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  • 1. Abbas, S
    et al.
    Linseisen, J
    Rohrmann, S
    Beulens, JWJ
    Buijsse, B
    Amiano, P
    Ardanaz, E
    Balkau, B
    Boeing, H
    Clavel-Chapelon, F
    Fagherazzi, G
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gavrila, D
    Grioni, S
    Kaaks, R
    Key, TJ
    Khaw, KT
    Kuehn, T
    Mattiello, A
    Molina-Montes, E
    Nilsson, PM
    Overvad, K
    Quiros, JR
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sacerdote, C
    Saieva, C
    Slimani, N
    Sluijs, I
    Spijkerman, AMW
    Tjonneland, A
    Tumino, R
    van der A, DL
    Zamora-Ros, R
    Sharp, SJ
    Langenberg, C
    Forouhi, NG
    Riboli, E
    Wareham, NJ
    Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study2014In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 68, no 2, 196-202 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation.

    SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires.

    RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D.

    CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

  • 2. Abrahamsson, Niclas
    et al.
    Borjesson, Joey Lau
    Sundbom, Magnus
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, F. Anders
    Eriksson, Jan W.
    Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, 2667-2675 p.Article in journal (Refereed)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 3. Ahmad, S
    et al.
    Poveda, A
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Barroso, I
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 9, 1346-1352 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent cross-sectional genome-wide scans have reported associations of 97 independent loci with body mass index (BMI). In 3541 middle-aged adult participants from the GLACIER Study, we tested whether these loci are associated with 10-year changes in BMI and other cardiometabolic traits (fasting and 2-h glucose, triglycerides, total cholesterol, and systolic and diastolic blood pressures).

    METHODS: A BMI-specific genetic risk score (GRS) was calculated by summing the BMI-associated effect alleles at each locus. Trait-specific cardiometabolic GRSs comprised only the loci that show nominal association (P⩽0.10) with the respective trait in the original cross-sectional study. In longitudinal genetic association analyses, the second visit trait measure (assessed ~10 years after baseline) was used as the dependent variable and the models were adjusted for the baseline measure of the outcome trait, age, age(2), fasting time (for glucose and lipid traits), sex, follow-up time and population substructure.

    RESULTS: The BMI-specific GRS was associated with increased BMI at follow-up (β=0.014 kg m(-2) per allele per 10-year follow-up, s.e.=0.006, P=0.019) as were three loci (PARK2 rs13191362, P=0.005; C6orf106 rs205262, P=0.043; and C9orf93 rs4740619, P=0.01). Although not withstanding Bonferroni correction, a handful of single-nucleotide polymorphisms was nominally associated with changes in blood pressure, glucose and lipid levels.

    CONCLUSIONS: Collectively, established BMI-associated loci convey modest but statistically significant time-dependent associations with long-term changes in BMI, suggesting a role for effect modification by factors that change with time in this population.

  • 4.
    Alanentalo, Tomas
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Hörnblad, Andreas
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Mayans, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Nilsson, Anna Karin
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sharpe, James
    Larefalk, Åsa
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Ahlgren, Ulf
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Holmberg, Dan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Quantification and 3-D imaging of the insulitis-induced destruction of β-cells in murine type 1 diabetes2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 7, 1756-1764 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining beta-cell volume during the progression of type 1 diabetes in the NOD mouse model of the disease.

    Research design and methods: Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the 3D spatial development and progression of insulitis and beta-cell destruction in pancreas from diabetes prone NOD and non-diabetes prone congenic NOD.H-2b mice between 3 and 16 weeks of age.

    Results: Together with results showing the spatial dynamics of the insulitis process we provide data of beta-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression.

    Conclusions: Our data provides a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes.

  • 5. Albertsson-Wikland, Kerstin
    et al.
    Mårtensson, Anton
    Sävendahl, Lars
    Niklasson, Aimon
    Bang, Peter
    Dahlgren, Jovanna
    Gustafsson, Jan
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norgren, Svante
    Pehrsson, Nils-Gunnar
    Oden, Anders
    Birth Characteristics Explain One Third of Expected Deaths in rhGH-treated Patients Diagnosed with IGHD, ISS & SGA2016In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 86, 49-49 p.Article in journal (Other academic)
  • 6. Alssema, M
    et al.
    Vistisen, D
    Heymans, MW
    Nijpels, G
    Glümer, C
    Zimmet, PZ
    Shaw, JE
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stehouwer, CDA
    Tabák, AG
    Colagiuri, S
    Borch-Johnsen, K
    Dekker, JM
    The evaluation of screening and early detection strategies for type 2 diabetes and impaired glucose tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 5, 1004-1012 p.Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors.

    METHODS: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques.

    RESULTS: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726-0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity.

    CONCLUSIONS/INTERPRETATION: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.

  • 7.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Goedecke, Julia
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The human visceral fat depot has a unique inflammatory profile2010In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 18, no 5, 879-883 p.Article in journal (Refereed)
    Abstract [en]

    Obesity can be considered as a low-grade inflammatory condition, strongly linked to adverse metabolic outcomes. Obesity-associated adipose tissue inflammation is characterized by infiltration of macrophages and increased cytokine and chemokine production. The distribution of adipose tissue impacts the outcomes of obesity, with the accumulation of fat in visceral adipose tissue (VAT) and deep subcutaneous adipose tissue (SAT), but not superficial SAT, being linked to insulin resistance. We hypothesized that the inflammatory gene expression in deep SAT and VAT is higher than in superficial SAT. A total of 17 apparently healthy women (BMI: 29.3 +/- 5.5 kg/m2) were included in the study. Body fat (dual-energy X-ray absorptiometry) and distribution (computed tomography) were measured, and insulin sensitivity, blood lipids, and blood pressure were determined. Inflammation-related differences in gene expression(real-time PCR) from VAT, superficial and deep SAT biopsies were analyzed using univariate and multivariate data analyses. Using multivariate discrimination analysis, VAT appeared as a distinct depot in adipose tissue inflammation,while the SAT depots had a similar pattern, with respect to gene expression. A significantly elevated (P < 0.01)expression of the CC chemokine receptor 2 (CCR2) and macrophage migration inhibitory factor (MIF) in VAT contributed strongly to the discrimination. In conclusion, the human adipose tissue depots have unique inflammatory patterns, with CCR2 and MIF distinguishing between VAT and the SAT depots.

  • 8. Andersen, Mette K.
    et al.
    Sterner, Maria
    Forsen, Tom
    Käräjämäki, Annemari
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Forsblom, Carol
    Groop, Per-Henrik
    Lahti, Kaj
    Nilsson, Peter M.
    Groop, Leif
    Tuomi, Tiinamaija
    Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 9, 1859-1868 p.Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA). Methods We assessed 41 type 2 diabetes-associated gene variants in Finnish (phase I) and Swedish (phase II) patients with LADA (n=911) or type 1 diabetes (n=406), all diagnosed after the age of 35 years, as well as in non-diabetic control individuals 40 years or older (n=4,002). Results Variants in the ZMIZ1 (rs12571751, p=4.1 x 10(-5)) and TCF7L2 (rs7903146, p=5.8 x 10(-4)) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p=0.0012), HHEX (rs1111875, p=0.0024 in Finns) and MTNR1B (rs10830963, p=0.0039) loci showed the strongest association in patients with low GADA, supporting the hypothesis that the disease in these patients is more like type 2 diabetes. In contrast, variants in the KLHDC5 (rs10842994, p=9.5 x 10(-4) in Finns), TP53INP1 (rs896854, p=0.005), CDKAL1 (rs7756992, p=7.0 x 10(-4); rs7754840, p=8.8 x 10(-4)) and PROX1 (rs340874, p=0.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p=3.2 x 10(-6)) and HNF1A (rs2650000, p=0.0012). Conclusions/interpretation LADA and adult-onset type 1 diabetes share genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form of diabetes and distinguishing them from patients with classical young-onset type 1 diabetes.

