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  • 301.
    Harvey, N. C.
    et al.
    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Oxford, England..
    Oden, A.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    Orwoll, E.
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, J.
    Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA..
    Kwok, T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, M.
    Lund Univ, Dept Orthopaed & Clin Sci, Skane Univ Hosp, Malmo, Sweden..
    Rosengren, B.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Cooper, C.
    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Oxford, England..
    Kanis, J. A.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    Ohlsson, C.
    Univ Gothenburg, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenberg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Johansson, H.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    McCloskey, E. V.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    Mobility Related Risk Factors Predict Incident Fractures Independently Of Frax: The Osteoporotic Fractures In Men (MROS) Study2017Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, s. S61-S61Artikel i tidskrift (Övrigt vetenskapligt)
  • 302.
    Harvey, N. C.
    et al.
    Univ Oxford, Musculoskeletal Epidemiol, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England..
    Oden, A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Orwoll, E.
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, J.
    Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA..
    Kwok, T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, M.
    Lund Univ, Dept Orthopaed & Clin Sci, Skane Univ Hosp, Malmo, Sweden..
    Rosengren, B.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Cooper, C.
    Univ Oxford, Musculoskeletal Epidemiol, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England..
    McCloskey, E.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Kanis, J. A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Ohlsson, C.
    Univ Gothenburg, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenberg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    Johansson, H.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    PRIOR FALLS PREDICT INCIDENT FRACTURES INDEPENDENTLY OF FRAX: The Osteoporotic Fractures In Men (MROS) Study2017Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, s. S259-S259Artikel i tidskrift (Övrigt vetenskapligt)
  • 303.
    Harvey, Nicholas C.
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England..
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA..
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, Magnus K.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Rosengren, Björn E.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.;Univ Oxford, NIHR Oxford Biomed Res Ctr, Oxford, England..
    McCloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Univ Sheffield, Ctr Integrated Res Musculoskeletal Ageing CIMA, Mellanby Ctr Bone Res, Sheffield, S Yorkshire, England..
    Kanis, John A.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Mellström, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Johansson, Helena
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia..
    Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 3, s. 510-516Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although prior falls are a well-established predictor of future fracture, there is currently limited evidence regarding the specific value of falls history in fracture risk assessment relative to that of other clinical risk factors and bone mineral density (BMD) measurement. We therefore investigated, across the three Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted future fracture independently of FRAX and whether these associations varied with age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong, and USA. Baseline data included falls history (over the preceding 12 months), clinical risk factors, BMD at femoral neck, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the associations between falls, FRAX probability, and incident fracture, adjusting for age, time since baseline, and cohort in base models; further models were used to investigate interactions with age and follow-up time. Random-effects meta-analysis was used to synthesize the individual country associations. Information on falls and FRAX probability was available for 4365 men in USA (mean age 73.5 years; mean follow-up 10.8 years), 1823 men in Sweden (mean age 75.4 years; mean follow-up 8.7 years), and 1669 men in Hong Kong (mean age 72.4 years; mean follow-up 9.8 years). Rates of past falls were similar at 20%, 16%, and 15%, respectively. Across all cohorts, past falls predicted incident fracture at any site (hazard ratio [HR]=1.69; 95% confidence interval [CI] 1.49, 1.90), major osteoporotic fracture (MOF) (HR=1.56; 95% CI 1.33, 1.83), and hip fracture (HR=1.61; 95% CI 1.27, 2.05). Relationships between past falls and incident fracture remained robust after adjustment for FRAX probability: adjusted HR (95% CI) any fracture: 1.63 (1.45, 1.83); MOF: 1.51 (1.32, 1.73); and hip: 1.54 (1.21, 1.95). In conclusion, past falls predicted incident fracture independently of FRAX probability, confirming the potential value of falls history in fracture risk assessment.

  • 304.
    Harvey, Nicholas
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants.
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland.
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland.
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong.; Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Lund.; Skåne Univ Hosp, Dept Orthoped, Lund.
    Rosengren, Bjorn
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Lund.; Skåne Univ Hosp, Dept Orthoped, Lund.
    Ljunggren, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants.
    Cawthon, Peggy
    Univ Calif, Dept Epidemiol & Biostat, Oakland.
    Kanis, John
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg.
    Johansson, Helena
    Catholic Univ Australia, Inst Hlth & Aging, Sydney, NSW.
    McCloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire.
    Measures of physical performance or function, but not appendicular lean mass, predict new fractures independently of FRAX probability: Findings from MrOS2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr S1, s. S30-S30, artikel-id Meeting Abstract: 1085Artikel i tidskrift (Övrigt vetenskapligt)
  • 305.
    Hawinkels, Lukas J A C
    et al.
    Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
    ten Dijke, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Exploring anti-TGF-β therapies in cancer and fibrosis2011Ingår i: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 29, nr 4, s. 140-152Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transforming growth factor-β (TGF-β) is a multifunctional cytokine, with important roles in maintaining tissue homeostasis. TGF-β signals via transmembrane serine/threonine kinase receptors and intracellular Smad transcriptional regulators. Perturbed TGF-β signaling has been implicated in a large variety of pathological conditions. Increased TGF-β levels have been found in patients with cancer, fibrosis, and systemic sclerosis, and were correlated with disease severity. In cancer, TGF-β mediates tumor invasion and metastasis by affecting both tumor cells and the tumor microenvironment including fibroblast activation and immune suppression. Furthermore, TGF-β is a strong stimulator of extracellular matrix deposition. On the basis of these observations, small molecule inhibitors of the TGF-β receptor kinases, neutralizing antibodies that interfere with ligand?receptor interactions, antisense oligonucleotides reducing TGF-β expression, and soluble receptor ectodomains that sequester TGF-β have been developed to intervene with excessive TGF-β signaling activity in the aforementioned disorders. Here, we review the current state of anti-TGF-β therapy in clinical trials.

  • 306.
    Heany, Sarah J.
    et al.
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa..
    van Honk, Jack
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa.;Univ Utrecht, Dept Psychol, Utrecht, Netherlands.;Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa..
    Stein, Dan J.
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa..
    Brooks, Samantha J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi. Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa..
    A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain2016Ingår i: Metabolic brain disease, ISSN 0885-7490, E-ISSN 1573-7365, Vol. 31, nr 1, s. 157-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.

  • 307.
    Heather, Natasha L.
    et al.
    Auckland Dist Hlth Board, Newborn Metab Screening Programme, LabPlus, Auckland, New Zealand;Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Derraik, Jose G. B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Webster, Dianne
    Auckland Dist Hlth Board, Newborn Metab Screening Programme, LabPlus, Auckland, New Zealand.
    Hofman, Paul L.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Auckland Dist Hlth Board, Starship Childrens Hosp, Auckland, New Zealand.
    The impact of demographic factors on newborn TSH levels and congenital hypothyroidism screening2019Ingår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 91, nr 3, s. 456-463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context

    Optimal newborn screening thyroid‐stimulating hormone (TSH) cut‐offs are contentious. Analysis of demographic factors that impact screen TSH levels may help explain international variance and provide guidance to screening programmes.

    Objective

    To determine the influence of demographic factors on newborn screening TSH levels and screening performance parameters.

    Design and Setting

    National, retrospective population study using blood spot TSH cards from the New Zealand newborn screening programme in 2010‐2015.

    Patients

    325 685 blood spot cards.

    Main Outcome Measures

    Likelihood of exceeding specific TSH thresholds (TSH ≥5, ≥10 and ≥15 mIU/L) and group‐specific screening performance parameters.

    Results

    The likelihood of high TSH levels differed between ethnic groups. Pacific Island infants were more than twice as likely to have high‐normal TSH levels (≥5 and ≥10 mIU/L) and nearly twice as likely to have a positive screen (≥15 mIU/L) as New Zealand Europeans. Māori or Chinese ethnicity, male sex, younger gestational age and greater socio‐economic deprivation scores were also associated with high‐normal TSH levels. At a TSH threshold ≥15 mIU/L, screening sensitivity was lowest (88.89% vs 95.83% overall) and PPV greatest (88.89% vs 62.84%) amongst Asian infants. Early samples were more than three times as likely to reach the screen‐positive threshold and more likely to yield a false‐positive result (PPV 20.00% vs 68.87%, P = 0.004).

    Conclusions

    Newborn TSH levels are impacted by a number of demographic variables, particularly ethnicity and age at sample collection. Screening performance may be improved through the use of targeted thresholds.

