oru.sePublikasjoner
Endre søk
Begrens søket
1234567 1 - 50 of 315
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy,University of Gothenburg, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sports Diving Federation, Farsta, Sweden.
    Eriksson, Bengt M.
    Hyperbaric Medicine, Department of Anesthesiology, Karolinska University Hospital, Solna, Sweden.
    Cooper, Ken
    Medtronic Diabetes (Sensor R&D), Northridge CA, USA.
    Jendle, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Örebro University Hospital, Örebro, Sweden; Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    Continuous glucose monitoring: a study of the Enlite sensor during hypo- and hyperbaric conditions2012Inngår i: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 14, nr 6, s. 527-532Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The performance and accuracy of the Enlite(™) (Medtronic, Inc., Northridge, CA) sensor may be affected by microbubble formation at the electrode surface during hypo- and hyperbaric conditions. The effects of acute pressure changes and of prewetting of sensors were investigated.

    Materials and Methods: On Day 1, 24 sensors were inserted on the right side of the abdomen and back in one healthy individual; 12 were prewetted with saline solution, and 12 were inserted dry. On Day 2, this procedure was repeated on the left side. All sensors were attached to an iPro continuous glucose monitoring (CGM) recorder. Hypobaric and hyperbaric tests were conducted in a pressure chamber, with each test lasting 105 min. Plasma glucose values were obtained at 5-min intervals with a HemoCue(®) (Ängelholm, Sweden) model 201 glucose analyzer for comparison with sensor glucose values.

    Results: Ninety percent of the CGM systems operated during the tests. The mean absolute relative difference was lower during hyperbaric than hypobaric conditions (6.7% vs. 14.9%, P<0.001). Sensor sensitivity was slightly decreased (P<0.05) during hypobaric but not during hyperbaric conditions. Clarke Error Grid Analysis showed that 100% of the values were found in the A+B region. No differences were found between prewetted and dry sensors.

    Conclusions: The Enlite sensor performed adequately during acute pressure changes and was more accurate during hyperbaric than hypobaric conditions. Prewetting the sensors did not improve accuracy. Further studies on type 1 diabetes subjects are needed under various pressure conditions.

  • 2.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Center, Department of Pediatrics, Institute for the Health of Women and Children, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sports Diving Federation, Farsta, Sweden.
    Jendle, Johan
    Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden; Faculty of Health Sciences, Örebro University Hospital, Örebro, Sweden.
    Accuracy and reliability of continuous glucose monitoring in individuals with type 1 diabetes during recreational diving2009Inngår i: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 11, nr 8, s. 493-497Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: This study evaluated the accuracy and function of the Continuous Glucose Monitoring System (CGMS, Minneapolis, MN) during recreational scuba diving in individuals with type 1 diabetes.

    METHODS: Twenty-four adults, 12 with type 1 diabetes and 12 healthy controls, were studied during five recreational scuba dives performed on three consecutive days. All the participants used the CGMS on all the days and during all the dives. Comparisons were made between plasma glucose at specific time intervals and the CGMS.

    RESULTS: The recording by the CGMS was robust, with few sensor problems. The mean sensor survival time was >48 h. Eighty-five percent of the individuals used one sensor during the entire length of the trial. The overall mean absolute difference (MAD) within the group with diabetes was 14.4 +/- 6%, and the corresponding daily figures were 23.2 +/- 19.3% on day 1, 11.6 +/- 4.5% on day 2, and 11.2 +/- 5.7% on day 3. A significant improvement regarding MAD when day 1 was compared with day 2 and 3 (P < 0.05). With a limit set at 70 mg/dL, hypoglycemia pre- and post-dive was detected with a positive predictive value of 0.39, negative predictive value of 0.98, sensitivity of 0.64, and specificity of 0.94.

    CONCLUSIONS: We demonstrate that the CGMS was used with accuracy in such difficult conditions as scuba diving and provided robust information on glucose variations.

  • 3.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Centre, Department of Pediatrics, Institute for the Health of Women and Children, the Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sportsdiving Federation, Farsta, Sweden.
    Jendle, Johan
    Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden; Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    The benefits of continuous glucose monitoring and a glucose monitoring schedule in individuals with type 1 diabetes during recreational diving2008Inngår i: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 2, nr 5, s. 778-784Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Our objective is to evaluate the Medtronic CGMS continuous glucose monitoring system and plasma glucose (PG) measurement performed in a monitoring schedule as tools to identify individuals with type 1 diabetes at risk when diving.

    METHODS: We studied 24 adults, 12 type 1 diabetes subjects and 12 controls, during 5 recreational scuba dives performed on 3 consecutive days. The CGMS was used by all participants on all the days and all the dives. Comparisons were made between PG performed in a monitoring schedule during the days of diving, self-monitored blood glucose (SMBG) performed 2 weeks prior to diving, and the CGMS during the study.

    RESULTS: One hundred seventeen dives were performed. Hypoglycemia (<70 mg/dl) was found in six individuals and on nine occasions. However, no symptoms of hypoglycemia were present during or immediately postdiving. In one case, repetitive hypoglycemia prediving gave rise to a decision not to dive. None of the dives were aborted. The number of hypoglycemic episodes, 10 min prediving or immediately postdiving, were related to the duration of diabetes, r = 0.83 and p =0.01, and the percentage of SMBG values below target (<72 mg/dl), r = 0.65 and p =0.02. Moreover, the number of hypoglycemic episodes was also related to the total duration below low limit (<70 mg/dl), measured by the CGMS, r =0.74 and p =0.006.

    CONCLUSION: Safe dives are possible to achieve by well-informed, well-controlled individuals with type 1 diabetes. Using downloaded SMBG, CGMS, and repetitive PG in a monitoring schedule, it is possible to identify those subjects who are suitable for diving.

  • 4.
    Agardh, Carl-David
    et al.
    Lund University, Lund, Sweden.
    Ahrén, Bo
    Lund University, Lund, Sweden.
    Hanås, Ragnar
    Jansson, Stefan
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper. Uppsala University, Uppsala, Sweden.
    Smith, Ulf
    Gothenburg University, Gothenburg, Sweden.
    Toft, Eva
    Karolinska Institutet, Stockholm, Sweden.
    Östenson, Claes-Göran
    Karolinska Institutet, Stockholm, Sweden.
    Varning för okritisk användning av överviktskirurgi vid typ 2-diabetes2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 25, s. 1208-1209Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Överviktskirurgi diskuteras nu som ett behandlingsalternativ även för patienter med typ 2-diabetes där BMI inte överstiger nuvarande indikationsgräns 35 kg/m2. Artikelförfattarna vill varna för en sådan utveckling i avvaktan på kritisk värdering av denna typ av kirurgi.

  • 5. Albertsson-Wikland, Kerstin
    et al.
    Aronson, A. Stefan
    Gustafsson, Jan
    Hagenäs, Lars
    Ivarsson, Sten A.
    Jonsson, Björn
    Kriström, Berit
    Marcus, Claude
    Nilsson, Karl Olof
    Ritzén, E. Martin
    Tuvemo, Torsten
    Westphal, Otto
    Åman, Jan
    Örebro universitet, Hälsoakademin.
    Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency2008Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, nr 11, s. 4342-4350Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).

    OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.

    DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.

    INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.

    SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.

    MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.

    RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.

    CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls. 

  • 6.
    Albertsson-Wikland, Kerstin
    et al.
    Goteborg Pediat Growth Res Ctr, Dept Pediat, Inst Clin Sci, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Kriström, Berit
    Dept Clin Sci, Pediat Unit, Umeå Univ, Umeå, Sweden.
    Lundberg, Elena
    Dept Clin Sci, Pediat Unit, Umeå Univ, Umeå, Sweden.
    Aronson, A. Stefan
    Dept Pediat, Halmstad Cty Hosp, Halmstad, Sweden.
    Gustafsson, Jan
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden.
    Hagenäs, Lars
    Dept Womens & Childrens Hlth, Karolinska Inst, Stockholm, Sweden.
    Ivarsson, Sten-A.
    Dept Pediat, Lund Univ, Malmö, Sweden.
    Jonsson, Björn
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden.
    Ritzen, Martin
    Dept Womens & Childrens Hlth, Karolinska Inst, Stockholm, Sweden.
    Tuvemo, Torsten
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden.
    Westgren, Ulf
    Dept Pediat, Lund Univ, Malmo, Sweden.
    Westphal, Otto
    Goteborg Pediat Growth Res Ctr, Dept Pediat, Inst Clin Sci, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Åman, Jan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Growth hormone dose-dependent pubertal growth: a randomized trial in short children with low growth hormone secretion2014Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, nr 3, s. 158-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i. e. idiopathic isolated GH deficiency.

    Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height.

    Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS.

    Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.

  • 7. Alibegovic, A.
    et al.
    Gannerdahl, P.
    Debeer, L.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Sweden.
    The effect of alpha 2 receptor agonists on central haemodynamic and blood glucose during hemorrhagic stress in the rat1998Inngår i: Surgical Research Communications, ISSN 0882-9233, Vol. 9, nr 2-4, s. 151-164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The effect of the selective alpha 2 agonist Mivazerol on catecholamine levels in plasma, and on central hemodynamics and blood glucose levels developments during hemorrhagic stress in rats was investigated. The animals were randomly given either saline, low dose of Mivazerol (0.6 μg/ml) or high dose (2.0 μg/ml) at a rate of 30 μl/100 g/min, beginning the infusions intravenously 30 min before onset and throughout 60 min of hemorrhagic stress. Before hemorrhage, Mivazerol raised mean arterial pressure, and reduced heart rate, adrenaline and noradrenaline levels in a dose dependent fashion. High dose infusion also resulted in an elevation in blood glucose. During hemorrhage, the high dose effectively dampened the catecholamine response. Simultaneously, the same group maintained better mean arterial pressure in response to hemorrhage. Blood glucose levels were elevated to similar levels regardless of treatment. These data indicate that Mivazerol effectively reduced the catecholamine response to severe hemorrhagic stress, while central hemodynamic and blood glucose responses were maintained or improved.