  • 9. Andersson, B.
    et al.
    Swolin-Eide, D.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gelander, L.
    Magnusson, P.
    Albertsson-Wikland, K.
    Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment2015In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 38, no 12, 1309-1317 p.Article in journal (Refereed)
    Abstract [en]

    Purpose This study investigated the relationship between seasonal variations in 25-hydroxyvitamin D (25(OH) D) levels and growth in prepubertal children during both the pretreatment year and the first year of GH treatment. Methods The study included 249 short prepubertal children with a broad range of GH secretion, GH(max) during a 24 h profile median 23; range 1-127 mU/L, 191 boys (mean age +/- SD, 8.6 +/- 2.6 years), 58 girls (7.5 +/- 1.9 years) receiving GH treatment (mean 43 mu g/kg/day; range 17-99 mu g/kg/day). Serum 25(OH) D was measured using an automated IDS-iSYS immunoassay. Results 25(OH) D levels showed seasonal variation, and decreased significantly during GH treatment. 25(OH) D levels at start and first year reduction in 25(OH) D, correlated (-) with the first year growth response during treatment. The degree of GH secretion capacity within our study population of mainly non-GH deficient children and 25(OH) D sufficient (67 +/- 29 nmol/L) had no influence on 25(OH) D levels. Growth during GH treatment were independent of seasonal variations in 25(OH) D. Multiple regression analysis showed that 25(OH) D levels at treatment start, together with auxological data and IGF-binding protein-3(SDS), explained 61 % of the variation in first year gain in height(SDS). Conclusion 25(OH) D levels were associated with first year growth response to GH and may be a useful contribution to future growth prediction models.

  • 10.
    Andersson, Håkan
    Umeå University, Faculty of Medicine.
    Clinical Reproductive Endocrinology2008In: Clinical Biochemistry of Domestic Animals, 6th Edition, Amsterdam: Elsevier, 2008, 635-662 p.Chapter in book (Refereed)
    Abstract [en]

    This chapter helps in understating the basics of clinical reproductive endocrinology. Clinical reproductive endocrinology includes the study of diseases and secretory status of the endocrine glands involved in reproduction and their secretory products, the reproductive hormones. To obtain a satisfactory understanding of the complex endocrinological events that occur during normal and abnormal reproductive function, it is necessary to quantify specific hormones. The best understood humoral control system in the body is the endocrine system. This system uses specific messengers, termed hormones, to regulate important body functions. Hormones are chemical substances synthesized and secreted directly into the blood vascular system by ductless endocrine glands in minute quantities and are transported to a remote target organ, where they regulate the rates of specific biochemical processes. The classic endocrine glands include the pituitary, thyroid, parathyroid, adrenal, pancreas, ovary, testis, placenta, and pineal gland. This chapter emphasizes the determination of hormones and the use of the data as diagnostic aids. General reproductive endocrinology in domestic species is broadly covered in this chapter.

  • 11.
    Andersson, Therese
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    McInnes, Kerry
    Endocrine Unit, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
    Simonyte, Kotryna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rask, Eva
    Institutionen för medicin, Örebro universitetssjukhus, Örebro, Sverige.
    Mattsson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Seckl, Jonathan R
    Endocrinology Unit, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Estrogen upregulates 11β-hydroxysteroid dehydrogenase type 1 in adipose tissues via estrogen receptor βManuscript (preprint) (Other academic)
  • 12.
    Andersson, Therése
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Estrogen and Glucocorticoid Metabolism2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Cardiovascular disease (CVD) is the leading cause of death among women in Sweden. The risk of CVD increases rapidly after the menopause. A major contributing factor may be the redistribution of adipose tissue, from the peripheral to central depots, associated with menopause. This change in body composition is commonly attributed to declining estrogen levels but may also be affected by tissue-specific alterations in exposure to other steroid hormones, notably glucocorticoids – mainly cortisol in humans. Indeed, adipose tissue-specific overexpression of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) induces central obesity, insulin resistance and hypertension in mice. Interestingly, estrogen may regulate this enzyme. The aim of this thesis was to investigate putative links between estrogen and glucocorticoid activation by 11βHSD1. Materials and Methods: 11βHSD1 expression and/or activity in adipose tissue and liver, and adipose estrogen receptor α and β (ERα and ERβ) gene expression, were investigated in lean pre- and postmenopausal women and ovariectomized rodents with and without estrogen supplementation. In lean women measures of 11βHSD1 were correlated to risk markers for CVD. The association between adipose 11βHSD1 and ER mRNA expression was investigated in both lean women and rats and in an additional cohort of obese premenopausal women. In vitro experiments with adipocyte cell lines were used to explore possible pathways for estrogen regulation of 11βHSD1. Results: Subcutaneous adipose tissue transcript levels and hepatic activity of 11βHSD1 were higher in postmenopausal vs. premenopausal women. In rodents, estrogen treatment to ovariectomized rats decreased visceral adipose tissue 11βHSD1, resulting in a shift towards higher subcutaneous (vs. visceral) 11βHSD1 mRNA expression/activity. Increased adipose and hepatic 11βHSD1 were associated with increased blood pressure and a disadvantageous blood lipid profile in humans. We found significant positive associations between 11βHSD1 and ERβ transcript levels in adipose tissue. The in vitro experiments showed upregulation of 11βHSD1 mRNA expression and activity with estrogen or ERβ-agonist treatment at low (corresponding to physiological) concentrations. Conclusions: Our studies show for the first time increased local tissue glucocorticoid activation with menopause/age in women. This may contribute to an increased risk of CVD. Estrogen treatment in rodents induces a shift in 11βHSD1 activity towards the subcutaneous adipose tissue depots, which may direct fat accumulation to this metabolically “safer” depot. The in vitro studies suggest that low-dose estrogen treatment upregulates 11βHSD1 via ERβ. In summary, estrogen - glucocorticoid metabolism interactions may be key in the development of menopause-related metabolic dysfunction and in part mediate the beneficial effects of postmenopausal estrogen treatment on body fat distribution.

  • 13.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Att förebygga diabetes: vilka är styrinstrumenten?2008In: DiabetologNytt, ISSN 1401-2618, Vol. 21, no 7-8Article in journal (Other academic)
  • 14. Atabaki-Pasdar, Naeimeh
    et al.
    Ohlsson, Mattias
    Shungin, Dmitry
    Kurbasic, Azra
    Ingelsson, Erik
    Pearson, Ewan R.
    Ali, Ashfaq
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Statistical power considerations in genotype-based recall randomized controlled trials2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 37307Article in journal (Refereed)
    Abstract [en]

    Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.

  • 15. Atiomo, William
    et al.
    Shafiee, Mohamad Nasir
    Chapman, Caroline
    Metzler, Veronika M.
    Abouzeid, Jad
    Latif, Ayşe
    Chadwick, Amy
    Kitson, Sarah
    Sivalingam, Vanitha N.
    Stratford, Ian J.
    Rutland, Catrin S.
    Persson, Jenny L.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Clinical Research Center, Lund University, Malmö, Sweden.
    Ødum, Niels
    Fuentes-Utrilla, Pablo
    Jeyapalan, Jennie N.
    Heery, David M.
    Crosbie, Emma J.
    Mongan, Nigel P.
    Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome2017In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, no 5, 557-565 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). Aim: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Design and Methods: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. Results: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P < .0001). Conclusions: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.

  • 16. Avall, Karin
    et al.
    Ali, Yusuf
    Leibiger, Ingo B.
    Leibiger, Barbara
    Moede, Tilo
    Paschen, Meike
    Dicker, Andrea
    Dare, Elisabetta
    Kohler, Martin
    Ilegems, Erwin
    Abdulreda, Midhat H.
    Graham, Mark
    Crooke, Rosanne M.
    Tay, Vanessa S. Y.
    Refai, Essam
    Nilsson, Stefan K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Jacob, Stefan
    Selander, Lars
    Berggren, Per-Olof
    Juntti-Berggren, Lisa
    Apolipoprotein CIII links islet insulin resistance to beta-cell failure in diabetes2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 20, E2611-E2619 p.Article in journal (Refereed)
    Abstract [en]

    Insulin resistance and beta-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and beta-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of beta-cell cytoplasmic free Ca2+ concentration ([Ca2+](i)) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca2+](i) response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of beta-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.

