| 1. |
- Dalin, Frida, 1984-, et al.
(author)
-
Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
-
In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
-
Journal article (peer-reviewed)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
|
|
| 2. |
- Eriksson, Maria A, 1965-, et al.
(author)
-
Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis
- 2008
-
In: Blood Coagulation and Fibrinolysis. - : Lippincott Williams & Wilkins. - 1473-5733 .- 0957-5235. ; 19:7, s. 625-632
-
Journal article (peer-reviewed)abstract
- The adipocyte-derived hormone leptin is associated with insulin resistance and reduced fibrinolytic status - or dysfibrinolysis - in humans. As leptin associates differentially to the development of cardiovascular disease and diabetes in men and women, we hypothesized that leptin and insulin sensitivity are related to dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were recruited from the Monitoring of trends and determinants in Cardiovascular disease (MONICA) population sample, representing the highest and lowest quartiles of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding globulin were measured. Insulin sensitivity was estimated using the euglycaemic clamp technique. Body composition was determined by bioimpedance. Determinants for circulating levels of fibrinolytic factors were explored in a multivariate linear regression analysis. Levels of fibrinolytic variables and estimated insulin sensitivity did not differ between men and women. Leptin was independently associated with reduced fibrinolytic status high PAI-1 activity, low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P<0.001-0.002). In women, fat mass and/or insulin sensitivity were related to these factors (P<0.001-0.03), and leptin only to reduced tPA activity (P = 0.002). Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate differentially in men and women. Blood Coagul Fibrinolysis 19:625-632 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
|
|
| 3. |
- Eriksson, Maria, 1965-, et al.
(author)
-
Improved fibrinolytic activity during exercise may be an effect of the adipocyte-derived hormones leptin and adiponectin
- 2008
-
In: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 122:5, s. 701-708
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Physical activity is associated with improved fibrinolytic activity and reduced risk for cardiovascular disease. High levels of leptin and low levels of adiponectin, both adipocyte-derived hormones, or adipokines, are related to dysfibrinolysis and risk for cardiovascular disease. In this study, we explored if improved fibrinolytic activity during exercise could be linked to changes in leptin and adiponectin levels.MATERIALS AND METHODS: Twenty healthy men (mean age 36 years) participated in a 14-day long skiing expedition in the Swedish mountains. They were randomly assigned to either a 40% or a 30% fat-based diet. Anthropometry, lipids, fibrinolytic activity (PAI-1 activity, tPA activity and mass) and adipokines (leptin and adiponectin) were measured before, during and six weeks after the expedition.RESULTS: PAI-1 activity and circulating levels of leptin decreased whereas levels of adiponectin increased during exercise. The fall in PAI-1 activity showed a strong linear association with changes in leptin and adiponectin levels (p = 0.001 and p < 0.001, respectively). Changes in leptin and adiponectin levels were independent of decreasing waist circumference. However, the association between anthropometric measures and adipokines changed considerably during the expedition. Adiponectin was weakly and negatively associated with BMI at baseline. In contrast, there was a strong positive association between adiponectin and BMI after two weeks of exercise, whereas the association between leptin and BMI became less pronounced. In addition, increasing leptin and decreasing adiponectin levels were associated with increasing PAI-1 activity during the six weeks following the expedition. After six weeks of normal activity, fibrinolytic activity and hormone levels returned towards baseline levels.CONCLUSION: Heavy exercise induced improved fibrinolytic activity, which was associated independently with changes in circulating levels of the adipocyte-derived hormones leptin and adiponectin. Improved fibrinolytic activity (and reduced risk for cardiovascular disease) related to physical activity could possibly be mediated by leptin and adiponectin.
|
|
| 4. |
- Lindahl, Bernt, et al.