  • 308. Heck, Ansgar
    et al.
    Emblem, Kyrre E
    Casar-Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Bollerslev, Jens
    Ringstad, Geir
    Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly2016Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 52, nr 2, s. 333-343Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In growth hormone (GH)-producing adenomas, T2-weighted MRI signal intensity is a marker for granulation pattern and response to somatostatin analogs (SSA). Prediction of treatment response is necessary for individualized treatment, and T2 intensity assessment might improve preoperative classification of somatotropinomas. The objectives of this study are (I) to explore the feasibility of quantitative T2-weighted MRI histogram analyses in newly diagnosed somatotroph adenomas and their relation to clinical and histological parameters and (II) to compare the quantitative method to conventional, visual assessment of T2 intensity. The study was a retrospective cohort study of 58 newly diagnosed patients. In 34 of these, response to primary SSA treatment after median 6 months was evaluated. Parameters from the T2 histogram analyses (T2 intensity ratio and T2 homogeneity ratio) were correlated to visually assessed T2 intensity (hypo-, iso-, hyperintense), baseline characteristics, response to SSA treatment, and histological granulation pattern (anti-Cam5.2). T2 intensity ratio was lowest in the hypointense tumors and highest in the hyperintense tumors (0.66 ± 0.10 vs. 1.07 ± 0.11; p < 0.001). T2 intensity at baseline correlated with reduction in GH (r = -0.67; p < 0.001) and IGF-1 (r = -0.36; p = 0.037) after primary SSA treatment (n = 34). The T2 homogeneity ratio correlated with adenoma size reduction (r = -0.45; p = 0.008). Sparsely granulated adenomas had a higher T2 intensity than densely or intermediately granulated adenomas. T2 histogram analyses are an applicable tool to assess T2 intensity in somatotroph adenomas. Quantitatively assessed T2 intensity ratio in GH-producing adenomas correlates with conventional assessment of T2 intensity, baseline characteristics, response to SSA treatment, and histological granulation pattern.

  • 309. Heck, Ansgar
    et al.
    Emblem, Kyrre E
    Casar-Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Ringstad, Geir
    Bollerslev, Jens
    MRI T2 characteristics in somatotroph adenomas following somatostatin analog treatment in acromegaly2016Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 53, nr 1, s. 327-330Artikel i tidskrift (Refereegranskat)
  • 310. Hellgren, G.
    et al.
    Glad, C. A.
    Jonsson, B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Johannsson, G.
    Albertsson-Wikland, K.
    The growth hormone receptor exon 3-deleted/full-length polymorphism and response to growth hormone therapy in prepubertal idiopathic short children2015Ingår i: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 25, nr 3, s. 127-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The primary aim of the study was to evaluate d3-GHR as a possible cause of increased GH sensitivity in children with delayed infancy-childhood transition (DICT). The secondary aim was to investigate the impact of the GHR exon 3 deleted/full-length (d3/f1) polymorphism on GH treatment response in prepubertal children classified as having idiopathic short stature (ISS). Design: Study subjects included 167 prepubescent longitudinally followed children classified as having ISS. Children were randomized to standard-dose GH treatment (33 mu g kg(-1) day(-1)), to double-dose treatment (67 mu g kg(-1) day(-1)), or to an untreated control group. Growth and metabolic outcome were evaluated at birth (n = 166), after one year of treatment (n = 59) and at adult height (n = 145). Genotyping of the GHR d3/f1 polymorphism was performed using TaqMan SNP genotyping of tagSNP rs6873545. Results: Birth and early growth data did not reach the predetermined level of statistical significance for difference between genotypes. Growth and IGF-1 response after one year of GH treatment did not differ between genotypes. IGFBP-3(SDS) was higher in untreated d3-GHR carriers than in untreated fl/fl individuals, whereas there was insufficient evidence for higher IGFBP-3(SDS) in treated d3-GHR carriers. Genotype did not explain the growth response to treatment, and no differences in height(SDS), height gain, or difference in height to midparental height(SDS) between genotype groups were found at adult height. Conclusion: The common GHR d3/fl polymorphism is probably not a cause of DICT in children with ISS, and our results do not suggest that the d3-GHR genotype is associated with increased sensitivity to GH in children with ISS.

  • 311.
    Hellman, Bo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Dansk, Heléne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Grapengiesser, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Somatostatin promotes glucose generation of Ca2+ oscillations in pancreatic islets both in the absence and presence of tolbutamide2018Ingår i: Cell Calcium, ISSN 0143-4160, E-ISSN 1532-1991, Vol. 74, s. 35-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Many cellular processes, including pulsatile release of insulin, are triggered by increase of cytoplasmic Ca2+. This study examines how somatostatin affects glucose generation of cytoplasmic Ca2+ oscillations in mouse islets in absence and presence of tolbutamide blockade of the K-ATP channels. Ca2+ was measured with dual wavelength microflurometry in isolated islets loaded with the indicator Fura-2. Rise of glucose from 3 to 20 mM evoked introductory lowering of Ca2+ prolonged by activation of somatostatin receptors. During continued superfusion exposure to somatostatin triggered oscillations mediated by periodic increase from the basal level (absence of tolbutamide) or by periodic interruption of an elevated level (presence of tolbutamide). In the latter situation the oscillations were transformed into sustained elevation by activation of muscarinic receptors (acetylcholine) or increase of cyclic AMP (IBMX, 8-bromo-cyclic AMP, forskolin). The observed effect of cyclic AMP raises the question whether high proportions of the glucagon-producing alpha-cells promote steady-state elevation of Ca2+. In support for this idea somatostatin was found to trigger glucose-induced Ca2+ oscillations essentially in small islets that contain very few alpha-cells. The results indicate that somatostatin promotes glucose generation of Ca2+ oscillations with similar characteristics both in the absence and presence of functional K-ATP channels.

  • 312.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    GLP-1 analogue liraglutide as adjunct treatment in diabetes type 2 after failed bariatric/metabolic surgery2019Ingår i: Annals of Translational Medicine, ISSN 2305-5839, E-ISSN 2305-5847, Vol. 7, artikel-id S240Artikel i tidskrift (Övrigt vetenskapligt)
  • 313.
    Hellström-Lindahl, Ewa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Danielsson, Angelika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Czernichow, Paul
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    GPR44 is a pancreatic protein restricted to the human beta cell2016Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 53, nr 3, s. 413-421Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To address questions regarding onset and progression of types 1 and 2 diabetes (T1D/T2D), surrogate imaging biomarkers for beta cell function and mass are needed. Here, we assess the potential of GPR44 as a surrogate marker for beta cells, in a direct comparison with clinically used biomarker VMAT2.

    METHODS: GPR44 surface availability was assessed by flow cytometry of human beta cells. RNA transcription levels in different pancreas compartments were evaluated. The density of GPR44 receptor in endocrine and exocrine tissues was assessed by the radiolabeled GPR44 ligand [(3)H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [(3)H]DTBZ.

    RESULTS: GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [(3)H]AZD 3825 had nanomolar affinity for GPR44 in human islets and EndoC-βH1 beta cells, and the specific binding to human beta cells was close to 50 times higher than in exocrine preparations. The endocrine-to-exocrine binding ratio was approximately 10 times higher for [(3)H]AZD 3825 than for [(3)H]DTBZ.

    CONCLUSION: GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.

  • 314.
    Hellström-Lindahl, Ewa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Åberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Ericsson, Cecilia
    AstraZeneca R&D, SE-43150 Molndal, Sweden..
    O'Mahony, Gavin
    AstraZeneca R&D, SE-43150 Molndal, Sweden..
    Johnström, Peter
    Karolinska Inst, Karolinska Univ Hosp, AstraZeneca PET Sci Ctr, Personalised Healthcare & Biomarkers, SE-17176 Stockholm, Sweden..
    Skrtic, Stanko
    AstraZeneca R&D, SE-43150 Molndal, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, SE-41345 Gothenburg, Sweden..
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Toward molecular imaging of the free fatty acid receptor 12017Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 54, nr 7, s. 663-668Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([H-3]AZ1, [H-3]AZ2 and [H-3]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma. [H-3]AZ1 showed improved specificity to FFAR1, with decreased off-target binding compared to [H-3]AZ2 and [H-3]TAK-875, while retaining high affinity in the nanomolar range. FFAR1 density in human islets was approximately 50% higher than in exocrine tissue. AZ1 is a suitable lead compound for PET labeling for molecular imaging of FFAR1 in humans, due to high affinity and reduced off-target binding.

