| 1. |
- Jain, Ruchi, et al.
(författare)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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| 2. |
- Keindl, Magdalena, et al.
(författare)
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Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms
- 2020
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic beta cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naive to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care.
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| 3. |
- Ozgumus, T., et al.
(författare)
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Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.
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| 4. |
- Brunström, Mattias, et al.
(författare)
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SCORE2 – ett uppdaterat verktyg för att skatta kardiovaskulär risk : [SCORE2 - an updated model for cardiovascular risk prediction]
- 2021
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease is the most important cause of death and life-years lost in Sweden today. Cardiovascular risk prediction is a cornerstone in primary prevention; the use of antihypertensive and lipid-lowering therapy is guided by absolute cardiovascular risk. The Systematic COronary Risk Evaluation (SCORE) model has been the most widely applied model in Sweden for almost two decades. Recently, an updated model called SCORE2 was published. The new risk prediction model is based on contemporary data, predicts the risk of incident cardiovascular disease in addition to cardiovascular mortality, and accounts for competing risks, thus overcoming some major limitations with SCORE. Sweden is classified as a moderate-risk country according to the new model; here we report the risk chart for moderate-risk countries translated into Swedish.
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| 5. |
- Byhamre, Marja Lisa, et al.
(författare)
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Association between snus use and lipid status in Swedish men
- 2023
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 83:4, s. 241-250
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Tidskriftsartikel (refereegranskat)abstract
- Snus is a common tobacco product in Sweden, but the cardiovascular risk profile for snus users is less known than for cigarette smokers. We examined the association of snus use with lipid status, particularly in comparison to non-tobacco use and cigarette smoking, using data from 5930 men in the Northern Sweden MONICA study. Tobacco use was self-reported in 1986 to 2014 (24.4% used snus) and blood samples were collected at the same time. Harmonized analyses on non-high-density lipoprotein (non-HDL) cholesterol, HDL cholesterol, and triglycerides were conducted in 2016 to 2018. Three hundred eighty-one snus users had also been examined more than once, allowing us to study the effect of discontinued use (achieved by 21.0%). In multivariable linear regression models, snus use was associated with higher HDL cholesterol and triglyceride concentrations compared to non-tobacco use (p values ≤ 0.04), and it was associated with higher HDL cholesterol concentrations and lower triglyceride concentrations compared to cigarette smoking (p values ≤ 0.02). Snus use was not associated with non-HDL cholesterol concentrations, irrespective of the comparison group (p values ≥ 0.07). There was no indication that higher intensity of snus use led to a worse lipid profile, given that high-consumers had higher HDL cholesterol concentrations than low-consumers (p value = 0.02), or that discontinuation of snus use led to a better lipid profile, given that continued users had lower triglyceride concentrations than discontinued users (p value = 0.03). Further studies are needed to confirm or refute our findings.
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| 6. |
- Eliasson, Jonas, et al.
(författare)
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Transport Mode and the Value of Accessibility-A Potential Input for Sustainable Investment Analysis
- 2020
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Accessibility plays an essential role in determining real estate prices and land use. An understanding of how accessibility and changes in accessibility influence real estate prices is key to making decisions regarding investments in infrastructure projects. From an accessibility point of view, it is not clear that there should be differences in valuation depending on the mode of public transport, road, or rail. There are, however, other differences that may affect real estate prices differently. For example, railway stations more often than bus stations, tend to be associated with a higher level of service. In addition, an investment in a railway station may signal a long-term decision from the policymaker. A third possible explanation concerns differences in perceived safety, comfort, and security. This paper aims to study if and how capitalization of accessibility differs between modes of transportation. The findings indicate that rail has a higher impact, both for single-family and multifamily houses. The implication of these findings may be of importance for future infrastructure investments and their corresponding cost-benefit analyses. Incorrect valuations of the benefits of infrastructure investments may result in sub-optimal investments.
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| 7. |
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| 8. |
- Landgren, Anton J., 1989, et al.
(författare)
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Cardiovascular risk factors are highly overrepresented in Swedish patients with psoriatic arthritis compared with the general population.
