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  • 1.
    Eriksson, Maria A
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rask, Eva
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Carlström, Kjell
    Unit of Obstetrics and Gynecology, Department of Clinical Science, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Ahrén, Bo
    Department of Medicine, Lund University, Lund, Sweden.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis2008In: Blood Coagulation and Fibrinolysis, ISSN 0957-5235, E-ISSN 1473-5733, Vol. 19, no 7, p. 625-632Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Eriksson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hellsten, Gideon
    Norsjö District Health Centre, Norsjö; Sweden.
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Improved fibrinolytic activity during exercise may be an effect of the adipocyte-derived hormones leptin and adiponectin2008In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 122, no 5, p. 701-708Article in journal (Refereed)
    Abstract [en]
    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.

  • 3.
    Fjellström, Mona
    et al.
    Umeå University, Faculty of Arts, Centre for Teaching and Learning (UPC).
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sawert, Bertil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    En bro mellan högre utbildning och profession: Utbildning för kliniska handledare i läkarutbildning2012In: Nu 2012 Göteborg 17-19 oktober 2012: Gränslöst lärande, Göteborg, 2012, p. 131-132Conference paper (Refereed)
    Abstract [sv]

    I samband med att läkarutbildningen vid Umeå universitet skulle regionaliseras togs beslut om att samtliga kliniska handledare, varav flertalet är landstingsanställda läkare, i regionen (Västerbotten, Norrbotten, Jämtland och Västernorrland) skulle erbjudas handledarutbildning. Utbildningen skulle stärka kopplingen mellan de högskoleförlagda och de verksamhetsförlagda delarna av utbildningen samt stödja en handledarroll starkt utmanad av sjukvårdens verksamhetskrav.  Läkarutbildningen har utökats kraftigt de senaste femton åren samtidigt som kraven ökat på produktivitet inom hälso- och sjukvården. Resultatet har blivit många studenter ute i klinisk verksamhet med kliniska handledare som ofta varken har en tydlig rolldefinition som handledare, aktuell kunskap om vilka mål som skall uppnås eller redskap för hur handledning skall genomföras i en splittrad och tidspressad vardag. För studenterna har problemen yttrat sig i form av brist på tid med, eller avsaknad av, handledare och sämre möjligheter att fullfölja praktiska utbildningsmoment (Läkartidningen, 2008:38; MSF Handledningsenkät 2011). Socialstyrelsen har också uppmärksammat behovet av handledarutbildning genom att ställa krav på handledarutbildning för handledare i specialiseringstjänstgöring (ST) för läkare (SOSFS 2008:17, 3 kap).

    Fokus för handledarutbildningen blev att utveckla de kliniska handledarnas kunskaper om och förmåga att handleda i kliniska situationer samt att stimulera ett reflekterande och prövande förhållningssätt till studenternas lärande och den egna handledarrollen. Teman som ingår är: Mål och regelverk för läkarprogrammet, planering av klinisk handledning, att stödja ett reflekterat och handlingsinriktat lärande, att handleda, samtal, feedback och bedömning samt den professionella handledaren. Utbildningen, som genomförs som ett samarbete mellan universitetet och de fyra landstingen, omfattar tre dagar med ett eget arbete som genomförs av deltagarna mellan kursdag 2 och 3. Sedan 2009 har 177 kliniska handledare utbildats. Utvärderingar genomförda i samband med kursens genomförande har visat att de kliniska handledarna genomgående är mycket positiva till utbildningen. Det som särskilt lyfts fram är möjligheten till egen reflektion, praktisk problemlösning tillsammans med andra handledare samt en starkare koppling till utbildningsuppdraget genom den ökade kunskapen om lärande och högskolans regelverk.