  • 315.
    Helte, Emilie
    et al.
    Karolinska Inst, Inst Environm Med, Unit Nutr & Cardiovasc Epidemiol, Stockholm, Sweden.
    Akesson, Agneta
    Karolinska Inst, Inst Environm Med, Unit Nutr & Cardiovasc Epidemiol, Stockholm, Sweden.
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Nutr & Cardiovasc Epidemiol, Stockholm, Sweden.
    Assessing Causality in Associations of Serum Calcium and Magnesium Levels With Heart Failure: A Two-Sample Mendelian Randomization Study2019Ingår i: Frontiers in Genetics, ISSN 1664-8021, E-ISSN 1664-8021, Vol. 10, artikel-id 1069Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence from observational studies suggests that increased exposure to calcium may increase the risk of coronary heart disease and stroke whereas magnesium might have a protective effect on disease risk. However, studies of the associations of these minerals with heart failure are scarce and limited by potential biases introduced by confounding and reverse causality. We applied a two-sample Mendelian randomization design using summary estimates to assess whether serum calcium and magnesium concentrations are causally associated with heart failure. Summary statistics data were collected for seven and six single-nucleotide polymorphisms associated with calcium and magnesium, respectively, from the hitherto largest genome-wide association studies on these minerals. Corresponding summary statistics for genetic associations with heart failure were available from publicly available data based on the UK Biobank study and based on participants of European ancestry. The findings showed that neither serum calcium nor magnesium concentrations were associated with heart failure. In the standard inverse-variance weighted analysis, the odds ratios of heart failure per genetically predicted one standard deviation increase in mineral concentrations were 0.89 (95% confidence interval 0.67-1.17; p = 0.41) for serum calcium and 0.89 (95% confidence interval 0.72-1.10; p = 0.28) for serum magnesium. Results were robust in sensitivity analyses, including the weighted median and Mendelian randomization Egger analyses. In conclusion, these findings do not support previous findings suggesting a link between serum calcium and magnesium and heart failure, but this study was underpowered to detect weak associations.

  • 316.
    Hering, Bernhard J.
    et al.
    Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN 55455 USA.;Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA..
    Clarke, William R.
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Bridges, Nancy D.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Eggerman, Thomas L.
    NIDDK, NIH, Bethesda, MD 20892 USA..
    Alejandro, Rodolfo
    Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA..
    Bellin, Melena D.
    Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN 55455 USA.;Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA..
    Chaloner, Kathryn
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Czarniecki, Christine W.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Goldstein, Julia S.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Hunsicker, Lawrence G.
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Kaufman, Dixon B.
    Univ Wisconsin, Dept Surg, Div Transplantat, Madison, WI USA..
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsen, Christian P.
    Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA..
    Luo, Xunrong
    Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA..
    Markmann, James F.
    Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA USA..
    Naji, Ali
    Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA..
    Oberholzer, Jose
    Univ Illinois Hosp & Hlth Sci Syst, Div Transplantat, Chicago, IL USA..
    Posselt, Andrew M.
    Univ Calif San Francisco, Dept Surg, San Francisco, CA USA..
    Rickels, Michael R.
    Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA..
    Ricordi, Camillo
    Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA..
    Robien, Mark A.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Senior, Peter A.
    Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada.;Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada..
    Shapiro, A. M. James
    Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada.;Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada..
    Stock, Peter G.
    Univ Calif San Francisco, Dept Surg, San Francisco, CA USA..
    Turgeon, Nicole A.
    Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA..
    Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia2016Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 39, nr 7, s. 1230-1240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA(1c) <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA(1c) level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.

  • 317.
    Herisson, F. M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi. Univ Waikato, Dept Biol Sci, Fac Sci & Engn, Private Bag 3105, Hamilton, New Zealand..
    Waas, J. R.
    Univ Waikato, Dept Biol Sci, Fac Sci & Engn, Private Bag 3105, Hamilton, New Zealand..
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Levine, A. S.
    Univ Minnesota, Dept Food Sci & Nutr, 1334 Eckles Ave, St Paul, MN USA..
    Olszewski, P. K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi. Univ Waikato, Dept Biol Sci, Fac Sci & Engn, Private Bag 3105, Hamilton, New Zealand.;Univ Minnesota, Dept Food Sci & Nutr, 1334 Eckles Ave, St Paul, MN USA..
    Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake2016Ingår i: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 28, nr 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting.

  • 318.
    Hero, C.
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Stockholm, Sweden..
    Ritsinger, V.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Cardiol Unit, Stockholm, Sweden.;Reg Kronoberg, Dept Res & Dev, Gothenburg, Sweden..
    Svensson, A. -M
    Saleh, N.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Norhammar, A.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Eeg-Olofsson, K.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Stockholm, Sweden..
    Gender aspects in type 1 diabetes patients undergoing angiography: a registry report2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S139-S139Artikel i tidskrift (Övrigt vetenskapligt)
  • 319. Herrera, Miguel F.
    et al.
    Åkerström, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Angelos, Peter
    Grant, Clive S.
    Hoff, Ana O.
    Pantoja, Juan Pablo
    Perez-Johnston, Rocio
    Sahani, Dushyant V.
    Wong, Richard J.
    Randolph, Gregory
    AACE/ACE DISEASE STATE CLINICAL REVIEW: PANCREATIC NEUROENDOCRINE INCIDENTALOMAS2015Ingår i: Endocrine Practice, ISSN 1530-891X, E-ISSN 1934-2403, Vol. 21, nr 5, s. 546-553Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Incidental detection of pancreatic neuroendocrine tumors (PNETs) has substantially increased over the last decade due to widespread use of advanced imaging studies. Reliable initial imaging-based characterization is crucial for the differential diagnosis from other exocrine neoplasms and to determine the appropriate management plan. Measurements of chromogranin A, pancreatic polypeptide, and calcitonin are recommended for the biochemical evaluation. A thorough medical history needs to be performed to rule out multiple endocrine neoplasia (MEN) type 1. The European Neuroendocrine Tumor Society (ENETS)/Tumor Node Metastasis (TNM) staging system together with a grading based on the Ki-67 proliferation index and mitotic counts has proven to give more appropriate prognostic information than the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) TNM staging but may still fail to safely differentiate benign from malignant lesions. Poorly differentiated PNETs generally present with metastases and are rarely amenable for resection. Well-or intermediately differentiated tumors >= 2 cm with imaging evidence of malignancy or with a Ki-67 > 2% should be resected. It has been suggested that non-MEN related, nonfunctioning, and asymptomatic PNETs < 2 cm with a Ki-67 index >= 2% carry a low risk of metastasis and may be observed in the absence of clinical or radiologic criteria of malignancy or progression, especially in older patients. However, because metastases may occur with long delay with smaller PNETS, physicians should consider patient age, lesion location, and the risks of operation, and patients not undergoing surgery need to be closely followed closely.

  • 320. Hesse, Bernhard
    et al.
    Varga, Peter
    Langer, Max
    Pacureanu, Alexandra
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Schrof, Susanne
    Maennicke, Nils
    Suhonen, Heikki
    Maurer, Peter
    Cloetens, Peter
    Peyrin, Francoise
    Raum, Kay
    Canalicular Network Morphology is the Major Determinant of the Spatial Distribution of Mass Density in Human Bone Tissue: Evidence by Means of Synchrotron Radiation Phase-Contrast nano-CT2015Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 30, nr 2, s. 346-356Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p<0.001) and canaliculi (p<0.001) is different from the mean matrix mass density, resulting in gradients with respect to the distance from both pore-matrix interfaces, which diminish with increasing tissue age. Though limited by the sample size, these findings support our hypotheses. Moreover, the density gradients are more pronounced around the lacunae than around the canaliculi, which are explained by geometrical considerations in the LCN morphology. In addition, we speculate that mineral exchange occurs at all interfaces of the LCN, not only in mineralization but also in mineral homeostasis.