- 2020
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Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 49:3, s. 195-99
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We aimed to determine the prevalence of cardiovascular risk factors in patients with psoriatic arthritis (PsA) followed at a large Swedish Rheumatology Clinic, and to compare differences in cardiovascular risk factors between men and women with PsA and with the general population. Method: A questionnaire was sent to patients with PsA registered at the Rheumatology Clinic at Sahlgrenska University Hospital, Gothenburg (n=982). Comparisons with the general population were made using data from the Swedish National Public Health Survey. Descriptive statistics are presented. Body mass index (BMI) was calculated using self-reported height and weight. Results: Overall, 692 (70.6%) of the patients with PsA responded. The mean±sd age was 55.6±11.4years and 52% were women. Obesity (BMI ≥30 kg/m2) was more prevalent (p<0.001) in patients with PsA (28.6%) than in matched subjects from the general population (16.3%). Hypertension was also more prevalent (p<0.001) in PsA (40.3%) than in matched subjects from the general population (24.1%), as was diabetes, with a prevalence of 10.5% in the PsA population compared with 6.2% in matched subjects (p<0.001). Conclusion: We found obesity to be highly overrepresented in patients with PsA compared with matched subjects from the general population. This difference was particularly seen in women with PsA. Hypertension and ever smoking were also more prevalent in women with PsA compared with matched subjects from the general population.
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| 9. |
- Landgren, Anton J., 1989, et al.
(författare)
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Serum IL-23 significantly decreased in obese patients with psoriatic arthritis six months after a structured weight loss intervention.
- 2023
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Ingår i: Arthritis research & therapy. - 1478-6362. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Patients with psoriatic arthritis (PsA) are frequently obese. We have previously shown decreased disease activity in patients with PsA with a body mass index (BMI)≥33kg/m2 following weight loss treatment with Very Low Energy Diet (VLED), resulting in a median weight loss of 18.6% at six months (M6) after baseline (BL). In this study we assessed the effects of VLED on cytokines and adipokines at M6 in the same patients with PsA and controls (matched on sex, age and weight).VLED (640kcal/day) during 12 or 16weeks, depending on BL BMI<40 or≥40kg/m2, was taken and followed by an energy-restricted diet. Cytokines and adipokines were measured with Magnetic Luminex Assays at BL and M6.Serum interleukin (IL)-23, (median (interquartile range) 0.40 (0.17-0.54) ng/mL vs. 0.18 (0.10-0.30) ng/mL, p<0.001) and leptin (26.28 (14.35-48.73) ng/mL vs. 9.25 (4.40-16.24) ng/mL, p<0.001) was significantly decreased in patients with PsA. Serum total (tot)-adiponectin and high molecular weight (HMW) adiponectin increased significantly. Similar findings were found in controls. Also, in patients with PsA, ∆BMI was positively correlated with ∆IL-23 (rS=0.671, p<0.001). In addition, significant positive correlations were found between ΔBMI and ΔDisease Activity Score (DAS28CRP), ΔCRP, Δtumor necrosis factor (TNF)-α, ΔIL-13, ∆IL-17 and Δleptin, and negative correlations between ΔBMI and Δtot-adiponectin.Weight loss was associated with decreased levels of leptin and cytokines, in particular IL-23. These findings may partly explain the anti-inflammatory effect of weight reduction in PsA.ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.
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| 10. |
- Landgren, Anton J., 1989, et al.
(författare)
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Sex differences in cytokines and adipokines in obese patients with PsA and controls undergoing a weight loss intervention.
- 2024
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Ingår i: RMD open. - 2056-5933. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In this post hoc analysis of a previously published study, we compared cytokines and adipokine levels in women and men with psoriatic arthritis (PsA) at baseline (BL) and 6 months (M6) following a weight loss intervention.Patients with PsA (n=41) between 25 and 75 years of age, with body mass index (BMI)≥33 kg/m2 were included in a weight loss intervention with a very low energy diet (VLED) for 12 or 16 weeks depending on BL BMI<40 or ≥40 kg/m2. As controls (n=39), obese individuals, already planned for VLED treatment were recruited and matched for sex, age and weight to the patients with PsA. Cytokines and adipokines were measured at BL and M6.At BL, serum levels of interleukin (IL)-23, leptin and high molecular weight-adiponectin were higher in women with PsA compared with men, whereas serum levels of interferon (IFN)-γ, IL-12/IL-23 p40 and IL-13 were significantly lower in women. Serum IL-23 was significantly reduced at M6 compared with BL in women but not in men with PsA. In women with PsA, the reduction in IL-23 at M6, ∆IL-23, were positively correlated with ∆Disease Activity Score 28 C reactive protein (CRP) (Spearman's correlation (rS)=0.486, p=0.016), ∆CRP (rS=0.468, p=0.021), ∆leptin (rS=0.683, p<0.001) and negatively correlated with ∆total-adiponectin (rS=-0.433, p=0.035). Also in women, ∆Disease Activity in Psoriatic Arthritis was positively correlated with ∆tumour necrosis factor-α (rS=0.417, p=0.034), ∆IL-1β (rS=0.550, p=0.034), ∆IFN-γ (rS=0.414, p=0.035) and ∆leptin (rS=0.410, p=0.038). None of these correlations were significant in men with PsA.Women and men with PsA differed with regard to serum levels of cytokines and adipokines before and after weight loss.
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