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- Keindl, Magdalena, et al.
(author)
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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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In: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 11
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Journal article (peer-reviewed)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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| 2. |
- Magnusson, Karin, et al.
(author)
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Long term type 1 diabetes is associated with hand pain, disability and stiffness but not with structural hand osteoarthritis features - The Dialong hand study
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
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Journal article (peer-reviewed)abstract
- Objective: To explore whether having long-term type 1 diabetes (>45 years) is associated with a higher prevalence of radiographic hand OA, erosive hand OA and increased hand pain, disability and stiffness. Methods: In total N = 96 persons with type 1 diabetes diagnosed before 1970 were included (mean [SD] age: 62.2 [7.4], mean [SD] HbA1c: 7.43 [0.80] and N = 49 [51%] men). Regular measurements of their HbA1c were obtained till 2015. We included N = 69 healthy controls without any diabetes (mean [SD] age: 63.0 [7.0], mean [SD] HbA1c: 5.41 [0.32], N = 29 [42%] men). The groups were compared for radiographic hand OA (Kellgren-Lawrence grade ≥2 in ≥1 joint) and erosive hand OA (central erosions in ≥1 joint), Australian/Canadian index (AUSCAN) for hand pain, disability and stiffness using regression analyses adjusted for age, sex, educational level and waist circumference. Results: We found no associations between having long term type 1 diabetes and more prevalent radiographic hand OA (OR = 0.83, 95% CI = 0.38-1.81). We found a trend towards higher prevalence of erosive hand OA in diabetes patients (OR = 2.96, 95% CI = 0.82-10.64). Strong and consistent associations were observed between long term type 1 diabetes and increased hand pain (B = 2.78, 95% CI = 1.65-3.91), disability (B = 5.30, 95% CI = 3.48-7.12) and stiffness (B = 2.00, 95% CI = 1.33-2.67). These associations were particularly strong for women and participants below the median age of 61 years. Conclusion: Long-term type 1 diabetes was not associated with radiographic hand OA, but was strongly associated with hand pain, disability and stiffness. The association between diabetes and erosive hand OA warrants further investigation.
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| 3. |
- Sveen, Kari Anne, et al.
(author)
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Autoantibodies against methylglyoxal-modified apolipoprotein B100 and apob100 peptide are associated with less coronary artery atherosclerosis and retinopathy in long-term type 1 diabetes
- 2021
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:6, s. 1402-1409
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Journal article (peer-reviewed)abstract
- OBJECTIVE Methylglyoxal (MGO), a reactive aldehyde forming advanced glycation end products (AGEs), is increased in diabetes and recognized by the immune system, resulting in anti-AGE-specific autoantibodies. The association of these immune responses with macro- and microvascular complications in type 1 diabetes remains unclarified. We investigated associations between MGO-modified apolipoprotein B100 (apoB100) and apoB100 peptide 5 (MGO-p5) autoantibodies and coronary atherosclerosis and retinopathy in type 1 diabetes. RESEARCH DESIGN AND METHODS IgM and IgG against MGO-apoB100 and MGO-p5 were measured by ELISA in plasma from 103 subjects with type 1 diabetes and 63 control subjects (Dialong study) and in a replication cohort of 27 subjects with type 1 diabetes (Oslo study). Coronary atherosclerosis was assessed by computed tomography coronary angiography or intravascular ultrasound. Retinopathy was classified by retinal photos. RESULTS MGO-apoB100 IgM and MGO-p5 IgM levels were higher in subjects with diabetes with no coronary artery stenosis compared with subjects with significant stenosis (median [interquartile range]: 96.2 arbitrary units [AU] [71-126.8] vs. 54 AU [36.1-85.4], P 5 0.003 for MGO-apoB100; and 77.4 AU [58-106] vs. 36.9 AU [28.9-57.4], P 5 0.005 for MGO-p5). MGO-apoB100 IgM and MGO-p5 IgM were associated with less severe coronary stenosis after adjusting for confounders (odds ratio 0.2 [95% CI 0.05-0.6], P 5 0.01; and 0.22 [0.06-0.75], P 5 0.02). The inverse association of MGO-p5 IgM and coronary stenosis was confirmed in the replication cohort. Subjects with proliferative retinopathy had significantly lower MGO-apoB100 IgM and MGO-p5 IgM than those with background retinopathy. CONCLUSIONS Autoantibodies against AGE-modified apoB100 are inversely associated with coronary atherosclerosis and proliferative retinopathy, suggesting vascular protective effects of these autoantibodies in type 1 diabetes.
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