  • 321.
    Hicks, Rodney J.
    et al.
    Peter MacCallum Canc Ctr, Canc Imaging & Neuroendocrine Serv, 305 Grattan St.
    Kwekkeboom, Dik J.
    Erasmus MC, ENETS Ctr Excellence Rotterdam, Div Nucl Med, Dept Internal Med.
    Krenning, Eric
    Erasmus MC, Cyclotron Rotterdam BV.
    Bodei, Lisa
    Mem Sloan Kettering Canc Ctr.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ, Med Ctr, Neuroendocrine Tumor Unit, Endocrinol & Metab Serv,Dept Med.
    Arnold, Rudolf
    Munich, Germany.
    Borbath, Ivan
    Clin Univ St Luc, Serv Gastroenterol.
    Cwikla, Jaroslaw
    Univ Warmia & Mazury, Dept Radiol, Fac Med Sci.
    Toumpanakis, Christos
    Royal Free Hosp, Neuroendocrine Tumour Unit.
    Kaltsas, Greg
    Natl Univ Athens, Div Endocrinol, Dept Pathophysiol.
    Davies, Philippa
    Royal Free Hosp, Neuroendocrine Tumour Unit.
    Hoersch, Dieter
    Gastroenterol & Endocrinol Ctr Neuroendocrine Tum.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Ramage, John
    Hampshire Hosp NHS Trust, Gastroenterol Dept, Basingstoke.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues2017Ingår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, nr 3, s. 295-309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of these guidelines is to assist physicians caring for patients with neuroendocrine neoplasia in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT) and in defining the minimum requirements for PRRT. It is not these guidelines' aim to give recommendations on the use of specific radiolabelled somatostatin analogues for PRRT as different analogues are being used, and their availability is governed by varying international regulations. However, a recent randomized controlled trial, NETTER-1, has provided evidence that may establish Lu-177-DOTA-octreotate (LutaThera (R)) as the first widely approved agent. It also makes recommendations on what minimal patient, tumour, and treatment outcome characteristics should be reported for PRRT to facilitate robust comparisons between studies.

  • 322. Hightower, C. Makena
    et al.
    Zhang, Kuixing
    Miramontes-Gonzalez, Jose P.
    Rao, Fangwen
    Wei, Zhiyun
    Schork, Andrew J.
    Nievergelt, Caroline M.
    Biswas, Nilima
    Mahata, Manjula
    Elkelis, Nina
    Taupenot, Laurent
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Ziegler, Michael G.
    O'Connor, Daniel T.
    Genetic variation at the delta-sarcoglycan (SGCD) locus elevates heritable sympathetic nerve activity in human twin pairs2013Ingår i: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 127, nr 6, s. 750-761Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Syrian Cardiomyopathic Hamster (BIO-14.6/53.58 strains) model of cardiac failure, resulting from naturally occurring deletion at the SGCD (delta-sarcoglycan) locus, displays widespread disturbances in catecholamine metabolism. Rare Mendelian myopathy disorders of human SGCD occur, although common naturally occurring SGCD genetic variation has not been evaluated for effects on human norepinephrine (NE) secretion. This study investigated the effect of SGCD genetic variation on control of NE secretion in healthy twin pairs. Genetic associations profiled SNPs across the SGCD locus. Trait heritability (h(2)) and genetic covariance (pleiotropy; shared h(2)) were evaluated. Sympathochromaffin exocytosis in vivo was probed in plasma by both catecholamines and Chromogranin B (CHGB). Plasma NE is substantially heritable (p=3.19E-16, at 65.2 +/- 5.0% of trait variance), sharing significant (p<0.05) genetic determination with circulating and urinary catecholamines, CHGB, eGFR, and several cardio-metabolic traits. Participants with higher pNE showed significant (p<0.05) differences in several traits, including increased BP and hypertension risk factors. Peak SGCD variant rs1835919 predicted elevated systemic vascular compliance, without changes in specifically myocardial traits. We used a chimeric-regulated secretory pathway photoprotein (CHGA-EAP) to evaluate the effect of SGCD on the exocytotic pathway in transfected PC12 cells; in transfected cells, expression of SGCD augmented CHGA trafficking into the exocytotic regulated secretory pathway. Thus, our investigation determined human NE secretion to be a highly heritable trait, influenced by common genetic variation within the SGCD locus. Circulating NE aggregates with BP and hypertension risk factors. In addition, coordinate NE and CHGB elevation by rs1835919 implicates exocytosis as the mechanism of release.

  • 323.
    Hilden, K.
    et al.
    Univ Orebro, Sch Hlth & Med Sci, Dept Obstet & Gynaecol, Orebro, Sweden..
    Hanson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Univ Orebro, Sch Hlth & Med Sci, Dept Obstet & Gynaecol, Orebro, Sweden.
    Persson, M.
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden..
    Fadl, H.
    Univ Orebro, Sch Hlth & Med Sci, Dept Obstet & Gynaecol, Orebro, Sweden..
    Overweight and obesity: a remaining problem in women treated for severe gestational diabetes2016Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, nr 8, s. 1045-1051Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To analyse the impact of overweight and obesity on the risk of adverse maternal outcomes and fetal macrosomia in pregnancies of women treated for severe gestational diabetes.

    Methods: This was a population-based cohort study including all singleton pregnancies in Sweden without pre-existing diabetes in the period 1998-2012. Only mothers with an early-pregnancy BMI of >= 18.5 kg/m(2) were included. Logistic regression analysis was used to determine odds ratios with 95% CIs for maternal outcomes and fetal growth. Analyses were stratified by maternal gestational diabetes/non-gestational diabetes to investigate the impact of overweight/obesity in each group.

    Results: Of 1 249 908 singleton births, 13 057 were diagnosed with gestational diabetes (1.0%). Overweight/obesity had the same impact on the risks of caesarean section and fetal macrosomia in pregnancies with and without gestational diabetes, but the impact of maternal BMI on the risk of preeclampsia was less pronounced in women with gestational diabetes. Normal-weight women with gestational diabetes had an increased risk of caesarean section [odds ratio 1.26 (95% CI 1.16-1.37)], preeclampsia [odds ratio 2.03 (95% CI 1.71-2.41)] and large-for-gestational-age infants [odds ratio 2.25 (95% CI 2.06-2.46)]. Risks were similar in the overweight group without gestational diabetes, caesarean section [odds ratio 1.34 (1.33-1.36)], preeclampsia odds ratio [1.76 (95% CI 1.72-1.81)], large-for-gestational-age [odds ratio 1.76 (95% CI 1.74-1.79)].

    Conclusions: Maternal overweight and obesity is associated with similar increments in risks of adverse maternal outcomes and delivery of large-for-gestational-age infants in women with and without gestational diabetes. Obese women with gestational diabetes are defined as a high-risk group. Normal-weight women with gestational diabetes have similar risks of adverse outcomes to overweight women without gestational diabetes.

  • 324.
    Hilden, K.
    et al.
    Orebro Univ, Sch Med Sci, Dept Obstet & Gynaecol, Orebro, Sweden.
    Hanson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Orebro Univ, Sch Med Sci, Orebro, Sweden.
    Persson, M.
    Karolinska Univ Sjukhuset, Dept Med, Clin Epidemiol Unit, Solna, Sweden.
    Magnuson, A.
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden.
    Simmons, D.
    Orebro Univ, Sch Med Sci, Orebro, Sweden;Western Sydney Univ, Sch Med, Campbelltown, NSW, Australia.
    Fadl, H.
    Orebro Univ, Sch Med Sci, Dept Obstet & Gynaecol, Orebro, Sweden.
    Gestational diabetes and adiposity are independent risk factors for perinatal outcomes: a population based cohort study in Sweden2019Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 36, nr 2, s. 151-157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims To evaluate the interaction effects of gestational diabetes (GDM) with obesity on perinatal outcomes. Methods A population-based cohort study in Sweden excluding women without pre-gestational diabetes with a singleton birth between 1998 and 2012. Logistic regression was performed to evaluate the potential independent associations of GDM and BMI with adverse perinatal outcomes as well as their interactions. Main outcome measures were malformations, stillbirths, perinatal mortality, low Apgar score, fetal distress, prematurity and Erb's palsy. Results Some 1,294,006 women were included, with a GDM prevalence of 1% (n = 14,833). The rate of overweight/obesity was 67.7% in the GDM-group and 36.1% in the non-GDM-group. No significant interaction existed. Offspring of women with GDM had significantly increased risk of malformations, adjusted odds ratio (aOR) 1.16 (95% confidence intervals 1.06-1.26), prematurity, aOR 1.86 (1.76-1. 98), low Apgar score, aOR 1.36 (1.10-1.70), fetal distress, aOR 1.09 (1.02-1.16) and Erb's palsy aOR 2.26 (1.79-2.86). No risk for stillbirth or perinatal mortality was seen. Offspring of overweight (BMI 25-29.9 kg/m(2)), obese (BMI 30-34.9 kg/m(2)) and severely obese women (BMI >= 35.0 kg/m(2)) had significantly increased risks of all outcomes including stillbirth 1.51 (1.40-1.62) to 2.85 (2.52-3.22) and perinatal mortality 1.49 (1.40-1.59) to 2.83 (2.54-3.15). Conclusions There is no interaction effect between GDM and BMI for the studied outcomes. Higher BMI and GDM are major independent risk factors for most serious adverse perinatal outcomes. More effective pre-pregnancy and antenatal interventions are required to prevent serious adverse pregnancy outcomes among women with either GDM or high BMI.