(author)
-
A randomized lifestyle intervention with 5-year follow-up in subjects with impaired glucose tolerance : pronounced short-term impact but long-term adherence problems
- 2009
-
In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 37:4, s. 434-442
-
Journal article (peer-reviewed)abstract
- AIMS: To compare data on cardiovascular risk factor changes in lipids, insulin, proinsulin, fibrinolysis, leptin and C-reactive protein, and on diabetes incidence, in relation to changes in lifestyle. METHODS: The study was a randomized lifestyle intervention trial conducted in northern Sweden between 1995 and 2000, in 168 individuals with impaired glucose tolerance (IGT) and body mass index above 27 at start. The intensive intervention group (n = 83) was subjected to a 1-month residential lifestyle programme. The usual care group (n = 85) participated in a health examination ending with a single counselling session. Follow-up was conducted at 1, 3 and 5 years. RESULTS: At 1-year follow-up, an extensive cardio-metabolic risk factor reduction was demonstrated in the intensive intervention group, along with a 70% decrease of progress to type 2 diabetes. At 5-year follow-up, most of these beneficial effects had disappeared. Reported physical activity and fibre intake as well as high-density lipoprotein cholesterol were still increased, and fasting insulin and proinsulin were lower. CONCLUSIONS: The intervention affected several important cardio-metabolic risk variables beneficially, and reduced the risk for type 2 diabetes, but the effects persisted only as long as the new lifestyle was maintained. Increased physical activity seemed to be the behaviour that was most easy to preserve.
|
|
| 5. |
- Mattsson, Cecilia, et al.
(author)
-
Gender-specific links between hepatic 11beta reduction of cortisone and adipokines
- 2007
-
In: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 15:4, s. 887-894
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones. RESEARCH METHODS AND PROCEDURES: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol. RESULTS: Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. DISCUSSION: Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.
|
|
| 6. |
- Midhage, Robin, et al.
(author)
-
Psychometric evaluation of the Swedish self-rated 36-item version of WHODAS 2.0 for use in psychiatric populations - using classical test theory.
- 2021
-
In: Nordic Journal of Psychiatry. - : Taylor & Francis. - 0803-9488 .- 1502-4725. ; 75:7, s. 494-501
-
Journal article (peer-reviewed)abstract
- Aim The aim of this study was to evaluate the reliability and validity of the Swedish version of the self-rated 36-item WHODAS 2.0 in patients from Swedish psychiatric outpatient settings, using classical test theory.Methods The 36-item WHODAS 2.0, together with the Sheehan Disability Scale (SDS), was filled in by a sample of 780 participating psychiatric patients: 512 (65.6%) women, 263 (33.7%) men, and 5 (0.6%) who did not report any sex.Results The internal consistency, measured by Cronbach’s alpha, for the different domains of functioning were between 0.70 and 0.94, and interpreted as good. The confirmatory factor analysis (CFA) revealed two levels: the first level consisted of a general disability factor, while the second level consisted of the six domains of the scale, respectively. The model had borderline fit. There was a significant correlation between WHODAS 2.0 36-item and SDS (n = 395). The WHODAS 2.0 differed significantly between diagnostic groups.Conclusion The present study demonstrates that the Swedish self-rated 36-item version of WHODAS 2.0, within a psychiatric outpatient population, showed good reliability and convergent validity. We conclude that the self-rated 36-item Swedish version of WHODAS 2.0 can be used for valid interpretations of disability in patients with psychiatric health conditions.
|
|
| 7. |
- Ramklint, Mia, Professor, et al.
(author)
-
Validity of the self-rated 36-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 as a measure of functioning in Swedish psychiatric outpatients
- 2023
-
In: Nordic Journal of Psychiatry. - : Taylor & Francis. - 0803-9488 .- 1502-4725. ; 77:3, s. 276-281
-
Journal article (peer-reviewed)abstract
- Purpose: The aim of this study was to investigate concurrent validity of the Swedish self-rated 36-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 by comparison with professional Global Assessment of Functioning (GAF) ratings in psychiatric outpatients.Material and methods: A cross-sectional convenience sample of 444 patients was recruited from their regular psychiatric outpatient settings. The patients filled out the WHODAS 2.0; their clinicians provided clinical information and performed GAF ratings blinded to the patients' assessments. Analyses of correlations, variance components, and ROC curves were performed to investigate the validity of the WHODAS 2.0 through comparison with the GAF. The variance component analyses included working status, psychosocial problems, number of diagnostic groups, and remission status. GAF ratings were separated as total (GAF-T), symptoms (GAF-S), and functioning (GAF-F).Results: There was significant correlation (p < 0.001) between WHODAS 2.0 total and domain scores and GAF-S, GAF-F, and GAF-T ratings. The correlations varied from r = 0.29 to r = 0.48, with the highest being between GAF-F rating and WHODAS 2.0 total score. Repeating the analyses for separate diagnostic groups replicated the findings, though not for psychotic, substance-related, and eating disorders. The WHODAS 2.0 showed good ability to distinguish impaired functioning below a fixed GAF-T cut-off of 70 (area under the curve: 0.74-0.78). The explained variance was lower for the WHODAS 2.0 than for the GAF (38.9% vs. 59.2%).Conclusions: Concurrent validity was found when comparing the Swedish self-administered 36-item version of WHODAS 2.0 with the expert-rated GAF in psychiatric outpatients.
