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- Agardh, Emilie E, et al.
(author)
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Burden of type 2 diabetes attributed to lower educational levels in Sweden
- 2011
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In: Population Health Metrics. - : Springer Science and Business Media LLC. - 1478-7954. ; 9, s. 60-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Type 2 diabetes is associated with low socioeconomic position (SEP) in high-income countries. Despite the important role of SEP in the development of many diseases, no socioeconomic indicator was included in the Comparative Risk Assessment (CRA) module of the Global Burden of Disease study. We therefore aimed to illustrate an example by estimating the burden of type 2 diabetes in Sweden attributed to lower educational levels as a measure of SEP using the methods applied in the CRA.METHODS: To include lower educational levels as a risk factor for type 2 diabetes, we pooled relevant international data from a recent systematic review to measure the association between type 2 diabetes incidence and lower educational levels. We also collected data on the distribution of educational levels in the Swedish population using comparable criteria for educational levels as identified in the international literature. Population attributable fractions (PAF) were estimated and applied to the burden of diabetes estimates from the Swedish burden of disease database for men and women in the separate age groups (30-44, 45-59, 60-69, 70-79, and 80+ years).RESULTS: The PAF estimates showed that 17.2% of the diabetes burden in men and 20.1% of the burden in women were attributed to lower educational levels in Sweden when combining all age groups. The burden was, however, most pronounced in the older age groups (70-79 and 80+), where lower educational levels contributed to 22.5% to 24.5% of the diabetes burden in men and 27.8% to 32.6% in women.CONCLUSIONS: There is a considerable burden of type 2 diabetes attributed to lower educational levels in Sweden, and socioeconomic indicators should be considered to be incorporated in the CRA.
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- Agardh, Hanna E
(author)
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Identification of inflammatory genes involved in the pathogenesis of human and experimental atherosclerosis
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Atherosclerosis is a chronic systemic inflammatory disease of large and medium sized arteries, developing slowly and silently over decades. The disease is usually not apparent until occurrence of a sudden clinical symptom, such as myocardial infarction (MI) or stroke. Several classical risk factors have been established to play a role in the progression of disease over a long period of time. However, markers recognizing vulnerable patients being at risk of having an event in the near future are lacking. Thus, more knowledge about the ongoing complex pathogenesis is needed for identification of potential biomarkers and therapeutic targets of atherosclerosis. Patients with carotid atherosclerosis experiencing cerebral symptoms within one month before undergoing carotid endarterectomy (CEA) are classified having vulnerable plaques. Based on the classification above, I show in this thesis that mRNA levels of enzymes in the leukotriene 5-lipoxygenase pathway, 5-lipoxygenase (5-LO) and leukotriene A4 hydrolase (LTA4H), are associated with plaque vulnerability. Gene expression can be investigated on a single target level using real-time PCR or by analyzing thousands of genes simultaneously, using global transcription microarrays. Based on correlations to microarrays we argue for using total RNA mass in normalization of real-time PCR data, when analyzing heterogeneous human specimen. To identify new candidates of plaque vulnerability an unbiased approach was used - transcript profiles of symptomatic plaques were compared to asymptomatic plaques, demonstrating an increase of fatty acid binding protein 4 (FABP4), which was associated with vulnerability, independent of age or gender. FABP4 localize mainly to the numerous macrophages present in the atherosclerotic plaque. This study suggests FABP4 to play a role in plaque vulnerability and to be a potential valuable biomarker within the carotid atherosclerotic plaque. To determine if any atherosclerosis-related changes can be detected in circulating cells the transcriptome of leukocytes in the circulation from an experimental atherosclerotic model Apoe-/-was analyzed. Surprisingly, we also here identify FABP4 as a marker in neutrophils and monocytes reflecting atherosclerotic lesion progression. Moreover, I observe human monocytes and neutrophils from the circulation to be positive for FABP4. Our findings make FABP4 in circulating cells interesting for functional investigations, and an appealing and easy accessible biomarker target for potential future translation into clinical purposes. In conclusion, I have studied inflammatory genes being involved in the pathogenic process during atherosclerosis using human and experimental models. In brief, we demonstrate that human vulnerable plaques display increased mRNA levels of 5-LO and LTA4H, and FABP4. In addition, the latter is shown in an experimental model, to be a potential valuable biomarker in circulating leukocytes reflecting the extent of atherosclerotic lesion. Our discoveries in the human plaque may be of future clinical relevance to identify vulnerable plaques, whereas FABP4 in leukocytes potentially could be useful for recognizing asymptomatic patients before onset of symptoms.
