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  • 1.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?2013In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 169, no 6, p. 885-889Article in journal (Refereed)
    Abstract [en]

    Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

  • 2.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hypoglycemia in everyday life after gastric bypass and duodenal switch2015In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, no 1, p. 91-100Article in journal (Refereed)
    Abstract [en]

    Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

  • 3.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umea Univ, Biomed Engn, Dept Radiat Sci, Umea, Sweden.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gastric bypass reduces symptoms and hormonal responses to hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed)
    Abstract [en]

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

  • 4.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation2011In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, no 8, p. e61-e66Article in journal (Refereed)
    Abstract [en]

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

  • 5.
    Billing, Ewa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    McKenna, S. P.
    Staun, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lindqvist, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Adaptation of the Psoriatic Arthritis Quality of Life (PsAQoL) instrument for Sweden2010In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 39, no 3, p. 223-228Article in journal (Refereed)
    Abstract [en]

    Objective: The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire is the first disease-specific patient-derived instrument for assessing QoL in patients with PsA and has been extensively validated in this population. The aim of the adaptation process reported here was to develop a Swedish version of the PsAQoL that was equivalent to, and met the same psychometric and acceptability standards as, the original instrument, which was developed in the UK. Method:Translation of the original questionnaire into Swedish was performed by a professional and a lay panel. Field testing for face and content validity was performed by interviewing 13 patients. Finally, 123 patients with PsA were included in a test-retest postal survey designed to test reproducibility and construct validity. The PsAQoL was administered on two occasions approximately 2 weeks apart. The Nottingham Health Profile (NHP) was used as a comparator instrument. Results: The Swedish version of the PsAQoL questionnaire showed good reliability at both time points and, as expected, correlated with the NHP. The scale was able to distinguish between groups based on self-reported general health and flare-up. Patients with active symptoms of both arthritis and psoriasis had worse QoL. The results also indicated that duration of disease has a progressive impact on PsAQoL scores. Conclusions: This study provides evidence that the adapted PsAQoL can be used for clinical studies in Swedish patients. The instrument provides valuable information on the long-term effects of PsA on QoL.

  • 6.
    Bodegard, J.
    et al.
    AstraZeneca, Sodertalje, Sweden..
    Nathanson, D.
    Karolinska Inst, Dept Clin Sci & Educa, Stockholm, Sweden..
    Nystrom, T.
    Karolinska Inst, Stockholm, Sweden..
    Thuresson, M.
    Statisticon AB, Uppsala, Sweden..
    Norhammar, A.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Second-line treatment with sulfonylurea compared to DPP4 inhibitors demonstrated associations with earlier treatment intensification with insulin2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S189-S189Article in journal (Other academic)
  • 7.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;AstraZeneca, Dept Med, Gothenburg, Sweden..
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S80-S80Article in journal (Other academic)
  • 8.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;Univ Gothenburg, Dept Med, Gothenburg, Sweden..
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Panagiotou, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skeletal muscle and liver, but not brain, account for impaired glucose utilisation in type 2 diabetes: whole-body PET/MR during hyperinsulinaemic euglycaemic clamp2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S33-S33Article in journal (Refereed)
  • 9.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Johns Hopkins University, School of Medicine, Department of Psychiatry and Behavioral Sciences.
    Smeltzer, Michael D.
    University of Cincinnati Medical Center, Department of Psychiatry and Behavioral Neuroscience.
    Scott, Karen A.
    University of Cincinnati Medical Center, Department of Psychiatry and Behavioral Neuroscience; University College Cork, Department of Anatomy and Neuroscience.
    Scheurink, Anton J.
    University of Groningen, Department of Neuroendocrinology, GELIFES, Neurobiology.
    Tamashiro, Kellie L.
    Johns Hopkins University, School of Medicine, Department of Psychiatry and Behavioral Sciences.
    Sakai, Randall R.
    University of Cincinnati Medical Center, Department of Psychiatry and Behavioral Neuroscience.
    Stress coping style does not determine social status, but influences the consequences of social subordination stress2017In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 178, p. 126-133Article in journal (Refereed)
    Abstract [en]

    Chronic stress exposure may have negative consequences for health. One of the most common sources of chronic stress is stress associated with social interaction. In rodents, the effects of social stress can be studied in a naturalistic way using the visual burrow system (VBS). The way an individual copes with stress, their "stress coping style", may influence the consequences of social stress. In the current study we tested the hypothesis that stress coping style may modulate social status and influence the consequences of having a lower social status. We formed 7 VBS colonies, with 1 proactive coping male, 1 passive coping male, and 4 female rats per colony to assess whether a rat's coping style prior to colony formation could predict whether that individual is more likely to become socially dominant. The rats remained in their respective colonies for 14 days and the physiological and behavioral consequences of social stress were assessed. Our study shows that stress coping style does not predict social status. However, stress coping style may influence the consequences of having a lower social status. Subordinate passive and proactive rats had distinctly different wound patterns; proactive rats had more wounds on the front of their bodies. Behavioral analysis confirmed that proactive subordinate rats engaged in more offensive interactions. Furthermore, subordinate rats with a proactive stress coping style had larger adrenals, and increased stress responsivity to a novel acute stressor (restraint stress) compared to passive subordinate rats or dominant rats, suggesting that the allostatic load may have been larger in this group. (c) 2017 Elsevier Inc. All rights reserved.