|
|
| 8. |
- Rask, Eva, 1958-, et al.
(author)
-
Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men
- 2001
-
In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 24:9, s. 1640-1645
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake.RESEARCH DESIGN AND METHODS:From a population-based study, 35 men were recruited, representing a wide spectrum of insulin sensitivity and body weight. Each subject underwent a hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured.RESULTS:Insulin resistance was associated with impaired GIP and GLP-1 responses to a mixed meal. The total area under the curve (AUC) of the GIP response after the mixed meal was associated with insulin sensitivity (r = 0.54, P < 0.01). There was a significant difference between the highest and the lowest tertile of insulin sensitivity (P < 0.05). GLP-1 levels 15 min after food intake were significantly lower in the most insulin-resistant tertile compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.47, P < 0.01). Multiple linear regression analysis showed that insulin resistance, but not obesity, was an independent predictor of these decreased incretin responses.CONCLUSIONS:In insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and are related to the degree of insulin resistance. Decreased incretin responsiveness may be of importance for the development of impaired glucose tolerance.
|
|
| 9. |
|
|
| 10. |
- Rask, Eva, 1958-, et al.
(author)
-
Tissue-specific changes in peripheral cortisol metabolism in obese women : increased adipose 11beta-hydroxysteroid dehydrogenase type 1 activity
- 2002
-
In: Journal of Clinical Endocrinology and Metabolism. - : Williams & Wilkins Co.. - 0021-972X .- 1945-7197. ; 87:7, s. 3330-6
-
Journal article (peer-reviewed)abstract
- Cushing's syndrome and the metabolic syndrome share clinical similarities. Reports of alterations in the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, however, in the metabolic syndrome. Recent data highlight the importance of adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which regenerates cortisol from cortisone and, when overexpressed in fat, produces central obesity and glucose intolerance. Here we assessed the HPA axis and 11beta-HSD1 activity in women with moderate obesity and insulin resistance. Forty women were divided into tertiles according to body mass index (BMI; median, 22.0, 27.5, and 31.4, respectively). Serum cortisol levels were measured after iv CRH, low dose dexamethasone suppression, and oral cortisone administration. Urinary cortisol metabolites were measured in a 24-h sample. A sc abdominal fat biopsy was obtained in 14 participants for determination of 11beta-HSD type 1 activity in vitro. Higher BMI was associated with higher total cortisol metabolite excretion (r = 0.49; P < 0.01), mainly due to increased 5alpha- and, to a lesser extent, 5beta-tetrahydrocortisol excretion, but no difference in plasma cortisol basally, after dexamethasone, or after CRH, and only a small increase in the ACTH response to CRH. Hepatic 11beta-HSD1 conversion of oral cortisone to cortisol was impaired in obese women (area under the curve, 147,736 +/- 28,528, 115,903 +/- 26,032, and 90,460 +/- 18,590 nmol/liter.min; P < 0.001). However, 11beta-HSD activity in adipose tissue was positively correlated with BMI (r = 0.55; P < 0.05). In obese females increased reactivation of glucocorticoids in fat may contribute to the characteristics of the metabolic syndrome. Increased inactivation of cortisol in liver may be responsible for compensatory activation of the HPA axis. These alterations in cortisol metabolism may be a basis for novel therapeutic strategies to reduce obesity-related complications.
|
|
