| 1. |
- Saevik, Ase Bjorvatn, et al.
(författare)
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Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study
- 2023
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 189:4, s. 438-447
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Increased prevalence of cardiovascular disease has been reported in autoimmune Addisons disease (AAD), but pathomechanisms are poorly understood.Design: Cross-sectional study.Methods: We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 mu g tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH.Results: Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively).Conclusions: We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.
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| 2. |
- Wahlberg, Jeanette, 1969-, et al.
(författare)
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Altered Chemokine Th1/Th2 Balance in Addison's Disease: Relationship with Hydrocortisone Dosing and Quality of Life
- 2014
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 46:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- The adrenalitis found in autoimmune Addison’s disease (AAD) is considered having a Th1-driven pathogenesis. Circulating Th1- and Th2-associated chemokines responsible for the trafficking of leukocytes to inflammatory sites are markers for the Th1/Th2 balance. The aim of the study was to assess if the same daily hydrocortisone dose of 30 mg given in either 2 or 4 doses to patients with AAD could affect the Th1/Th2 balance of circulating chemokines.Fifteen patients (6 women) with AAD were included in this randomised, placebo controlled, double blind cross-over study. Samples for chemokines, Th1-associated (CXCL10, CXCL11) and Th2-associated (CCL17, CCL22), were drawn 5 times during a 24-h period at the end of each treatment period and analysed with Luminex. Seven control subjects did the same diurnal blood sampling once. Subjects with AAD had higher median diurnal levels of the Th1-associated chemokines than controls, CXCL10 [43 (33–56) pg/ml vs. 22 (19–34) pg/ml, p<0.01] and CXCL11 [37 (29–48) pg/ml vs. 16 (9–24) pg/ml, p<0.001], whereas no significant difference was found regarding the Th2-related chemokines. Similar chemokine levels were found when the same hydrocortisone dose of 30 mg was divided in 2 or 4 doses. Levels of CXCL11 correlated negatively with scores of SF-36 domains (high score indicate better health) of General Health (GH) and total score for Physical Component Summary (PCS), and these negative correlations were most pronounced at 04:00 h on the 2-dose regimen. Patients with AAD have a dominant Th1 chemokine profile that partially correlates to reduced quality of life.
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| 3. |
- Arlien-Soborg, Mai C., et al.
(författare)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 4. |
- Arlien-Soborg, Mai C., et al.
(författare)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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Ingår i: CLINICAL ENDOCRINOLOGY. - : WILEY. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 5. |
- Axfors, Cathrine, et al.
(författare)
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Preferences for Gender Affirming Treatment and Associated Factors Among Transgender People in Sweden
- 2023
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Ingår i: Sexuality Research & Social Policy. - : Springer Nature. - 1868-9884 .- 1553-6610. ; 20:2, s. 479-490
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionGender affirming surgery of primary and/or secondary sex characteristics has been shown to alleviate gender dysphoria. A descriptive snapshot of current treatment preferences is useful to understand the needs of the transgender population seeking health care. This study aimed to describe preferences for gender affirming treatment, and their correlates, among individuals seeking health care for gender dysphoria in Sweden after major national legislative reforms.MethodsCross-sectional study where transgender patients (n = 232) recruited from all six Gender Dysphoria centers in Sweden 2016–2019, answered a survey on treatment preferences and sociodemographic, health, and gender identity-related information during the same time-period. Factors associated with preferring top surgery (breast augmentation or mastectomy), genital surgery, and other surgery (e.g., facial surgery) were examined in univariable and multivariable regression analyses in the 197 people without prior such treatment. Main study outcomes were preferences for feminizing or masculinizing hormonal and surgical gender affirming treatment.ResultsThe proportion among birth assigned male and assigned female patients preferring top surgery was 55.6% and 88.7%, genital surgery 88.9% and 65.7%, and other surgery (e.g., facial surgery) 85.6% and 22.5%, respectively. Almost all participants (99.1%) wanted or had already received hormonal treatment and most (96.7%) wished for some kind of surgical treatment; 55.0% wanted both top and genital surgery. Preferring a binary pronoun (he/she) and factors indicating more severe gender incongruence were associated with a greater wish for surgical treatment. Participants with somatic comorbidities were less likely to want genital surgery, while aF with lacking social support were less likely to want internal genital surgery, in the multivariable analyses.ConclusionsIn this sample of Swedish young adults seeking health care for gender dysphoria, preferences for treatment options varied according to perceived gender identity.Policy ImplicationsThe study fndings underline the need for individualized care and fexible gender afrming treatmentoptions. The role of somatic comorbidities should be further explored, and support should be ofered to transgender peoplein need. There is an unmet need for facial surgery among aM
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| 6. |
- Baldimtsi, Evangelia, et al.