  • 8.
    Alnemo, John
    et al.
    Department of Prosthetics and Orthotics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lundqvist, Lars-Olov
    Örebro universitet, Institutionen för hälsovetenskaper. University Health Care Research Center.
    Tranberg, Roy
    Department of Orthopaedics, Institute of Clinical Sciences, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Jarl, Gustav
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 1Department of Prosthetics and Orthotics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Attitudes and attributes of women and men using therapeutic shoes for diabetic foot complications2019Inngår i: 8th International symposium on diabetic foot: Absttaract book, 2019, s. 117-117, artikkel-id P35.05Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Background: Therapeutic shoes can prevent diabetic foot reulcerations but their use is complicated by the fact that shoes have psychological and social meanings, which is believed to put a larger burden on women than men. The aim was to compare attitudes and attributes of women and men using therapeutic shoes for diabetic foot complications.

    Methods: A questionnaire was posted to 1230 people with diabetes who had been fitted with therapeutic shoes. Women's and men's answers were compared using t-tests, Mann-Whitney U tests and chi-square tests with Fischer's exact tests. P-values < 0.05 were considered statistically significant.

    Results: Questionnaires from 443 (36.0%) respondents (294 men, 149 women, mean age 69.2 years) were analyzed. More men than women (p < 0.05) had paid employment (20.4% vs 9.4%), had someone who reminded them to wear their therapeutic shoes (27.6% vs 10.0%), and had a history of foot ulcers (62.9% vs 46.3%) or minor amputation (17.7% vs 6.7%). More women than men received disability pension (18.8% vs 10.2%). Women reported worse general health, lower internal locus of control regarding ulcer prevention, and more negative attitudes to the appearance and price of therapeutic shoes and how they felt about wearing them in public. Other comparisons were non-significant: other shoe attributes, education, diabetes type, current foot ulcers, major amputations, satisfaction with shoe services, understanding of neuropathy as a risk factor, locus of control regarding ulcer healing, belief in the shoes' efficacy to prevent and heal ulcers, worries about ulcer healing and new ulcerations, self-efficacy, depression, shoe use/adherence, paying a fee for therapeutic shoes, and social support.

    Conclusions: Men had worse foot complications. Women had worse general health, lower internal locus of control regarding ulcer prevention, and more negative attitudes toward therapeutic shoes. Clinicians should pay more attention to their female patients' concerns. Future research and development should focus on improving the weight and appearance of therapeutic shoes, particularly for women. Research is also needed on how to facilitate the adaption and reevaluation process where patients change from viewing shoes purely as items of clothing to also viewing them as medical interventions

  • 9.
    Alnemo, John
    et al.
    Department of Prosthetics and Orthotics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tranberg, Roy
    Department of Orthopaedics, Institute of Clinical Sciences, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Lundqvist, Lars-Olov
    Örebro universitet, Institutionen för hälsovetenskaper. University Health Care Research Center.
    Jarl, Gustav
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Prosthetics and Orthotics.
    Are the left and right limbs unequally affected by diabetic foot complications?2019Inngår i: 8th International symposium on diabetic foot: Abstract book, 2019, s. 140-140, artikkel-id P45.04Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Aim: There is some debate about laterality for diabetic foot complications, that is, whether the right and left limbs are unequally affected. Coxon and Gallen (1) found that more amputations were performed on the right limb and Evans et al. (2) interpreted this in the context of foot dominance: they found that most foot ulcers occured on the dominant limb (which for most people is the right one) and speculated that the dominant limb may be more exposed to mechanical stresses and injuries. However, Demetriou et al. (3) did not find any laterality in foot ulcer location. The aim was to investigate laterality for foot ulcers and amputations. Methods: A questionnaire was posted to 1245 people who had diabetes, experience of using therapeutic shoes, and who had attended one of two prosthetics and orthotics clinics during a 12 months’ period. The number of ulcers or amputations on the right and left limb were compared with a two-sided chi-square test. Results: 469 (37.7%) questionnaires were returned. 118 (25.2%) participants reported unilateral foot ulcers, 54 (11.5%) reported unilateral minor amputation, and 21 (4.5%) reported unilateral major amputation. There was no statistically significant right-left difference in foot ulcers, minor amputations or major amputations (Table 1, p-values 0.713-1.000). Conclusions: Our results do not support the hypothesis about laterality for foot ulcers and amputations.

  • 10. Alnemo, John
    et al.
    Tranberg, Roy
    Lundqvist, Lars-Olov
    Örebro universitet, Institutionen för hälsovetenskaper.
    Jarl, Gustav
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Are the left and right limbs unequally affected by diabetic foot complications?2019Konferansepaper (Annet vitenskapelig)
  • 11.
    Alston-Smith, J.
    et al.
    Uppsala University, Biomedical Center, Department of Medicine, Sweden.
    Ljungqvist, Olle
    Ware, J.
    Nilsson Ekdahl, K. N.
    Regulation of rat hepatocyte fructose 1,6-diphosphatase activity during endotoxemia1991Inngår i: Surgical Research Communication, ISSN 0882-9233, Vol. 11, nr 1-2, s. 67-75Artikkel i tidsskrift (Fagfellevurdert)
  • 12.
    Alvehus, M.
    et al.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå University, Umeå, Sweden.
    Simonyte, K.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå University, Umeå, Sweden.
    Andersson, T.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå University, Umeå, Sweden.
    Söderström, I.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå University, Umeå, Sweden.
    Burén, J.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå University, Umeå, Sweden.
    Rask, Eva
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Mattsson, C.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå University, Umeå, Sweden.
    Olsson, T.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå University, Umeå, Sweden.
    Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 5, s. 684-690Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease that are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared with premenopausal women. We also wanted to determine whether these markers are reduced by stable weight loss in obese women.

    DESIGN AND METHODS:

    Anthropometric data, blood samples and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass (GBP) surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated.

    RESULTS:

    IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal vs premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal vs premenopausal women. Two years after GBP surgery, adipose expression of IL-8, tumour necrosis factor-α and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before GBP surgery, but these associations disappeared after surgery.

    CONCLUSION:

    Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss.

  • 13.
    Andersen, Gregers Stig Tig
    et al.
    Steno Diabetes Center, Gentofte, Denmark.
    Thybo, Tanja
    Steno Diabetes Center, Gentofte, Denmark.
    Cederberg, Henna
    Department of Medicine, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. Steno Diabetes Center, Gentofte, Denmark.
    Esteller, Manel B.
    Cancer Epigenetics and Biology Program, Spanish Biomedical Research Centre Network for Epidemiology and Public Health, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain.
    Zorzano, Antonio
    Institute for Research in Biomedicine, Barcelona, Spain; Departament de Bioquímica I Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
    Carr, Bernadette M.
    Voluntary Health Insurance Board, Dublin, Ireland.
    Walker, Mark G.
    University of Newcastle-on-Tyne, Newcastle, United Kingdom.
    Cobb, Jeff E.
    Metabolon Inc., Durham NC, United States.
    Clissmann, C.
    Pintail Ltd., Dublin, Ireland.
    O'Gorman, Donal J.
    Centre for Preventive Medicine, School of Health and Human Performance, Dublin City University, Dublin, Ireland.
    Nolan, John J.
    Steno Diabetes Center, Gentofte, Denmark.
    The DEXLIFE study methods: identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals2014Inngår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 106, nr 2, s. 383-389, artikkel-id S0168-8227(14)00319-2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.

  • 14.
    Andrade, Anenisia C.
    et al.
    Karolinska Inst, Stockholm, Sweden; Karolinska Univ Hosp, Stockholm, Sweden.
    Gkourogianni, Alexandra
    Karolinska Inst, Stockholm, Sweden; Karolinska Univ Hosp, Stockholm, Sweden.
    Segerlund, Emma
    Sunderby Hosp, Sunderby, Sweden.
    Werner-Sperker, Antje
    Sunderby Hosp, Sunderby, Sweden.
    Horemuzova, Eva
    Karolinska Inst, Stockholm, Sweden; Karolinska Univ Hosp, Stockholm, Sweden.
    Dahlgren, Jovanna
    Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Nilsson, Ola
    Örebro universitet, Institutionen för medicinska vetenskaper. Karolinska Inst, Stockholm, Sweden; Karolinska Univ Hosp, Stockholm, Sweden.
    Short Stature Due To Two Novel Heterozygous Igf1r Mutations and Response To Gh Treatment2017Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, nr Suppl. 1, s. 130-131, artikkel-id P1-842Artikkel i tidsskrift (Annet vitenskapelig)
  • 15.
    Andrade, Anenisia C.
    et al.
    Division of Pediatric Endocrinology, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Jee, Youn Hee
    Section of Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, USA.
    Nilsson, Ola
    Örebro universitet, Institutionen för medicinska vetenskaper. Division of Pediatric Endocrinology, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Örebro University Hospital, Örebro, Sweden.
    New Genetic Diagnoses of Short Stature Provide Insights into Local Regulation of Childhood Growth2017Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, nr 1, s. 22-37Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Idiopathic short stature is a common condition with a heterogeneous etiology. Advances in genetic methods, including genome sequencing techniques and bioinformatics approaches, have emerged as important tools to identify the genetic defects in families with monogenic short stature. These findings have contributed to the understanding of growth regulation and indicate that growth plate chondrogenesis, and therefore linear growth, is governed by a large number of genes important for different signaling pathways and cellular functions, including genetic defects in hormonal regulation, paracrine signaling, cartilage matrix, and fundamental cellular processes. In addition, mutations in the same gene can cause a wide phenotypic spectrum depending on the severity and mode of inheritance of the mutation.

