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  • 1.
    Abdelgadir, Moawia
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Abbas, M
    Jarvi, A
    Elbagir, M
    Eltom, M
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Glycaemic and insulin responses of six traditional Sudanese carbohydrate-rich meals in subjects with Type 2 diabetes mellitus.2005In: Diabet Med, ISSN 0742-3071, Vol. 22, no 2, p. 213-217Article in journal (Refereed)
  • 2.
    Abdelgadir, Moawia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Low serum adiponectin concentrations are associated with insulin sensitivity independent of obesity in Sudanese subjects with type 2 diabetes mellitus2013In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 5, p. 15-Article in journal (Refereed)
    Abstract [en]

    Aims: Prevalence of Type 2 diabetes mellitus among Sudanese population was found to be 3.4% and associated with high rates of complications and obesity. Different adipocytokines are secreted from adipose tissues, among them adiponectin, which was shown to have insulins ensitizing properties and anti-inflammatory, anti-atherogenic effect. The aim of this study was to characterize type 2 diabetes in Sudanese diabetic subjects and controls in respect to hormones influencing or influenced by glucose metabolism. Methods: 104 type 2 diabetic patients (45 men and 59 women), and 75 matched control subjects (34 men and 41 women) were studied. Fasting serum samples were used to measure adiponectin, leptin, insulin, proinsulin, ghrelin and glucose. Body mass index, insulin/proinsulin ratio and (HOMA) insulin resistance and beta cell function were also calculated. Results: Adiponectin serum concentrations were significantly lower in subjects with type 2 diabetes compared with controls subjects (P = 0.002), comparison between males and females did not reach significant levels in both diabetic (P = 0.06) or controls (P = 0.16) groups. In the diabetic group adiponectin correlated positively with serum glucose, negatively with serum proinsulin and HOMA beta cell function (P = 0.03) respectively and serum ghrelin (P = 0.003), but not with BMI, HOMA insulin resistance, insulin or leptin. In controls serum adiponectin correlated negatively with BMI (P = 0.002) but not with other variables. Conclusions: The findings of this study suggest that, adiponectin concentrations independent on BMI as a measure of adiposity, were mostly linked to insulin sensitivity and not to insulin resistance in Sudanese type 2 diabetic subjects, where race specific regulation mechanisms or different type 2 diabetes phenotype suggested being a major contributory factor in clarification the findings of this study.

  • 3.
    Arne, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Staffan
    Karlstad University, Department of Social Sciences.
    Boman, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindqvist, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Physical activity and quality of life in subjects with chronic disease: chronic obstructive pulmonary disease compared with rheumatoid arthritis and diabetes mellitus2009In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 27, no 3, p. 141-147Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Chronic diseases interfere with the life situation of the affected person in different ways. The aim was to compare the burden of disease in three chronic diseases - chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), diabetes mellitus (DM) - and in healthy subjects, with a particular interest in physical activity, quality of life, and psychological health. DESIGN: Cross-sectional, observational study. SETTING AND SUBJECTS: Postal survey questionnaire to a stratified, random population of 68 460 subjects aged 18-84 years in Sweden. The subjects included were 40-84 years old (n = 43 589) and data were analysed for COPD (n = 526), RA (n = 1120), DM (n = 2149) and healthy subjects (n = 6960). RESULT: Some 84% of subjects with COPD, 74% (RA), 72% (DM), and 60% in healthy subjects (p < 0.001, COPD versus RA, DM, and healthy subjects) had a physical activity level considered too low to maintain good health according to guidelines. Quality of life (EuroQol five-dimension questionnaire, EQ-5D) was lower in COPD and RA than in DM. Anxiety/depression was more common in subjects with COPD (53%) than in those with RA (48%) and DM (35%) (p < 0.001, COPD versus RA and DM), whereas mobility problems were more common in RA (55%) than COPD (48%) and DM (36%) (p < 0.001, RA versus COPD and DM). All differences between groups remained significant after adjusting for age, sex, and socioeconomic background factors. CONCLUSION: Subjects with chronic diseases had a low level of physical activity, most evident in subjects with COPD. COPD and RA had a higher negative impact on quality of life than DM. Our results indicate that increased attention regarding physical inactivity in subjects with chronic diseases is needed to minimize the burden of disease.

  • 4.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 6, p. 1371-1375Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood.

    RESEARCH DESIGN AND METHODS: Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects.

    RESULTS: The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements.

    CONCLUSIONS: These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.

  • 5.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men2011In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 4, no 2, p. 164-168Article in journal (Refereed)
    Abstract [en]

    Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL-6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 -0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease.

  • 6.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 1, p. 35-40Article in journal (Refereed)
    Abstract [en]

    Introduction

    Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated.

    Aims

    To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men.

    Methods

    Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors.

    Results

     During winter, insulin sensitivity (M/I, unit = 100 × mg × min-1 × kg-1/(mU × L-1)) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29–0.82, P < 0.0001) per 10°C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results.Read More:http://informahealthcare.com/doi/abs/10.3109/03009734.2011.628422

    Conclusions

    Insulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients.

  • 7.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Early Insulin Response and Insulin Sensitivity are Equally Important as Predictors of Glucose Tolerance after Correction for Measurement Errors2009In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 86, no 3, p. 219-224Article in journal (Refereed)
    Abstract [en]

    Aims: We estimated measurement error (ME) corrected effects of   insulin sensitivity (M/I), from euglycaemic insulin clamp, and insulin   secretion, measured as early insulin response (EIR) from oral glucose   tolerance test (OGTT), on fasting plasma glucose, HbA1c and type 2   diabetes longitudinally and cross-sectional.   Methods: : In a population-based study (n = 1128 men) 17 men made   replicate measurements to estimate ME at age 71 years. Effect of 1 SD   decrease of predictors M/I and EIR on longitudinal response variables   fasting plasma glucose (FPG) and HbA1c at follow-ups up to 11 years,   were estimated using uncorrected and ME-corrected (with the regression   calibration method) regression models.   Results: : Uncorrected effect on FPG at age 77 years was larger for M/I   than for EIR (effect difference 0.10 mmol/l, 95% CI 0.00;0.21), while   ME-corrected effects were similar (0.02 mmol/l, 95% CI -0.13;0.15   mmol/l). EIR had greater ME-corrected impact than M/I on HbA1c at age   82 years (-0.11%, -0.28; -0.01%).   Conclusions: : Due to higher ME effect of EIR on glycaemia is   underestimated as compared with M/I. By correcting for ME valid   estimates of relative contributions of insulin secretion and insulin   sensitivity on glycaemia are obtained.