(författare)
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HbA1c and the risk of developing peripheral neuropathy in childhood-onset type 1 diabetes : A follow-up study over 3 decades
- 2024
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 40:5
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We have evaluated long-term weighted mean HbA1c (wHbA1c), HbA1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes.MATERIALS AND METHODS: In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA1c by integrating the area under all HbA1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA1c variability were computed as the standard deviation of all HbA1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records.RESULTS: In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA1c, and increased HbA1c variability. The lowest wHbA1c value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy.CONCLUSIONS: More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA1c of less than 62 mmol/mol (7.8%).
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| 7. |
- Baldimtsi, Evangelia, 1981-
(författare)
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Studies on risk factors for long-term development of peripheral neuropathy in Type 1 Diabetes Patients
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetic peripheral neuropathy (DPN) is a highly prevalent microvascular complication of both type 1 and type 2 diabetes. As many as 30% of individuals with type 1 diabetes and 50% of patients with type 2 diabetes develop DPN after 25 and 10 years of disease, respectively. Type 1 diabetes often develops in younger ages of life. This means that when DPN occurs, the individuals with type 1 diabetes are still at a relatively young age. On the contrary, type 2 diabetes, with an even higher prevalence of DPN, mainly affects older people already having other risk factors and an age-related decline in nerve functions.Despite advancements in glucose control, the treatment with new insulin analogues, the introduction of insulin pumps, or the extended use of glucose sensors, the risk of this diabetes complication is not significantly declining. DPN is still a leading cause of non-traumatic limb amputation and significantly increases cardiovascular and all-cause mortality. Based on previous studies, it is suggested that there is a cluster of factors, including long-term metabolic control, obesity, hypertension, dyslipidemia, and especially high triglyceride levels, which impact the onset and progression of neuropathy. Moreover, recent studies have highlighted that low-grade inflammation plays an important role in the pathogenesis of DPN by leading to a cascade of events, including altered function of chemokines and imbalances in atherosclerotic plaque stability and platelet function. Overall, there is a great need to better understand the pathogenesis of DPN and the underlying risk factors for manifest disease to develop new preventive and curative strategies for patients with diabetes.This thesis aimed to examine the cumulative incidence and prevalence of diabetic neuropathy, the natural course of neurophysiological changes, and novel biomarkers associated with DPN among patients with childhood-onset type 1 diabetes longitudinally followed for 30 years. This study was an observational, longitudinal follow-up study, and the primary data were collected prospectively.More specifically, we investigated the role of circulating inflammatory factors, chemokines, and metalloproteinases in the risk of developing DPN. We also examined the impact of longterm metabolic control on the prevalence of DPN over a 30-year follow-up period in this cohort.In Paper I, we explored the occurrence of biomarkers of ongoing inflammatory processes, particularly chemokines, in DPN through a cross-sectional analysis. Chemokines are a subgroup of cytokines that regulate various immune system reactions. They contribute to increased inflammatory systematic response, leading to increased co-morbidity. Our main hypothesis was that patients with type 1 diabetes and concomitant DPN would exhibit increased circulating chemokines levels compared to control subjects and patients without DPN. The main result of this analysis was the detection of higher levels of the CXCL9 chemokine in patients with type 1 diabetes and DPN in comparison to healthy control subjects. Furthermore, CXCL8 and CXCL10 chemokines were correlated with impaired nerve function in all patients with diabetes.In Paper II, we examined the association between markers for atherosclerotic plaque stability, inflammation, and platelet function and the prevalence of diabetic neuropathy and nephropathy. The main biomarkers analyzed were Matrix Metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1, soluble P-selectin (sP-selectin), and Neutrophil Gelatinaseassociated Lipocalin-2 (NGAL).Our findings revealed that TIMP-1 and high-sensitive CRP levels were increased in patients with DPN compared to controls and patients without DPN. sP-selectin levels were elevated in the patients with DPN compared with healthy controls. TIMP-1, NGAL, and MMP-9 were associated with diabetic nephropathy and albuminuria. Our findings indicate that circulating biomarkers might be involved in microvascular complications.In Paper III, we comprehensively examined the importance of long-term metabolic control for the progression of DPN in patients with type 1 diabetes followed for 30 years. In a longitudinal cohort study, 49 patients with type 1 diabetes diagnosed in childhood were investigated with nerve conduction tests. Weighted HbA1c (wHbA1c) and HbA1c variability were calculated after a diabetes duration of up to 30.6 (±5.2) years.A high DPN prevalence of 51% was found using nerve conduction tests after a median diabetes duration of 30 years. Deterioration in the amplitudes of both sural and peroneal nerves was found. Moreover, in the repeated nerve conduction tests (NCS), amplitudes showed a gradual deterioration more consistently than velocities, suggesting that measurements of amplitudes are particularly useful in evaluating nerve conduction changes in DPN.No patient developed neuropathy while preserving a weighted mean HbA1c of less than 62 mmol/mol (7.8%). Corresponding wHbA1c for avoiding nephropathy were wHbA1c < 68 mmol/mol (8.4 %) and for severe retinopathy < 56 mmol/mol (7.3%).Risk factors in our study associated with DPN included long diabetes duration and impaired glycemic control with higher wHbA1c and significant variability of HbA1c over time, high triglyceride levels, and low HDL-cholesterol levels.In summary, the findings of this thesis highlight the importance of maintaining stable glycemic control and treating traditional cardiovascular covariates such as dyslipidemia in order to reduce DPN. The results also indicate that patients with type 1 diabetes and concomitant diabetes neuropathy display higher levels of chemokines and metalloproteinases, supporting the hypothesis that atherosclerosis and low-grade inflammation may contribute to the pathogenesis of diabetic neuropathy.