  • 16.
    Arora, Tulika
    et al.
    Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Velagapudi, Vidya
    VTT Technical Research Centre of Finland, Espoo, Finland; Metabolomics Unit, Institute for Molecular Medicine Finland FIMM, Helsinki, Finland.
    Pournaras, Dimitri J.
    Department of Bariatric Surgery, Musgrove Park Hospital, Taunton, United Kingdom.
    Welbourn, Richard
    Department of Bariatric Surgery, Musgrove Park Hospital, Taunton, United Kingdom.
    le Roux, Carel W.
    Diabetes Complications Research Centre, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Gastrosurgical Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
    Bäckhed, Fredrik
    Department of Molecular and Clinical Medicine, Institute of Medicie, University of Gothenburg, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, University of Copenhagen, Copenhagen, Denmark.
    Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 5, artikkel-id e0126401Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3), which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

  • 17.
    Arvidsson, Bo
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden; Centre for Health Care Sciences, Örebro County Council, Örebro, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Rask, Eva
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    Schwarcz, Erik
    Region Örebro län. Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    Möller, Margareta
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Reference data for bone mineral density in Swedish women using digital X-ray radiometry2013Inngår i: Journal of clinical densitometry, ISSN 1094-6950, E-ISSN 1559-0747, Vol. 16, nr 2, s. 183-188Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    During the last decade, digital X-ray radiometry (DXR) has been used to measure bone mineral density (BMD) in the metacarpal bones. The aim of this study was to establish Swedish reference material for bone mass in women, measured in the metacarpal bones with DXR, and compare these data with the data from the manufacturer. A sample of 1440 women aged 20-79yr living in Örebro County was randomly assigned from the population register. Microdose mammography was used (Sectra MDM L30; Sectra Imtec AB, Linköping, Sweden) to measure BMD. Cole's LMS method was used to calculate DXR. Six hundred sixty-nine (48.3%) women participated. Peak bone mass occurred at the age of 43.4yr with a BMD of 0.597g/cm(2) (standard deviation: 0.050). Our Swedish data correlated well with the manufacturer's material. Only among women aged 50-59yr did BMD differ, where the Swedish sample had lower values. The LMS method can be used to describe the DXR data and provide a more detailed picture of bone density distribution. DXR-BMD in Swedish women aged 20-79yr is equivalent to findings from other studies, showing the same distribution of BMD in most age groups except for ages 50-59yr.

  • 18.
    Axelsson, K. F.
    et al.
    Geriatric Medicine, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
    Werling, M.
    Department of Gastrosurgical Research & Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eliasson, B.
    Department of Molecular a nd Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, sweden.
    Szabo, Eva
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Surgery.
    Näslund, I.
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Wedel, H.
    Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lundh, D.
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Lorentzon, M.
    Geriatric Medicine, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
    Fracture Risk After Gastric Bypass Surgery: A Retrospective Cohort Study2018Inngår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, nr Suppl. 1, s. S491-S491Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Objectives: Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone oss but fracture risk following surgery has been insufficiently studied. Our objective was to investigate if gastric bypass surgery in obese patients, with and without diabetes, was associated with fracture risk, and if the fracture risk was associated with post-surgery weight loss or insufficient calcium and vitamin D supplementation.

    Methods: Using large databases, 38 971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31 213 without. Through multivariable 1:1 propensity score matching, well-balanced controls were identified. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation one year post-surgery was investigated.

    Results: 77 942 patients had a median and total follow-up time of 3.1 (IQR 1.7-4.6) and 251 310 person-years, respectively. Gastric bypass was associated with increased risk of any fracture, in patients with diabetes and without diabetes using a multivariable Cox model (HR 1.26, 95%CI 1.05-1.53 and HR 1.32, 95%CI 1.18-1.47, respectively). The risk of fall injury without fracture was also increased after gastric bypass, both in patients with (HR 1.26 95%CI 1.04-1.52) and without diabetes (HR 1.24 95%CI 1.12-1.38). Weight loss or degree of calcium and vitamin D supplementation after gastric bypass were not associated with fracture risk.

    Conclusions: Gastric bypass was associated with an increased risk of fracture and fall injury. Weight loss or calcium and vitamin D supplementation following surgery were not associated with fracture risk. These findings indicate that gastric bypass increases fracture risk, which could at least partly be due to increased susceptibility to falls.

  • 19.
    Axelsson, Kristian F.
    et al.
    Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden; Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Werling, Malin
    Department of Gastrosurgical Research & Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eliasson, Björn
    Department of Molecular and Clinical Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Szabo, Eva
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Surgery.
    Näslund, Ingmar
    Department of Surgery. Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Wedel, Hans
    Health Metrics, Sahlgrenska Academin, University of Gothenburg, Gothenburg, Sweden.
    Lundh, Dan
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Lorentzon, Mattias
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
    Fracture Risk After Gastric Bypass Surgery: A Retrospective Cohort Study2018Inngår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 12, s. 2122-2131Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38,971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31,213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation 1-year postsurgery was investigated. During a median follow-up time of 3.1 (interquartile range [IQR], 1.7 to 4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (hazard ratio [HR] 1.26; 95% CI, 1.05 to 1.53; and HR 1.32; 95% CI, 1.18 to 1.47; respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk.

  • 20.
    Backman, Olof
    et al.
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Surgical and Perioperative Science (Hand and Plastic Surgery), Umeå University, Umeå, Sweden.
    Bruze, Gustaf
    Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Näslund, Ingmar
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ottosson, Johan
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Surgery.
    Marsk, Richard
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Neovius, Martin
    Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Näslund, Erik
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels: A Nationwide Cohort Study From Sweden2019Inngår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 269, nr 5, s. 895-902Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.

    SUMMARY OF BACKGROUND DATA: Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.

    METHODS: The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.

    RESULTS: Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67-0.89; P < 0.001).

    CONCLUSIONS: Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetes but also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.

  • 21. Balagopal, P.
    et al.
    Ljungqvist, Olle
    Dept. of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Nair, K. S.
    Endocrine Research Unit, Mayo Clinic and Foundation, Rochester, MN, United States.
    Skeletal muscle heavy-chain synthesis rate in healthy humans1997Inngår i: American Journal of Physiology, ISSN 0002-9513, E-ISSN 2163-5773, Vol. 272, nr 1, s. 45-50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mixed muscle protein synthetic rate has been measured in humans. These measurements represent the average of synthetic rates of all muscle proteins with variable rates. We determined to what extent the synthesis rate of mixed muscle protein in humans reflects that of myosin heavy chain (MHC), the main contractile protein responsible for the conversion of ATP to mechanical energy as muscle contraction. Fractional synthetic rates of MHC and mixed muscle protein were measured from the increment of [C-13]leucine in these proteins in vastus lateralis biopsy samples taken at 5 and 10 h during a primed continuous infusion of L-[1-C-13]leucine in 10 young healthy subjects. Calculations were done by use of plasma [C-13]ketoisocaproate (KIC) and muscle tissue fluid [C-13]leucine as surrogate measures of leucyl-tRNA. Fractional synthetic rate of MHC with plasma KIC (0.0299 +/- 0.0043%/h) and tissue fluid leucine (0.0443 +/- 0.0056%/h) were only 72 +/- 3% of that of mixed muscle protein (0.0408 +/- 0.0032 and 0.0603 +/- 0.0059%/h, respectively, with KIC and tissue fluid leucine). Contribution of MHC (7 +/- 1 mg . kg(-1) . h(-1)) to synthetic rates of whole body mixed muscle protein (36 +/- 5 mg . kg(-1) . h(-1)) and whole body protein (127 +/- 4 mg . kg(-1) . h(-1)) is only 18 +/- 1 and 5 +/- 1%, respectively. This relatively low contribution of MHC to whole body and mixed muscle protein synthesis warrants direct measurement of synthesis rate of MHC in conditions involving abnormalities of muscle contractile function.

  • 22.
    Bang, P.
    et al.
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
    Nygren, J.
    Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Carlsson-Skwirut, C.
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
    Thorell, A.
    Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Postoperative induction of insulin-like growth factor binding protein-3 proteolytic activity: relation to insulin and insulin sensitivity1998Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 83, nr 7, s. 2509-2515Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increased serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolytic activity (IGFBP-3-PA) has been demonstrated in a number of clinical states of insulin resistance, including severe illness, after surgery, and in noninsulin-dependent diabetes mellitus. In the present study we assessed the role of insulin sensitivity in expression of IGFBP-3-PA in serum. In 18 patients studied, a significant increase in IGFBP-3-PA (P < 0.005) was demonstrated after cole-rectal surgery. Eight patients receiving an oral glucose load before surgery demonstrated a significant greater relative increase in IGFBP-3-PA compared with 10 patients not receiving glucose (32.9 +/- 7.1% vs. 8.6 +/- 6.7%, respectively; P < 0.05). Both groups had reduced insulin sensitivity after surgery(-58 +/- 4%; P < 0.0001; n = 18), as determined by hyperinsulinemic, normoglycemic clamps; however, the group not receiving glucose displayed 18% less insulin sensitivity than the oral glucose load group (P < 0.05). Multiple regression analysis demonstrated that the relative changes in IGFBP-3-PA and C peptide levels were inversely correlated (P < 0.05), suggesting that increased IGFBP-3-PA, presumably increasing IGF bioavailability, may be associated with decreased insulin demands. Interestingly, insulin infusion during the 4-h hyperinsulinemic, normoglycemic clamp performed 24 h after surgery (post-op) resulted in a further increase in IGFBP-3-PA in both groups (P < 0.005), whereas no significant responses could be demonstrated during the pre-op clamp. The expression of increased IGFBP-3-PA was accompanied by conversion of endogenous intact 39/42-kDa IGFBP-3 into its 30-kDa fragmented form as determined by Western immunoblotting, and this conversion was virtually complete after the 4-h post-op clamp in patients displaying marked increases in IGFBP-3-PA. Characterization of the IGFBP-3-PA demonstrated that it was specific for IGFBP-3, as no degradation of IGFBP-1 and -2 was detected, and the use of various protease inhibitors demonstrated that serine proteases and possibly matrix metalloproteinases contribute to the increased IGFBP-3-PA level after surgery. We propose that IGF bioavailability may be increased by the induction of IGFBP-3-PA in insulin-resistant subjects, and that insulin regulates IGFBP-3-PA in this state.

  • 23.
    Barbarroja, Nuria
    et al.
    Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Instituto Maimónides de Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain.
    Rodriguez-Cuenca, Sergio
    Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Nygren, Heli
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Camargo, Antonio
    Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Lipids and Atherosclerosis Research Unit, Instituto Maimónides de Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain.
    Pirraco, Ana
    Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal.
    Relat, Joana
    Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain.
    Cuadrado, Irene
    Departamento de Farmacología, Universidad Complutense de Madrid, Madrid, Spain.
    Pellegrinelli, Vanessa
    Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Medina-Gomez, Gema
    Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Lopez-Pedrera, Chary
    Instituto Maimónides de Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain.
    Tinahones, Francisco J.
    CIBER in Physiopathology of Obesity and Nutrition (CB06/03), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Biomédica de Málaga, Hospital Virgen de la Victoria, Malaga, Spain.
    Symons, J. David
    College of Health, University of Utah, Salt Lake City UT, United States; Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City UT, United States.
    Summers, Scott A.
    Program in Cardiovascular and Metabolic Disorders, Duke-National University, Singapore Graduate Medical School, Singapore, Singapore.
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
    Vidal-Puig, Antonio
    Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function2015Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, nr 4, s. 1180-1192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adipose tissue dysfunction is an important determinant of obesity-associated, lipid-induced metabolic complications. Ceramides are well-known mediators of lipid-induced insulin resistance in peripheral organs such as muscle. DEGS1 is the desaturase catalyzing the last step in the main ceramide biosynthetic pathway. Functional suppression of DEGS1 activity results in substantial changes in ceramide species likely to affect fundamental biological functions such as oxidative stress, cell survival, and proliferation. Here, we show that degs1 expression is specifically decreased in the adipose tissue of obese patients and murine models of genetic and nutritional obesity. Moreover, loss-of-function experiments using pharmacological or genetic ablation of DEGS1 in preadipocytes prevented adipogenesis and decreased lipid accumulation. This was associated with elevated oxidative stress, cellular death, and blockage of the cell cycle. These effects were coupled with increased dihydroceramide content. Finally, we validated in vivo that pharmacological inhibition of DEGS1 impairs adipocyte differentiation. These data identify DEGS1 as a new potential target to restore adipose tissue function and prevent obesity-associated metabolic disturbances.