  • 8.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    A randomized study of orlistat in combination with a weight management programme in obese patients with Type 2 diabetes treated with metformin.2005In: Diabet Med, ISSN 0742-3071, Vol. 22, no 5, p. 612-618Article in journal (Refereed)
  • 9.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Diabetes: Internmedicin2006Chapter in book (Refereed)
  • 10.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Intensiv satsning på framtidens diabetesläkemedel2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 45, p. 2815-2819Article in journal (Refereed)
    Abstract [en]

    Adverse reactions, particularly hypoglyceamia, and the relatively modest effects of intensive glucose-lowering therapy on cardiovascular disease in recent large-scale trials have emphasized the need for a development of new therapeutic alternatives. The recently approved incretins have shown promising results but require daily injections. Therefore, intense efforts have been made to prolong the action or to find alternative routes of administration. Exenatide LAR and insulin glargine has recently been compared in a large RCT and shown similar effects on glucose control. Still, some concerns regarding risk of pancreatitis and thyroid cancers exist for GLP-1 agonists. Inhibitors of the sodium glucose cotransporter 2 have shown promising results as add-on therapy to metformin in a recent pivotal trial, with mild adverse effects. Genital infections may be a problem. A trial with an IL-1 receptor antagonist shows a new interesting concept with a putative action to preserve beta-cells. Glucokinase activators and 11_HSD1 inhibitors have shown promising results in phase II trials, but the risk of adverse phenomena with these drugs that interact with important metabolic and hormonal pathways have to be further investigated in humans.

  • 11.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Läkarens roll i diabetesteamet: Omvårdnad vid diabetes2006Chapter in book (Refereed)
  • 12.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Metabola syndromet: Endokrinologi2007Chapter in book (Refereed)
  • 13.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    The metabolic syndrome: Stress in health and disease2007Chapter in book (Refereed)
  • 14.
    Berne, Christian
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Montjarret, Blandine
    Guountti, Yasmina
    Garcia, Daniel
    Tributyl phosphate degradation by Serratia odorifera.2004In: Biotechnol Lett, ISSN 0141-5492, Vol. 26, no 8, p. 681-6Article in journal (Refereed)
  • 15.
    Berne, Christian
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Siewert-Delle, Annica
    Comparison of rosuvastatin and atorvastatin for lipid lowering in patients with type 2 diabetes mellitus: results from the URANUS study.2005In: Cardiovasc Diabetol, ISSN 1475-2840, Vol. 4, p. 7-Article in journal (Refereed)
  • 16.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation2011In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, no 8, p. e61-e66Article in journal (Refereed)
    Abstract [en]

    We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.

  • 17. Biglarnia, Ali-Reza
    et al.
    Yamamoto, Shinji
    Gustafsson, Bengt I
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Wagner, Michael
    von Zur-Mühlen, Bengt
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Transplantation av pankreas botande alternativ vid typ 1-diabetes: [Transplantation of pancreas, a curative option for type 1 diabetes]2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 39-40, p. 1754-1757Article in journal (Refereed)
    Abstract [en]

    In the past decade, pancreas transplantation (PTx) has become increasingly attractive as a curative treatment in patients with labile diabetes and secondary complications. In the United Kingdom, the percentage of deceased-donors utilized for PTx increased 5-fold between 2003 and 2007. The trend towards a higher number of annual pancreas transplantations is also observed in Sweden. The increasing activity and the excellent outcome are consequences of meticulous surgery, effective immunsuppression and adequate follow-up. The present report descibes the current status of PTx and shows the short- and long-term results during the last decade in Sweden.

  • 18.
    Bjuhr, Mathias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    External quality assessment of HbA(1c) for point of care testing2006In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 111, no 2, p. 201-207Article in journal (Refereed)
    Abstract [en]

    Objectives. To evaluate the long term total imprecision of HbA(1c) testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) < 3% for HbA(1c) and to study the cost of an external quality assurance program for point-of-care HbA(1c) The county uses Bayer DCA 2000 (TM) for point-of care HbA(1c) testing currently having 23 of these instruments.

    Methods. Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA(1c) testing. The samples were first analysed on a Bayer DCA 2000 (TM) and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II (TM), Biorad). The testing was performed approximately 8 times per year with each instrument.

    Results. The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%.

    Conclusion. The DCA 2000 (TM) systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.

  • 19.
    Carlsson, Per-Ola
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology. Department of Medical Sciences.
    Berne, Christian
    Department of Medical Sciences.
    Östenson, Claes-Göran
    Department of Medical Sciences.
    Andersson, Arne
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Hypoglycaemia induces decreased islet blood perfusion mediated by thecentral nervous system in normal and Type 2 diabetic GK rats.2003In: Diabetologia, Vol. 46, no 8, p. 1124-30Article in journal (Refereed)
  • 20.
    Dahlgren, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Variants of the TCF7L2 gene are associated with beta cell dysfunction and confer an increased risk of type 2 diabetes mellitus in the ULSAM cohort of Swedish elderly men2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 9, p. 1852-1857Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis:

    In a population-based cohort of elderly men with well-defined phenotypes and biochemical markers related to type 2 diabetes mellitus, we analysed two single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, in the transcription factor 7-like 2 gene (TCF7L2), which are associated with an increased risk of type 2 diabetes mellitus.

    Materials and methods:

    The 1,142 subjects were from the population-based Uppsala Longitudinal Study of Adult Men cohort study (see http://www.pubcare.uu.se/ULSAM/ , last accessed in May 2007). Insulin sensitivity was assessed using a euglycaemic-hyperinsulinaemic clamp; fasting intact and 32-33 split proinsulin, immunoreactive insulin and specific insulin were measured in plasma samples. The SNPs rs7903146 and rs12255372 were genotyped using a fluorescent homogeneous single base extension assay. The SNP genotypes were analysed against diabetes prevalence at age 70 using logistic regression and against quantitative biochemical measures using linear regression analysis.

    Results:

    We replicated the association with type 2 diabetes mellitus for both SNPs in this cohort of elderly males. The highest significant odds ratio (2.15, 95% CI 1.20-3.85) was found for SNP rs7903146. The odds ratio for SNP rs12255372 was 1.69 (95% CI 1.20-2.39). Both TCF7L2 SNPs were found to be significantly associated with plasma proinsulin when adjusting for insulin sensitivity, both in the whole cohort and when the diabetic subjects were excluded. Analysis for fasting plasma insulin or insulin sensitivity did not give significant results.