  • 325.
    Hill, Tom R.
    et al.
    Newcastle Univ, Human Nutr Res Ctr, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Verlaan, Sjors
    Nutricia Adv Med Nutr, Danone Nutricia Res, Utrecht, Netherlands; Amsterdam UMC, Dept Internal Med, Sect Gerontol & Geriatr, Amsterdam, Netherlands.
    Biesheuvel, Egbert
    Nutricia Adv Med Nutr, Danone Nutricia Res, Utrecht, Netherlands.
    Eastell, Richard
    Univ Sheffield, Northern Gen Hosp, Metab Bone Ctr, Acad Unit Bone Metab, Sheffield, S Yorkshire, England.
    Bauer, Juergen M.
    Carl von Ossietzky Univ Oldenburg, Dept Geriatr Med, Oldenburg, Germany.
    Bautmans, Ivan
    Vrije Univ Brussel VUB, Frailty Ageing Res Grp FRIA, Brussels, Belgium.
    Brandt, Kirsten
    Newcastle Univ, Human Nutr Res Ctr, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Donini, Lorenzo M.
    Sapienza Univ Rome, Dept Expt Med, Sect Med Pathophysiol Endocrinol & Human Nutr, Rome, Italy.
    Maggio, Marcello
    Univ Parma, Sect Geriatr, Dept Clin & Expt Med, Parma, Italy.
    Mets, Tony
    Vrije Univ Brussel VUB, Frailty Ageing Res Grp FRIA, Brussels, Belgium.
    Seal, Chris J.
    Newcastle Univ, Human Nutr Res Ctr, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Wijers, Sander L. J.
    Nutricia Adv Med Nutr, Danone Nutricia Res, Utrecht, Netherlands.
    Sieber, Cornel
    Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Ageing, Erlangen, Germany.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Aspray, Terry J.
    Newcastle Univ, Freeman Hosp, Bone Clin, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study2019Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 105, nr 4, s. 383-391Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

  • 326.
    Hjort, R.
    et al.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden..
    Alfredsson, L.
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Andersson, T.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Grill, V.
    Norwegian Univ Sci & Technol, NTNU Inst Canc Res & Mol Med, Trondheim, Norway.;Trondheim Reg & Univ Hosp, Dept Endocrinol, Trondheim, Norway..
    Groop, L.
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Rasouli, B.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden..
    Storm, P.
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Div Endocrinol, Abdominal Ctr, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland.;Helsinki Univ Hosp, Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, S.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden..
    Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)2017Ingår i: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 43, nr 6, s. 536-542Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. - A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods. - Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age < 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. Results. - Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-Tl D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576). Conclusion. - The risk of LADA is substantially increased with FHD-Tl D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-Tl D had more T1D-like features, emphasizing the heterogeneity of LADA. (C) 2017 Elsevier Masson SAS. All rights reserved.

  • 327. Hjort, R.
    et al.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Dorkhan, M.
    Groop, L.
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Rasouli, B.
    Toumi, T.
    Carlsson, S.
    Low birth weight is associated with an increased risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes: results from ESTRID a Swedish case-control study2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr S1, s. S80-S80Artikel i tidskrift (Övrigt vetenskapligt)
  • 328.
    Hjort, R.
    et al.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Lofvenborg, J. E.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Ahlqvist, E.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Alfredsson, L.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Andersson, T.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Groop, L.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Rasouli, B.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Rosengren, A.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Res Program Diabet & Obes, Div Endocrinol,Abdominal Ctr, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, S.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Overweight, obesity, genetic susceptibility and the risk of LADA: Latent Autoimmune Diabetes in Adults2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, nr S1, s. S118-S118, artikel-id 252Artikel i tidskrift (Övrigt vetenskapligt)
  • 329.
    Hjort, Rebecka
    et al.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Box 210, S-17177 Stockholm, Sweden.
    Ahlqvist, Emma
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Grill, Valdemar
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, NTNU, Trondheim, Norway;Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Endocrinol, Trondheim, Norway.
    Groop, Leif
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Rasouli, Bahareh
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Box 210, S-17177 Stockholm, Sweden.
    Rosengren, Anders
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden.
    Tuomi, Tiinamaija
    Univ Helsinki, Helsinki Univ Hosp, Div Endocrinol, Abdominal Ctr,Res Program Diabet & Obes, Helsinki, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Asvold, Bjorn Olav
    Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Endocrinol, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, KG Jebsen Ctr Genet Epidemiol, NTNU, Trondheim, Norway.
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Box 210, S-17177 Stockholm, Sweden.
    Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 6, s. 1333-1343Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies. Methods Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case-control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984-2008). We present adjusted ORs and HRs with 95% CI. Results In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD. Conclusions/interpretation Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

  • 330.
    Hjort, Rebecka
    et al.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden..
    Alfredsson, Lars
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, S-17177 Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Groop, Leif
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Storm, Petter
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Tuomi, Tiinamaija
    Helsinki Univ Hosp, Div Endocrinol, Abdominal Ctr, Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden..
    Low birthweight is associated with an increased risk of LADA and type 2 diabetes: results from a Swedish case-control study2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr 11, s. 2525-2532Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis Our aim was to investigate the association between birthweight and latent autoimmune diabetes in adults (LADA), a common diabetes form with features of both type 1 and type 2 diabetes. Methods We used data from the Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes (ESTRID), a Swedish population-based study. Eligible for the analysis were 134 incident LADA cases (glutamic acid decarboxylase antibody [GADA] positive), 350 incident type 2 diabetes cases (GADA negative) and 603 randomly selected controls. We present ORs and 95% CIs for LADA and type 2 diabetes in relation to birthweight, adjusted for sex, age, BMI and family history of diabetes. Results Low birthweight increased the risk of LADA as well as the risk of type 2 diabetes; OR per kg reduction was estimated as 1.52 (95% CI 1.12, 2.08) and 1.58 (1.23, 2.04), respectively. The OR for participants weighing < 3 kg compared with >= 4 kg at birth was estimated as 2.38 (1.23, 4.60) for LADA and 2.37 (1.37, 4.10) for type 2 diabetes. A combination of low birthweight (< 3 kg) and current overweight (BMI >= 25) further augmented the risk: LADA, OR 3.26 (1.69, 6.29); and type 2 diabetes, OR 39.93 (19.27, 82.71). Family history of diabetes had little impact on these estimates. Conclusions/interpretation Our results suggest that low birthweight may be a risk factor for LADA of the same strength as for type 2 diabetes. These findings support LADA, despite its autoimmune component, having an aetiology that includes factors related to type 2 diabetes.

  • 331.
    Hodik, Monika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Skog, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lukinius, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Isaza-Correa, J. M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands..
    Kuipers, J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands..
    Giepmans, B. N. G.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands..
    Frisk, Gun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Enterovirus infection of human islets of Langerhans affects beta-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure2016Ingår i: BMJ OPEN DIABETES RESEARCH & CARE, ISSN 2052-4897, Vol. 4, nr 1, artikel-id e000179Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: In type 1 diabetes (T1D), most insulin-producing beta cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus replication on cellular macromolecules and organelles involved in insulin secretion. Methods: Isolated human islets were infected with different strains of coxsackievirus B (CVB) virus and the glucose-stimulated insulin release (GSIS) was measured in a dynamic perifusion system. Classical morphological electron microscopy, large-scale electron microscopy, so-called nanotomy, and immunohistochemistry were used to study to what extent virus-infected beta cells contained insulin, and real-time PCR was used to analyze virus induced changes of islet specific genes. Results: In islets infected with CVB, GSIS was reduced in correlation with the degree of virus-induced islet disintegration. The expression of the gene encoding insulin was decreased in infected islets, whereas the expression of glucagon was not affected. Also, in islets that were somewhat disintegrated, there were uninfected beta cells. Ultrastructural analysis revealed that virus particles and virus replication complexes were only present in beta cells. There was a significant number of insulin granules remaining in the virus-infected beta cells, despite decreased expression of insulin mRNA. In addition, no typical Golgi apparatus was detected in these cells. Exposure of islets to synthetic dsRNA potentiated glucose-stimulated insulin secretion. Conclusions/interpretation: Glucose-stimulated insulin secretion; organelles involved in insulin secretion and gene expression were all affected by CVB replication in beta cells.

  • 332.
    Hogenkamp, Pleunie S.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Zhou, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Dahlberg, Linda Solstrand
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Stark, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Larsen, A. L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Olivo, Gaia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Wiemerslage, Lyle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Benedict, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake2016Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, nr 11, s. 1687-1692Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied.

    OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI).

    METHODS: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m(-)(2)) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m(-)(2)), both before and 30 min after consumption of a standardized meal (~260 kcal).