  • 24.
    Beger, Richard D.
    et al.
    Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, USA.
    Dunn, Warwick
    School of Biosciences, Phenome Centre Birmingham and Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, UK.
    Schmidt, Michael A.
    Advanced Pattern Analysis and Countermeasures Group, Research Innovation Center, Colorado State University, Fort Collins, USA.
    Gross, Steven S.
    Department of Pharmacology, Weill Cornell Medical College, New York, USA.
    Kirwan, Jennifer A.
    School of Biosciences, University of Birmingham, Birmingham, UK.
    Cascante, Marta
    Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain; Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain.
    Brennan, Lorraine
    UCD Institute of Food and Health, UCD, Belfield, Ireland.
    Wishart, David S.
    Departments of Computing Science and Biological Sciences, University of Alberta, Edmonton, Canada.
    Oresic, Matej
    Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Hankemeier, Thomas
    Division of Analytical Biosciences and Cluster Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University & Netherlands Metabolomics Centre, Leiden, The Netherlands.
    Broadhurst, David I.
    School of Science, Edith Cowan University, Perth, Australia.
    Lane, Andrew N.
    Center for Environmental Systems Biochemistry, Department Toxicology and Cancer Biology, Markey Cancer Center, Lexington, USA.
    Suhre, Karsten
    Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar.
    Kastenmüller, Gabi
    Institute of Bioinformatics and Systems Biology, Helmholtz Center Munich, Oberschleißheim, Germany.
    Sumner, Susan J.
    Discovery Sciences, RTI International, Research Triangle Park, Durham, USA.
    Thiele, Ines
    University of Luxembourg, Luxembourg Centre for Systems Biomedicine, Campus Belval, Esch-Sur-Alzette, Luxembourg.
    Fiehn, Oliver
    West Coast Metabolomics Center, UC Davis, Davis, USA; Biochemistry Department, King Abdulaziz University, Jeddah, Saudi Arabia.
    Kaddurah-Daouk, Rima
    Psychiatry and Behavioral Sciences, Duke Internal Medicine and Duke Institute for Brain Sciences and Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, USA.
    Metabolomics enables precision medicine: "A White Paper, Community Perspective"2016Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, nr 10, artikkel-id 149Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION BACKGROUND TO METABOLOMICS: Metabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or "-omics" level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person's metabolic state provides a close representation of that individual's overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates.

    OBJECTIVES OF WHITE PAPER—EXPECTED TREATMENT OUTCOMES AND METABOLOMICS ENABLING TOOL FOR PRECISION MEDICINE: We anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and stratification of patients based on metabolic pathways impacted; (4) reveal biomarkers for drug response phenotypes, providing an effective means to predict variation in a subject's response to treatment (pharmacometabolomics); (5) define a metabotype for each specific genotype, offering a functional read-out for genetic variants: (6) provide a means to monitor response and recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and extreme environments. Importantly, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to measure thousands of metabolites in blood, other body fluids, and tissues. Such tools also enable more robust analysis of response to treatment. New insights have been gained about mechanisms of diseases, including neuropsychiatric disorders, cardiovascular disease, cancers, diabetes and a range of pathologies. A series of ground breaking studies supported by National Institute of Health (NIH) through the Pharmacometabolomics Research Network and its partnership with the Pharmacogenomics Research Network illustrate how a patient's metabotype at baseline, prior to treatment, during treatment, and post-treatment, can inform about treatment outcomes and variations in responsiveness to drugs (e.g., statins, antidepressants, antihypertensives and antiplatelet therapies). These studies along with several others also exemplify how metabolomics data can complement and inform genetic data in defining ethnic, sex, and gender basis for variation in responses to treatment, which illustrates how pharmacometabolomics and pharmacogenomics are complementary and powerful tools for precision medicine.

    CONCLUSIONS KEY SCIENTIFIC CONCEPTS AND RECOMMENDATIONS FOR PRECISION MEDICINE: Our metabolomics community believes that inclusion of metabolomics data in precision medicine initiatives is timely and will provide an extremely valuable layer of data that compliments and informs other data obtained by these important initiatives. Our Metabolomics Society, through its "Precision Medicine and Pharmacometabolomics Task Group", with input from our metabolomics community at large, has developed this White Paper where we discuss the value and approaches for including metabolomics data in large precision medicine initiatives. This White Paper offers recommendations for the selection of state of-the-art metabolomics platforms and approaches that offer the widest biochemical coverage, considers critical sample collection and preservation, as well as standardization of measurements, among other important topics. We anticipate that our metabolomics community will have representation in large precision medicine initiatives to provide input with regard to sample acquisition/preservation, selection of optimal omics technologies, and key issues regarding data collection, interpretation, and dissemination. We strongly recommend the collection and biobanking of samples for precision medicine initiatives that will take into consideration needs for large-scale metabolic phenotyping studies.

  • 25.
    Beraki, Åsa
    et al.
    Linköping University, Linköping, Sweden.
    Magnusson, Anders
    Clinical Epidemiology and Biostatistic Unit, Örebro University Hospital, Örebro, Sweden.
    Särnblad, Stefan
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Åman, Jan
    Region Örebro län. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Samuelsson, Ulf
    Department of Clinical and Experimental Medicine, Division of Pediatrics and Diabetes Research Centre, Linköping University, Linköping, Sweden.
    Increase in physical activity is associated with lower HbA1c levels in children and adolescents with type 1 diabetes: results from a cross-sectional study based on the Swedish pediatric diabetes quality registry (SWEDIABKIDS)2014Inngår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 105, nr 1, s. 119-125Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: To evaluate the associations between physical activity (PA) and metabolic control, measured by glycated hemoglobin (HbA1c), in a large group of children and adolescents with type 1 diabetes.

    Methods: Cross-sectional analysis of data from 4655 patients, comparing HbA1c values with levels of physical activity. The data for the children and adolescents were obtained from the Swedish pediatric diabetes quality registry, SWEDIABKIDS. The patients were 7-18 years of age, had type 1 diabetes and were not in remission. Patients were grouped into five groups by frequency of PA.

    Results: Mean HbA1c level was higher in the least physically active groups (PA0: 8.8% +/- 1.5 (72 +/- 16 mmol/mol)) than in the most physically active groups (PA4: 7.7% +/- 1.0 (60 +/- 11 mmol/mol)) (p < 0.001). An inverse dose-response association was found between PA and HbA1c (beta: -0.30, 95%CI: -0.34 to -0.26, p < 0.001). This association was found in both sexes and all age groups, apart from girls aged 7-10 years. Multiple regression analysis revealed that the relationship remained significant (beta: -0.21, 95% CI: -0.25 to -0.18, p < 0.001) when adjusted for possible confounding factors.

    Conclusions: Physical activity seems to influence HbA1c levels in children and adolescents with type 1 diabetes. In clinical practice these patients should be recommended daily physical activity as a part of their treatment.

  • 26.
    Berg, Marie
    et al.
    Centre for Person-Centred Care (GPCC), Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Linden, Karolina
    Centre for Person-Centred Care (GPCC), Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Adolfsson, Annsofie
    Örebro universitet, Institutionen för hälsovetenskaper.
    Sparud-Lundin, Carina
    Centre for Person-Centred Care (GPCC), Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ranerup, Agneta
    Department of Applied Information Technology, University of Gothenburg, Gothenburg, Sweden.
    Web-Based Intervention for Women With Type 1 Diabetes inPregnancy and Early Motherhood: Critical Analysis of Adherenceto Technological Elements and Study Design2018Inngår i: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 20, nr 5, artikkel-id e160Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Numerous Web-based interventions have been implemented to promote health and health-related behaviors inpersons with chronic conditions. Using randomized controlled trials to evaluate such interventions creates a range of challenges, which in turn can influence the study outcome. Applying a critical perspective when evaluating Web-based health interventions is important.

    Objective: The objective of this study was to critically analyze and discuss the challenges of conducting a Web-based health intervention as a randomized controlled trial.

    Method: The MODIAB-Web study was critically examined using an exploratory case study methodology and the framework for analysis offered through the Persuasive Systems Design model. Focus was on technology, study design, and Web-based support usage, with special focus on the forum for peer support. Descriptive statistics and qualitative content analysis were used.

    Results: The persuasive content and technological elements in the design of the randomized controlled trial included all four categories of the Persuasive Systems Design model, but not all design principles were implemented. The study duration was extended to a period of four and a half years. Of 81 active participants in the intervention group, a maximum of 36 women were simultaneously active. User adherence varied greatly with a median of 91 individual log-ins. The forum for peer support was used by 63 participants. Although only about one-third of the participants interacted in the forum, there was a fairly rich exchange of experiences and advice between them. Thus, adherence in terms of social interactions was negatively affected by limited active participation due to prolonged recruitment process and randomization effects. Lessons learned from this critical analysis are that technology and study design matter and might mutually influence each other. In Web-based interventions, the use of design theories enables utilization of the full potential of technology and promotes adherence. The randomization element in a randomized controlled trial design can become a barrier to achieving a critical mass of user interactions in Web-based interventions, especially when social support is included. For extended study periods, the technology used may need to be adapted in line with newly available technical options to avoid the risk of becoming outdated in the user realm, which in turn might jeopardize study validity in terms of randomized controlled trial designs.

    Conclusions: On the basis of lessons learned in this randomized controlled trial, we give recommendations to consider when designing and evaluating Web-based health interventions.