  • 17.
    Awad, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Public Health and Clinical Medicine, Sunderby Research Unit, Umeå University, Sweden..
    Lundqvist, Robert
    Research and Innovation Unit, Norrbotten County Council, Luleå, Sweden..
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Public Health and Clinical Medicine, Sunderby Research Unit, Umeå University, Sweden..
    Lower cognitive performance among long-term type 1 diabetes survivors: A case-control study2017In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 31, no 8, 1328-1331 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Patients with type 1 diabetes (T1D) have an increased risk of cognitive dysfunction. The cognitive decrement is believed to depend on macro- and microvascular complications and long disease duration. Some patients do not develop these complications, but still report cognitive symptoms. We examined if long-standing T1D without complications is associated with lower cognitive performance.

    METHODS: A group of patients (n=43) with long-standing T1D (>30years) without micro- or macro vascular complications was compared with a non-diabetic control group (n=86) on six cognitive tests which probed episodic memory, semantic memory, episodic short-term memory, visual attention and psychomotor speed. Each patient was matched with two controls regarding age, gender and education. A linear mixed effect model was used to analyze the data.

    RESULTS: The mean age was 57years and mean duration was 41years. Patients with diabetes had lower diastolic blood pressure but BMI, waist circumference, systolic blood pressure and smoking did not differ between groups. Patients had lower results than non-diabetic controls in episodic short-term memory (p<0.001) and also lower values on a test that mirrors visual attention and psychomotor speed (p=0.019).

    CONCLUSIONS: Long-standing T1D was associated with lower cognitive performance, regardless of other diabetes-related complications.

  • 18. Azizi, F
    et al.
    Mehran, L
    Sheikholeslam, R
    Ordookhani, A
    Naghavi, M
    Hedayati, M
    Padyab, Mojgan
    Mirmiran, P
    Sustainability of a well-monitored salt iodization program in Iran: marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt.2008In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 31, no 5, 422-31 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Two yr after legislation of salt iodization of 40 parts per million (ppm) in 1994, goiter was still endemic and urinary iodine concentration (UIC) remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households.

    METHODS:

    Schoolchildren (7-10 yr) of all provinces were randomly selected by cluster sampling from December 2000 to June 2001. Goiter rate, UIC, and household salt iodine values were compared to those in 1996. Factory salt iodine was also compared in 2001 vs 1996. Ultrasonographically determined thyroid volumes of 7-10 yr old children were compared in 2001 vs 1999.

    RESULTS:

    In 2001 (no.=33600) vs 1996 (no.=36178), total, grade 1, and grade 2 goiter rates were 13.9 vs 53.8%, 11.0 vs 44.8%, and 2.9 vs 9.0%, respectively (p<0.0001). Weighted total goiter rate was 9.8% in 2001. Median (range) UIC in 2001 (no.=3329) was 165 (18-499) microg/l and in 1996 (no.=2917) was 205 (10-2300) microg/l (p<0.0001). In 2001 vs 1996, mean+/-SD for iodine salt content was 32.7+/-10.1 vs 33.0+/-10.2 ppm (p=0.68) in households and was 33.2+/-13.4 and 33.8+/-13.2 ppm (p=0.57) in factories, respectively. Among 7-10 yr old children in 2001 (no.=400) vs 1999 (no.=396), only 7-yr-old children in 2001 (the only group with probably no history of iodine deficiency) showed significant smaller thyroid volumes by ultrasonography compared to those in 1999.

    CONCLUSIONS:

    After 7 yr of optimized iodized-salt supplementation in Iran, adequate UIC values and marked reduction in goiter rate have been achieved.

  • 19.
    Backeström, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nilsson, Lars-Göran
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study2015In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 7, 20Article in journal (Refereed)
    Abstract [en]

    Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. 

    Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. 

    Results: A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. 

    Conclusions: This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

  • 20.
    Bang, P
    et al.
    Department of Women’s and Children’s Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
    Bjerknes, R
    Department of Clinical Medicine, Section for Pediatrics, University of Bergen, Norway.
    Dahlgren, J
    Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Dunkel, L
    Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
    Gustafsson, J
    Department of Women’s and Children’s Health, University of Uppsala, Sweden.
    Juul, A
    Department of Growth and Reproduction, University of Copenhagen, Denmark.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Tapanainen, P
    Department of Pediatrics and Adolescence, University of Oulu, Finland.
    Åberg, V
    Institut Produits Synthèse (IPSEN) AB, Kista, Sweden.
    A comparison of different definitions of growth response in short prepubertal children treated with growth hormone2011In: Hormone research in paediatrics, ISSN 1663-2826, Vol. 75, no 5, 335-345 p.Article in journal (Refereed)
    Abstract [en]

    Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial.

    Aim: Assess various criteria of poor response.

    Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) ≤-2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS -3.2.

    Results: Median [25-75 percentile] first-year gain in Ht SDS was 0.65 (0.40-0.90) and height velocity (HtV) 8.67 (7.51-9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 μg/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5.

    Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients.

  • 21. Barkhordari, Mahnaz
    et al.
    Padyab, Mojgan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Sardarinia, Mahsa
    Hadaegh, Farzad
    Azizi, Fereidoun
    Bozorgmanesh, Mohammadreza
    Survival Regression Modeling Strategies in CVD Prediction2016In: INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM, ISSN 1726-913X, Vol. 14, no 2, UNSP e32156Article in journal (Refereed)
    Abstract [en]

    Background: A fundamental part of prevention is prediction. Potential predictors are the sine qua non of prediction models. However, whether incorporating novel predictors to prediction models could be directly translated to added predictive value remains an area of dispute. The difference between the predictive power of a predictive model with (enhanced model) and without (baseline model) a certain predictor is generally regarded as an indicator of the predictive value added by that predictor. Indices such as discrimination and calibration have long been used in this regard. Recently, the use of added predictive value has been suggested while comparing the predictive performances of the predictive models with and without novel biomarkers. Objectives: User-friendly statistical software capable of implementing novel statistical procedures is conspicuously lacking. This shortcoming has restricted implementation of such novel model assessment methods. We aimed to construct Stata commands to help researchers obtain the aforementioned statistical indices. Materials and Methods: We have written Stata commands that are intended to help researchers obtain the following. 1, Nam-D'Agostino X-2 goodness of fit test; 2, Cut point-free and cut point-based net reclassification improvement index (NRI), relative absolute integrated discriminatory improvement index (IDI), and survival-based regression analyses. We applied the commands to real data on women participating in the Tehran lipid and glucose study (TLGS) to examine if information relating to a family history of premature cardiovascular disease (CVD), waist circumference, and fasting plasma glucose can improve predictive performance of Framingham's general CVD risk algorithm. Results: The command is adpredsurv for survival models. Conclusions: Herein we have described the Stata package "adpredsurv" for calculation of the Nam-D'Agostino X2 goodness of fit test as well as cut point-free and cut point-based NRI, relative and absolute IDI, and survival-based regression analyses. We hope this work encourages the use of novel methods in examining predictive capacity of the emerging plethora of novel biomarkers.

  • 22.
    Benckert, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lilja, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Improved metabolic health among the obesein six population surveys 1986 to 2009: the Northern Sweden MONICA study2015In: BMC Obesity, ISSN 2052-9538, Vol. 2, no 7Article in journal (Refereed)
    Abstract [en]

    Background

    The incidence of CVD is decreasing in spite of increasing BMI in the population. We examined trends in metabolic health among overweight and obese individuals and the influence of lifestyle and socioeconomic status. Six cross sectional population surveys in the Northern Sweden MONICA Study between 1986 and 2009. 8 874 subjects 25 to 64 years participated (74% participation rate). Metabolic health was defined as a total cholesterol level below 5.0 mmol/l, blood pressure below 140/90 mmHg and not having diabetes. In 2009 the age span 25 to 74 years was studied.

    Results

    The prevalence of metabolic health among obese subjects increased by 7.9 % per year (95% confidence interval 5.4; 10.5), reaching 21.0% in 2009. The corresponding figures for overweight subjects were 5.9% per year (4.6; 7.3), reaching 18% in 2009, whereas for the normal-weight subjects, the increase was 6.2% per year (5.3; 7.2), reaching 39% in 2009. The prevalence of metabolic health among subjects with abdominal obesity increased by 5.8% (4.6; 7.0) per year, reaching 17.3% in 2009. Among those with no abdominal obesity the increase was 6.2% (5.2; 7.1), reaching 38% in 2009 (p = <0.001 for all groups). Only among non-obese men and obese women did the increase continue between 2004 and 2009. In the other groups a slight decline or levelling off was noted.