    Conclusions/interpretation:

    The association between the risk alleles of the two SNPs studied and levels of proinsulin in plasma, identified when adjusting for insulin sensitivity using euglycaemic-hyperinsulinaemic clamp measurements in this study, is an important novel finding.

  • 21. Ekberg, Karin
    et al.
    Brismar, Tom
    Johansson, Bo-Lennart
    Lindström, Per
    Juntti-Berggren, Lisa
    Norrby, Anders
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arnqvist, Hans J.
    Bolinder, Jan
    Wahren, John
    C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 1, p. 71-76Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function. RESEARCH DESIGN AND METHODS - This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo. RESULTS - The age of the 139 patients who completed the protocol was 44.2 ± 0.6 (mean ± SE) years and their duration of diabetes was 30.6 ± 0.8 years. Clinical neurological impairment (NIA) (score >7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 ± 0.08 SD below body height-corrected normal values at baseline and improved similarly within the two C-peptide groups (P < 0.007). The number of patients responding with a SCV peak potential improvement >1.0 m/s was greater in C-peptide-treated patients than in those receiving placebo (P < 0.03). In the least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide-treated groups (P < 0.011 and P < 0.002). A1C levels (7.6 ± 0.1% at baseline) decreased slightly but similarly in C-peptide- and placebo-treated patients during the study. CONCLUSIONS - C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.

  • 22.
    Engström, Sevek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gahnberg, Lars
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Effectiveness of screening for diabetes mellitus in dental health care2013In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 30, no 2, p. 239-245Article in journal (Refereed)
    Abstract [en]

    Aims:  The aim of the present study was to test the effectiveness of opportunistic blood glucose screening in a cooperational framework between dental and primary health care.

    Methods:  Altogether, 1568 subjects, age 20-75 years, with no previous history of diabetes, who came for a regular dental examination, had their non-fasting blood glucose measured with a portable blood glucose meter. Subjects with a concentration of ≥ 6.7 mmol/l (121 mg dl(-1) ) were referred to their primary healthcare centre for follow-up. The outcome, a diagnosis of diabetes mellitus, was obtained from primary healthcare centre and hospital patient records, during 3 years after screening.

     Results:  Of the 155 (9.9%) subjects who screened positive, 139 (89.7%) came to their primary healthcare centre within the 3-year follow-up period and nine (5.8%) were diagnosed as having diabetes mellitus according to the World Health Organization criteria. Of the 1413 subjects who screened negative, 1137 (80.5%) came to the primary healthcare centre and eight (0.6%) were found to have diabetes mellitus. Screening sensitivity was 52.9%, specificity 90.6% and positive predictive value 5.8%. The number of subjects needed to screen to find one case of diabetes was 196. Delineating the study population to those 40- to 75-year-olds with a BMI ≥ 25 kg/m(2) , and 30-to 75-year-olds with a BMI ≥ 30 kg/m(2) , the numbers needed to screen was reduced to 96.

    Conclusions:  Cooperation between dental and primary care for high blood glucose screening and follow-up appears to be a feasible method for early diagnosis of diabetes.

  • 23.
    Engström, Sevek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Borgquist, Lars
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Gahnberg, Lars
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Can costs of screening for hypertension and diabetes in dental care and follow-up in primary health care be predicted?2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 256-262Article in journal (Refereed)
    Abstract [en]

    Aim. The purpose was to assess the direct costs of screening for high blood pressure and blood glucose in dental care and of follow-up in primary health care and, based on these data, arrive at a prediction function. Study population. All subjects coming for routine check-ups at three dental health clinics were invited to have blood pressure or blood glucose measurements; 1,623 agreed to participate. Subjects screening positive were referred to their primary health care centres for follow-up. Methods. Information on individual screening time was registered during the screening process, and information on accountable time, costs for the screening staff, overhead costs, and analysis costs for the screening was obtained from the participating dental clinics. The corresponding items in primary care, i.e. consultation time, number of follow-up appointments, accountable time, costs for the follow-up staff, overhead costs, and analysis costs during follow-up were obtained from the primary health care centres. Results. The total screening costs per screened subject ranged from (sic)7.4 to (sic)9.2 depending on subgroups, corresponding to 16.7-42.7 staff minutes. The corresponding follow-up costs were (sic)57-(sic)91. The total resource used for screening and follow-up per diagnosis was 563-3,137 staff minutes. There was a strong relationship between resource use and numbers needed to screen (NNS) to find one diagnosis (P < 0.0001, degree of explanation 99%). Conclusions. Screening and follow-up costs were moderate and appear to be lower for combined screening of blood pressure and blood glucose than for separate screening. There was a strong relationship between resource use and NNS.

  • 24. Fall, T.
    et al.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The role of obesity-related genetic loci in insulin sensitivity2012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 7, p. E62-E66Article in journal (Refereed)
    Abstract [en]

    Aims Despite rapid advancements and many new diabetes susceptibility loci found in the past few years, few genetic variants associated with insulin sensitivity have been described, potentially attributable to the lack of larger cohorts examined with gold standard methods for insulin sensitivity assessment. There is a strong link between obesity and insulin sensitivity, and we hypothesized that known obesity susceptibility loci may act via effects on insulin sensitivity. Methods A cohort of 71-year-old men without diabetes (Uppsala Longitudinal Study of Adult Men) underwent a euglycaemichyperinsulinaemic clamp and genotyping for genetic variants representing 32 loci recently reported to be associated with BMI (n = 926). The effect of these loci on the insulin sensitivity index (M/I ratio) was examined using linear regression. An in silico replication was performed in publically available data for the three top single-nucleotide polymorphisms from the Meta-Analyses of Glucose and Insulin-related traits Consortium analyses of homeostasis model assessment of insulin resistance (n = 37 037). Results Three loci (SH2B1, MTCH2 and NEGR1) were associated with decreased insulin sensitivity at a nominal significance (P = 0.05) after adjustment for BMI, but did not hold for multiple comparison correction. SH2B1 rs7359397 was also associated with homeostasis model assessment of insulin resistance in the Meta-Analyses of Glucose and Insulin-related traits Consortium data set (P = 3.9 x 10(3)). Conclusions Our study supports earlier reports of SH2B1 to be of importance in insulin sensitivity and, in addition, suggests potential roles of NEGR1 and MTCH2.