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| 8. |
- Baldimtsi, Evangelia, 1981-, et al.
(författare)
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Systemic biomarkers of microvascular alterations in type 1 diabetes associated neuropathy and nephropathy : A prospective long-term follow-up study
- 2023
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Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 37:12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: This study aimed to investigate circulating biomarkers associated with the risk of developing diabetic peripheral neuropathy (DPN) and nephropathy in type 1 diabetes (T1D).MATERIALS AND METHODS: Patients with childhood-onset T1D (n = 49, age 38.3 ± 3.8 yrs.) followed prospectively were evaluated after 30 years of diabetes duration. DPN was defined as an abnormality in nerve conduction tests. Matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1, neutrophil gelatinase-associated lipocalin-2 (NGAL), soluble P-selectin (sP-selectin), estimated GFR (eGFR), micro/macroalbuminuria and routine biochemistry were assessed. For comparison, control subjects were included (n = 30, age 37.9 ± 5.5 yrs.).RESULTS: In all, twenty-five patients (51 %) were diagnosed with DPN, and nine patients (18 %) had nephropathy (five microalbuminuria and four macroalbuminuria). Patients with DPN had higher levels of TIMP-1 (p = 0.036) and sP-selectin (p = 0.005) than controls. Patients with DPN also displayed higher levels of TIMP-1 compared to patients without DPN (p = 0.035). Patients with macroalbuminuria had kidney disease stage 3 with lower eGFR, higher levels of TIMP-1 (p = 0.038), and NGAL (p = 0.002). In all patients, we found only weak negative correlations between eGFR and TIMP-1 (rho = -0.304, p = 0.040) and NGAL (rho = -0.277, p = 0.062, ns), respectively. MMP-9 was higher in patients with microalbuminuria (p = 0.021) compared with normoalbuminuric patients.CONCLUSIONS: Our findings indicate that TIMP-1 and MMP-9, as well as sP-selectin and NGAL, are involved in microvascular complications in T1D. Monitoring and targeting these biomarkers may be a potential strategy for treating diabetic nephropathy and neuropathy.
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| 9. |
- Baldimtsi, Evangelia, et al.
(författare)
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The role of chemokines in type 1 diabetes-associated neuropathy
- 2023
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Ingår i: Endocrinology, diabetes & metabolism. - : John Wiley & Sons. - 2398-9238. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To investigate whether circulating chemokines contribute to the development of diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes (T1D).METHODS: Fifty-two patients with childhood-onset T1D (mean age 28 ± 4 yrs.; diabetes duration 19.5 ± 5.5 yrs.) and 19 control subjects (mean age 26.5 ± 4.5 yrs.) were included in a cross-sectional analysis of this long-term longitudinal cohort study. A subgroup of 24 patients was followed prospectively for a further 10 yrs. Plasma levels of Th1- (CXCL9, CXCL10 and CXCL11), Th2- (CCL17 and CCL22) and Th17-associated (CXCL8 and CCL20) chemokines were assessed in all subjects. Additionally, the TID patients underwent clinical examination and electroneurography.RESULTS: The frequency of neuropathy was 21% (11/52). Higher levels of CXCL9 levels were found in patients with DPN compared with control subjects (p = .019); by contrast, no difference between patients without DPN and control subjects was seen after adjustment for multiple comparisons. In patients with DPN, CXCL10 correlated negatively with suralis MCV and suralis SNAP (rho -0.966, p < .001 and rho -0.738, p < .001, respectively) and was positively correlated with the vibration perception threshold (rho 0.639, p = .034), while CXCL8 correlated negatively with the cold perception threshold (rho -0.645, p = .032). The frequency of neuropathy increased to 54% (13/24) in the subgroup of 23 TID patients, followed by an additional 10 yrs.CONCLUSIONS: Changes in Th1- and Th17-associated chemokines were associated with impaired peripheral sensory nerve function and nerve conduction after long disease duration in childhood-onset T1D.
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| 10. |
- Barcenilla, Hugo, et al.
(författare)
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Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+ CD8+ T Cells in Patients With Recent-Onset Type 1 Diabetes
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.
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