    In 2009 women had a 27% higher prevalence of metabolic health than men. The prevalence of metabolic health among the obese was 19.8% which declined to 15.8% if subjects treated for hypertension or hypercholesterolemia were classified as not healthy. Overweight and obese subjects were less often metabolically healthy (odds ratio 0.54 and 0.59 respectively) compared with normal-weight subjects, independent of sex and age as were subjects with abdominal obesity (odds ratio 0.52). Adjustments for smoking, physical activity and education level did not influence any estimates.

    Conclusions

    This report shows a large increase in prevalence of metabolic health from 1986 to 2009 for all anthropometric categories. Metabolic health remains considerably less prevalent among overweight and obese subjects than among those with normal weight.

  • 23.
    Bendix, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Uvnäs-Moberg, Kerstin
    Petersson, Maria
    Kaldo, Viktor
    Åsberg, Marie
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Insulin and glucagon in plasma and cerebrospinal fluid in suicide attempters and healthy controls2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 81, 1-7 p.Article in journal (Refereed)
    Abstract [en]

    Mental disorders and related behaviors such as suicidality and violence have been associated to dysregulation of e g carbohydrate metabolism. We hypothesized that patients after suicide attempt, compared to healthy controls, would have higher insulin and lower glucagon levels in plasma and cerebrospinal fluid and that these changes would be associated to violent behavior. Twenty-eight medication-free patients (10 women, 18 men), hospitalized after suicide attempt, and 19 healthy controls (7 women, 12 men) were recruited with the aim to study risk factors for suicidal behavior. Psychological/psychiatric assessment was performed with SCID I and II or the SCID interview for healthy volunteers respectively, the Karolinska Interpersonal Violence Scale (KIVS) for assessment of lifetime violence expression behavior, the Montgomery-Asberg-Depression-Scale (MADRS) and the Comprehensive Psychological Rating Scale (CPRS) for symptomatic assessment of depression and appetite. Fasting levels of insulin and glucagon were measured in plasma (P) and cerebrospinal fluid (CSF). Suicide attempters had higher insulin- and lower glucagon-levels in plasma- and CSF compared to controls. Except for P-glucagon these associations remained significant after adjusting for age and/or BMI. Patients reported significantly more expressed interpersonal violence compared to healthy volunteers. Expressed violence was significantly positively correlated with P- and CSF-insulin and showed a significant negative correlation with P-glucagon in study participants. These findings confirm and extend prior reports that higher insulin and lower glucagon levels in plasma and cerebrospinal fluid are associated with suicidal behavior pointing towards a potential autonomic dysregulation in the control of insulin and glucagon secretion in suicidal patients. 

  • 24. Benetou, V
    et al.
    Orfanos, P
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Berrino, F
    Tumino, R
    Borch, K B
    Lund, E
    Peeters, P H M
    Grote, V
    Li, K
    Altzibar, J M
    Key, T
    Boeing, H
    von Ruesten, A
    Norat, T
    Wark, P A
    Riboli, E
    Trichopoulou, A
    Mediterranean diet and incidence of hip fractures in a European cohort2013In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, no 5, 1587-1598 p.Article in journal (Refereed)
    Abstract [en]

    Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

  • 25.
    Bengtsson, Sara K. S.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nyberg, Sigrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Hedström, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Zingmark, Elisabeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Jonsson, Bjorn
    Bäckström, Torbjörn
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 52, 22-31 p.Article in journal (Refereed)
    Abstract [en]

    Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of gamma-amino-butyric acid (GABA) on the GABA type A (GABA(A)) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABA(A) receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.

  • 26. Bennet, L.
    et al.
    Lindblad, U.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A family history of diabetes determines poorer glycaemic control and younger age of diabetes onset in immigrants from the Middle East compared with native Swedes2015In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 41, no 1, 45-54 p.Article in journal (Refereed)
    Abstract [en]

    Aims. - Immigrant populations from the Middle East develop diabetes earlier than indigenous European populations; however, the underlying etiology is poorly understood. This study looked at the risk factors associated with early diabetes onset and, in non-diabetics, glycaemic control in immigrants from Iraq compared with native Swedes.

    Methods. - This cross-sectional population-based study comprised 1398 Iraqi immigrants and 757 Swedes (ages 30-75 years) residing in the same area of Malmo, Sweden. Outcomes were age at diabetes onset and glycaemic control (HbA(1c)) as assessed by Cox proportional hazards and linear regression, respectively.

    Results. - In Iraqis vs Swedes, clustering in the family history (in two or more relatives) was more prevalent (23.2% vs 3.6%, P<0.001) and diabetes onset occurred earlier (47.6 years vs 53.4 years, P=0.001). Having an Iraqi background independently raised the hazard ratio (HR) for diabetes onset. Diabetes risk due to family history was augmented by obesity, with the highest HRs observed in obese participants with clustering in the family history (HR: 5.1, 95% CI: 3.2-8.2) after adjusting for country of birth and gender. In participants without previously diagnosed diabetes (Iraqis: n=1270; Swedes: n=728), HbA(1c), levels were slightly higher in Iraqis than in Swedes (4.5% vs 4.4%, P=0.038). This difference was explained primarily by clustering in the family history rather than age, obesity, lifestyle or socioeconomic status.

    Conclusion. - The study shows that the greater predisposition to diabetes in Middle Eastern immigrants may be explained by a more extensive family history of the disorder; clinical interventions tailored to Middle Eastern immigrants with such a family history are thus warranted.

  • 27. Bennet, Louise
    et al.
    Groop, Leif
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Malmö, Sweden.
    Country of birth modifies the association of fatty liver index with insulin action in Middle Eastern immigrants to Sweden2015In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 110, no 1, 66-74 p.Article in journal (Refereed)
    Abstract [en]

    Aims: Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FLI >= 70) given country of origin and further to investigate the associations between ISI and FLI. Methods: In 2010-2012 we conducted a population-based study of individuals aged 30-75 years born in Iraq or Sweden, in whom anthropometrics, fasting blood samples and oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors characterized. Results: A higher proportion of Iraqis (N = 1085) than Swedes (N = 605) had a high probability of NAFLD (FLI >= 70, 32.5 vs. 22.6%, p < 0.001, age-and sex-adjusted data) and ISI was more severely impaired (70.7 vs. 95.9%, p < 0.001). Independently of traditional risk factors for NAFLD, being born in Iraqi increased the risk of FLI >= 70 (OR 1.59: 95% CI 1.15, 2.20). Furthermore, country of birth presented a stronger association between ISI and FLI >= 70 in Iraqis than in Swedes (P-interaction = 0.019). Conclusions: Our data indicate that immigrants from Iraq are at higher risk of NAFLD. The finding that country of birth modifies the relationship of FLI with ISI, suggests that liver fat may be a stronger determinant of impaired insulin action and increased risk of type 2 diabetes in Iraqis than in Swedes.

  • 28. Bennet, Louise
    et al.
    Groop, Leif
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ethnic differences in the contribution of insulin action and secretion to type 2 diabetes in immigrants from the Middle East compared to native Swedes2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 105, no 1, 79-87 p.Article in journal (Refereed)
    Abstract [en]

    Aims: We investigated insulin action (insulin sensitivity index, ISI) and insulin secretion (oral disposition indices, DIo) and studied metabolic, demographic and lifestyle-related risk factors for type 2 diabetes and insulin action, in the largest non-European immigrant group to Sweden, immigrants from Iraq and native Swedes.

    Methods: Population-based, cross-sectional study conducted 2010-2012 including residents 30-75 years of age born in Iraq or Sweden, in whom oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors were characterized.

    Results: In Iraqis compared to Swedes, ISI was more impaired (76.9 vs. 102.3, p < .001) whereas corrected insulin response CIR was higher (226.6 vs. 188.6, p = .016). However, insulin secretion was inadequate given the substantial insulin resistance, as indicated by lower DIo indices in Iraqis than in Swedes (DIo 12,712.9 vs. 14,659.2, p < .001). The crude ethnic difference in ISI was not offset by traditional risk factors like waist circumference, body mass index or family history of diabetes. In Iraqis, ISI conveyed somewhat higher odds of type 2 diabetes than in Swedes (odds ratio OR 0.98, 95% CI 0.97-0.99) vs. OR 0.95, 0.92-0.99), as indicated by an interaction between country of birth and ISI (P-interaction = .044).