  • 27.
    Bergens, Oscar
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper.
    Nilsson, Andreas
    Örebro universitet, Institutionen för hälsovetenskaper.
    Kadi, Fawzi
    Örebro universitet, Institutionen för hälsovetenskaper.
    Cardiorespiratory Fitness Does Not Offset Adiposity-Related Systemic Inflammation in Physically Active Older Women2019Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, nr 9, s. 4119-4126Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: Chronic inflammation increases diabetes risk and may be exacerbated by excess adipose tissue. Whether cardiovascular fitness can offset chronic inflammation associated with excess adipose tissue in older adults is unclear.

    OBJECTIVE: The study aimed to examine the influence of cardiorespiratory fitness on links between adiposity and pro- and anti-inflammatory biomarkers related to metabolic risk in physically active older women.

    DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study comprising older community-dwelling women (n = 109; age, 65-70 yr).

    MAIN OUTCOME: Cardiorespiratory fitness was assessed using a standardized submaximal test and participants were categorized into high and low adiposity-related metabolic risk (body mass index, waist-to-hip ratio (WHR) and total fat mass). The inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, IL-18, adiponectin, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP-1α) were analyzed.

    RESULTS: Regardless of adiposity measure, women in the metabolic high-risk group had significantly (P<0.05) elevated CRP and lower adiponectin levels. Levels of IL-6 and MIP1-α were significantly elevated in the high-risk group defined by WHR and total fat mass. IL-18 level was significantly elevated in the high-risk group based on WHR only. Importantly, a high cardiorespiratory fitness level did not attenuate the detrimental links between adiposity measures and inflammation.

    CONCLUSIONS: Altogether, cardiorespiratory fitness does not offset the detrimental links between adiposity and several inflammatory biomarkers related to metabolic risk in physically active older women. Reducing abdominal adipose tissue in older adults should be emphasized in efforts aiming to attenuate age-related systemic inflammation and metabolic risk regardless of cardiorespiratory fitness.

  • 28.
    Bjornsdottir, Sigridur
    et al.
    Dept Mol Med & Surg, Karolinska Inst, Stockholm, Sweden.
    Sundstrom, Anders
    Dept Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Region Örebro län. Dept Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden.
    Blomqvist, Paul
    Dept Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden.
    Kampe, Olle
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Bensing, Sophie
    Dept Mol Med & Surg, Karolinska Inst, Stockholm, Sweden; Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Drug Prescription Patterns in Patients With Addison's Disease: A Swedish Population-Based Cohort Study2013Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, nr 5, s. 2009-2018Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: There are no published data on drug prescription in patients with Addison's disease ( AD). Objective: Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls. Design and Setting: We conducted a population-based cohort study in Sweden. Patients: Through the Swedish National Patient Register and the Swedish Prescribed Drug Register, we identified 1305 patients with both a diagnosis of AD and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient charts was not available. We identified 11 996 matched controls by the Register of Population. Main Outcome Measure: We determined the ratio of observed to expected number of patients treated with prescribed drugs. Results: Overall, Swedish AD patients received more prescribed drugs than controls, and 59.3% of the AD patients had medications indicating concomitant autoimmune disease. Interestingly, both before and after the diagnosis of AD, patients used more gastrointestinal medications, antianemic preparations, lipid-modifying agents, antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive airway disease (all P values < .05). Notably, an increased prescription of several antihypertensive drugs and high-ceiling diuretics was observed after the diagnosis of AD. Conclusion: Gastrointestinal symptoms and anemia, especially in conjunction with autoimmune disorders, should alert the physician about the possibility of AD. The higher use of drugs for cardiovascular disorders after diagnosis in patients with AD raises concerns about the replacement therapy.

  • 29.
    Blonde, Lawrence
    et al.
    Department of Endocrinology, Ochsner Medical Center, New Orleans LA, USA.
    Jendle, Johan
    Örebro universitet, Institutionen för medicinska vetenskaper. Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    Gross, Jorge
    Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
    Woo, Vincent
    Section of Endocrinology and Metabolism, University of Manitoba, Winnipeg MB, Canada.
    Jiang, Honghua
    Lilly Diabetes, Eli Lilly and Company, Indianapolis IN, USA.
    Fahrbach, Jessie L.
    Diabetes, Eli Lilly and Company, Indianapolis IN, USA.
    Milicevic, Zvonko
    Lilly Research Laboratories, Vienna, Austria.
    Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study2015Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, nr 9982, s. 2057-2066Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment, advancing to a basal-bolus insulin regimen is often recommended. We aimed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine, both combined with prandial insulin lispro, in patients with type 2 diabetes.

    Methods: We did this 52 week, randomised, open-label, phase 3, non-inferiority trial at 105 study sites in 15 countries. Patients (aged ≥18 years) with type 2 diabetes inadequately controlled with conventional insulin treatment were randomly assigned (1:1:1), via a computer-generated randomisation sequence with an interactive voice-response system, to receive once-weekly dulaglutide 1·5 mg, dulaglutide 0·75 mg, or daily bedtime glargine. Randomisation was stratified by country and metformin use. Participants and study investigators were not masked to treatment allocation, but were unaware of dulaglutide dose assignment. The primary outcome was a change in glycated haemoglobin A1c (HbA1c) from baseline to week 26, with a 0·4% non-inferiority margin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01191268.

    Findings: Between Dec 9, 2010, and Sept 21, 2012, we randomly assigned 884 patients to receive dulaglutide 1·5 mg (n=295), dulaglutide 0·75 mg (n=293), or glargine (n=296). At 26 weeks, the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg (-1·64% [95% CI -1·78 to -1·50], -17·93 mmol/mol [-19·44 to -16·42]) and dulaglutide 0·75 mg (-1·59% [-1·73 to -1·45], -17·38 mmol/mol [-18·89 to -15·87]) than in those receiving glargine (-1·41% [-1·55 to -1·27], -15·41 mmol/mol [-16·92 to -13·90]). The adjusted mean difference versus glargine was -0·22% (95% CI -0·38 to -0·07, -2·40 mmol/mol [-4·15 to -0·77]; p=0·005) for dulaglutide 1·5 mg and -0·17% (-0·33 to -0·02, -1·86 mmol/mol [-3·61 to -0·22]; p=0·015) for dulaglutide 0·75 mg. Five (<1%) patients died after randomisation because of septicaemia (n=1 in the dulaglutide 1·5 mg group); pneumonia (n=1 in the dulaglutide 0·75 mg group); cardiogenic shock; ventricular fibrillation; and an unknown cause (n=3 in the glargine group). We recorded serious adverse events in 27 (9%) patients in the dulaglutide 1·5 mg group, 44 (15%) patients in the dulaglutide 0·75 mg group, and 54 (18%) patients in the glargine group. The most frequent adverse events, arising more often with dulaglutide than glargine, were nausea, diarrhoea, and vomiting.

    Iinterpretation: Dulaglutide in combination with lispro resulted in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment.

    FUNDING: Eli Lilly and Company.

  • 30.
    Bogl, Leonie H.
    et al.
    Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland.
    Tuvblad, Catherine
    Örebro universitet, Institutionen för juridik, psykologi och socialt arbete. Department of Psychology, University of Southern California, Los Angeles CA, United States.
    Kaprio, Jaakko
    Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland.
    Does the sex of one's co-twin affect height and BMI in adulthood?: A study of dizygotic adult twins from 31 cohorts2017Inngår i: Biology of Sex Differences, ISSN 2042-6410, Vol. 8, nr 1, artikkel-id 14Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs.

    Methods: The data were derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) database, and included 68,494 SS and 53,808 OS dizygotic twin individuals above the age of 20 years from 31 twin cohorts representing 19 countries. Zygosity was determined by questionnaires or DNA genotyping depending on the study. Multiple regression and logistic regression models adjusted for cohort, age, and birth year with the twin type as a predictor were carried out to compare height and BMI in twins from OS pairs with those from SS pairs and to calculate the adjusted odds ratios and 95% confidence intervals for being overweight or obese.

    Results: OS females were, on average, 0.31 cm (95% confidence interval (CI) 0.20, 0.41) taller than SS females. OS males were also, on average, taller than SS males, but this difference was only 0.14 cm (95% CI 0.02, 0.27). Mean BMI and the prevalence of overweight or obesity did not differ between males and females from SS and OS twin pairs. The statistically significant differences between OS and SS twins for height were small and appeared to reflect our large sample size rather than meaningful differences of public health relevance.

    Conclusions: We found no evidence to support the hypothesis that prenatal hormonal exposure or postnatal socialization (i.e., having grown up with a twin of the opposite sex) has a major impact on height and BMI in adulthood.

  • 31.
    Bondia-Pons, Isabel
    et al.
    VTT Technical Research Centre of Finland, Espoo, Finland; Department of Food Science and Physiology, University of Navarra, Pamplona, Spain.
    Maukonen, Johanna
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Rissanen, Aila
    Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
    Saarela, Maria
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Kaprio, Jaakko
    Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland.
    Hakkarainen, Antti
    Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
    Lundbom, Jesper
    Department of Radiology, Hospital District of Helsinki and Uusimaa (HUS) Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland.
    Lundbom, Nina
    Department of Radiology, Hospital District of Helsinki and Uusimaa (HUS) Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland.
    Hyötyläinen, Tuulia
    Örebro universitet, Institutionen för naturvetenskap och teknik. VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
    Pietiläinen, Kirsi H.
    Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
    Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge2014Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, nr 9, s. 4169-4179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Postprandial responses to food are complex, involving both genetic and environmental factors. We studied postprandial responses to a Big Mac meal challenge in monozygotic co-twins highly discordant for body weight. This unique design allows assessment of the contribution of obesity, independent of genetic liability. Comprehensive metabolic profiling using 3 analytical platforms was applied to fasting and postprandial serum samples from 16 healthy monozygotic twin pairs discordant for weight (body mass index difference >3 kg/m(2)). Nine concordant monozygotic pairs were examined as control pairs. Fecal samples were analyzed to assess diversity of the major bacterial groups by using 5 different validated bacterial group specific denaturing gradient gel electrophoresis methods. No differences in fecal bacterial diversity were detected when comparing co-twins discordant for weight (ANOVA, P<0.05). We found that within-pair similarity is a dominant factor in the metabolic postprandial response, independent of acquired obesity. Branched chain amino acids were increased in heavier as compared with leaner co-twins in the fasting state, but their levels converged postprandially (paired t tests, FDR q<0.05). We also found that specific bacterial groups were associated with postprandial changes of specific metabolites. Our findings underline important roles of genetic and early life factors in the regulation of postprandial metabolite levels.

