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      Soluble CD163 was linked to galectin-3, diabetic retinopathy and antidepressants in type 1 diabetes


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          Depression has been associated with diabetic retinopathy and increased plasma levels of galectin-3, a lectin expressed in activated macrophages. Increased levels of sCD163, the soluble form of a macrophage expressed scavenger receptor involved in several inflammatory processes, have been demonstrated in the vitreous of the eye in type 1 diabetes (T1D) patients with severe diabetic retinopathy. The aim was to explore whether circulating sCD163 was associated with diabetic retinopathy, depression and/or galectin-3 in T1D patients, controlling for gender, metabolic factors, other diabetes complications, life style and medication.


          Cross sectional.


          Two hundred eighty-seven T1D patients, men 56%, age 18–59 years, diabetes duration ≥1 year, were consecutively recruited from one specialist diabetes clinic. Depression was assessed by Hospital Anxiety and Depression Scale-Depression subscale. Blood samples, anthropometrics and blood pressure values were collected, supplemented with data from electronic medical records and the Swedish National Diabetes Registry. High plasma sCD163 was defined as ≥0.575 mg/L (corresponding to the 80th percentile) and high plasma galectin-3 as ≥4.659 µg/L (corresponding to the 95th percentile).


          The prevalence of depression was 10%, antidepressant medication 8%, diabetic retinopathy 72%, high sCD163 20% and high galectin 3 5%. High galectin-3 (AOR 9.7), antidepressants (AOR 3.8), diabetic retinopathy (AOR 2.4) and systolic blood pressure (per mmHg) (AOR 1.03) were associated with high sCD163.


          This is the first study to show that circulating sCD163 was independently associated with galectin-3, the use of antidepressants and diabetic retinopathy, in patients with T1D. Depression was not associated with sCD163.

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          Most cited references20

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          Soluble CD163.

          J Möller (2012)
          CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function of sCD163 is unknown, but during inflammation and macrophage activation, sCD163 levels increase acutely due to metalloproteinase-mediated cleavage near the cell membrane. It is now evident that sCD163 is very useful as a biomarker of macrophage activation in various inflammatory diseases, such as macrophage activation syndrome, sepsis, and liver disease. Moreover, sCD163 is a general risk marker of comorbidity and mortality in several chronic inflammatory disease states. Recently, sCD163 has been shown to be strongly associated with later development of type 2 diabetes in both lean and obese subjects, likely due to macrophage infiltration of adipose tissue and the liver. This review summarizes the current knowledge on the regulation of sCD163 in normal and pathological states and also deals with analytical aspects of sCD163 measurements in biological samples.
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            A validation study of the Hospital Anxiety and Depression Scale (HADS) in a large sample of French employees

            Background The Hospital Anxiety and Depression Scale (HADS) is a questionnaire widely used for detecting anxiety and depressive disorders. It is used extensively in France, but has never been the subject of a full study in a population at work. The objectives of this study were to present some psychometric properties of the HADS on a large sample of French employees. Method The HADS questionnaire was given to salaried employees at 19 major French companies as part of their biennial occupational medical examination. In 2011, 20992 employees filled in the questionnaire. HADS’s structure was studied first by exploratory, then confirmatory factorial analyses. Results The model selected was the original two-factor structure. The two subscales showed good internal consistency. Women scored higher than the men for anxiety and depression; the scores increased with age; engineers and managers had lower average scores than other occupational status (blue- or white-collar workers and technicians). Conclusion The results of the analyses are consistent with those in literature relating to other populations studied in other countries. The HADS questionnaire is pertinent for detecting symptoms of anxiety and depression in a population of people at work.
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              Effects of antidepressants on the production of cytokines.

              There is now evidence that major depression is associated with an up-regulation of the inflammatory response system (IRS). One of the major factors in this IRS activation is the hyperproduction of pro-inflammatory cytokines. Recently, a number of studies examined whether there is a causative role of these inflammatory mediators in the aetiology of major depression. Studies with animal models and cytokine immune therapy in humans suggest that pro-inflammatory cytokines induce depressive symptomatology. Moreover, these depressive symptoms can be effectively reversed by antidepressant treatment. Thus, it may be suggested that antidepressants suppress pro-inflammatory cytokine production and/or action, resulting in improvement of depressive symptoms. The influence of antidepressants on cytokine production has been examined in culture systems in vitro, and in animal models of depression - in which cytokine production is induced by endotoxin administration. Results suggest that antidepressants of several classes decrease the production of pro-inflammatory cytokines such as interferon-gamma and tumour necrosis factor-alpha, and increase that of interleukin-10, an anti-inflammatory cytokine. Further, the effect of antidepressive treatment on cytokine secretion and on plasma levels of cytokines in depressed patients has been studied. Unfortunately, different approaches to examine cytokine production and different techniques to measure cytokines in plasma are used in these studies. Despite this, current data indicate a normalization of cytokine plasma levels and cytokine production after antidepressant treatment. It is clear, however, that more research is warranted and we strongly argue the need for higher standardization in the methodology used to examine the cytokine network in depressed patients.

                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                December 2018
                24 October 2018
                : 7
                : 12
                : 1343-1353
                [1 ]Department of Clinical Sciences , Endocrinology and Diabetes, Lund University, Lund, Sweden
                [2 ]Department of Research and Development , Växjö, Sweden
                [3 ]Primary Care , Växjö, Sweden
                [4 ]Department of Clinical Sciences Lund , Diabetes Research Laboratory, Lund University, Lund, Sweden
                [5 ]Department of Internal Medicine , Endocrinology and Diabetes, Central Hospital, Växjö, Sweden
                Author notes
                Correspondence should be addressed to E O Melin: eva.melin@ 123456kronoberg.se
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                : 10 October 2018
                : 24 October 2018

                antidepressants,biomarkers,depression,diabetic retinopathy,galectin-3,inflammation,scd163,type 1 diabetes


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