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| 52. |
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| 53. |
- Freisling, Heinz, et al.
(författare)
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Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases : a multinational cohort study
- 2020
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. CONCLUSION: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
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| 54. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 55. |
- Hallmans, Göran, et al.
(författare)
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Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort : evaluation of risk factors and their interactions.
- 2003
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Ingår i: Scandinavian Journal of Public Health. Supplement Links. - : SAGE Publications. - 1403-4956 .- 1403-4948 .- 1651-1905. ; 61, s. 18-24
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.
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| 56. |
- Hampe, Christiane S., et al.
(författare)
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Geographic location determines beta-cell autoimmunity among adult Ghanaians : Findings from the RODAM study
- 2020
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Ingår i: Immunity, Inflammation and Disease. - : John Wiley & Sons. - 2050-4527. ; 8:3, s. 299-309
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Beta‐cell autoantibodies are established markers of autoimmunity, which we compared between Ghanaian adults with or without diabetes, living in rural and urban Ghana and in three European cities.Methods: In the multicenter cross‐sectional Research on Obesity and Diabetes among African Migrants (RODAM) study (N = 5898), we quantified autoantibodies against glutamic acid decarboxylase (GAD65Ab) by radioligand binding assay (RBA) and established cut‐offs for positivity by displacement analysis. In a subsample, we performed RBA for zinc transporter‐8 autoantibodies (ZnT8Ab). Associations of environmental, sociodemographic, and clinical factors with GAD65Ab were calculated.Results: In this study population (age: 46.1 ± 11.9 years; female: 62%; Ghana‐rural: 1111; Ghana‐urban: 1455; Europe: 3332), 9.2% had diabetes with adult‐onset. GAD65Ab concentrations were the highest in Ghana‐rural (32.4; 10.8‐71.3 U/mL), followed by Ghana‐urban (26.0; 12.3‐49.1 U/mL) and Europe (11.9; 3.0‐22.8 U/mL) with no differences between European cities. These distributions were similar for ZnT8Ab. Current fever, history of fever, and higher concentrations of liver enzymes marginally explained site‐specific GAD65Ab concentrations. GAD65Ab positivity was as frequent in diabetes as in nondiabetes (5.4% vs 6.1%; P = .25). This was also true for ZnT8Ab positivity.Conclusion: Geographic location determines the occurrence of GAD65Ab and ZnT8Ab more than the diabetes status. Beta‐cell autoimmunity may not be feasible to differentiate diabetes subgroups in this population.
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| 57. |
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| 58. |
- Hampe, C. S., et al.
(författare)
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Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform : relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus
- 2019
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Ingår i: Diabetic Medicine. - : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 36:11, s. 1375-1383
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate whether the N‐terminal truncated glutamic acid decarboxylase 65 (GAD65) isoform is as well recognized by people with stiff person syndrome as it is by people with Type 1 diabetes, and whether conformational GAD65 antibody epitopes are displayed properly by the isoform.Methods: GAD65 antibody‐positive healthy individuals (n=13), people with stiff‐person syndrome (n=15) and children with new‐onset Type 1 diabetes (n=654) were analysed to determine binding to full‐length GAD65 and the N‐terminal truncated GAD65 isoform in each of these settings. GAD65 autoantibody epitope specificity was correlated with binding ratios of full‐length GAD65/N‐terminal truncated GAD65.Results: The N‐terminal truncated GAD65 isoform was significantly less recognized in GAD65Ab‐positive people with stiff‐person syndrome (P=0.002) and in healthy individuals (P=0.0001) than in people with Type 1 diabetes. Moreover, at least two specific conformational GAD65Ab epitopes were not, or were only partially, presented by the N‐terminal truncated GAD65 isoform compared to full‐length GAD65. Finally, an N‐terminal conformational GAD65Ab epitope was significantly less recognized in DQ8/8 positive individuals with Type 1 diabetes (P=0.02).Conclusions: In people with stiff person syndrome preferred binding to the full‐length GAD65 isoform over the N‐terminal truncated molecule was observed. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N‐terminal truncated molecule. These findings support the notion of disease‐specific GAD65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.
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| 59. |
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| 60. |
- Husdal, Rebecka
(författare)
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Key Features for Successful Swedish Primary Diabetes Care – Reality or Fiction? : Nationwide studies of longitudinal follow-up, HbA1c levels and all-cause mortality in an organizational context
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims To extend knowledge about the changes in Swedish primary diabetes care from 2006 to 2013 and investigate associations of personnel resources, organizational features and quality-of-work conditions of primary health-care centres (PHCCs) with individual HbA1c levels and all-cause mortality in people with type 2 diabetes mellitus (T2DM).Methods Information about organizational features, personnel resources and quality-of-work conditions were collected from responses of PHCC managers to the Swedish National Survey of the Quality and Organisation of Diabetes Care in Primary HealthCare (Swed-QOP) questionnaire. The longitudinal cross-sectional study included 74.3% and 76.4% of PHCCs in 2006 and 2013, respectively. Individual clinical data for 230,958 people with T2DM obtained from the Swedish National Diabetes Register were linked to the data from the Swed-QOP questionnaire. Individual data were linked to socio-economic and comorbidity data. All-cause mortality was followed up for a median of 4.2 years for 187,570 people with T2DM.Results The longitudinal follow-up study showed a decreased median PHCC list size but an increased median number of people with T2DM. The mean European Credit Transfer and Accumulation System (ECTS) credits in diabetes-specific education for registered nurses (RNs) increased. The number of PHCCs providing group education programs and involving the patient in goal setting remained low (I). PHCCs having diabetes teams and group education programs were associated with decreased HbA1c levels. Using call-recall system to general practitioners (GPs) was associated with increased HbA1c levels (II). Seven quality-of-work features were identified, of which Individualized treatment was associated with decreased HbA1c levels in people with controlled (≤ 52 mmol/mol), intermediate (53–69 mmol/mol) and uncontrolled (≥ 70 mmol/mol) HbA1c (III). GP staffing was associated with a decreased risk of early death and the mean ECTS credits in diabetes-specific and pedagogical education of RNs was associated with a decreased risk of early death in people aged ≥ 55 years and in men, respectively (IV).Conclusion This thesis adds to previous work on significant but less pronounced key features for successful organization of primary diabetes care, and indicates that the complexity of diabetes disease makes it difficult to identify success factors applicable to all people living with T2DM.
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