  • 32.
    Brunner, G. A.
    et al.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Balent, B.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Ellmerer, M.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Schaupp, L.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Siebenhofer, A.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Jendle, Johan
    Novo Nordisk A/S, Copenhagen, Denmark.
    Okikawa, J.
    Aradigm Corp., Hayward, California, USA.
    Pieber, T. R.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Dose-response relation of liquid aerosol inhaled insulin in type I diabetic patients.2001Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, nr 3, s. 305-308Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS/HYPOTHESIS: The AERx insulin Diabetes Management system (AERx iDMS) is a liquid aerosol device that enables insulin to be administered to the peripheral parts of the lung. This study aimed to compare the pharmacokinetic and pharmacodynamic properties of insulin which is inhaled using AERx iDMS with insulin which is subcutaneously administered.

    METHODS: In total, 18 C-peptide negative patients with Type I (insulin-dependent) diabetes mellitus participated in this randomised, open-label, 5-period crossover trial. Human regular insulin was administered subcutaneously (0.12 U/kg body weight) or inhaled by means of the AERx iDMS (dosages 0.3, 0.6, 1.2, and 1.8 U/kg body weight). Thereafter plasma glucose was kept constant at 7.2 mmol/l for a 10-h period (glucose clamp technique).

    RESULTS: Inhaled insulin provided a dose-response relation that was close to linear for both pharmacokinetic (AUC-Ins(0-10 h); Cmax-Ins) and pharmacodynamic (AUC-GIR(0-10 h); GIRmax) parameters. Time to maximum insulin concentration (Tmax-Ins) and time to maximum glucose infusion rate (TGIRmax) were shorter with inhaled insulin than with subcutaneous administration. The pharmacodynamic system efficiency of inhaled insulin (AUC-GIR(0-6 h) was 12.7% (95% C.I.: 10.2-15.6).

    CONCLUSION/INTERPRETATION: The inhalation of soluble human insulin using the AERx iDMS is feasible and provides a clear dose response. Further long-term studies are required to investigate safety aspects, HbA1c values, incidence of hypoglycaemic events and the quality of life.

  • 33. Cameron, F. J.
    et al.
    Skinner, T. C.
    de Beaufort, C. E.
    Hoey, H.
    Swift, P. G. F.
    Aanstoot, H.
    Åman, Jan
    Örebro universitet, Hälsoakademin.
    Martul, P.
    Chiarelli, F.
    Daneman, D.
    Danne, T.
    Dorchy, H.
    Kaprio, E. A.
    Kaufman, F.
    Kocova, M.
    Mortensen, H. B.
    Njølstad, P. R.
    Phillip, M.
    Robertson, K. J.
    Schoenle, E. J.
    Urakami, T.
    Vanelli, M.
    Ackermann, R. W.
    Skovlund, S. E.
    Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?2008Inngår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 25, nr 4, s. 463-468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries.

    METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood.

    RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen.

    CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres 

  • 34.
    Carlsson, Lena M. S.
    et al.
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Peltonen, Markku
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
    Ahlin, Sofie
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Anveden, Åsa
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bouchard, Claude
    Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge LA, United States.
    Carlsson, Björn
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Jacobson, Peter
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lönroth, Hans
    Institute of Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Maglio, Cristina
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Näslund, Ingmar
    Department of Surgery, Örebro University Hospital, Region Örebro län, Örebro, Sweden.
    Pirazzi, Carlo
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Romeo, Stefano
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sjöholm, Kajsa
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sjöström, Elisabeth
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wedel, Hans
    Nordic School of Public Health, Gothenburg, Sweden.
    Svensson, Per-Arne
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sjöström, Lars
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects2012Inngår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 367, nr 8, s. 695-704Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes.

    METHODS: In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination.

    RESULTS: During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P< 0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P = 0.002 for the interaction) but not by BMI (P = 0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications.

    CONCLUSIONS: Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.)

  • 35.
    Carobbio, Stefania
    et al.
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Hagen, Rachel M.
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Lelliott, Christopher J.
    Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden.
    Slawik, Marc
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians University, Munich, Germany.
    Medina-Gomez, Gema
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, , Madrid, Spain.
    Tan, Chong-Yew
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Sicard, Audrey
    Laboratory of Obesity, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse, France.
    Atherton, Helen J.
    MRC Human Nutrition Research, Elsie Widdowson Laboratory, University of Cambridge, Cambridge, United Kingdom.
    Barbarroja, Nuria
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Hospital Virgen de la Victoria, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Malaga, Spain.
    Bjursell, Mikael
    Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden.
    Bohlooly-Y, Mohammad
    Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden.
    Virtue, Sam
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Tuthill, Antoinette
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    Lefai, Etienne
    Lyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France.
    Laville, Martine
    Lyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France.
    Wu, Tingting
    Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden.
    Considine, Robert V.
    Division of Endocrinology and Metabolism, School of Medicine, Indiana University, Indianapolis IN, United States.
    Vidal, Hubert
    Lyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France.
    Langin, Dominique
    Laboratory of Obesity, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse, France; Laboratory of Clinical Biochemistry, Toulouse, France.
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Medicine, Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland.
    Tinahones, Francisco J.
    Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.
    Fernandez-Real, Jose Manuel
    Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, CIBERobn Fisiopatología de la Obesidad y Nutrición, Girona, Spain.
    Griffin, Julian L.
    MRC Human Nutrition Research, Elsie Widdowson Laboratory, University of Cambridge, Cambridge, United Kingdom.
    Sethi, Jaswinder K.
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
    López, Miguel
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
    Vidal-Puig, Antonio
    Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity2013Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 62, nr 11, s. 3697-3708Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.

  • 36.
    Cheng, Helen
    et al.
    Department of Psychology, University College London, London, United Kingdom; ESRC Centre for Learning and Life Chances in Knowledge Economies and Societies, Institute of Education, University of London, London, United Kingdom .
    Treglown, Luke
    Department of Psychology, University College London, London, United Kingdom; Department of Psychology, University of Bath, Bath, United Kingdom .
    Montgomery, Scott
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Research Department of Epidemiology and Public Health, UCL, London, United Kingdom .
    Furnham, Adrian
    Department of Psychology, University College London, London, United Kingdom; Norwegian Business School, Oslo, Norway .
    Associations between familial factor, trait conscientiousness, gender and the occurrence of type 2 diabetes in adulthood: evidence from a British cohort2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 5, artikkel-id e0122701Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate social, familial, and psychological factors in influencing the occurrence of type 2 diabetes in adulthood.

    Method: Some 17,415 babies born in Great Britain in 1958 and followed up at 7, 11, 33, and 50 years of age. The prevalence of type 2 diabetes at age 50 years was the outcome measure.

    Results: Some 5,032 participants with data on parental social class, childhood cognitive ability tests scores at age 11 years, educational qualifications at age 33 years, personality traits, occupational levels, and type 2 diabetes (all measured at age 50 years) were included in the study. Available information also included whether cohort members' parents or siblings had diabetes. Using logistic regression analyses, results showed that sex (OR= 0.63: 0.42-0.92, p<. 05), family history (OR= 3.40: 1.76-6.55, p<. 01), and trait conscientiousness (OR= 0.76: 0.64-0.90, p<. 001) were all significantly and independently associated with the occurrence of type 2 diabetes in adulthood. It appears that the occurrence of type 2 diabetes is greater among men than women (4.3% vs 2.5%).

    Conclusion: Familial (genetic and non-genetic) and psychological factors are significantly associated with the prevalence of type 2 diabetes in adulthood.

  • 37.
    Coenen Schimke, J. M.
    et al.
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
    Ljungqvist, Olle
    Department of Medicine, University of Vermont, Burlington, VT, USA.
    Sarkar, G.
    Department of Medicine, University of Vermont, Burlington, VT, USA.
    Conover, C. A.
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
    Nair, K. S.
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
    A quantitative PCR measurement of messenger RNA expression of IGF-I, IGF-II and IGFBP-5 in human skeletal muscle1999Inngår i: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 9, nr 3, s. 179-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin-like growth factor-I and -II (IGF-I and IGF-II) and their binding proteins are important components in growth promotion and tissue maintenance. We determined the presence of IGF-I, -II, and binding protein 5 (IGFBP-5) gene expression in human skeletal muscle and that mRNA abundance is not altered by nutrients and insulin. In the first protocol, (control) subjects were given water. In the second protocol, half of these subjects drank Polycose (carbohydrate) and the remaining subjects drank equal calories as a mixed meal. Quadriceps muscle biopsies were taken at 10 h. A semi-quantitative polymerase chain reaction was designed to measure gene expression. IGF-I, IGF-II and IGFBP-5 mRNA are present in adult human skeletal muscle, but no significant changes between meal groups were observed for IGF-I, IGF-II or IGFBP-5 mRNA levels, indicating that the expression of these genes are not altered acutely by nutrients and insulin.

  • 38.
    Dahlqvist, Ake
    et al.
    Department of Otorhinolaryngology, University Hospital of Umeå, Umeå, Sweden.
    Rask, Eva
    Department of Internal Medicine, University Hospital of Umeå, Umeå, Sweden.
    Rosenqvist, Carl-Johan
    Department of Pediatrics, University Hospital of Umeå, Umeå, Sweden.
    Sahlin, Carin
    Department of Respiratory Medicine, University Hospital of Umeå, Umeå, Sweden.
    Franklin, Karl A.
    Department of Respiratory Medicine, University Hospital of Umeå, Umeå, Sweden.
    Sleep apnea and Down's syndrome2003Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 123, nr 9, s. 1094-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Obstructive sleep apnea has been reported to occur in 20-50% of children with Down's syndrome in case series of patients referred for evaluation of suspected sleep apnea. In this population-based controlled study, we aimed to investigate whether sleep apnea is related to Down's syndrome.

    MATERIAL AND METHODS: Every child aged 2-10 years with Down's syndrome residing in the Umeå healthcare district (n = 28) was invited to participate in the study, with their siblings acting as controls. Successful overnight sleep apnea recordings and echocardiography were performed in 17/21 children with Down's syndrome and in 21 controls.

