS: Individuals with type 1 diabetes have an increased risk of ischaemic and haemorrhagic stroke, increasing markedly with poor glycaemic control.
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