  • 25. Fritz, Tomas
    et al.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Läkemedelsboken 2007-2008: Diabetes mellitus2007Chapter in book (Refereed)
  • 26. Frystyk, Jan
    et al.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Flyvbjerg, Allan
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 2, p. 571-576Article in journal (Refereed)
    Abstract [en]

    Context: Cross-sectional and nested case-control studies indicate a relationship between adiponectin, obesity, and coronary heart disease (CHD). Objective: Our objective was to investigate whether adiponectin could predict CHD in a population-based cohort of elderly men. Design and Setting: From 1991-1995 a baseline investigation was carried out in 832 healthy men aged 70 yr in the Uppsala Longitudinal Study of Adult Men (ULSAM study). They were followed up to 10.4 yr using Swedish national registry data. The baseline investigation included anthropometry, blood pressure, smoking, serum lipids, a euglycemic insulin clamp, and fasting serum adiponectin. Main Outcome Measures: Main outcome measures were defined as death or first-time hospitalization for CHD (n = 116), recorded in the Cause of Death Registry or in the Hospital-Discharge Registry of the National Board of Health and Welfare, Sweden. Associations were analyzed using Cox's proportional hazards regression, presented as hazard ratios (HR) with 95% confidence intervals (CI) for 1 SD increase in the predictor variable. Results: In a multivariable analysis including total cholesterol (HR, 1.24; CI, 1.02-1.50), high-density lipoprotein cholesterol (HR, 0.72; CI, 0.58-0.89), smoking (HR, 1.39; CI, 0.91-2.14), and systolic blood pressure (HR, 1.26; CI, 1.05-1.52), serum adiponectin was associated with lower risk for CHD (HR, 0.81; CI, 0.66-0.99). The association was independent of BMI and remained significant after adjustment for insulin sensitivity index. Conclusions: In this population-based cohort of healthy men, elevated serum levels of adiponectin were associated with a lower risk for CHD. Importantly, the association between adiponectin and CHD was independent of other well-known risk factors.

  • 27.
    Fugmann, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Millgård, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sarabi, Mahziar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal2003In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 105, no 6, p. 715-721Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the haemodynamic changes during hyperinsulinaemia, hyperglycaemia or hypertriglyceridaemia in relation to those following a mixed meal. Ten subjects were subjected to hypertriglyceridaemia (3.9 mmol/l) for 2 h by an infusion of Intralipid and heparin. Nine subjects received a hyperglycaemic clamp (12.5 mmol/l) with octreotide and low-dose insulin infusion to maintain normoinsulinaemia (10 m-units/l). Ten subjects received saline for 2 h as a control and, thereafter, 2 h of normoglycaemic hyperinsulinaemic clamp (80 m-units/l). Finally, ten subjects were evaluated for 2 h following an ordinary mixed meal. Calf blood flow was measured by venous occlusion plethysmography and cardiac index by thoracic bioimpedance. Both the mixed meal and normoglycaemic hyperinsulinaemia lowered total peripheral resistance, and increased calf blood flow and cardiac index, whereas blood pressure decreased (P <0.05-0.001). Both hyperglycaemia and hypertriglyceridaemia increased calf blood flow, but blood pressure was unchanged. Total peripheral resistance was unchanged in hypertriglyceridaemia, whereas hyperglycaemia induced a significant increase. Normoglycaemic hyperinsulinaemia induced a haemodynamic pattern similar, but to a lesser extent, to the pattern seen following a mixed meal. Hyperinsulinaemia seems to be a major mediator of the haemodynamic response, but other factors are obviously also of great importance. Hypertriglyceridaemia and hyperglycaemia induced haemodynamic responses that are not similar to those seen following a mixed meal.

  • 28.
    Fugmann, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sarabi, Mahziar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Blood flow is an important determinant of forearm glucose uptake following a mixed meal2003In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 40, no 3, p. 113-117Article in journal (Refereed)
    Abstract [en]

    Insulin-mediated vasodilation has been suggested to be of importance for glucose uptake during normoglycemic hyperinsulinemia. If this also is valid after an ordinary mixed meal remains to be evaluated. Forearm blood flow (FBF) and forearm glucose uptake change (evaluated by venous occlusion plethysmography) and glucose arteriovenous differences were evaluated over 120 minutes in 10 healthy volunteers following an ordinary mixed meal (700-900 kcal, 34% of energy from fat). Fasting arterial glucose level was 4.9+/-0.9 mmol/l, and the maximum glucose level was reached 30 minutes after the start of ingestion (6.6+/-0.8 mmol/l, p<0.0001). Plasma insulin levels were increased four-fold. FBF increased rapidly within 20 minutes after the start of ingestion and reached its maximum after 50 minutes (94% higher than baseline level, p<0.01). After 2 hours FBF was still substantially elevated (75% above baseline level, p<0.01). Forearm glucose uptake increased fivefold already after 20 minutes ( p<0.01). During the 2 hours, the increase in FBF contributed to 41% of the forearm glucose uptake ( p<0.05). The present study showed that the increase in FBF seen after an ordinary mixed meal is important for the change in forearm glucose uptake. These results support the view that modulation of limb blood flow is a determinant of glucose uptake.

  • 29. Gudbjörnsdottir, Soffia
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Nilsson, Peter M
    Eliasson, Björn
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Adamson, Ulf
    Nationella diabetesregistret 1996-2003: Kvalitetsvärdering visar att diabetesvården har förbättrats2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 47, p. 3790-3797Article in journal (Other academic)
    Abstract [en]

    The Swedish National Diabetes Register presents results during the period 1996- 2003. Quality of care data from more than 75,000 diabetic patients (2003) treated at medical departments and primary health care centres are evaluated concerning national goals of HbA1c <6,5% and BP <140/85 mm Hg, the prevalence of lipid treatment, smoking etc. The national goals of HbA1c and BP were reached with increasing degree in cross-sectional analysis during the period, and were achieved by 33% and 71% at medical departments, and by 61% and 48% in primary health care in 2003. A similar tendency was also seen in longitudinal analysis of subgroups 1996-2003. The use of antihypertensive and lipid-lowering drugs was also considerably increased. This should imply a reduction of the risk for diabetic complications. As the national goals are still difficult to reach, individual goals should be set for the treatment.

  • 30.
    Hudecova, Miriam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Holte, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome: a long-term follow-up study2011In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 95, no 3, p. 1146-1148Article in journal (Refereed)
    Abstract [en]

    Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and β-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered.

  • 31.
    Hudecova, Miriam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Holte, Jan
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundstrom-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up2011In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, no 5, p. 1271-1274Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the prevalence of the metabolic syndrome (MetS) according to the scientific statement of the American Heart Association and the US National Cholesterol Education Program/Adult Treatment Panel III in middle-aged Swedish women previously diagnosed with polycystic ovary syndrome (PCOS) in comparison with age-matched healthy controls.

    DESIGN: Long-term follow-up study.

    SETTING: Department of Obstetrics and Gynecology, Uppsala University.

    PATIENT(S): Eighty-four women diagnosed with PCOS between 1987 and 1995; and 87 controls randomly selected from the general population.

    INTERVENTION(S): Anthropometric measurements and blood tests.

    MAIN OUTCOME MEASURE(S): Body mass index, waist circumference, blood pressure, lipids, and glucose.

    RESULT(S): The prevalence of MetS in women with PCOS (mean ± SD age, 43.0 ± 5.8 years) was 23.8% and in controls was 8.0%, and it did not differ according to PCOS phenotype at the index assessment (polycystic ovaries [PCO], oligomenorrhea, and hirsutism: 10 [22.7%]; PCO and oligomenorrhea: 8 [22.2%]) or according to the persistence of PCOS features at follow-up (persisting PCOS: 25.8%; resolved PCOS: 16.7%).

    CONCLUSION(S): The MetS occurred more often in patients with PCOS than in controls and did not depend on phenotypic presentation at the index assessment or the persistence of PCOS at follow-up.

  • 32.
    Hudecova, Miriam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Jan, Holte
    Christian, Berne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Long-term Reproductive and Metabolic Consequences of PCOS2012In: Current diabetes reviews, ISSN 1875-6417, Vol. 8, no 6, p. 444-451Article in journal (Refereed)
    Abstract [en]

    Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic consequences. The review of findings indicate that the long-term reproductive outcomes of women with PCOS are surprisingly similar compared to women with normal ovaries, and that they have an ovarian reserve possibly superior to women with normal ovaries. The typical features of PCOS, specifically the anovulatory cycles tend to normalize over time, but in spite of a decrease over time, free androgen levels remain elevated compared to age-matched control subjects. Women with PCOS diagnosed at young age continue to display reduced insulin sensitivity in the perimenopausal age, independent from phenotypic expression of PCOS, both at diagnosis and at follow-up. Insulin resistance does not seem to deteriorate further, however. Overall, the accumulated data from several European cohort studies of older women with a previous diagnosis of PCOS suggest an increased incidence of type 2 diabetes, increased prevalence of several features of the metabolic syndrome, but no increased incidence of mortality from CVD.

  • 33. Ingberg, C-M
    et al.
    Palmér, M
    Aman, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Arvidsson, B
    Schvarcz, E
    Berne, C
    Department of Medical Sciences.
    Body composition and bone mineral density in long-standing type 1 diabetes.2004In: J Intern Med, ISSN 0954-6820, Vol. 255, no 3, p. 392-8Article in journal (Refereed)
  • 34.
    Ingelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Langenberg, Claudia
    Hivert, Marie-France
    Prokopenko, Inga
    Lyssenko, Valeriya
    Dupuis, Josée
    Mägi, Reedik
    Sharp, Stephen
    Jackson, Anne U.
    Assimes, Themistocles L.
    Shrader, Peter
    Knowles, Joshua W.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Abbasi, Fahim A.
    Bergman, Richard N.
    Bergmann, Antje
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Boehnke, Michael
    Bonnycastle, Lori L.
    Bornstein, Stefan R.
    Buchanan, Thomas A.
    Bumpstead, Suzannah J.
    Böttcher, Yvonne
    Chines, Peter
    Collins, Francis S.
    Cooper, Cyrus C.
    Dennison, Elaine M.
    Erdos, Michael R.
    Ferrannini, Ele
    Fox, Caroline S.
    Graessler, Jürgen
    Hao, Ke
    Isomaa, Bo
    Jameson, Karen A.
    Kovacs, Peter
    Kuusisto, Johanna
    Laakso, Markku
    Ladenvall, Claes
    Mohlke, Karen L.
    Morken, Mario A.
    Narisu, Narisu
    Nathan, David M.
    Pascoe, Laura
    Payne, Felicity
    Petrie, John R.
    Sayer, Avan A.
    Schwarz, Peter E. H.
    Scott, Laura J.
    Stringham, Heather M.
    Stumvoll, Michael
    Swift, Amy J.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Tönjes, Anke
    Valle, Timo T.
    Williams, Gordon H.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barroso, Inês
    Quertermous, Thomas
    Walker, Mark
    Wareham, Nicholas J.
    Meigs, James B.
    McCarthy, Mark I.
    Groop, Leif
    Watanabe, Richard M.
    Florez, Jose C.
    Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 5, p. 1266-1275Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action.

    RESEARCH DESIGN AND METHODS

    We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084).

    RESULTS

    The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction.

    CONCLUSIONS

    Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.

  • 35.
    Ingelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Frystyk, Jan
    Flyvbjerg, Allan
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Adiponectin and risk of congestive heart failure2006In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 295, no 15, p. 1772-1774Article in journal (Refereed)
  • 36.
    Johansson, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
    Lukinius, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Moberg, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
    Lundgren, Torbjörn
    Berne, Christian
    Foss, Aksel
    Felldin, Marie
    Källen, Ragnar
    Salmela, Kaija
    Tibell, Annika
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
    Elgue, Graciela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
    Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation2005In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 54, no 6, p. 1755-62Article in journal (Refereed)
    Abstract [en]

    There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.

  • 37.
    Korsgren, Olle
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nilsson, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Berne, Christian
    Department of Medical Sciences.
    Felldin, M
    Foss, A
    Kallen, R
    Lundgren, T
    Salmela, K
    Tibell, A
    Tufveson, G
    Department of Surgical Sciences.
    Current status of clinical islet transplantation.2005In: Transplantation, ISSN 0041-1337, Vol. 79, no 10, p. 1289-1293Article in journal (Refereed)
  • 38.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fugmann, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Millgård, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ageing impairs insulin-mediated vasodilatation but not forearm glucose uptake2001In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 31, no 10, p. 860-864Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is unclear if insulin-mediated vasodilatation is altered by ageing and if this affects insulin-mediated glucose uptake. MATERIAL AND METHODS: A 2-h euglycaemic hyperinsulinaemic clamp (56 mU m(-2) min(-1)) was performed in 10 healthy, nonobese elderly men (70-75 years) and 13 young men (23-28 years). Forearm blood flow (FBF) was measured by venous occlusion plethysmography and forearm glucose uptake was calculated by arterial and venous serum glucose determinations in the forearm. RESULTS: Insulin induced an increase in FBF in the younger men (from 3.9 +/- 1.1 SD to 5.9 +/- 2.2 mL min(-1) 100(-1)mL tissue, P < 0.001), but this insulin-mediated vasodilatation was completely blunted in the elderly subjects. Glucose extraction during the clamp was significantly higher in the elderly subjects (1.2 +/- 0.76 vs. 0.82 +/- 0.37 mmol L(-1) at 120 min, P < 0.01), resulting in a similar forearm glucose uptake in the two groups. On the other hand, whole-body glucose uptake was significantly decreased in the elderly subjects (5.3 +/- 1.8 vs. 8.0 +/- 1.1 mg kg(-1) min(-1), P < 0.001). CONCLUSION: The present study showed that the ability of insulin to induce vasodilatation is blunted in the forearm in healthy, nonobese elderly subjects. However, the elderly compensate for this impairment with an increased glucose extraction from arterial blood to maintain an unaltered forearm glucose uptake.