    RESULTS: Obstructive sleep apnea could not be diagnosed, either in children with Down's syndrome or in the control children. The apnea-hypopnea index in the children with Down's syndrome was 1.2 +/- 1.5 and did not differ from that in controls. Snoring and hypertrophy of the tonsils were more common in children with Down's syndrome than in controls. Children with Down's syndrome slept for a shorter time (p < 0.001) and changed body position more often (p < 0.05) than the control children.

    CONCLUSIONS: Snoring, restless sleep and hypertrophy of the tonsils were common among children with Down's syndrome. Obstructive sleep apnea was, however, not related to Down's syndrome in the present population-based controlled study.

  • 39.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ohlson, Anna-Lena
    Department of Laboratory Medicine, Pathology, University Hospital Örebro, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Giunchi, Francesca
    Department of Hematology-Oncology, Molecular Pathology Laboratory, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    Rider, Jennifer R.
    Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.
    Fiorentino, Michelangelo
    Department of Hematology-Oncology, Molecular Pathology Laboratory, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer2018Inngår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, nr 1, s. 40-47Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs ). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer.

    METHODS: Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area.

    RESULTS: In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart.

    CONCLUSIONS: Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established.

  • 40.
    de Beaufort, Carine E.
    et al.
    Pediat Clin, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg.
    Lange, Karin
    Dept Med Psychol, Hannover Medical School, Hannover, Germany.
    Swift, Peter G. F.
    Childrens Hosp, Leicester Royal Infirmary, Leicester, England..
    Åman, Jan
    Region Örebro län. Dept Pediat, Örebro University Hospital, Örebro, Sweden.
    Cameron, Fergus
    Dept Endocrinol & Diabet, Royal Childrens Hosp, Parkville Vic, Australia.
    Castano, Luis
    Endocrinol & Diabet Res Grp, Hosp Cruces, Univ Basque Country, Baracaldo, Spain.
    Dorchy, Harry
    Diabetol Clin, Univ Hosp Reine Fabiola, Brussels, Belgium.
    Fisher, Lynda K.
    Dept Endocrinol & Diabet, Childrens Hosp Los Angeles, Los Angeles CA, USA..
    Hoey, Hilary
    Natl Childrens Hosp, Univ Dublin Trinity Coll, Dublin, Ireland.
    Kaprio, Eero
    Dept Paediat, Peijas Hosp, Helsinki, Finland.
    Kocova, Mirjana
    Dept Endocrinol & Genet, Univ Pediat Clin, Skopje, Macedonia.
    Neu, Andreas
    Clin Children & Adolescence, Univ Tubingen, Tubingen, Germany.
    Njolstad, Pal R.
    Dept Clin Med, Univ Bergen, Bergen, Norway; Dept Pediat, Haukeland Hosp, Bergen, Norway.
    Phillip, Moshe
    Natl Ctr Childhood Diabet, Schneiders Med Ctr Israel, Petah Tiqwa, Israel.
    Schoenle, Eugen
    Dept Diabet & Endocrinol, Univ Childrens Hosp, Zurich, Switzerland.
    Robert, Jean J.
    Dept Childhood & Adolescent Diabet, Hop Necker Enfants Malad, Paris, France.
    Urukami, Tatsuhiko
    Sch Med, Nihon Univ, Tokyo, Japan.
    Vanelli, Maurizio
    Pediat Clin, Ctr Diabetol, Parma, Italy.
    Danne, Thomas
    Krankenhaus Bult, Hannover, Germany.
    Barrett, Tim
    Inst Child Hlth, Univ Birmingham, Birmingham, England; Birmingham Childrens Hosp, Univ Birmingham, Birmingham, England.
    Chiarelli, Franco
    Pediat Clin, Osped Policlin, Chieti, Italy.
    Aanstoot, Henk J.
    Ctr Pediat & Adolescent Diabet Care & Res, Rotterdam, Netherlands.
    Mortensen, Henrik B.
    Herlev Hosp, Dept Pediat, Herlev, Denmark; Fac Hlth Sci, Univ Copenhagen, Copenhagen, Denmark.
    Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 20092013Inngår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, nr 6, s. 422-428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate whether center differences in glycemic control are present in prepubertal children <11yr with type 1 diabetes mellitus. Research Design and Methods: This cross-sectional study involved 18 pediatric centers worldwide. All children, <11 y with a diabetes duration 12months were invited to participate. Case Record Forms included information on clinical characteristics, insulin regimens, diabetic ketoacidosis (DKA), severe hypoglycemia, language difficulties, and comorbidities. Hemoglobin A1c (HbA1c) was measured centrally by liquid chromatography (DCCT aligned, range: 4.4-6.3%; IFFC: 25-45mmol/mol). Results: A total of 1133 children participated (mean age: 8.0 +/- 2.1 y; females: 47.5%, mean diabetes duration: 3.8 +/- 2.1 y). HbA1c (overall mean: 8.0 +/- 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p<0.001 resp. p=0.179). Language difficulties showed a negative relationship with HbA1c (8.3 +/- 1.2% vs. 8.0 +/- 1.0%; p = 0.036). Frequency of blood glucose monitoring demonstrated a significant but weak association with HbA1c (r=-0.17; p<0.0001). Although significant different HbA1c levels were obtained with diverse insulin regimens (range: 7.3-8.5%; p<0.001), center differences remained after adjusting for insulin regimen (p<0.001). Differences between insulin regimens were no longer significant after adjusting for center effect (p=0.199). Conclusions: Center differences in metabolic outcomes are present in children <11yr, irrespective of diabetes duration, age, or gender. The incidence of severe hypoglycemia is lower than in adolescents despite achieving better glycemic control. Insulin regimens show a significant relationship with HbA1c but do not explain center differences. Each center's effectiveness in using specific treatment strategies remains the key factor for outcome.

  • 41. de Valk, H.W.
    et al.
    Feher, M.
    Krarup Hansen, T.
    Jendle, Johan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Merchante, A.
    Koefoed, M.M.
    Rizi, E.P.
    Zimmermann, E.
    Fadini, G.P.
    Switching to insulin degludec from other basal insulins reduces rates of hypoglycaemia across patient subgroups in routine clinical care: The ReFLeCT study2019Konferansepaper (Annet vitenskapelig)
  • 42. de Valk, H.W.
    et al.
    Feher, M.
    Krarup Hansen, T.
    Jendle, Johan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Merchante, A.
    Koefoed, M.M.
    Rizi, E.P.
    Zimmermann, E.
    Fadini, G.P.
    Switching to insulin degludec from other basal insulins reduces rates of hypoglycemia (according to different definitions) in routine clinical care: The ReFLeCT Study2019Konferansepaper (Annet vitenskapelig)
  • 43. de Valk, H.W.
    et al.
    Feher, M.
    Krarup Hansen, T.
    Jendle, Johan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Merchante, A.
    Koefoed, M.M.
    Rizi, E.P.
    Zimmermann, E.
    Fadini, G.P.
    Switching to insulin degludec from other basal insulins reduces rates of hypoglycemia across patient subgroups in routine clinical care: The ReFleCT study2019Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    ReFLeCT, a multicenter, prospective, observational study evaluated the safety and effectiveness of switching from other basal insulins to insulin degludec (degludec) in patients with type 1 (T1D) or type 2 diabetes (T2D) in routine clinical practice. ReFLeCT comprised a 4-week baseline period (pre-switch basal insulin) and 12-month follow-up period (degludec). The primary endpoint of overall hypoglycemia reported in patient diaries was reduced during the 12-month follow-up period vs. baseline, without compromising glycemic control. In pre-specified subgroup analyses of the primary endpoint, we assessed if the overall result was robust in different subgroups, characterized according to baseline A1C (<7.5, ≥7.5-<8.5, ≥8.5-<9.5, ≥9.5%), diabetes duration (quartiles) and physician’s reason for initiating degludec (hypoglycemia [Yes/No]). The estimated rate ratios of hypoglycemia were similar within subgroups (no significant interactions), and demonstrated overall lower rates (the majority significantly lower) during the 12-month follow-up periods vs. baseline in patients with T1D or T2D (Figure). Irrespective of baseline characteristics or physician’s reason for initiating degludec, switching to degludec from other basal insulins reduced rates of overall hypoglycemia in patients with T1D or T2D, in routine clinical practice.

  • 44.
    Derakhshan, Arash
    et al.
    Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, The Netherlands; Department of internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
    Shu, Huan
    Department of Environmental Science and Analytical Chemistry, Stockholm University, Stockholm, Sweden.
    Broeren, Maarten A. C.
    Laboratory of Clinical Chemistry and Haematology, Máxima Medical Centre, Veldhoven, De Run, The Netherlands.
    de Poortere, Ralph A.
    Laboratory of Clinical Chemistry and Haematology, Máxima Medical Centre, Veldhoven, De Run, The Netherlands.
    Wikström, Sverre
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Peeters, Robin P.
    Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, The Netherlands; Department of internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
    Demeneix, Barbara
    Laboratoire d'Evolution des Régulations Endocriniennes, Muséum National d'Histoire Naturelle, Paris, France.
    Bornehag, Carl-Gustaf
    Division of Public Health Sciences, Karlstad University, Karlstad, Sweden; Icahn School of Medicine at Mount Sinai, New York City NY, USA.
    Korevaar, Tim I. M.
    Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, The Netherlands; Department of internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
    Reference ranges and determinants of thyroid function during early pregnancy: the SELMA study2018Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, nr 9, s. 3548-3556Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Establishing reference ranges as well as identifying and quantifying the determinants of thyroid function during pregnancy is important for proper clinical interpretation and optimizing research efforts. However, such data are sparse, specifically for (F)T3 measurements and most studies do not take into account thyroid antibodies or hCG.

    Objective: To determine reference ranges and to identify/quantify determinants of TSH, FT4, FT3, TT4 and TT3.

    Design, Setting and Participants: This study included 2,314 participants of the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study, a population-based prospective pregnancy cohort of mother-child pairs. Reference ranges were calculated by 2.5-97.5th percentiles after excluding TPOAb and/or TgAb positive women.

    Intervention: None.

    Main Outcome Measures: TSH, FT4, FT3, TT4 and TT3 in prenatal serum.

    Results: After exclusion of TPOAb positive women, reference range were: TSH: 0.11-3.48 mU/L, FT4: 11.6-19.4 pmol/L, FT3: 3.72-5.92 pg/mL, TT4: 82.4-166.2 pmol/L and TT3: 1.28-2.92 nmol/L. Additional exclusion of TgAb positive women did not change the reference ranges substantially. Exposure to tobacco smoke, as assessed by questionnaires and serum cotinine, was associated with lower TSH and higher FT3 and TT3. BMI and gestational age were the main determinants of TSH (only for BMI), FT4, FT3, TT4 and TT3.