    RESULTS: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups.

    CONCLUSION: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.International Journal of Obesity advance online publication, 28 June 2016; doi:10.1038/ijo.2016.105.

  • 333.
    Holmlund-Suila, Elisa
    et al.
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Viljakainen, Heli
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Hytinantti, Timo
    Helsinki Matern Hosp, Helsinki, Finland..
    Andersson, Sture
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Makitie, Outi
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden..
    Fibroblast Growth Factor 23 Concentrations Reflect Sex Differences in Mineral Metabolism and Growth in Early Infancy2016Ingår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 85, nr 4, s. 232-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The role of fibroblast growth factor 23 (FGF23) in the regulation of mineral homeostasis in early life is inadequately understood. We aimed to explore the effects of vitamin D supplementation on serum FGF23 and to elucidate longitudinal changes in FGF23, in addition to studying its association with mineral metabolism in early infancy. Methods: Altogether 113 healthy infants received vitamin D 3 10, 30 or 40 mu g/day from age 0.5 to 3.0 months. Cord blood at birth and capillary blood samples at 3 months were analyzed for serum 25-hydroxyvitamin D, parathyroid hormone, phosphate, calcium and intact and C-terminal FGF23. Results: In repeated-measures ANCOVA, intact FGF23 concentration increased with time (p < 0.001) and C-terminal FGF23 decreased (p < 0.001). At 3 months, girls had a higher concentration of intact FGF23 (51 vs. 26 pg/ml, p < 0.001) and a greater increase over time (Delta FGF23 intact 45 vs. 16 pg/ml, p = 0.001) than boys. Vitamin D did not affect serum intact or C-terminal FGF23 concentrations. Girls showed a positive correlation between phosphate and intact FGF23 (p = 0.004), whereas in boys phosphate and C-terminal FGF23 correlated inversely (p = 0.006). Conclusions: A substantial sex-related difference in intact FGF23 concentration exists during early infancy, possibly related to differences in skeletal growth between boys and girls. (C) 2016 S. Karger AG, Basel

  • 334. Hong, N-S
    et al.
    Kim, K-S
    Lee, I-K
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jacobs, D R
    Lee, D-H
    The association between obesity and mortality in the elderly differs by serum concentrations of persistent organic pollutants: a possible explanation for the obesity paradox2011Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, nr 9, s. 1170-1175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Numerous studies have documented an obesity paradox in which the overweight and obese elderly have a better prognosis than those with ideal body weight. Good prognosis among the overweight or obese elderly may reflect the relative safety of storing the harmful lipophilic chemicals, known as persistent organic pollutants (POPs), in adipose tissue rather than in other critical organs. Therefore, we hypothesized lower mortality among the obese elderly with a higher body burden of POPs, but this pattern may not exist among the obese elderly with a lower body burden of POPs.

    PARTICIPANTS: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2004 study with a mean 4.2-year follow-up, we tested whether the association between fat mass and total mortality in 635 (652 for organochlorine pesticides) elderly participants aged >= 70 years differed depending on serum concentrations of 23 POPs.

    RESULTS: There were statistically significant interactions between fat mass and POPs in predicting total mortality. In those with low POP concentrations, there was no obesity paradox; mortality increased with fat mass (hazard ratios about 2-3 in the highest vs lowest quintile of fat mass). However, consistent with an obesity paradox, these patterns completely disappeared in those with high POP concentrations. Compared with the lowest quintile of fat mass, statistically significantly lower mortality was observed in the elderly in the third to fifth quintiles of fat mass. In the case of polychlorinated biphenyls, the mortality in the highest quintile of fat mass was only one-fifth of that in the lowest quintile.

    CONCLUSION: These findings are consistent with our hypothesis that adipose tissue provides relatively safe storage of toxic lipophilic chemicals, a phenomenon that could explain the obesity paradox. Although weight loss may be beneficial among the obese elderly with low POP concentrations, weight loss in the obese elderly with higher serum concentrations of POPs may carry some risk.

  • 335.
    Hopfgarten, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Stenwall, Per-Anton
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Wiberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Anagandula, Mahesh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Ingvast, Sofie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Rosenling, Therese
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Skog, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Gene expression analysis of human islets in a subject at onset of type 1 diabetes2014Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 51, nr 2, s. 199-204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Swollen islet cells have been repeatedly described at onset of type 1 diabetes, but the underlying mechanism of this observation, termed hydropic degeneration, awaits characterization. In this study, laser capture microdissection was applied to extract the islets from an organ donor that died at onset of type 1 diabetes and from an organ donor without pancreatic disease. Morphologic analysis revealed extensive hydropic degeneration in 73 % of the islets from the donor with type 1 diabetes. Expression levels of genes involved in apoptosis, ER stress, beta cell function, and inflammation were analyzed in isolated and laser-captured islets by qPCR. The chemokine MCP-1 was expressed in islets from the donor with type 1 diabetes while undetectable in the control donor. No other signs of inflammation were detected. There were no signs of apoptosis on the gene expression level, which was also confirmed by negative immunostaining for cleaved caspase-8. There was an increased expression of the transcription factor ATF4, involved in transcription of ER stress genes, in the diabetic islets, but no further signs of ER stress were identified. In summary, on the transcription level, islets at onset of type 1 diabetes in which many beta cells display hydropic degeneration show no obvious signs of apoptosis, ER stress, or inflammation, supporting the notion that these cells are responding normally to high glucose and eventually succumbing to beta cell exhaustion. Also, this study validates the feasibility of performing qPCR analysis of RNA extracted from islets from subjects with recent onset of T1D and healthy controls by laser capture microdissection.

  • 336.
    Hrsch, D.
    et al.
    Zent Klin Bad Berka, Bad Berka, Germany..
    Kulke, M.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Caplin, M.
    Royal Free Hosp, London, England..
    Anthony, L.
    Univ Kentucky, Lexington, KY 40506 USA..
    Bergsland, E.
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Warner, R.
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA..
    Lombard-Bohas, C.
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France..
    Kunz, P.
    Stanford Univ, Palo Alto, CA 94304 USA..
    Valle, J.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England..
    Fleming, D.
    Ipsen BioSci, Cambridge, MA USA..
    Lapuerta, P.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Banks, P.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Pavel, M.
    Charite, Berlin, Germany..
    Efficacy and Safety of Telotristat Etiprate in Patients with Carcinoid Syndrome Not Adequately Controlled by Somatostatin Analog Therapy: Analysis of the Ongoing TELESTAR Extension Period2016Ingår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, s. 88-88Artikel i tidskrift (Refereegranskat)
  • 337. Huang, Xiaoyan
    et al.
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lindholm, Bengt
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Carrero, Juan Jesús
    Serum and adipose tissue fatty acid composition as biomarkers of habitual dietary fat intake in elderly men with chronic kidney disease2014Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 1, s. 128-136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Fatty acid (FA) composition in serum cholesterol esters (CE) and adipose tissue (AT) reflect the long-term FA intake in the general population. Because both dietary intake and FA biomarkers associate with renal function, our aim was to identify which CE and AT FAs are useful biomarkers of habitual FA intake in individuals with chronic kidney disease (CKD).

    Methods

    Cross-sectional analysis was performed in 506 men (aged 70 years) with a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2) from the Uppsala Longitudinal Study of Adult Men cohort. Dietary habits were evaluated with a 7-day dietary record. FA compositions in CE and AT were analyzed by gas-liquid chromatography in two random subsamples of 248 and 318 individuals, respectively.

    Results

    Both CE and AT linoleic acid and docosahexaenoic acid (DHA) were strongly associated with their corresponding intake, after adjustments for non-dietary factors. The proportions of eicosapentaenoic acid (EPA) and palmitic acid in CE and AT moderately correlated with dietary intake, whereas correlations of other FAs were weaker or absent. Proportions of EPA and DHA in CE and AT were positively associated with the total energy-adjusted fish intake. Results were confirmed in adequate reporters as identified by the Goldberg cutoff method. These relationships held constant, regardless of a GFR above or below 45 mL/min per 1.73 m(2) or the prevalence of microalbuminuria.

    Conclusions

    Proportions of EPA, DHA, palmitic and linoleic acid in serum CE and AT are good indicators of their dietary intake in men with CKD. They can be considered valid biomarkers for epidemiological studies and assessment of compliance.