  • 39.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fugmann, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Millgård, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Insulin-mediated vasodilatation, but not glucose uptake or endothelium-mediated vasodilatation, is enhanced in young females compared with males2002In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 102, no 2, p. 241-246Article in journal (Refereed)
    Abstract [en]

    In order to evaluate possible differences between men and women with regard to the ability of insulin to induce vasodilatation, promote glucose uptake and enhance endothelium-dependent vasodilatation, 12 young (22-28 years), non-obese women and 15 corresponding males were subjected to 2 h of euglycaemic hyperinsulinaemia (insulin infusion rate of 56 m-units x min(-1) x m(-2)). Forearm blood flow was measured by venous occlusion plethysmography. Endothelium-dependent vasodilatation was evaluated by the local intra-arterial infusion of methacholine into the brachial artery (2-4 microg/min). The cardiac index was measured by thoracic bioimpedance. A 2 h period of hyperinsulinaemia increased the plasma insulin concentration to a similar degree in both sexes (females, 84 +/- 8.8 m-units/l; males, 87 +/- 7.5 m-units/l), but induced a more marked increase in forearm blood flow in females than in males (+104 +/- 67% and +52 +/- 30% respectively; P<0.01; 95% confidence interval for difference 11-94%). Furthermore, a significant decrease in total peripheral resistance (-20 +/- 6.9%; P<0.01) and an increase in cardiac index (+23 +/- 13%; P<0.01) were seen in women only (P<0.05 compared with men). Blood pressure and heart rate were not altered in either sex. Whole-body insulin-mediated glucose uptake and forearm glucose uptake did not differ between the sexes, and the ability of insulin to enhance endothelium-dependent vasodilatation (+19%; P<0.01) was similar in men and women. In conclusion, the present study shows that the ability of insulin to cause vasodilatation was greater in non-obese young women compared with men. However, no differences between the sexes were seen with regard to insulin-mediated glucose uptake and the ability of insulin to enhance endothelium-dependent vasodilatation.

  • 40.
    Lindberg, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Elmasry, Ahmed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hedner, Jan
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    CPAP treatment of a population-based sample-what are the benefits and the treatment compliance?2006In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 7, no 7, p. 553-560Article in journal (Refereed)
    Abstract [en]

    Background & purpose: Continuous positive airway pressure (CPAP) treatment has positive effects, including improved insulin sensitivity in sleep-laboratory cohorts with obstructive sleep apnea syndrome. There is still a lack of data on benefits obtained and possibilities to treat less symptomatic individuals. The aim of this study was to evaluate the effect of CPAP treatment on metabolic profile and quality of life (QoL) in a population-based sample of men with sleep apnea. Another purpose was to investigate the compliance to CPAP in this population.

    Patients and methods: A population-based sample of 38 men with an AHI >= 10 were treated with CPAP regardless of symptom profile. The controls included men with AIR < 10 matched for age and hypertension. The effects were evaluated after 3 weeks and 6 months. Insulin resistance was quantified using the homeostasis model assessment (HOMA). Daytime sleepiness, QoL and subjective symptom load was assessed using the Epworth Sleepiness Scale (ESS), the Medical Outcomes Study Short Form Health Survey (SF-36) and the Minor Symptoms Evaluation-Profile (MSE-P) questionnaires, respectively.

    Results: Complete three-week data were obtained from 28 treated men and 28 controls. Compared with controls, the CPAP group displayed a greater reduction of fasting serum insulin (P=0.02), decrease in insulin resistance (P=0.01) and an increase in IGF-1 (P=0.005). The CPAP group further showed an improvement in the SF-36 domains of mental health (P=0.03) and vitality (P=0.06) and a reduction in symptom load in the sleep dimension of the MSE-P. Only 11 (29%) of subjects starting CPAP were still on treatment after 6 months. Those who still used CPAP had a higher score on ESS at baseline (11.3 (4.4) vs. 5.9 (3.4), P<0.0001).

    Conclusions: Benefits of short-term treatment included signs of reduced insulin resistance and improved QoL. However, in this population-based sample compliance with CPAP was very low. More severe sleepiness was a positive predictive factor for treatment compliance.

  • 41.
    Lindberg, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Franklin, Karl A.
    Svensson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Snoring and daytime sleepiness as risk factors for hypertension and diabetes in women--a population-based study2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 6, p. 1283-1290Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to analyze whether snoring and excessive daytime sleepiness (EDS), the main symptoms of obstructive sleep apnea syndrome (OSAS), are associated with hypertension and diabetes in women. A random sample of 6779 women aged 20–99 years answered questionnaires on sleep disturbances, daytime symptoms and somatic diseases. The women were categorized into four groups: “no EDS or snoring” (reference group), “snoring but no EDS”, “EDS but no snoring” and “snoring and EDS”. Prevalences of hypertension and diabetes were lowest in the reference group (8.7% and 1.6%, respectively) and highest among women with both snoring and EDS (hypertension: 26.3%, diabetes: 5.8%). In a multivariate model adjusting for age, body mass index, smoking, physical activity and alcohol dependency, “snoring and EDS” was a risk factor for hypertension (adjusted OR 1.82 (95% CI 1.30–2.55)) while isolated snoring or EDS was not. “Snoring and EDS” was more closely related to hypertension among women aged <50 years (adj. OR 3.41 (1.78–6.54) vs. 1.50 (1.02–2.19), P=0.01). For diabetes, both “EDS but no snoring” and “snoring and EDS” were risk factors and the associations were most pronounced in women aged >50 years (adj. OR 2.33 (1.28–4.26) for “EDS but no snoring” and 2.00 (1.05–3.84) for “snoring and EDS”). We conclude that the combination of snoring and EDS is a risk factor for hypertension and diabetes in women. For hypertension, the risk is partly age dependent and, for diabetes, EDS without snoring is a risk factor of similar magnitude. These differences might indicate differences in pathophysiologic mechanisms underlying the association between sleep-disordered breathing and hypertension and diabetes respectively.