    Conclusions: We show that the exclusion of TgAb positive women on top of excluding TPOAb positive women hardly affects clinical reference ranges. We identified various relevant clinical determinants of TSH, FT4, FT3, TT4 and TT3 which could reflect endocrine disrupting effects and/or effects on thyroid hormone transport or deiodination.

  • 45.
    Derks, Ivonne P. M.
    et al.
    Department of Child & Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands; Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands.
    Bolhuis, Koen
    Department of Child & Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands; Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands.
    Yalcin, Zeynep
    Department of Child & Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
    Gaillard, Romy
    Department of Pediatrics, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
    Hillegers, Manon H. J.
    Department of Child & Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands; Department of Psychiatry, Rudolf Magnus Brain Center, Utrecht University Medical Center, Utrecht, the Netherlands.
    Larsson, Henrik
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Lundström, Sebastian
    Center for Ethics, Law and Mental Health, University of Gothenborg, Gothenborg, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    van Beijsterveldt, Catharina E. M.
    Department of Biological Psychology, Vrije University, Amsterdam, the Netherlands.
    Bartels, Meike
    Department of Biological Psychology, Vrije University, Amsterdam, the Netherlands.
    Boomsma, Dorret I.
    Department of Biological Psychology, Vrije University, Amsterdam, the Netherlands.
    Tiemeier, Henning
    Department of Child & Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands; Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
    Jansen, Pauline W.
    Department of Child & Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands; Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, the Netherlands.
    Testing Bidirectional Associations Between Childhood Aggression and BMI: Results from Three Cohorts2019Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 27, nr 5, s. 822-829Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: This study examined the prospective, potentially bidirectional association of aggressive behavior with BMI and body composition across childhood in three population-based cohorts.

    METHODS: Repeated measures of aggression and BMI were available from the Generation R Study between ages 6 and 10 years (N = 3,974), the Netherlands Twin Register (NTR) between ages 7 and 10 years (N = 10,328), and the Swedish Twin Study of Child and Adolescent Development (TCHAD) between ages 9 and 14 years (N = 1,462). In all samples, aggression was assessed with the Child Behavior Checklist. Fat mass and fat-free mass were available in the Generation R Study. Associations were examined with cross-lagged modeling.

    RESULTS: Aggressive behavior at baseline was associated with higher BMI at follow-up in the Generation R Study (β = 0.02, 95% CI: 0.00 to 0.04), in NTR (β = 0.04, 95% CI: 0.02 to 0.06), and in TCHAD (β = 0.03, 95% CI: -0.02 to 0.07). Aggressive behavior was prospectively associated with higher fat mass (β = 0.03, 95% CI: 0.01 to 0.05) but not fat-free mass. There was no evidence that BMI or body composition preceded aggressive behavior.

    CONCLUSIONS: More aggressive behavior was prospectively associated with higher BMI and fat mass. This suggests that aggression contributes to the obesity problem, and future research should study whether these behavioral pathways to childhood obesity are modifiable.

  • 46. Devlieger, Roland
    et al.
    Fadl, Helena
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Deruelle, Philippe
    Assessment of fetal and neonatal growth (including growth pattern in diabetes)2016Inngår i: 2016 AUDIT MEETING: Diabetic Pregnancy Study Group of the EASD, 2016Konferansepaper (Fagfellevurdert)
  • 47.
    Elfström, Peter
    et al.
    Örebro universitet, Hälsoakademin.
    Montgomery, Scott M.
    Örebro universitet, Hälsoakademin.
    Kämpe, Olle
    Uppsala Universitet.
    Ekbom, Anders
    Karolinska Institutet.
    Ludvigsson, Jonas F.
    Risk of primary adrenal insufficiency in patients with celiac disease2007Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, nr 9, s. 3595-3598Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD).Wehave here investigated the risk of AD in individuals with CD from a general population cohort.Methods: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964–2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.Results: There was a statistically significantly positive association between CD and subsequent AD [HR _ 11.4; 95% confidence interval (CI) _ 4.4 –29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI _ 1.9 –11.4). Individuals with prior AD were at increased risk of CD (odds ratio _ 8.6; 95% CI _ 3.4 –21.8).Conclusions: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.

  • 48.
    Elfström, Peter
    et al.
    Örebro universitet, Hälsoakademin.
    Montgomery, Scott M.
    Kämpe, Olle
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Risk of Thyroid Disease in Individuals with Celiac Disease2008Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, nr 10, s. 3915-3921Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort.Methods: A total of 14,021 individuals with celiac disease (1964–2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up ofmorethan 1 yr and withnothyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease.Results: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR)_4.4;95% confidence interval (CI) _ 3.4 –5.6; P _ 0.001], thyroiditis (HR _ 3.6; 95% CI _1.9–6.7; P _ 0.001) and hyperthyroidism (HR_2.9;95%CI_2.0–4.2; P_0.001). The highest risk estimates were found in children (hypothyroidism, HR _ 6.0 and 95% CI _ 3.4 –10.6; thyroiditis, HR _ 4.7 and 95% CI _ 2.1–10.5; hyperthyroidism, HR _ 4.8 and 95% CI _ 2.5–9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI_2.7– 4.4; P_0.001), 3.3 for thyroiditis(95%CI_1.5–7.7; P_0.001), and 3.1 for hyperthyroidism (95% CI _ 2.0–4.8; P _ 0.001).Conclusion: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.

  • 49.
    Eliasson, Bjorn
    et al.
    Dept Mol & Clin Med, Univ Gothenburg, Gothenburg, Sweden; Dept Med, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Liakopoulos, Vasileios
    Dept Mol & Clin Med, Univ Gothenburg, Gothenburg, Sweden.
    Franzen, Stefan
    Natl Diabetes Register, Registercentrum Västra Götaland, Gothenburg, Sweden.
    Näslund, Ingmar
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Dept Surg, Örebro University Hospital, Örebro, Sweden.
    Svensson, Ann-Marie
    Dept Mol & Clin Med, Univ Gothenburg, Gothenburg, Sweden; Natl Diabetes Register, Registercentrum Västra Götaland, Gothenburg, Sweden.
    Ottosson, Johan
    Dept Surg, Örebro University Hospital, Örebro, Sweden.
    Gudbjornsdottir, Soffia
    Dept Mol & Clin Med, Univ Gothenburg, Gothenburg, Sweden; Natl Diabetes Register, Registercentrum Västra Götaland, Gothenburg, Sweden.
    Cardiovascular disease and mortality in patients with type 2 diabetes after bariatric surgery in Sweden: a nationwide, matched, observational cohort study2015Inngår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 3, nr 11, s. 847-854Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background In patients with diabetes and obesity specifically, no studies have examined mortality after bariatric surgery. We did a nationwide study in Sweden to examine risks of cardiovascular disease and mortality in patients with obesity and diabetes who had undergone bariatric surgery (Roux-en-Y gastric bypass [RYGB]). Methods In this nationwide, matched, observational cohort study, we merged data for patients who had undergone RYGB registered in the Scandinavian Obesity Surgery Registry with other national databases, and identified matched controls (on the basis of sex, age, BMI, and calendar time [year]) who had not undergone bariatric surgery from the National Diabetes Registry. We assessed risks of cardiovascular disease and death using a Cox proportional-hazards regression model and other methods to examine the treatment effect while accounting for residual confounding. Primary outcomes were total mortality, cardiovascular death, and fatal or non-fatal myocardial infarction. Findings Between Jan 1, 2007, and Dec 31, 2014, we obtained data for 6132 patients who had undergone RYGB and 6132 control patients who had not. Median follow-up was 3.5 years (IQR 2.1-4.7). We noted a 58% relative risk reduction (hazard ratio [HR] 0.42, 95% CI 0.30-0.57; p< 0.0001) in overall mortality in the RYGB group compared with the controls. The risk of fatal or non-fatal myocardial infarction was 49% lower (HR 0.51, 0.29-0.91; p= 0.021) and that of cardiovascular death was 59% lower (0.41, 0.19-0.90; p= 0.026) in the RYGB group than in the control group. 5 year absolute risks of death were 1.8% (95% CI 1.5-2.2) in the RYGB group and 5.8% (5.0-6.8) in the control group. Interpretation Our findings provide support for the benefits of RYGB surgery for patients with obesity and type 2 diabetes. The causes of these beneficial effects may be the weight reduction per se, changes in physiology and metabolism, improved care and treatment, improvements in lifestyle and risk factors, or combinations of these factors.

  • 50.
    Eliman, A.
    et al.
    Department of Paediatrics, Endocrine Research Unit, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Tjäder, I.
    Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Norgren, S.
    Department of Paediatrics, Endocrine Research Unit, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Wernerman, J.
    Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Essén, P.
    Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Marcus, C.
    Department of Paediatrics, Endocrine Research Unit, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Totalparenteral nutrition after surgery rapidly increases serum leptin levels2001Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 144, nr 2, s. 123-128Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: In humans, leptin is regulated by long-term changes in energy intake. However, short-term regulation of serum leptin by nutrients has been difficult to show. The aim of this study was to investigate whether short periods of fasting and stress sensitise the leptin response to nutrients.

    Subjects and experimental protocol: Fourteen patients of normal weight undergoing elective open cholecystectomy were randomised into two groups. One group received saline infusion during surgery and for 24 h postoperatively. The other group also received saline during the surgical procedure, but total parenteral (TPN) was started immediately after surgery. Blood samples were drawn before as well as 2, 4, 8, 16, and 24 h after the start of surgery to determine the serum levels of leptin and other hormones.

    Results: Postoperative TPN induced a significant rise in serum leptin within 6 h, reaching a more than fourfold increase within 14 h (P < 0.001). Serum glucose and insulin levels increased within 2 h. Growth hormone and IGF-1 serum levels also increased significantly in the group receiving TPN. Serum cortisol levels increased postoperatively in both groups, which may explain why no significant reduction in serum leptin was observed in the group receiving saline. Free tri-iodothyronine (T3) decreased in both groups, while catecholamines were similar in the groups.

    Conclusion: During fasting and surgical stress, nutrients rapidly increased the serum leptin levels in humans in a manner similar to that previously reported in rodents. This may be mediated by increases in serum glucose, insulin and cortisol.

1234567 1 - 50 of 315
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf