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  • 1. Almby, Kristina E.
    et al.
    Abrahamsson, Niclas
    Lundqvist, Martin H.
    Hammara, Ulf
    Thombare, Ketan
    Panagiotou, Amalia
    Karisson, F. Anders
    Sundbom, Magnus
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eriksson, Jan W.
    Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery2019In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, no 2, p. 161-171Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

    Design: Experimental hyperinsulinemic–hypoglycemic clamp study.

    Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

    Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

    Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

  • 2.
    Andréen, Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nyberg, Sigrid
    Sundström-Poromaa, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Progesterone effects during sequential hormone replacement therapy2003In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 148, no 5, p. 571-577Article in journal (Refereed)
  • 3. Bjarnason, R
    et al.
    Boguszewski, M
    Dahlgren, J
    Gelander, L
    Kriström, B
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosberg, S
    Carlsson, B
    Albertsson-Wikland, K
    Carlsson, L M
    Leptin levels are strongly correlated with those of GH-binding protein in prepubertal children.1997In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 137, no 1, p. 68-73Article in journal (Refereed)
    Abstract [en]

    There was a highly significant correlation between serum levels of leptin and those of GHBP, except in children with GHD. The possibility that leptin could mediate the effects of body fat mass on GH sensitivity, therefore, merits further investigation.

  • 4.
    Burén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Liu, Hui-Xia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jensen, J.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Jan W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dexamethasone impairs insulin signalling and glucose transport by depletion of insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase B in primary cultured rat adipocytes.2002In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 146, no 3, p. 419-429Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Glucocorticoid excess leads to insulin resistance. This study explores the effects of glucocorticoids on the glucose transport system and insulin signalling in rat adipocytes. The interaction between glucocorticoids and high levels of insulin and glucose is also addressed. DESIGN AND METHODS: Isolated rat adipocytes were cultured for 24 h at different glucose concentrations (5 and 15 mmol/l) with or without the glucocorticoid analogue dexamethasone (0.3 micromol/l) and insulin (10(4) microU/ml). After the culture period, the cells were washed and then basal and insulin-stimulated glucose uptake, insulin binding and lipolysis as well as cellular content of insulin signalling proteins (insulin receptor substrate-1 (IRS-1), IRS-2, phosphatidylinositol 3-kinase (PI3-K) and protein kinase B (PKB)) and glucose transporter isoform GLUT4 were measured. RESULTS: Dexamethasone in the medium markedly decreased both basal and insulin-stimulated glucose uptake at both 5 and 15 mmol/l glucose (by approximately 40-50%, P<0.001 and P<0.05 respectively). Combined long-term treatment with insulin and dexamethasone exerted additive effects in decreasing basal, and to a lesser extent insulin-stimulated, glucose uptake capacity (P<0.05) compared with dexamethasone alone, but this was seen only at high glucose (15 mmol/l). Insulin binding was decreased (by approximately 40%, P<0.05) in dexamethasone-treated cells independently of surrounding glucose concentration. Following dexamethasone treatment a approximately 75% decrease (P<0.001) in IRS-1 expression and an increase in IRS-2 (by approximately 150%, P<0.001) was shown. Dexamethasone also induced a subtle decrease in PI3-K (by approximately 20%, P<0.01) and a substantial decrease in PKB content (by approximately 45%, P<0.001). Insulin-stimulated PKB phosphorylation was decreased (by approximately 40%, P<0.01) in dexamethasone-treated cells. Dexamethasone did not alter the amount of total cellular membrane-associated GLUT4 protein. The effects of dexamethasone per se on glucose transport and insulin signalling proteins were mainly unaffected by the surrounding glucose and insulin levels. Dexamethasone increased the basal lipolytic rate (approximately 4-fold, P<0.05), but did not alter the antilipolytic effect of insulin. CONCLUSIONS: These results suggest that glucocorticoids, independently of the surrounding glucose and insulin concentration, impair glucose transport capacity in fat cells. This is not due to alterations in GLUT4 abundance. Instead dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 and PKB accompanied by a parallel reduction in insulin-stimulated activation of PKB.

  • 5.
    Burén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Liu, Hui-Xia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lauritz, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Jan W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    High glucose and insulin in combination cause insulin receptor substrate-1 and -2 depletion and protein kinase B desensitisation in primary cultured rat adipocytes: possible implications for insulin resistance in type 2 diabetes2003In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 148, p. 157-167Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The purpose of this study was to investigate the cellular effects of long-term exposure to high insulin and glucose levels on glucose transport and insulin signalling proteins. DESIGN AND METHODS: Rat adipocytes were cultured for 24 h in different glucose concentrations with 10(4) microU/ml of insulin or without insulin. After washing, (125)I-insulin binding, basal and acutely insulin-stimulated d-[(14)C]glucose uptake, and insulin signalling proteins and glucose transporter 4 (GLUT4) were assessed. RESULTS: High glucose (15 and 25 mmol/l) for 24 h induced a decrease in basal and insulin-stimulated glucose uptake compared with control cells incubated in low glucose (5 or 10 mmol/l). Twenty-four hours of insulin treatment decreased insulin binding capacity by approximately 40%, and shifted the dose-response curve for insulin's acute effect on glucose uptake 2- to 3-fold to the right. Twenty-four hours of insulin treatment reduced basal and insulin-stimulated glucose uptake only in the presence of high glucose (by approximately 30-50%). At high glucose, insulin receptor substrate-1 (IRS-1) expression was downregulated by approximately 20-50%, whereas IRS-2 was strongly upregulated by glucose levels of 10 mmol/l or more (by 100-400%). Insulin treatment amplified the suppression of IRS-1 when combined with high glucose and also IRS-2 expression was almost abolished. Twenty-four hours of treatment with high glucose or insulin, alone or in combination, shifted the dose-response curve for insulin's effect to acutely phosphorylate protein kinase B (PKB) to the right. Fifteen mmol/l glucose increased GLUT4 in cellular membranes (by approximately 140%) compared with 5 mmol/l but this was prevented by a high insulin concentration. CONCLUSIONS: Long-term exposure to high glucose per se decreases IRS-1 but increases IRS-2 content in rat adipocytes and it impairs glucose transport capacity. Treatment with high insulin downregulates insulin binding capacity and, when combined with high glucose, it produces a marked depletion of IRS-1 and -2 content together with an impaired sensitivity to insulin stimulation of PKB activity. These mechanisms may potentially contribute to insulin resistance in type 2 diabetes.

  • 6. Gustafsson, Stefan
    et al.
    Lind, Lars
    Zethelius, Björn
    Venge, Per
    Flyvbjerg, Allan
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ingelsson, Erik
    Adiponectin and cardiac geometry and function in elderly: results from two community-based cohort studies2010In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 162, no 3, p. 543-550Article in journal (Refereed)
    Abstract [en]

    Serum adiponectin concentrations were associated with ejection fraction in men, and these associations were partially attenuated by NT-proBNP. Our results imply that adiponectin may be associated with systolic function through pathways that involve natriuretic peptides.

  • 7.
    Högström, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study.2008In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 158, no 5, p. 765-770Article in journal (Refereed)
    Abstract [en]

    CONTEXT: The association between retinol and bone mineral density (BMD) in males after puberty has not been fully investigated previously. OBJECTIVE: To investigate the association between retinol, retinol-binding protein-4 (RBP-4), BMD (g/cm(2)), abdominal fat mass, and markers of bone metabolism in young men. DESIGN: Longitudinal study. PARTICIPANTS: Seventy-eight healthy males with a mean age of 22.6+/-0.7 years at baseline. A follow-up was conducted in 73 of the participants 2.0+/-0.4 years later. MAIN OUTCOME MEASURES: Associations between serum concentrations of retinol and RBP-4, and BMD of the total body, lumbar spine, and hip, serum concentrations of osteocalcin, and carboxy terminal telopeptide of type 1 collagen (CTX), were investigated. RESULTS: Both retinol and RBP-4 showed an inverse relationship with that of osteocalcin (r=-0.23 to -0.25, P<0.05). Levels of RBP-4 (r=0.26, P=0.02) and osteocalcin (r=-0.23, P=0.04) were also related to abdominal fat mass, and the relationship between RBP-4, retinol, and osteocalcin disappeared after adjusting for this influence of abdominal fat mass. Neither retinol nor RBP-4 concentrations were associated with BMD at any site, CTX as baseline, or changes in BMD during the 2-year follow-up period. Levels of RBP-4 showed a strong association with levels of retinol (r=0.61, P<0.001). CONCLUSION: We found a negative association between the bone formation marker osteocalcin with retinol and RBP-4. The association disappeared when adjusting for the influence of abdominal fat mass. Neither retinol nor RBP-4 were associated with peak BMD in young men.

  • 8.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zeleniuch-Jacquotte, A
    Muti, P
    Mure, A
    Rinaldi, S
    Dossus, L
    Micheli, A
    Arslan, A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shore, R E
    Krogh, V
    Koenig, K L
    Riboli, E
    Berrino, F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Toniolo, P
    Kaaks, R
    Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.2004In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 150, no 2, p. 161-171Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

  • 9.
    Mohlin, Eric
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Filipsson Nyström, Helena
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Long-term prognosis after medical treatment of Graves' disease in a northern Swedish population 2000-20102014In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 170, no 3, p. 419-427Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the long-term prognosis of patients with Graves' disease (GD) after antithyroid drug (ATD) treatment and follow-up outside of highly specialised care. Design and methods: Medical records of all patients diagnosed with first-time GD in 2000-2010 with at least 6 months ATD treatment at a central hospital and follow-up in primary health care in the county of Norrbotten in northern Sweden were retrospectively reviewed. Patients were followed for relapse until 31st December 2012. We included 219 patients (mean age 46 years, 82.5% women) with follow-up of maximum 10 years and 829 observed patient years. Data were analysed using Kaplan-Meier estimates and log-rank test. Results: During the observation period, 43.5% of the patients had relapsed into active GD. The cumulative relapse rates were 22.6, 30.2, 36.9 and 41.5% after 6 months, 1, 3 and 5 years respectively. The presence of goitre (P=0.014) predicted relapse. Previous smoking was protective against relapse (P=0.003). The levels of free thyroxine or free tri-iodothyronine, age, gender, current smoking and ophthalmopathy did not predict relapse. Agranulocytosis was found in 1.7% (95% CI 0.7-4.0%). Conclusion: A long-term remission of 56.5%, in an iodine-sufficient area where ATD is offered to most patients in the real world of central and district hospitals, is higher than in most studies. Relapse was most common during the first year, and prognosis was excellent after 4 years without relapse. The protective effect of previous smoking merits further research.

  • 10. Nilsson, A G
    et al.
    Marelli, C
    Fitts, D
    Bergthorsdottir, R
    Burman, P
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekman, B
    Engström, B Edén
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ragnarsson, O
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wahlberg, J
    Lennernäs, H
    Skrtic, S
    Johannsson, G
    Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency2014In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 171, no 3, p. 369-377Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI).

    DESIGN: Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden.

    METHODS: Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness).

    RESULTS: In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure.

    CONCLUSIONS: This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.

  • 11. Nilsson, Anna G.
    et al.
    Bergthorsdottir, Ragnhildur
    Burman, Pia
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekman, Bertil
    Engstrom, Britt Eden
    Ragnarsson, Oskar
    Skrtic, Stanko
    Wahlberg, Jeanette
    Achenbach, Heinrich
    Uddin, Sharif
    Marelli, Claudio
    Johannsson, Gudmundur
    Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 176, no 6, p. 715-725Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).

    Design: Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.

    Methods: Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.

    Results: Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008).

    Conclusions: In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.

  • 12.
    Otten, Julia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Mellberg, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Andersson, Tomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Larsson, Christel
    Department of Food and Nutrition, and Sport Science, Goteborgs Universitet, Goteborg, Sweden.
    Holst, Jens Juul
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Postprandial levels of GLP-1, GIP, and glucagon after two years of weight loss with a Paleolithic diet: a randomized controlled trial in healthy obese women2019In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, no 6, p. 417-427Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate how weight loss by different diets impacts on postprandial levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon.

    METHODS: In this single-centre, parallel group 2-year trial, 70 healthy postmenopausal obese women were randomized to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations. Both diets were without calorie restriction. The primary outcome was the change in fat mass. Here, secondary analyses on GLP-1, GIP, and glucagon measured during an OGTT are described.

    RESULTS: In the Paleolithic diet group, mean weight loss compared to baseline was 11% at 6 months, and 10% at 24 months. In the control diet group, mean weight loss was 6% after 6 and 24 months (P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively). Compared to baseline, the mean incremental area under the curve (iAUC) for GLP-1 increased by 34% and 45% after 6 and 24 months in the Paleolithic diet group, and increased by 59% after 24 months in the control diet group. The mean iAUC for GIP increased only in the Paleolithic diet group. The AUC for glucagon increased during the first 6 months in both groups. The fasting glucagon increase correlated with the β-hydroxybutyrate increase.

    CONCLUSIONS: Weight loss caused an increase in postprandial GLP-1 levels and a further rise occurred during weight maintenance. Postprandial GIP levels increased only after the Paleolithic diet. Reduced postprandial glucagon suppression may be caused by a catabolic state.

  • 13.
    Stomby, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Region Jönköping County, Jönköping, Sweden.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lundquist, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Psychology, Stockholm University, Stockholm, Sweden.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women2016In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 175, no 2, p. 117-126Article in journal (Refereed)
    Abstract [en]

    Objective: Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance. Design: A cross-sectional study including 200 elderly (55-80 years old) men and women. Method: We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day. Results: Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal P < 0.001; rostral P = 0.006), right lateral orbitofrontal cortex (P = 0.004), and right rostral middle frontal gyrus (P = 0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P = 0.006). No relationship was found between cortisol levels and hippocampal volume. Conclusion: This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men.

  • 14.
    Stomby, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Region Jönköping County, Jönköping, Sweden.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Evang, Johan Arild
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bollerslev, Jens
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johannsson, Gudmundur
    Ragnarsson, Oskar
    Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing's syndrome in remission2019In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, no 5, p. 329-338Article in journal (Refereed)
    Abstract [en]

    Objective: Cushing's syndrome is associated with long-term cognitive deficits and affective symptoms such as depression and anxiety. The alterations in brain function under lying these deficits after Cushing's syndrome are unclear and therefore we aimed to explore alterations in resting-state functional connectivity in patients with Cushing's syndrome in remission. Design: Cross-sectional case-control study. Methods: Nineteen women with Cushing's syndrome in remission for a median time of 7 years (IQR: 6-10) and a mean age of 45 years were included at three university clinics. These patients and 38 age-matched female controls underwent brain imaging at a single center. The main outcome measure was functional connectivity at rest, measured with functional magnetic resonance imaging. Results: The medial temporal lobe (MTL) and prefrontal cortex networks, exhibited elevated functional connectivity among patients compared to controls. The degree of elevated functional connectivity in the MTL was negatively associated with time in remission. Conclusions: Resting-state functional connectivity within glucocorticoid receptor-rich regions, particularly the MTL and medial prefrontal cortex, was increased in patients. These differences in connectivity may provide a neural basis for the cognitive deficits and affective symptoms commonly experienced by patients with Cushing's syndrome in remission.

  • 15.
    Söderberg, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahrén, B
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dinesen, B
    Brismar, K
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women.2001In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 144, no 3, p. 283-290Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone-IGF-I axis are linked to obesity and cardiovascular diseases. However, whether the association between leptin and the GH-IGF-I axis is altered with increasing obesity is not known. We therefore examined the relationship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a population study.

    DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design.

    METHODS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for specific insulin and proinsulin.

    RESULTS: Leptin inversely correlated to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal women (P<0.05). The association between leptin and IGFBP-1 was lost after adjustment for insulin. In multivariate analyses taking measures of adiposity into account, low proinsulin, and IGF-I in combination with old age, but not leptin, predicted high IGFBP-1 levels.

    CONCLUSIONS: Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated with IGFBP-1 in non-obese men and premenopausal women. However, these associations were lost with increasing central obesity in men and premenopausal women and after control for insulin. Therefore, this study suggests (i) that leptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationship between leptin, IGFBP-1 and insulin.

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