  • 338.
    Husdal, Rebecka
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Karlsson, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eliasson, Björn
    Jansson, Stefan
    Jerden, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Steen, Lars
    Wallman, Thorne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Svensson, Ann-Marie
    Thors Adolfsson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Resources and organisation in primary health care are associated with HbA1c level: A nationwide study of 230958 people with Type 2 diabetes mellitus.2018Ingår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 12, nr 1, s. 23-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To examine the association between personnel resources and organisational features of primary health care centres (PHCCs) and individual HbA1c level in people with Type 2 diabetes mellitus (T2DM).

    METHODS: People with T2DM attending 846 PHCCs (n=230958) were included in this cross-sectional study based on PHCC-level data from a questionnaire sent to PHCCs in 2013 and individual-level clinical data from 2013 for people with T2DM reported in the Swedish National Diabetes Register, linked to individual-level data on socio-economic status and comorbidities. Data were analysed using a generalized estimating equations linear regression models.

    RESULTS: After adjusting for PHCC- and individual-level confounding factors, personnel resources associated with lower individual HbA1c level were mean credits of diabetes-specific education among registered nurses (RNs) (-0.02mmol/mol for each additional credit; P<0.001) and length of regular visits to RNs (-0.19mmol/mol for each additional 15min; P<0.001). Organisational features associated with HbA1c level were having a diabetes team (-0.18mmol/mol; P<0.01) and providing group education (-0.20mmol/mol; P<0.01).

    CONCLUSIONS: In this large sample, PHCC personnel resources and organisational features were associated with lower HbA1c level in people with T2DM.

  • 339.
    Husdal, Rebecka
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Rosenblad, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eliasson, Björn
    Jansson, Stefan
    Jerdén, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Steen, Lars
    Wallman, Thorne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Adolfsson, Eva Thors
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Resource allocation and organisational features in Swedish primary diabetes care: Changes from 2006 to 20132017Ingår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 11, nr 1, s. 20-28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To compare the resource allocation and organisational features in Swedish primary diabetes care for patients with type 2 diabetes mellitus (T2DM) between 2006 and 2013.

    METHODS: Using a repeated cross-sectional study design, questionnaires covering personnel resources and organisational features for patients with T2DM in 2006 and 2013 were sent to all Swedish primary health care centres (PHCCs) during the following year. In total, 684 (74.3%) PHCCs responded in 2006 and 880 (76.4%) in 2013.

    RESULTS: Compared with 2006, the median list size had decreased in 2013 (p<0.001), whereas the median number of listed patients with T2DM had increased (p<0.001). Time devoted to patients with T2DM and diabetes-specific education levels for registered nurses (RNs) had increased, and more PHCCs had in-house psychologists (all p<0.001). The use of follow-up systems and medical check-ups had increased (all p<0.05). Individual counselling was more often based on patients' needs, while arrangement of group-based education remained low. Patient participation in setting treatment targets mainly remained low.

    CONCLUSIONS: Even though the diabetes-specific educational level among RNs increased, the arrangement of group-based education and patient participation in setting treatment targets remained low. These results are of concern and should be prioritised as key features in the care of patients with T2DM.

  • 340.
    Husdal, Rebecka
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Rosenblad, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden..
    Thors Adolfsson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Hosp Vastmanland, Dept Primary Hlth Care, Reg Vastmanland, Vasteras, Sweden..
    Organisation of diabetes care is associated with systolic blood pressure level: a cross-sectional study of 230,958 people with type 2 diabetes2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, nr S1, s. S298-S299, artikel-id 657Artikel i tidskrift (Övrigt vetenskapligt)
  • 341.
    Husdal, Rebecka
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Thors Adolfsson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Eliasson, Björn
    Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.
    Jansson, Stefan
    Örebro Univ, Univ Hlth Care Res Ctr, Sch Med Sci, Örebro, Sweden.
    Jerdén, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Steen, Lars
    Sörmland Cty Council, Drug & Therapeut Comm, Eskilstuna, Sweden.
    Wallman, Thorne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Svensson, Ann-Marie
    Natl Diabet Register, Ctr Registers, Gothenburg, Sweden.
    Rosenblad, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Associations between quality of work features in primary health care and glycaemic control in people with Type 2 diabetes mellitus: A nationwide survey.2019Ingår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 13, nr 2, s. 176-186, artikel-id S1751-9918(18)30277-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: To describe and analyse the associations between primary health care centres’ (PHCCs’) quality of work (QOW) and individual HbA1c levels in people with Type 2 diabetes mellitus (T2DM).

    Methods: This cross-sectional study invited all 1152 Swedish PHCCs to answer a questionnaire addressing QOW conditions. Clinical, socio-economic and comorbidity data for 230,958 people with T2DM were linked to data on QOW conditions for 846 (73.4%) PHCCs.

    Results: Of the participants, 56% had controlled (≤52 mmol/mol), 31.9% intermediate (53–69 mmol/mol), and 12.1% uncontrolled (≥70 mmol/mol) HbA1c. An explanatory factor analysis identified seven QOW features. The features having a call-recall system, having individualized treatment plans, PHCCs’ results always on the agenda, and having a follow-up strategy combined with taking responsibility of outcomes/results were associated with lower HbA1c levels in the controlled group (all < 0.05). For people with intermediate or uncontrolled HbA1c, having individualized treatment plans was the only QOW feature that was significantly associated with a lower HbA1c level (< 0.05).

    Conclusions: This nationwide study adds important knowledge regarding associations between QOW in real life clinical practice and HbA1c levels. PHCCs’ QOW may mainly only benefit people with controlled HbA1c and more effective QOW strategies are needed to support people with uncontrolled HbA1c.

  • 342.
    Hänni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Treatment with a beta-blocker with beta-2-agonism improves glucose and lipid metabolism in essential hypertension1994Ingår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 43, s. 455-461Artikel i tidskrift (Refereegranskat)
  • 343.
    Hänni, Arvo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Falun Cent Hosp, Dept Surg, Bariatr Clin, Falun, Sweden.
    Nilsen, Inger
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Mora Hosp, Dept Surg, Mora, Sweden.
    Johansson, Hans-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Falun Cent Hosp, Dept Surg, Bariatr Clin, Falun, Sweden.
    Increased circulating magnesium concentrations after Roux-en-Y gastric bypass surgery in patients with type 2 diabetes2018Ingår i: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 14, nr 5, s. 576-582Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Low circulating magnesium concentrations predict cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D). Epidemiologic and clinical studies have indicated lower extra- and intracellular magnesium concentrations in patients with diabetes.

    Objective: We aimed to describe alterations, if any, in circulating magnesium concentrations after laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) in patients with obesity and T2D.

    Setting: Outpatient clinic of obesity and central hospital.

    Methods: Retrospective analysis of 1-year outcome of plasma magnesium (p-Mg) and glucometabolic status in all consecutive patients who underwent primary LRYGBP and who completed the follow-up visits, including biochemical test panels 6 and 12 months after surgery.

    Results: LRYGBP and complete follow-up visits were performed in 51 patients with T2D and 86 patients without T2D. All patients were given similar dietary advice and multivitamin and mineral supplementation after surgery. Before RYGB, the patients with T2D showed lower p-Mg compared with patients without T2D (.79 ± .06 mM and .82 ± .05 mM, respectively, P<.01). P-Mg was inversely correlated to fasting blood glucose and glycosylated hemoglobin levels. After surgery, mean p-Mg increased by 5.2% in the group with T2D compared with 1.4% in the patients without T2D (P<.01), ending at an equal level of .83 mM. The alterations in p-Mg were inversely related to the changes in fasting glucose and glycosylated hemoglobin concentrations.

    Conclusion: The lowered p-Mg associated with impaired glucometabolic status in patients with T2D was increased after LRYGBP, reaching similar concentrations as in patients without T2D.

  • 344.
    Höglund, Erika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Mattsson, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Tyrberg, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Andersson, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlsson, Carina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Growth Hormone Increases Beta-Cell Proliferation in Transplanted Human and Fetal Rat Islets2009Ingår i: Journal of the Pancreas, ISSN 1590-8577, E-ISSN 1590-8577, Vol. 10, nr 3, s. 242-248Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The aim of the study was to increase the number of human islet beta-cells after transplantation with injections of human growth hormone (hGH).

     

    Interventions Human islets and fetal rat islets were transplanted under the left kidney capsule and under the right kidney capsule, respectively in nude normoglycemic mice which were then given a daily injection of 200 µg hGH for 1-4 weeks.

     

    Main outcome measure Beta-cell proliferation was determined using thymidine incorporation and the beta-cell area was assessed using light microscopy.

     

    Results Mice given hGH increased their body weight one week after transplantation and had a more efficient removal of glucose after 3 and 4 weeks. Treatment with hGH resulted in increased beta-cell proliferation in human and fetal rat beta-cells, and the beta-cell area tended to increase. However, serum insulin concentrations and pancreas insulin content remained unchanged.