    Conclusion: This study reports ethnic differences in the contribution of insulin action to type 2 diabetes. Our data suggests that the impaired insulin action observed in immigrants from the Middle East to Sweden is not fully explained by established risk factors.

    (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  • 29.
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Epidemiological studies of childhood diabetes and important health complications to the disease2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims: The overall aim of this thesis was to increase knowledge regarding the occurrence of childhood onset T1D and T2D in Sweden and in relation to that describe and elucidate important aspects on two grave complications to diabetes; end-stage renal disease (ESRD) and mortality. The two first studies included in this thesis aimed to describe and analyze the cumulative incidence of childhood onset T1D in Sweden and to assess the occurrence of undetected T2D in Swedish children. The aim with the third study was to describe the cumulative incidence of ESRD, and to analyze how ESRD risk differs with age at-onset and sex. The aim of the fourth study was to show how parental socioeconomic status (SES) affects all cause mortality in Swedish patients with childhood onset T1D.

    Study populations: The foundation for the studies on T1D was data from the Swedish Childhood Diabetes Registry (SCDR). When studying ESRD we also included adult onset T1D cases from the Diabetes Incidence Study in Sweden (DISS). The study on T2D was a population-based screening study where BMI was measured in 5528 school-children and hemoglobin A1c was measured in children with overweight according to international age and sex specific BMI cut-offs. To study ESRD and mortality, we linked the SCDR to various nationwide registers containing individual information on SES, mortality and ESRD.

    Results: The incidence rates of childhood onset T1D has continued to increase in Sweden 1977–2007. Age- and sex-specific incidence rates varied from 21.6 (95% CI 19.4–23.9) during 1978–1980 to 43.9 (95% CI 40.7– 47.3) during 2005–2007. Cumulative incidence by birth-cohorts has shifted to a younger age at-onset over the first 22 years of incidence registration. From the year 2000 there was a significant reverse in this trend (p<0.01). In contrast to the increase of T1D, we found no evidence of undetected T2D among Swedish school children. Despite a relatively high incidence in T1D in Sweden there is low cumulative incidence of ESRD, 3.3% at maximum 30 years of duration. We found difference between the sexes regarding long-term risk of developing ESRD that was dependent on the age at onset of T1D. When analyzing how socioeconomic status affects mortality in different age at death groups, we found that having parents that received income support increased mortality up to three times in those who died after 18 years of age.

    Conclusion: The incidence of childhood onset T1D continued to increase in Sweden 1978-2007. Between the years 1978-1999 there was a shift to a younger age at-onset, but from the year 2000 there is a change in this shift indicating a possible trend break. The prevalence of T2D among Swedish children up to 12 years of age is probably very low. There is still a low cumulative incidence of T1D associated ESRD in Sweden. The risk of developing ESRD depends on age at-onset of T1D, and there is a clear difference in risk between men and woman. Excess mortality among subjects with childhood onset T1D still exists, and low parental socioeconomic status additionally increased mortality in this group.

  • 30.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Carlsson, Annelie
    Högberg, Lotta
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Screening for undiagnosed type-2 diabetes in Swedish 6th grade school childrenManuscript (preprint) (Other academic)
    Abstract [en]

    Aims: To estimate the prevalence of undiagnosed type-2 diabetes in overweight Swedish school children 11-13 years old.

    Methods: BMI was measured in 5 528 school-children (11-13 years of age) attending the 6th grade, in five different regions in Sweden. Overweight was defined by international age-sex specific BMI cut-offs, corresponding to adult BMI cut-offs of 25 kg/m² at 18 years of age (ISO-BMI ≥25, n=1 275). Haemoglobin A1c (HbA1c) was measured in 1 126 children with ISO-BMI ≥25. Children with a DCCT-aligned HbA1c ≥ 6.1% on two occasions underwent an oral glucose-tolerance test (OGTT) to establish diabetes diagnosis.

    Results: Twenty four children (2.1%) had at least one HbA1c-value ≥6.1%. Three of them had HbA1c ≥6.1% on two occasions and all of them had a normal OGTT.

    Conclusion: In this cross-sectional population-based screening study of a high risk group of 11-13 years old Swedish school children we found no indication of undiagnosed diabetes or impaired glucose tolerance.Key

  • 31.
    Billing, Ola
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Kao, Gautam
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Mitochondrial function is required for secretion of DAF-28/insulin in C. elegans.2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 1, e14507- p.Article in journal (Refereed)
    Abstract [en]

    While insulin signaling has been extensively studied in Caenorhabditis elegans in the context of ageing and stress response, less is known about the factors underlying the secretion of insulin ligands upstream of the insulin receptor. Activation of the receptor governs the decision whether to progress through the reproductive lifecycle or to arrest growth and enter hibernation. We find that animals with reduced levels of the mitochondrial outer membrane translocase homologue TOMM-40 arrest growth as larvae and have decreased insulin signaling strength. TOMM-40 acts as a mitochondrial translocase in C. elegans and in its absence animals fail to import a mitochondrial protein reporter across the mitochondrial membrane(s). Inactivation of TOMM-40 evokes the mitochondrial unfolded protein response and causes a collapse of the proton gradient across the inner mitochondrial membrane. Consequently these broadly dysfunctional mitochondria render an inability to couple food abundance to secretion of DAF-28/insulin. The secretion defect is not general in nature since two other neuropeptides, ANF::GFP and INS-22::VENUS, are secreted normally. RNAi against two other putative members of the TOMM complex give similar phenotypes, implying that DAF-28 secretion is sensitive to mitochondrial dysfunction in general. We conclude that mitochondrial function is required for C. elegans to secrete DAF-28/insulin when food is abundant. This modulation of secretion likely represents an additional level of control over DAF-28/insulin function.

  • 32.
    Billing, Ola
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Natarajan, Balasubramanian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Mohammed, Ateequrrahman
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Kao, Gautam
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    A directed RNAi screen based on larval growth arrest reveals new modifiers of C. elegans insulin signaling2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, e34507- p.Article in journal (Refereed)
    Abstract [en]

    Genes regulating Caenorhabditis elegans insulin/IGF signaling (IIS) have largely been identified on the basis of their involvement in dauer development or longevity. A third IIS phenotype is the first larval stage (L1) diapause, which is also influenced by asna-1, a regulator of DAF-28/insulin secretion. We reasoned that new regulators of IIS strength might be identified in screens based on the L1 diapause and the asna-1 phenotype. Eighty-six genes were selected for analysis by virtue of their predicted interaction with ASNA-1 and screened for asna-1-like larval arrest. ykt-6, mrps-2, mrps-10 and mrpl-43 were identified as genes which, when inactivated, caused larval arrest without any associated feeding defects. Several tests indicated that IIS strength was weaker and that insulin secretion was defective in these animals. This study highlights the role of the Golgi network and the mitochondria in insulin secretion and provides a new list of genes that modulate IIS in C. elegans.

  • 33.
    Borssén, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Foot lesions in diabetic patients aged 15-20 years: a population-based study1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Foot problems are not only the most common but in general also the most severe of the diabetic complications. The age group 15-50 yrs in this study was chosen because these patients were considered to be at their most active age and were felt to require optimal foot function.

    380 patients (96 %) participated, 78 % with Type 1, 20 % Type 2 and 1 % with secondary diabetes mellitus (DM) and 100 healthy controls. Only six patients had signs of peripheral ischaemia but half of the patients had deformities such as fallen forefoot arches and hammer toes. With sensory thresholds and clinical signs it was demonstrated that age, duration of DM and tall stature are major risk factors for diabetic neuropathy. Gender differences depend on differences in height. Dorsiflexion of the toes against resistance was used to test the function and volume of m.extensor digitorum brevis. When compared with measurements of sensory thresholds for vibration, perception and pain, it was found to be a valuable test for screening of distal motor neuropathy.

    To prevent worsening of foot deformities 266 patients with Type 1 DM were followed for 3 years. Those with the most pronounced deformities were fitted with custom-made insoles and had repeated examinations. Improvement was more common in patients with insoles compared to patients without insoles.

    Bone mineral density (BMD) was measured in nine patients with osteopathy in their feet and 18 controls. BMD was lower in L2-L3, but not in the proximal femur, implying osteopenia being a possible risk factor for distal osteopathy.

    Plaster cast treatment was used in 33 diabetic patients with severe foot ulcers who were selected because previous conservative treatment had been unsuccessful and they had been judged unsuitable for vascular surgery. The lesions healed in 19 patients.

    In conclusion, the main findings demonstrate the need for an increased awareness of early preventive foot care in young and middle-aged diabetic patients.

  • 34.
    Boström, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lundman, Bent
    Umeå University, Faculty of Medicine, Department of Nursing.
    Graneheim, Ulla H.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hörnsten, Åsa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Interaction between diabetes specialist nurses and patients during group sessions about self-management in type 2 diabetes2014In: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 94, no 2, 187-192 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to explore the interaction between diabetes specialist nurses (DSNs) and patients with type 2 diabetes (T2D) during group sessions about self-management. Methods: Ten DSNs and 44 patients were observed during group sessions about self-management, and thereafter the observations were analyzed using qualitative content analysis. Results: The interaction was characterized by three themes: becoming empowered, approaching each other from different perspectives, and struggling for authority. The interaction was not a linear process, but rather a dynamic process with distinct episodes that characterized the content of the sessions. Conclusion: It is important to achieve an interaction that is patient-centered, where the DSN is aware of each patient's individual needs and avoids responding to patients in a normative way. A satisfying interaction may strengthen patients' self-management, and also may strengthen the DSNs in their professional performance. Practice implications: Authority struggles between patients and DSNs could be a prerequisite for patients to become autonomous and decisive in self-management. DSNs might benefit from an increased awareness about this issue, because they can better support patients if they do not perceive authority struggles as threats to their professional role. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

  • 35.
    Boström, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lundman, Berit
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hällgren Graneheim, Ulla
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hörnsten, Åsa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Interaction between diabetes specialist nurses and patients during group sessions about self-management in type 2 diabetesIn: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134Article in journal (Refereed)
  • 36.
    Boström, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lundman, Berit
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lehuluante, Abraraw
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hörnsten, Åsa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Patient-centred care in type 2 diabetes: an altered professional role for diabetes specialist nurses2014In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 28, no 4, 675-682 p.Article in journal (Refereed)
    Abstract [en]

    Little research has been done to try to understand how patient-centred care is understood and practised by healthcare professionals specialising in patients with diabetes. Experiences from patient-centred practices need to be highlighted as a way of motivating diabetes specialist nurses to take a patient-centred approach. The aim of this study was to describe diabetes specialist nurses' experiences of practising patient-centred care in the context of a type 2 diabetes intervention. The study design was descriptive and used qualitative methods. Focus group interviews complemented by individual semi-structured interviews were analysed by qualitative content analysis. The main theme of the diabetes specialist nurses' experiences of practising patient-centred care was an altered professional role. The main theme was based on two themes: ambivalence towards practising patient-centred care and enriched relationships with the patients. The ambivalence towards practising patient-centred care was based on the three subthemes: a position of withdrawn expertise, inconvenience of changing routines and insights that patient-centred care is difficult but possible. Their experiences of enriched relationships with patients were based on the two subthemes: courage to discuss the severity of diabetes and increased engagement in patients' daily lives. The diabetes specialist nurses' experiences with practising patient-centred care included doubts about their ability to practise in such a way and about the feasibility of such care. At the same time, their enriched relationships with patients were seen as an opportunity to engage in patients' lives. Training and support for practising patient-centred care may improve diabetes specialist nurses skills in patient-centred care and self-management support in type 2 diabetes.

  • 37. Boucher, Marie-Josée
    et al.
    Simoneau, Mélanie
    Edlund, Helena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity2009In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 150, no 1, 87-97 p.Article in journal (Refereed)
    Abstract [en]

    The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. In humans, mutations in the IPF1 gene have been linked to diabetes. Hence, the identification of molecular mechanisms regulating the transcriptional activity of this key transcription factor is of great interest. Herein we analyzed homeodomain-interacting protein kinase (Hipk) 2 expression in the embryonic and adult pancreas by in situ hybridization and RT-PCR. Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. We show that Hipk2 is expressed in the developing pancreatic epithelium from embryonic d 12-15 but that the expression becomes preferentially confined to pancreatic endocrine cells at later developmental stages. Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. Taken together, our data provide evidence for a new mechanism by which IPF1/PDX1 transcriptional activity, and thus possibly pancreas development and/or beta-cell function, is regulated.

  • 38. Brand, J. S.
    et al.
    Onland-Moret, N. C.
    Eijkemans, M. J. C.
    Tjonneland, A.
    Roswall, N.
    Overvad, K.
    Fagherazzi, G.
    Clavel-Chapelon, F.
    Dossus, L.
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg.
    Grote, V.
    Bergmann, M. M.
    Boeing, H.
    Trichopoulou, A.
    Tzivoglou, M.
    Trichopoulos, D.
    Grioni, S.
    Mattiello, A.
    Masala, G.
    Tumino, R.
    Vineis, P.
    Bueno-de-Mesquita, H. B.
    Weiderpass, E.
    Redondo, M. L.
    Sanchez, M. J.
    Castano, J. M. Huerta
    Arriola, L.
    Ardanaz, E.
    Duell, E. J.
    Rolandsson, O.
    Franks, P. W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Butt, S.
    Nilsson, P.
    Khaw, K. T.
    Wareham, N.
    Travis, R.
    Romieu, I.
    Gunter, M. J.
    Riboli, E.
    van der Schouw, Y. T.
    Diabetes and Onset of Natural Menopause: Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT2015In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 70, no 8, 507-508 p.Article in journal (Other academic)
    Abstract [en]

    The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and environmental factors, chronic metabolic diseases may influence ANM. Some evidence suggests that diabetes may accelerate menopausal onset. With more women of childbearing age receiving a diagnosis of diabetes, it is important to examine the impact of diabetes on reproductive health. This study was designed to determine whether ANM occurs at an earlier age among women who have diabetes before menopause than in women without diabetes. Data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large multicenter prospective cohort study investigating the relationship between diet, lifestyle, and genetic factors and the incidence of cancer and other chronic diseases. A cohort of 519,978 men and women, mostly aged 27 to 70 years, were recruited primarily from the general population between 1992 and 2000. A total of 367,331 women participated in the EPIC study. After exclusions, 258,898 of these women met study inclusion criteria. Diabetes status at baseline and menopausal age were based on self-report and were obtained through questionnaires. Participants were asked if they had ever been diagnosed with diabetes and if so at what age. Associations of diabetes and age at diabetes diagnosis with ANM were estimated using time-dependent Cox regression analyses, with stratification by center and adjustments for age, smoking, reproductive, and known diabetes risk factors including smoking and with age from birth to menopause or censoring as the underlying time scale. Overall, there was no statistically significant lower risk of becoming menopausal among women with diabetes than women with no diabetes; the hazard ratio (HR) was 0.94, with a 95% confidence interval (CI) of 0.89 to 1.01. However, compared with women with no diabetes, women with diabetes before the age of 20 years had an earlier menopause (10-20 years [HR, 1.43; 95% CI, 1.02-2.01] and <10 years [HR, 1.59; 95% CI, 1.03-2.43]), whereas women with diabetes at age 50 years or older had a later menopause (HR, 0.81; 95% CI, 0.70-0.95). No association with ANM was found for diabetes onset between the ages 20 and 50 years. Strengths of the study include its large sample size and the measurement of a broad set of potential confounders. However, there were several limitations. First, results may have been underestimated because of survival bias. Second, the sequence of menopause and diabetes in women with a late age at diabetes is uncertain, as both events occur in a short period, and both diabetes and menopause status were based on self-report, not verified by medical records. Third, no distinction was made between types 1 and 2 diabetes. Although there is no overall association between diabetes and age at menopause, the data suggest that early-onset diabetes may accelerate menopause. The delaying effect of late-onset diabetes on ANM is not in agreement with other studies suggesting the opposite association.