    Under den period som handledarutbildningen genomförts har intresset väckts för att handledarutbildning för kliniska handledare skall genomföras i två steg. Ett inledande steg fokuserat på grundläggande handledarkunskap och handledning inom läkarprogrammet som skulle genomföras under läkares specialiseringstjänstgöring. Dessutom ett senare steg, riktat till färdiga specialistkompetenta läkare, som fokuserar på den mer långsiktiga och individnära handledning som genomförs under specialisttjänstgöringen. Idag för läkarprogrammet vid Umeå universitet samtal med två landsting i regionen om möjligheten att bedriva den grundläggande handledarutbildningen.

  • 4.
    Lindahl, Bernt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nilssön, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Borch-Johnsen, Knut
    Steno Diabetes Centre, Gentofte, Denmark.
    Røder, Michael E
    Department of Cardiology and Endocrinology, Nordsjaellands Hospital Hillerød, Hillerød, Denmark.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Widman, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A randomized lifestyle intervention with 5-year follow-up in subjects with impaired glucose tolerance: pronounced short-term impact but long-term adherence problems2009In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 37, no 4, p. 434-442Article in journal (Refereed)
    Abstract [en]

    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. Lindholm, Asa
    et al.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Obstetrik och gynekologi.
    Björn, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Wölner-Hanssen, Pål
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, Anders
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Poromaa, Inger Sundström
    Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.2007In: Fertil Steril, ISSN 1556-5653Article in journal (Refereed)
  • 6.
    Lysell-Bergström, Catharina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Widman, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Progressive conduction disease late after adriamycin treatment of lymphoma, despite normalised ejection fraction2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 3, p. 160-161Article in journal (Refereed)
  • 7.
    Ng, Nawi
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    A reversal of decreasing trends in population cholesterol levels in Västerbotten County, Sweden2012In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 5, p. 10367-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: High cholesterol is identified as a major risk factor for chronic non-communicable diseases, especially cardiovascular and cerebrovascular diseases. Monitoring trends of cholesterol levels and comparing trends across population groups are important to assess population distribution and risks related to cholesterol change over time. Cholesterol surveillance data are lacking, even in high-income countries.

    OBJECTIVES: To describe the trends in cholesterol and triglyceride levels in different population groups and to estimate the risk of developing hypercholesterolemia and hypertriglyceridemia in Västerbotten County, Sweden during 1990-2010.

    DESIGNS AND METHODS: Since 1990, 133,082 individuals living in Västerbotten County, Northern Sweden, invited on their 30th, 40th, 50th and 60th birthdays, participated in the Västerbotten Intervention Program. Ten years after baseline data collection, 34,868 individuals were surveyed for a second time. In addition to a self-administered health questionnaire (that included information on socioeconomic status, demographics, self-reported health and lifestyle behaviours), blood cholesterol and triglyceride were examined.

    RESULTS: The level and prevalence of hypercholesterolemia decreased significantly from 1990 to 2007, but the trends began to increase during 2008-2010 in men, women, and in all educational groups. Men had significantly higher serum triglyceride levels than women and their cholesterol levels were similar to those of the women. This study shows that those with basic education and who live in rural inlands had consistently higher triglyceride level than those who live in the city and have higher educational attainments. People with basic education are also at higher risk of developing hypercholesterolemia and hypertriglyceridemia at 10-year follow-up; the risk is much higher among the older cohorts, particularly women. During 1990-2010, the proportion of participants who reported treatment with lipid-lowering agents increased from 1.1% to 9.6% among men and 0.5% to 5.3% among women. About 60% of those treated achieved treatment goals for cholesterol or triglycerides.

    CONCLUSIONS: The increasing trend in cholesterol level in the Västerbotten population during 2008-2010 needs to be closely monitored. Addressing the unequal distribution of cholesterol, as well as other risk factors such as obesity, physical inactivity, high blood glucose, among those with basic education, and particularly among populations in rural areas are important to prevent higher burdens of chronic non-communicable diseases in this population.