     

    Conclusions hGH increased the proliferation of transplanted human beta-cells as well as improving the glucose tolerance of the transplanted mice.

  • 345.
    Iliadis, Stavros
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Sylvén, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Jocelien, Olivier
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Hellgren, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Hannefors, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Elfström, Dick
    Sundström-Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Comasco, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuropsykofarmakologi.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Corticotropin-releasing hormone and postpartum depression: A longitudinal study2015Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 61, s. 61-61Artikel i tidskrift (Övrigt vetenskapligt)
  • 346.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
    Kilpeläinen, Tuomas O.
    The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Genome-wide association studies (GWAS) of adiposity2016Ingår i: The Genetics of Type 2 Diabetes and Related Traits: Biology, Physiology and Translation / [ed] Jose C. Florez, Cham: Springer Publishing Company, 2016, s. 91-109Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Adiposity is strongly heritable and one of the leading risk factors for type 2 diabetes, cardiovascular disease, cancer, and premature death. In the past 8 years, genome-wide association studies (GWAS) have greatly increased our understanding of the genes and biological pathways that regulate adiposity by identifying more than 100 novel susceptibility loci for overall adiposity and more than 70 loci for body fat distribution. The results for overall adiposity highlight a significant neuronal component, whereas loci regulating body fat distribution demonstrate a central role for adipocyte biology and insulin resistance in the pathophysiology. The effect sizes of all identified loci are small, and even in aggregate, they explain <3 % of the variance in each adiposity trait. This and other evidence suggest that numerous new loci will be identified in extended meta-analyses in the future. The translation of the new discoveries into clinical care remains a major challenge. As the first step, further studies are required to establish the causal genes and variants and to disentangle the exact physiological mechanisms underlying each genotype-phenotype association.

  • 347.
    Isaksson, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Barn- och ungdomspsykiatri.
    Nilsson, Kent W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Lindblad, Frank
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Barn- och ungdomspsykiatri.
    Early psychosocial adversity and cortisol levels in children with attention-deficit/hyperactivity disorder2013Ingår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 22, nr 7, s. 425-432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies suggest a different regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis) with lower diurnal cortisol levels, especially in the morning, in children with attention-deficit/hyperactivity disorder (ADHD) compared with controls. Since exposure to foetal and childhood psychosocial adversity has been associated with both ADHD and HPA-axis functioning, such exposures may explain these low cortisol levels in ADHD via early programming of the HPA-axis. Thus, our main aim was to retrospectively study foetal and early childhood exposures to psychosocial adversity in children with ADHD and to relate these exposures to cortisol levels. Saliva samples were collected during a regular weekday in children, 6-17 years old, with clinically confirmed ADHD (n = 197) and non-affected comparisons (n = 221) for radioimmunoassay analysis of cortisol. Parental rating scales were used for categorising subtypes of ADHD and degree of exposure to adversity. Children with ADHD had more reports of at least one rated foetal adversity (p = 0.041) and childhood adversity (p < 0.001) than comparisons. The association between low morning cortisol levels and ADHD-symptoms remained when analyses were adjusted for adversities, age, sex, sampling time and symptoms of oppositional defiant disorder. No relation was found between exposures to foetal/childhood adversity and cortisol levels except for a positive relation between childhood adversity and cortisol morning increase in children with ADHD. The hypothesis that early adversity may influence the HPA-axis, leading to lower cortisol levels in children with ADHD, was not supported by our findings.

  • 348. Ishikawa, T.
    et al.
    Takemoto, M.
    Akimoto, Y.
    Yan, K.
    Kenichi, S.
    He, P.
    Ishibashi, R.
    Maezawa, Y.
    Betsholtz, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
    Tryggvason, K.
    Yokote, K.
    A novel podocyte gene, R3h domain containing-like inhibits non-canonical TGF-beta signalling2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr S1, s. S44-S44Artikel i tidskrift (Övrigt vetenskapligt)
  • 349.
    Iversen, Marjolein M.
    et al.
    Bergen Univ Coll, Fac Hlth & Social Sci, Ctr Evidence Based Practice, Bergen, Norway.;Stavanger Univ Hosp, Endocrinol Sect, Dept Med, Stavanger, Norway..
    Graue, Marit
    Bergen Univ Coll, Fac Hlth & Social Sci, Ctr Evidence Based Practice, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Smide, Bibbi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Zoffmann, Vibeke
    Rigshosp, Univ Copenhagen Hosp, Juliane Marie Ctr, Res Womens & Childrens Hlth, Copenhagen, Denmark..
    Sigurdardottir, Arun K.
    Univ Akureyri, Sch Hlth Sci, Akureyri, Iceland..
    Characteristics of nursing studies in diabetes research published over three decades in Sweden, Norway, Denmark and Iceland: a narrative review of the literature2016Ingår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 30, nr 2, s. 241-249Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Similarities and differences across borders of Nordic countries constitute a suitable context for investigating and discussing factors related to the development of diabetes nursing research over the last three decades. The present study reviewed the entire body of contemporary diabetes nursing research literature originating in four Nordic countries: Norway, Sweden, Denmark and Iceland. Our aims were (i) to catalogue and characterise trends in research designs and research areas of these studies published over time and (ii) to describe how research involving nurses in Nordic countries has contributed to diabetes research overall. The larger goal of our analyses was to produce a comprehensive picture of this research in order to guide future studies in the field. We conducted a narrative literature review by systematically searching Medline, Medline in process, EMBASE, CINAHL, PsycINFO and Cochrane databases. These searches were limited to studies published between 1979 and 2009 that had an abstract available in English or a Nordic language. Two researchers independently selected studies for analysis, leading to the inclusion of 164 relevant publications for analysis. In summary, Nordic nurse researchers have contributed to the development of new knowledge in self-management of diabetes in childhood, adolescence and adulthood, and to some extent also in the treatment and care of diabetes foot ulcers. Future research may benefit from (i) larger nurse-led research programmes organised in networks in order to share knowledge and expertise across national groups and borders, (ii) more multidisciplinary collaborations in order to promote patient-centred care and (iii) further research directed towards improving the dissemination and implementation of research findings. Using complex intervention designs and a mix of research methods will enrich the research.

  • 350. Jahan, Mahabuba
    et al.
    Johnström, Peter
    Selvaraju, Ramkumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Svedberg, Marie
    Winzell, Maria Sörhede
    Bernström, Jenny
    Kingston, Lee
    Schou, Magnus
    Jia, Zhisheng
    Skrtic, Stanko
    Johansson, Lars
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Farde, Lars
    Halldin, Christer
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    The development of a GPR44 targeting radioligand [11C]AZ12204657 for in vivo assessment of beta cell mass.2018Ingår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 8, artikel-id 113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The G-protein-coupled receptor 44 (GPR44) is a beta cell-restricted target that may serve as a marker for beta cell mass (BCM) given the development of a suitable PET ligand.

    METHODS: The binding characteristics of the selected candidate, AZ12204657, at human GPR44 were determined using in vitro ligand binding assays. AZ12204657 was radiolabeled using 11C- or 3H-labeled methyl iodide ([11C/3H]CH3I) in one step, and the conversion of [11C/3H]CH3I to the radiolabeled product [11C/3H]AZ12204657 was quantitative. The specificity of radioligand binding to GPR44 and the selectivity for beta cells were evaluated by in vitro binding studies on pancreatic sections from human and non-human primates as well as on homogenates from endocrine and exocrine pancreatic compartments.

    RESULTS: The radiochemical purity of the resulting radioligand [11C]AZ12204657 was > 98%, with high molar activity (MA), 1351 ± 575 GBq/μmol (n = 18). The radiochemical purity of [3H]AZ12204657 was > 99% with MA of 2 GBq/μmol. Pancreatic binding of [11C/3H]AZ12204657 was co-localized with insulin-positive islets of Langerhans in non-diabetic individuals and individuals with type 2 diabetes (T2D). The binding of [11C]AZ12204657 to GPR44 was > 10 times higher in islet homogenates compared to exocrine homogenates. In human islets of Langerhans GPR44 was co-expressed with insulin, but not glucagon as assessed by co-staining and confocal microscopy.

    CONCLUSION: We radiolabeled [11C]AZ12204657, a potential PET radioligand for the beta cell-restricted protein GPR44. In vitro evaluation demonstrated that [3H]AZ12204657 and [11C]AZ12204657 selectively target pancreatic beta cells. [11C]AZ12204657 has promising properties as a marker for human BCM.

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