  • 39. Brand, Judith S.
    et al.
    van der Schouw, Yvonne T.
    Onland-Moret, N. Charlotte
    Sharp, Stephen J.
    Ong, Ken K.
    Khaw, Kay-Tee
    Ardanaz, Eva
    Amiano, Pilar
    Boeing, Heiner
    Chirlaque, Maria-Dolores
    Clavel-Chapelon, Francoise
    Crowe, Francesca L.
    de Lauzon-Guillain, Blandine
    Duell, Eric J.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Grioni, Sara
    Groop, Leif C.
    Kaaks, Rudolf
    Key, Timothy J.
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    Feskens, Edith J. M.
    Langenberg, Claudia
    Forouhi, Nita G.
    Riboli, Elio
    Wareham, Nicholas J.
    Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 4, 1012-1019 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.

    RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.

    RESULTS-Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and >= 55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [ 1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).

    CONCLUSIONS-Early menopause is associated with a greater risk of type 2 diabetes. Diabetes Care 36:1012-1019, 2013

  • 40.
    Brunström, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cardiovascular outcomes in the Da Qing Diabetes Prevention Study2014In: The Lancet Diabetes & Endocrinology, ISSN 2213-8587, Vol. 2, no 7, 539-540 p.Article in journal (Refereed)
  • 41.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Peter M
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blood pressure treatment levels and choice of antihypertensive agent in people with diabetes mellitus: an overview of systematic reviews2017In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 35, 435-462 p.Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVE: Multiple systematic reviews address the effect of antihypertensive treatment in people with diabetes. Here, we summarize current systematic reviews concerning antihypertensive treatment effect at different blood pressure (BP) levels, and relative treatment effect of different antihypertensive agents.

    METHODS: We searched MEDLINE, BIOSIS, DARE and CDSR during years 2005-2016. Eligibility criteria, number of trials and participants, outcomes analysed, statistical methods used for data synthesis, and principal results were extracted for each review. Review quality was assessed using the assessment of multiple systematic reviews tool.

    RESULTS: We found four reviews concerning BP treatment level. These consistently showed that the effect of antihypertensive treatment on mortality, cardiovascular disease and coronary heart disease was attenuated at lower BP levels. If SBP was more than 140 mmHg, treatment reduced all-cause and cardiovascular mortality, cardiovascular disease, stroke, myocardial infarction and heart failure. If SBP was less than 140 mmHg, treatment increased the risk of cardiovascular death. We found eight reviews concerning choice of agent. We found no difference between angiotensin-converting enzyme inhibitors, angotensin receptor blockers, beta-blockers, calcium channel blockers and diuretics in preventing all-cause or cardiovascular mortality, combined cardiovascular disease, coronary heart disease and end-stage renal disease. Minor differences exist for stroke and heart failure. Data were limited on people with type 1 diabetes and very elderly patients with type 2 diabetes. None of the reviews concerning choice of agent included all relevant trials.

    CONCLUSION: The available evidence supports treatment in people with type 2 diabetes and SBP more than 140 mmHg, using any of the major antihypertensive drug classes.

  • 42. Buijsse, B.
    et al.
    Boeing, H.
    Drogan, D.
    Schulze, M. B.
    Feskens, E. J.
    Amiano, P.
    Barricarte, A.
    Clavel-Chapelon, F.
    de Lauzon-Guillain, B.
    Fagherazzi, G.
    Fonseca-Nunes, A.
    Franks, Paul
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Huerta, J. M.
    Jakobsen, M. U.
    Kaaks, R.
    Key, T. J.
    Khaw, K. T.
    Masala, G.
    Moskal, A.
    Nilsson, P. M.
    Overvad, K.
    Pala, V.
    Panico, S.
    Redondo, M. L.
    Ricceri, F.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sanchez, M-J
    Sluijs, I.
    Spijkerman, A. M.
    Tjonneland, A.
    Tumino, R.
    van der A, D. L.
    van der Schouw, Y. T.
    Langenberg, C.
    Sharp, S. J.
    Forouhi, N. G.
    Riboli, E.
    Wareham, N. J.
    Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries2015In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 69, no 4, 455-461 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES:

    Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D.

    SUBJECTS/METHODS:

    A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12 403 incident T2D cases and a subcohort of 16 835 people, identified from a cohort of 340 234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis.

    RESULTS:

    After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D.

    CONCLUSIONS:

    Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.

  • 43. Burger, Koert NJ
    et al.
    Beulens, Joline WJ
    van der Schouw, Yvonne T
    Sluijs, Ivonne
    Spijkerman, Annemieke MW
    Sluik, Diewertje
    Boeing, Heiner
    Kaaks, Rudolf
    Teucher, Birgit
    Dethlefsen, Claus
    Overvad, Kim
    Tjonneland, Anne
    Kyro, Cecilie
    Barricarte, Aurelio
    Bendinelli, Benedetta
    Krogh, Vittorio
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Nilsson, Peter M
    Orho-Melander, Marju
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Maria Huerta, Jose
    Crowe, Francesca
    Allen, Naomi
    Noethlings, Ute
    Dietary fiber, carbohydrate quality and quantity, and mortality risk of individuals with diabetes mellitus2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 8, e43127- p.Article in journal (Refereed)
    Abstract [en]

    Background: Dietary fiber, carbohydrate quality and quantity are associated with mortality risk in the general population. Whether this is also the case among diabetes patients is unknown.Objective: To assess the associations of dietary fiber, glycemic load, glycemic index, carbohydrate, sugar, and starch intake with mortality risk in individuals with diabetes. Methods: This study was a prospective cohort study among 6,192 individuals with confirmed diabetes mellitus (mean age of 57.4 years, and median diabetes duration of 4.4 years at baseline) from the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline (1992-2000) with validated dietary questionnaires. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, while adjusting for CVD-related, diabetes-related, and nutritional factors. Results: During a median follow-up of 9.2 y, 791 deaths were recorded, 306 due to CVD. Dietary fiber was inversely associated with all-cause mortality risk (adjusted HR per SD increase, 0.83 [95% CI, 0.75-0.91]) and CVD mortality risk (0.76[0.64-0.89]). No significant associations were observed for glycemic load, glycemic index, carbohydrate, sugar, or starch. Glycemic load (1.42[1.07-1.88]), carbohydrate (1.67[1.18-2.37]) and sugar intake (1.53[1.12-2.09]) were associated with an increased total mortality risk among normal weight individuals (BMI <= 25 kg/m(2); 22% of study population) but not among overweight individuals (P interaction <= 0.04). These associations became stronger after exclusion of energy misreporters. Conclusions: High fiber intake was associated with a decreased mortality risk. High glycemic load, carbohydrate and sugar intake were associated with an increased mortality risk in normal weight individuals with diabetes.

  • 44. Burman, P.
    et al.
    Mattsson, A. F.
    Johannsson, G.
    Höybye, C.
    Holmer, H.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berinder, K.
    Engström, B. E.
    Ekman, B.
    Erfurth, E. M.
    Svensson, J
    Wahlberg, J.
    Karlsson, F. A.
    Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 4, 1466-1475 p.Article in journal (Refereed)
    Abstract [en]

    Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified.

    Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up.

    Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed.

    Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up.

    Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy.

    Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

  • 45. Campmans-Kuijpers, Marjo J. E.
    et al.
    Sluijs, Ivonne
    Noethlings, Ute
    Freisling, Heinz
    Overvad, Kim
    Weiderpass, Elisabete
    Fagherazzi, Guy
    Kuehn, Tilman
    Katzke, Verena A.
    Mattiello, Amalia
    Sonestedt, Emily
    Masala, Giovanna
    Agnoli, Claudia
    Tumino, Rosario
    Spijkerman, Annemieke M. W.
    Barricarte, Aurelio
    Ricceri, Fulvio
    Chamosa, Saioa
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Winkvist, Anna
    Tjonneland, Anne
    Sluik, Diewertje
    Boeing, Heiner
    Beulens, Joline W. J.
    Isocaloric substitution of carbohydrates with protein: the association with weight change and mortality among patients with type 2 diabetes2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, 39Article in journal (Refereed)
    Abstract [en]

    Background: The health impact of dietary replacement of carbohydrates with protein for patients with type 2 diabetes is still debated. This study aimed to investigate the association between dietary substitution of carbohydrates with (animal and plant) protein and 5-year weight change, and all-cause and cardiovascular (CVD) mortality risk in patients with type 2 diabetes.