  • 8.
    Rantapää-Dahlqvist, Solbritt
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Engstrand, S
    Berglin, Eva
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Conversion towards an atherogenic lipid profile in rheumatoid arthritis patients during long-term infliximab therapy.2006In: Scand J Rheumatol, Vol. 35, no 2, p. 107-11Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To analyse the effects of infliximab infusions on serum levels of lipids in patients with rheumatoid arthritis (RA) treated for 2 years. METHODS: Fifty-two patients (41 females and 11 males) with RA undergoing infliximab treatment (3 mg/kg) were consecutively recruited into the study. The mean (+/-SD) age of the patients was 54.6+/-12.5 years and mean disease duration was 14.1+/-8.6 years. Blood was sampled before infusion at baseline, and at 3, 6, 12, 18 and 24 months. Forty-one of the patients were also treated with methotrexate, 13 with other disease-modifying anti-rheumatic drugs (DMARDs) and 28 with prednisolone (<10 mg daily). For comparison, lipid levels were followed for 2 years in 70 consecutively included patients with early RA during treatment with conventional DMARDs. RESULTS: There was an initial increase in plasma levels of cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, and LDL/HDL and total/HDL cholesterol ratios. However, after 3 months HDL-cholesterol decreased significantly, followed after 6 months by cholesterol and LDL-cholesterol. The LDL/HDL and total/HDL-cholesterol ratios remained significantly raised. HDL-cholesterol increased and the ratios improved in patients with early RA receiving conventional treatment. The changes over time differed significantly between the patient groups. CONCLUSION: During infliximab infusion a pro-atherogenic lipid profile developed despite reduced inflammatory activity. The long-term decrease in HDL-cholesterol was unexpected considering the known effects of tumour necrosis factor-alpha (TNFalpha).

  • 9. Rask, Eva
    et al.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Seckl, J
    Holst, J J
    Ahrén, B
    Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men.2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, no 9, p. 1640-1645Article in journal (Refereed)
    Abstract [en]

    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.

  • 10. Rask, Eva
    et al.
    Walker, Brian R
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Livingstone, Dawn E W
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Andrew, Ruth
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tissue-specific changes in peripheral cortisol metabolism in obese women: increased adipose 11beta-hydroxysteroid dehydrogenase type 1 activity.2002In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 87, no 7, p. 3330-3336Article in journal (Refereed)
    Abstract [en]

    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.

  • 11.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Lalau, Jean-Daniel
    Johnsson, Ove
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    In face of the increasing efficacy of lipid-lowering therapy, is there still a place for LDL-apheresis?2004In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 30, no 3, p. 213-220Article in journal (Refereed)
  • 12.
    Söderberg, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahrén, B
    Jansson, J H
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hallmans, G
    Asplund, K
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Leptin is associated with increased risk of myocardial infarction.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 246, no 4, p. 409-418Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES AND DESIGN: Leptin is involved in the regulation of bodyweight and metabolism in man and might also be involved in the pathophysiology of the insulin resistance syndrome, which is associated with the development of cardiovascular diseases. We tested whether leptin is a risk factor for acute myocardial infarction (AMI) in a nested case-referent study.

    SUBJECTS AND METHODS: Sixty-two men with first-ever AMI were identified who, prior to AMI, had participated in population-based health surveys in Northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographical region. Blood pressure, body mass index (BMI) and the presence of smoking, diabetes and hypertension were recorded. Total cholesterol, apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B), plasminogen activator inhibitor (PAI-1), insulin, and leptin were analysed in stored samples. Their influences on first-ever AMI were analysed by conditional logistic regression analysis.

    RESULTS: Men with first-ever AMI had higher BMI, plasma insulin and leptin, and diastolic blood pressure than the referents. Furthermore, they had lower plasma apo A-1 and were more often smokers. Smoking, high leptin, PAI-1 and cholesterol, and low apo A-1 levels were significant risk factors for first-ever AMI in univariate analysis. High leptin (OR 8.97; 95% CI: 1.73-46.5) and cholesterol (OR 5.18; 95% CI: 1.34-20.0) levels remained significant risk factors for AMI in a multivariate model. High apo A-1 was protective (OR = 0.13; 95% CI: 0.03-0.55). The combination of high leptin and low apo A-1 was associated with a particularly pronounced increased risk for AMI.

    CONCLUSION: Plasma leptin strongly predicts first-ever AMI. Our data support the hypothesis that leptin is an important link in the development of cardiovascular disease in obesity.

  • 13.
    Söderberg, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahrén, B
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, P G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Weinehall, L
    Hallmans, G
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort.1999In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 30, no 2, p. 328-337Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Leptin, important for body weight regulation, may be involved in the pathogenesis of the insulin resistance syndrome, associated with cardiovascular disease. We tested to determine whether leptin is a risk marker for first-ever stroke in a nested case-referent study.

    METHODS: We identified 113 patients with first-ever stroke (94 with ischemic and 19 with hemorrhagic stroke) who, before the stroke, had participated in population-based health surveys in northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographic region. Blood pressure (BP), body mass index (BMI), and presence of smoking, diabetes, and hypertension were recorded. Total cholesterol, insulin, and leptin were analyzed in stored samples. Risk markers for first-ever stroke were analyzed by conditional logistic regression analysis.

    RESULTS: Patients with hemorrhagic stroke had higher levels of BMI and systolic and diastolic BPs. Leptin levels were 72% and 59% higher in males and females, respectively, with hemorrhagic stroke versus referents. Patients with ischemic stroke more often had hypertension, diabetes mellitus, and higher fasting glucose and insulin levels. A diagnosis of hypertension and elevated systolic and diastolic BPs were significant risk markers for first-ever hemorrhagic stroke in univariate analysis. High leptin (OR=20.55; 95% CI, 1.12 to 376.7) levels together with hypertension (OR=16.28; 95% CI, 1.49 to 177.3) remained as significant risk markers in a multivariate model. The combination of high leptin and high systolic or diastolic BP were associated with a profoundly increased risk for hemorrhagic stroke (OR=22.11; 95% CI, 1.57 to 310.9). Diabetes, hypertension, and obesity (BMI >/=27), together with high levels of insulin, glucose, systolic and diastolic BP, were significant risk markers for first-ever ischemic stroke in univariate analysis. Hypertension (OR=2.10; 95% CI, 1.14 to 3.86) remained as an independent risk marker in a multivariate model.

    CONCLUSIONS: Plasma leptin is strongly associated with an increased risk for first-ever hemorrhagic stroke, independent of other risk markers for cardiovascular disease. Leptin may be an important link in the development of cardiovascular disease in obesity.

  • 14.
    Söderberg, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahrén, B
    Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, no 5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Leptin is a crucial mediator of satiety signals and energy balance, and its circulating levels are increased in obesity. It has recently been shown that plasma leptin levels in humans correlate with circulating insulin and to insulin secretion. This indicates that leptin may be an important link in metabolic consequences of the insulin resistance syndrome. Whether this includes abnormalities in fibrinolysis has not been studied.

    METHODS AND RESULTS: Healthy subjects (n = 165; 85 men and 80 women) from the Northern Sweden MONICA population were investigated. Anthropometric measurements, oral glucose tolerance tests and sampling for plasma leptin, lipids, fibrinogen and fibrinolytic variables were made. Leptin levels were 342% higher in women than in men and were in both sexes strongly correlated to body mass index (BMI). After adjustments for age and BMI, leptin levels correlated significantly to pre/post glucoseload insulin levels in both sexes. After further adjustment for baseline insulin levels, leptin levels were in males significantly associated with increased waist circumference (P<0.001), low HDL cholesterol (P<0.05), low tPA activity (P<0.01) and high PAI-1 activity (P<0.001). In postmenopausal females, a significant association between leptin and low tPA activity/high PAI-1 activity was seen after adjustment for age and BMI (P<0.05). Conclusions. Circulating levels of leptin are associated with components of the insulin resistance syndrome, including defective fibrinolysis, in men and postmenopausal women. This suggests that leptin may be involved in the mediation of consequences of insulin resistance.

  • 15.
    Söderberg, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Brismar, K
    Carlström, K
    Ahrén, B
    A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity.2001In: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, Vol. 25, no 1, p. 98-105Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity.

    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.

    MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated.

    RESULTS: After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were negatively associated with leptin in men with low waist circumference (r=-0.59, P<0.01). The following factors were associated with leptin in a multivariate model: low levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women.

    CONCLUSION: We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results we suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels. International Journal of Obesity (2001) 25, 98-105

  • 16.
    Söderström, Elisabet
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Plasma folate, but not homocysteine, is associated with Apolipoprotein A1 levels in a non-fortified population2013In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 12, p. 74-Article in journal (Refereed)
    Abstract [en]

    Background: Elevated total plasma homocysteine (tHcy) in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality. Reported reasons for this association have been that homocysteine and its major genetic determinant methylenetetrahydrofolate reductase (MTHFR) may have an effect on HDL and Apolipoprotein (Apo) A1 levels. We wanted to study if tHcy and its major determinants were correlated with Apo A1 levels in a large population without folate fortification. Methods: This study was a prospective incident nested case-referent study within the Northern Sweden Health and Disease Study Cohort (NSHDSC), including 545 cases with first myocardial infarction and 1054 matched referents, median age at inclusion was 59 years. Univariate and multiple regression analyzes was used to study the associations between apolipoproteins Apo A1 and B, tHcy, folate and vitamin B12 in plasma as well as MTHFR polymorphisms 677C>T and 1298A>C. Results: Apo A1 and Apo B were strongly associated with the risk of a first myocardial infarction. tHcy was not associated with Apo A1 levels. Instead, folate had an independent positive association with Apo A1 levels in univariate and multiple regression models. The associations were seen in all men and women, among referents but not among cases. MTHFR polymorphisms had no clear effect on Apo A1 levels. Conclusions: Analyzing over 1500 subjects we found an independent positive association between plasma folate (major dietary determinant of tHcy) and Apo A1 levels among those who later did not develop a first myocardial infarction. No association was seen between tHcy and Apo A1.

  • 17.
    Thøgersen, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlén, Gösta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Lundberg, Vivan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnsson, Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahrén, Bo
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction.2004In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 11, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The summarized importance of haemostatic and metabolic variables (insulin, lipids including lipoprotein (a) [Lp(a)] and leptin) in predicting first myocardial infarction, as well as possible interactions among these variables, have not been reported. DESIGN: A prospective case-control study nested within the Northern Sweden Health and Disease Cohort. METHODS: Sixty-two men diagnosed with a first myocardial infarction were sex- and age-matched with 124 controls. Conditional logistic regression was conducted including established risk factors, plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) mass concentration, von Willebrand factor, insulin, proinsulin, specific insulin, apolipoprotein A-I (apo A-I), Lp(a), and leptin. Interaction analysis was also performed for tPA, apo A-I, Lp(a), leptin and proinsulin. RESULTS: Smoking, low plasma levels of apo A-I and high plasma levels of cholesterol, Lp(a), tPA, PAI-1, proinsulin and leptin were associated with myocardial infarction in univariate conditional logistic regression analysis. High tPA [odds ratio (OR), 21.3; 95% confidence interval (CI), 2.04-222] and Lp(a) (OR, 7.21; 95% CI, 1.31-39.8) and low apo A-I (OR, 0.15; 95% CI, 0.02-0.93) remained significant risk determinants in multivariate analysis with smoking habits, body mass index, hypertension, cholesterol, and diabetes included as covariates. There were non-significant synergic interactions between high Lp(a) and leptin and tPA, respectively, and between high Lp(a) and low apo A-I. CONCLUSION: Plasma levels of tPA, Lp(a), and apo A-I are independently associated with subsequent development of a first myocardial infarction in men.

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