  • 42.
    Lindberg, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Svensson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Gislason, Thorarinn
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Sleep apnea and glucose metabolism: a long-term follow-up in a community-based sample2012In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 142, no 4, p. 935-942Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    It has been suggested that sleep-disordered breathing (SDB) is a risk factor for diabetes, but long-term follow-ups are lacking. The aim of this community-based study was to analyze the influence of SDB on glucose metabolism after more than 10 years.

    METHODS:

    Men without diabetes (n=141, mean age 57.5 years) were investigated at baseline, including whole-night respiratory monitoring. After a mean period of 11 years and 4 months, they were followed up with an interview, anthropometric measurements and blood sampling. Insulin resistance was quantified using the homeostasis model assessment (HOMA). ΔHOMA-IR was calculated as (HOMA-IR(follow-up) - HOMA-IR(baseline)). An oral glucose tolerance test was performed in 113 men to calculate the insulin sensitivity index (ISI).

    RESULTS:

    The mean apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) at baseline were 4.7 and 3.3, respectively. At the follow-up, 23 men had diabetes. An oxygen desaturation index (ODI) of >5 was a predictor of developing diabetes (adj. OR 4.4, 95% CI 1.1-18.1 after adjusting for age, BMI(baseline,) ΔBMI, hypertension and years with CPAP during the period). The ODI was inversely related to the ISI at the follow-up (r= -0.27, p=0.003). A deterioration in HOMA-IR was significantly related to all variables of sleep-disordered breathing (AHI, AHI>5, ODI, ODI>5 and MinSaO2) even when adjusting for confounders. When excluding the variable "years on CPAP" from the multivariate model, all associations weakened.

    CONCLUSIONS:

    SDB is independently related to the development of insulin resistance and thereby the risk of manifest diabetes mellitus.

  • 43. Locke, Adam E
    et al.
    Kahali, Bratati
    Berndt, Sonja I
    Justice, Anne E
    Pers, Tune H
    Day, Felix R
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L
    Yang, Jian
    Croteau-Chonka, Damien C
    Esko, Tonu
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ferreira, Teresa
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kutalik, Zoltán
    Luan, Jian'an
    Mägi, Reedik
    Randall, Joshua C
    Winkler, Thomas W
    Wood, Andrew R
    Workalemahu, Tsegaselassie
    Faul, Jessica D
    Smith, Jennifer A
    Hua Zhao, Jing
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karjalainen, Juha
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B
    Feenstra, Bjarke
    Feitosa, Mary F
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U
    Kanoni, Stavroula
    Kleber, Marcus E
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Medland, Sarah E
    Nalls, Michael A
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Shungin, Dmitry
    Stančáková, Alena
    Strawbridge, Rona J
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van Setten, Jessica
    Van Vliet-Ostaptchouk, Jana V
    Wang, Zhaoming
    Yengo, Loïc
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Arscott, Gillian M
    Attwood, Antony P
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Blagieva, Roza
    Blüher, Matthias
    Böhringer, Stefan
    Bonnycastle, Lori L
    Böttcher, Yvonne
    Boyd, Heather A
    Bruinenberg, Marcel
    Caspersen, Ida H
    Ida Chen, Yii-Der
    Clarke, Robert
    Warwick Daw, E
    de Craen, Anton J M
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S F
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M
    Garcia, Melissa E
    Geller, Frank
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Goodall, Alison H
    Gordon, Scott D
    Gorski, Mathias
    Grabe, Hans-Jörgen
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grönberg, Henrik
    Groves, Christopher J
    Gusto, Gaëlle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L
    Helmer, Quinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L
    Jeff, Janina M
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R
    Lichtner, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindström, Jaana
    Sin Lo, Ken
    Lobbens, Stéphane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L
    Morken, Mario A
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Musk, Arthur W
    Nagaraja, Ramaiah
    Nöthen, Markus M
    Nolte, Ilja M
    Pilz, Stefan
    Rayner, Nigel W
    Renstrom, Frida
    Rettig, Rainer
    Ried, Janina S
    Ripke, Stephan
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R
    Scott, William R
    Seufferlein, Thomas
    Shi, Jianxin
    Vernon Smith, Albert
    Smolonska, Joanna
    Stanton, Alice V
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Swertz, Morris A
    Swift, Amy J
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tan, Sian-Tsung
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C
    Vermeulen, Sita H
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Warren, Helen R
    Waterworth, Dawn
    Weedon, Michael N
    Wilkens, Lynne R
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Wright, Alan F
    Zhang, Qunyuan
    Brennan, Eoin P
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W
    Eriksson, Per
    Franco-Cereceda, Anders
    Gådin, Jesper R
    Gharavi, Ali G
    Goddard, Michael E
    Handsaker, Robert E
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McCarroll, Steven A
    McKnight, Amy J
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Okada, Yukinori
    Perry, John R B
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Scott, Robert A
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    Van't Hooft, Ferdinand M
    Vinkhuyzen, Anna A E
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T
    Heath, Andrew C
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I
    Chines, Peter S
    Collins, Francis S
    Crawford, Dana C
    Adrienne Cupples, L
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M
    Dominiczak, Anna F
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G
    Farrall, Martin
    Felix, Stephan B
    Ferrannini, Ele
    Ferrières, Jean
    Ford, Ian
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gejman, Pablo V
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hall, Alistair S
    Harris, Tamara B
    Hattersley, Andrew T
    Hicks, Andrew A
    Hindorff, Lucia A
    Hingorani, Aroon D
    Hofman, Albert
    Homuth, Georg
    Kees Hovingh, G
    Humphries, Steve E
    Hunt, Steven C
    Hyppönen, Elina
    Illig, Thomas
    Jacobs, Kevin B
    Jarvelin, Marjo-Riitta
    Jöckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Wouter Jukema, J
    Jula, Antti M
    Kaprio, Jaakko
    Kastelein, John J P
    Keinanen-Kiukaanniemi, Sirkka M
    Kiemeney, Lambertus A
    Knekt, Paul
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lyssenko, Valeriya
    Männistö, Satu
    Marette, André
    Matise, Tara C
    McKenzie, Colin A
    McKnight, Barbara
    Moll, Frans L
    Morris, Andrew D
    Morris, Andrew P
    Murray, Jeffrey C
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Madden, Pamela A F
    Pasterkamp, Gerard
    Peden, John F
    Peters, Annette
    Postma, Dirkje S
    Pramstaller, Peter P
    Price, Jackie F
    Qi, Lu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Rioux, John D
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schunkert, Heribert
    Schwarz, Peter E H
    Sever, Peter
    Shuldiner, Alan R
    Sinisalo, Juha
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Trégouët, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Völker, Uwe
    Waeber, Gérard
    Willemsen, Gonneke
    Witteman, Jacqueline C
    Zillikens, M Carola
    Adair, Linda S
    Amouyel, Philippe
    Asselbergs, Folkert W
    Assimes, Themistocles L
    Bochud, Murielle
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bornstein, Stefan R
    Bottinger, Erwin P
    Bouchard, Claude
    Cauchi, Stéphane
    Chambers, John C
    Chanock, Stephen J
    Cooper, Richard S
    de Bakker, Paul I W
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W
    Froguel, Philippe
    Groop, Leif C
    Haiman, Christopher A
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J
    Hveem, Kristian
    Kaplan, Robert C
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G
    März, Winfried
    Melbye, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E
    Schlessinger, David
    Eline Slagboom, P
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J
    Watkins, Hugh
    Weir, David R
    Wichmann, H-Erich
    Wilson, James F
    Zanen, Pieter
    Borecki, Ingrid B
    Deloukas, Panos
    Fox, Caroline S
    Heid, Iris M
    O'Connell, Jeffrey R
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Abecasis, Gonçalo R
    Franke, Lude
    Frayling, Timothy M
    McCarthy, Mark I
    Visscher, Peter M
    Scherag, André
    Willer, Cristen J
    Boehnke, Michael
    Mohlke, Karen L
    Lindgren, Cecilia M
    Beckmann, Jacques S
    Barroso, Inês
    North, Kari E
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hirschhorn, Joel N
    Loos, Ruth J F
    Speliotes, Elizabeth K
    Genetic studies of body mass index yield new insights for obesity biology2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, p. 197-206Article in journal (Refereed)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 44. Lundkvist, Jonas
    et al.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Bolinder, Björn
    Jonsson, Linus
    The economic and quality of life impact of hypoglycemia.2005In: Eur J Health Econ, ISSN 1618-7598, Vol. 6, no 3, p. 197-202Article in journal (Refereed)
  • 45.
    Moberg, Lisa
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Johansson, Helena
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Lukinius, Agneta
    Department of Genetics and Pathology.
    Berne, Christian
    Department of Medical Sciences.
    Foss, A
    Källen, R
    Ostraat, O
    Salmela, K
    Tibell, Annika
    Department of Surgical Sciences.
    Tufveson, Gunnar
    Department of Surgical Sciences.
    Elgue, Graciela
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Nilsson Ekdahl, Kristina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Korsgren, Olle
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Nilsson, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation.2002In: Lancet, Vol. 360, p. 2039-Article in journal (Refereed)
  • 46.
    Moberg, Lisa
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Olsson, Annika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Berne, Christian
    Department of Medical Sciences.
    Felldin, Marie
    Foss, Aksel
    Källen, Ragnar
    Salmela, Kaija
    Tibell, Annika
    Tufveson, Gunnar
    Department of Surgical Sciences.
    Nilsson, Bo
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Korsgren, Olle
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation.2003In: Transplantation, ISSN 0041-1337, Vol. 76, no 9, p. 1285-8Article in journal (Refereed)
  • 47.
    Molnár, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wennberg, Lars
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Islet Engraftment and Revascularization in Clinical and Experimental Transplantation2013In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 22, no 2, p. 243-251Article in journal (Refereed)
    Abstract [en]

    Background:

    Proper revascularization after transplantation is assumed to be crucial forappropriate islet graft function.

    Methods:

    We developed a novel non-invasive imagingmethod, based on adenoviral transduction of islets with a hypoxia responsive reporter gene,for continuous in vivo monitoring of hypoxia in islet grafts in a mouse model. In addition,morphological data was obtained from a deceased patient previously subject to intraportaltransplantation.

    Results:

    We detected only transient hypoxia in a minority of the animalstransplanted. Importantly, a clear response to hypoxia was observed in vitro after removal ofthe islet-grafts on day twenty-eight after transplantation. Also, the morphological data fromthe deceased patient demonstrated an extensive revascularization of the transplanted islets. Infact, no differences could be seen between native, in pancreas biopsies taken prior to isletisolation, and transplanted islets regarding the number, distribution and shape of the bloodvessels. However, fewer small islets (diameter <39μm) were found in the liver compared to those found in native pancreases. Notably, an absolute majority of the transplanted islets were found remaining within the venous lumen, in direct contact with the vessel wall.

    Conclusions:

    In conclusion results presented show less pronounced islet graft hypoxia after subcapsulartransplantation than previously reported using more invasive methods. Also, formation of anextensive intra-islet capillary network, similar to that seen in native islets in the pancreas, wasseen after clinical islet transplantation.

  • 48.
    Nilsson, Bo
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Berne, Christian
    Department of Medical Sciences.
    Korsgren, Olle
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The recent finding that tissue factor is produced by the pancreatic islets constitutes a possible link between insulin resistance and cardiovascular disease.2005In: Am J Ther, ISSN 1075-2765, Vol. 12, no 6, p. 551-554Article in journal (Refereed)
  • 49.
    Nowak, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Castillejo-Lopez, Casimiro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Cook, Naomi L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Shen, Xia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8691Article in journal (Refereed)
    Abstract [en]

    Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 +/- 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10-and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10-or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

  • 50.
    Nowak, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.;Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Brandmaier, Stefan
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany..
    Tukiainen, Taru
    Univ Helsinki, FIMM, Helsinki, Finland..
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA..
    Wang-Sattler, Rui
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany.;Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gieger, Christian
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Ripatti, Samuli
    Univ Helsinki, FIMM, Helsinki, Finland.;Univ Helsinki, Fac Med, Publ Hlth, Helsinki, Finland.;Wellcome Trust Sanger Inst, Hinxton, England..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study2016In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, no 10, article id e1006379Article in journal (Refereed)
    Abstract [en]

    Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or beta-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

12 1 - 50 of 77
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