    Methods: The study included 6,107 diabetes patients from 15 European cohorts. Patients with type 1 diabetes were excluded. At recruitment, validated country-specific food-frequency questionnaires were used to estimate dietary intake. Multivariable adjusted linear regression was used to examine the associations between dietary carbohydrate substitution with protein and 5-year weight change, and Cox regression to estimate hazard ratios (HRs) for (CVD) mortality.

    Results: Annual weight loss of patients with type 2 diabetes was 0.17 (SD 1.24) kg. After a mean follow-up of 9.2 (SD 2.3)y, 787 (13%) participants had died, of which 266 (4%) deaths were due to CVD. Substitution of 10 gram dietary carbohydrate with total (ß = 187 [75;299]g) and animal (ß = 196 [137;254]g) protein was associated with mean 5-year weight gain. Substitution for plant protein was not significantly associated with weight change (β = 82 [−421;584]g). Substitution with plant protein was associated with lower all-cause mortality risk (HR = 0.79 [0.64;0.97]), whereas substitution with total or animal protein was not associated with (CVD) mortality risk.

    Conclusions: In diabetes patients, substitution with plant protein was beneficial with respect to weight change and all-cause mortality as opposed to substitution with animal protein. Therefore, future research is needed whether dietary guidelines should not actively promote substitution of carbohydrates by total protein, but rather focus on substitution of carbohydrates with plant protein.

  • 46.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Proteinuria early in the development of hypertension2014In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, no 12, 2351-2352 p.Article in journal (Other academic)
  • 47. Carlsson, S
    et al.
    Andersson, T
    Araghi, M
    Galanti, R
    Lager, A
    Lundberg, M
    Nilsson, P
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Pedersen, N L
    Trolle-Lagerros, Y
    Magnusson, C
    Smokeless tobacco (snus) is associated with an increased risk of type 2 diabetes: results from five pooled cohorts2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 4, 398-406 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Smoking and nicotine exposure increase insulin resistance and the risk of type 2 diabetes. Swedish smokeless tobacco (snus) is high in nicotine, and its use is prevalent in Scandinavian countries, but few studies have investigated snus use in relation to diabetes risk.

    OBJECTIVE: To explore the association between snus use and risk of type 2 diabetes using pooled data from five cohorts.

    METHODS: Analyses were based on prospective studies conducted between 1990 and 2013 including 54 531 never-smoking men and 2441 incident cases of type 2 diabetes identified through screening, self-reporting and hospital and prescription registries. Hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed and adjusted for age, body mass index, educational level, alcohol consumption and physical activity.

    RESULTS: Compared to never users, the HR of type 2 diabetes was 1.15 (95% CI: 1.00-1.32) in current users of snus. In individuals consuming 5-6 boxes per week, the HR was 1.42 (95% CI: 1.07-1.87); in those consuming ≥7 boxes per week, the HR was 1.68 (95% CI: 1.17-2.41). Each additional box of snus consumed per week yielded an HR of 1.08 (95% CI: 1.01-1.16).

    CONCLUSION: Our findings indicate that high consumption of snus is a risk factor for type 2 diabetes. The risk was similar to that in smokers, implying that smokers will not reduce their risk of type 2 diabetes by changing to snus use. The results also support the notion that nicotine increases the risk of type 2 diabetes.

  • 48.
    Casar-Borota, Olivera
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Oslo University Hospital, University of Oslo and Uppsala University.
    Heck, Ansgar
    Schulz, Stefan
    Nesland, Jahn Marthin
    Ramm-Pettersen, Jon
    Lekva, Tove
    Alafuzoff, Irina
    Bollerslev, Jens
    Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in Somatotroph Adenomas Assessed by Monoclonal Antibodies Was Reduced by Octreotide and Correlated With the Acute and Long-Term Effects of Octreotide2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 11, E1730-E1739 p.Article in journal (Refereed)
    Abstract [en]

    Context: Reduced expression of somatostatin receptors (SSTRs) in somatotroph adenomas and their potential down-regulation after medical treatment may explain the unsatisfactory response to octreotide in particular acromegalic patients. The expression of SSTRs other than SSTR2a has not been studied in large, unselected cohorts using novel rabbit monoclonal antibodies. Objective: We aimed to determine the expression of SSTRs 1, 2a, 3, and 5 in somatotroph adenomas, to correlate expression with clinical characteristics and the response to octreotide, and to ascertain whether preoperative octreotide treatment affected SSTR expression. Design, Setting, Patients: The study included 78 adenomas from patients operated on consecutively during 2000 to 2010. After exclusion of 13 patients, immunohistochemical analysis with rabbit monoclonal antibodies against SSTRs 1, 2a, 3, and 5 (clones UMB-7, -1, -5, and -4) was performed on 65 adenomas. Intervention: Twenty-eight patients received preoperative octreotide, and 37 patients were operated on without pretreatment. Twenty-six patients were randomized to direct surgery (n = 13) or to octreotide pretreatment (n = 13). Main Outcome Measure: SSTR expression was evaluated using a 12-grade scoring system. The responses to the octreotide test dose (GH reduction) and to 6 months of octreotide (IGF-I reduction) were measured. Results: The majority of adenomas showed membranous expression of SSTRs 2a and 5. SSTR2a expression was reduced in the pretreated group and correlated with the acute octreotide test results and the effect of octreotide treatment. In a linear regression model with SSTR2 a expression as the determinant, the correlation with the acute test response improved after adjustment for medical pretreatment. Conclusion: Rabbit monoclonal antibodies are reliable markers of SSTRs in somatotroph adenomas. SSTR2a expression correlated with the response to octreotide and was reduced after octreotide treatment, indicating the need for adjustment when SSTR2a expression is correlated with baseline characteristics. Evaluation of SSTR subtypes may be an important aspect of improving the medical treatment for acromegaly.

  • 49. Chaplin, John E.
    et al.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jonsson, Bjorn
    Stenlid, Maria Halldin
    Aronson, A. Stefan
    Dahlgren, Jovanna
    Albertsson-Wikland, Kerstin
    When Do Short Children Realize They Are Short?: Prepubertal Short Children's Perception of Height during 24 Months of Catch-Up Growth Hormone Treatment2012In: Hormone Research in Paediatrics, ISSN 1663-2818, Vol. 77, no 4, 241-249 p.Article in journal (Refereed)
    Abstract [en]

    Aim: To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children. Methods: Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children's and parents' responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height. Results: Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother's height, parental sense of the child's tallness and age explained more variance in children's sense of tallness (34%) than measured height (0%). Conclusion: Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short.

  • 50. Chaplin, John Eric
    et al.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jonsson, Björn
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Tuvemo, Torsten
    Aronson, A Stefan
    Dahlgren, Jovanna
    Albertsson-Wikland, Kerstin
    Improvements in behaviour and self-esteem following growth hormone treatment in short prepubertal children2011In: Hormone research in paediatrics, ISSN 1663-2826, Vol. 75, no 4, 291-303 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: To evaluate effects of growth hormone (GH) treatment on behaviour and psychosocial characteristics in short-stature children.

    Methods: 99 referred prepubertal non-familiar short-stature children (32 GH deficiency; 67 idiopathic short stature) aged 3-11 years, randomized to fixed or individual GH doses and their parents completed questionnaires (Child Behaviour Checklist, Birleson Depression Self-Report Scale, Abbreviated Parent-Teacher Questionnaire, I Think I Am, Well-Being Visual-Analogue Scales for Short-Stature Children) at baseline (BL) and after 3, 12, and 24 months.

    Results: At BL, children showed higher levels of internalizing behaviour (p < 0.001), lower levels of externalizing behaviour (p < 0.006) and self-esteem (p < 0.001) compared to reference values. During GH treatment, behavioural measures (p < 0.001) and depression (p < 0.01) changed towards the mean of the population within the first 3 months and remained improved to 24 months. Self-esteem improved at all time points (p < 0.001), and in all subgroups, as did well-being dimensions stability and mood (p < 0.05). Multiple regression analysis showed that greater improvements were related to lower BL value, height gain, higher maximal GH value, being older, and being male.

    Conclusion: On GH treatment, prepubertal short children significantly improved on behavioural, depression, and psychosocial evaluations over a 2-year period of GH treatment. Most change occurred within the first 3 months, which highlights this short period as important not only for growth and metabolic changes but also for behaviour and psychosocial improvements following GH treatment.

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