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- Folkersen, Lasse, et al.
(author)
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Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease
- 2010
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In: Circulation. - 1942-325X .- 1942-3268. ; 3:4, s. 365-373
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Journal article (peer-reviewed)abstract
- BACKGROUND: Population-based genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with cardiovascular disease or its risk factors. Genes in close proximity to these risk-SNPs are often thought to be pathogenetically important based on their location alone. However, the actual connections between SNPs and disease mechanisms remain largely unknown. METHODS AND RESULTS: To identify novel susceptibility genes, we investigated how 166 SNPs previously found to be associated with increased cardiovascular risk and/or predisposing metabolic traits relate to the expression of nearby genes. Gene expression in 577 samples of aorta, liver, mammary artery, and carotid atherosclerotic plaque was measured using expression arrays. For 47 SNPs, the expression levels of proximal genes (located within 200 kb) were affected (P<0.005). More than 20 of these genes had not previously been identified as candidate genes for cardiovascular or related metabolic traits. SNP-associated gene effects were tissue-specific and the tissue specificity was phenotype-dependent. CONCLUSIONS: This study demonstrates several instances of association between risk-SNPs and genes immediately adjacent to them. It also demonstrates instances in which the associated gene is not the immediately proximal and obvious candidate gene for disease. This shows the necessity of careful studies of genetic marker data as a first step toward application of genome-wide association studies findings in a clinical setting.
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- Ortqvist, E, et al.
(author)
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Changes in GAD65Ab-Specific Antiidiotypic Antibody Levels Correlate with Changes in C-Peptide Levels and Progression to Islet Cell Autoimmunity.
- 2010
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 310-318
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Journal article (peer-reviewed)abstract
- Context: The previously reported absence of 65-kDa glutamate decarboxylase antibody (GAD65Ab)-specific antiidiotypic antibodies (anti-Id) in type 1 diabetes (T1D) patients at clinical onset could be due to an inability to mount an antibody response to GAD65Ab or a longitudinal decline in anti-Id levels. Objective and Design: We investigated anti-Id levels in longitudinal samples obtained from T1D patients (n = 41) (clinical diagnosis - 12 months), and latent autoimmune diabetes in adults (LADA) patients (n = 32) who received alum-formulated human recombinant GAD65 (baseline - 12 months). We also determined anti-Id levels in a small cohort of Type 2 diabetes patients during their development of autoimmune T cell responses. Results: At clinical onset T1D patients presented no or low anti-Id levels. However, 22/41 T1D patients showed >/=50% increase in GAD65Ab-specific anti-Id levels during follow-up; peaking at 3 (n = 1), 6 (n = 10), 9 (n = 10), or 12 (n = 1) months. Increasing anti-Id levels marked patients who experienced a temporary increase in C-peptide levels. Anti-Id levels correlated significantly with glycated hemoglobin and C-peptide levels at 6 and 9 months (P values ranged from <0.001 to <0.05). In LADA patients receiving placebo, anti-Id levels declined in seven of nine patients, whereas four of five patients receiving 20 mug alum-formulated human recombinant GAD65 showed increasing anti-Id levels. Changes in anti-Id and C-peptide levels closely correlated (P < 0.0001). The significant decline in anti-Id levels (P = 0.03) in T2D patients developing T cell autoimmune responses supports our hypothesis that declining anti-Id levels are associated with developing islet autoimmunity. Conclusions: The close association between GAD65Ab-specific anti-Id levels and beta-cell function may provide a novel marker for the progression of autoimmune diabetes.
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