  • 10.
    Brorsson, A. L.
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Olinder, A. Lindholm
    Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Stockholm, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Viklund, G.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    An intervention with a person-centered program, guided self-determination-young, in groups of adolescents starting on insulin pump: a randomized controlled trial2016In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 18, no Suppl. 1, p. A104-A104Article in journal (Other academic)
  • 11. Brorsson, Anna Lena
    et al.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Viklund, Gunnel
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    A multicentre randomized controlled trial of an empowerment-inspired intervention for adolescents starting continuous subcutaneous insulin infusion: a study protocol2013In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 13, p. 212-Article in journal (Refereed)
    Abstract [en]

    Background:

    Continuous subcutaneous insulin infusion (CSII) treatment among children with type 1 diabetes is increasing in Sweden. However, studies evaluating glycaemic control in children using CSII show inconsistent results. The distribution of responsibility for diabetes self-management between children and parents is often unclear and needs clarification. There is much published support for continued parental involvement and shared diabetes management during adolescence. Guided Self-Determination (GSD) is an empowerment-based, person-centred, reflection and problem solving method intended to guide the patient to become self-sufficient and develop life skills for managing difficulties in diabetes self-management. This method has been adapted for adolescents and parents as Guided Self-Determination-Young (GSD-Y). This study aims to evaluate the effect of an intervention with GSD-Y in groups of adolescents starting on insulin pumps and their parents on diabetes-related family conflicts, perceived health and quality of life (QoL), and metabolic control. Here, we describe the protocol and plans for study enrolment.

    Methods/design:

    This study is designed as a randomized, controlled, prospective, multicentre study. Eighty patients between 12-18 years of age who are planning to start CSII will be included. All adolescents and their parents will receive standard insulin pump training. The education intervention will be conducted when CSII is to be started and at four appointments in the first 4 months after starting CSII. The primary outcome is haemoglobin A1c levels. Secondary outcomes are perceived health and QoL, frequency of blood glucose self-monitoring and bolus doses, and usage of carbohydrate counting. The following instruments will be used: Disabkids, 'Check your health', the Diabetes Family Conflict Scale and the Swedish Diabetes Empowerment Scale. Outcomes will be evaluated within and between groups by comparing data at baseline, and at 6 and 12 months after starting treatment.

    Discussion:

    In this study, we will assess the effect of starting an CSII together with the model of GSD to determine whether this approach leads to retention of improved glycaemic control, QoL, responsibility distribution and reduced diabetes-related conflicts in the family.

  • 12.
    Brorsson, Anna Lena
    et al.
    Karolinska Inst & Hosp, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.
    Wikblad, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Viklund, Gunnel
    Karolinska Inst & Hosp, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Parent's perception of their children's health, quality of life and burden of diabetes: testing reliability and validity of 'Check your Health' by proxy.2017In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 31, no 3, p. 497-504Article in journal (Refereed)
    Abstract [en]

    AIM: To test the validity and reliability of the 'Check your Health by proxy' instrument in parents to children with diabetes aged 8-17 years.

    METHODS: One hundred and ninety-one caregivers and their children, aged 8-17 years, were included. All completed the 'Check your Health' questionnaire measuring quality of life and burden of diabetes, DISABKIDS self- or proxy version, and 45 completed the same questionnaires 2 weeks later.

    RESULTS: Test-retest reliability on the 'Check your Health' questionnaire by proxy was moderate to strong (r = 0.48-0.74), p < 0.002). Convergent validity was weak to moderate (r = 0.15-0.49, p < 0.05). The instrument showed acceptable discriminant validity. Parents reported lower scores than the children on emotional health and social relations and higher scores on physical and emotional burden and higher burden on quality of life. Poorer social relationships and quality of life were associated with higher reported disease severity. The diabetes burden domain of the questionnaire correlated to perceived severity of diabetes and to perceived health. Discriminant validity showed that poorer social relationships and quality of life were associated with higher severity of the disease. The diabetes burden domain of 'Check your Health' by proxy showed discriminant validity on perceived severity of diabetes.

    CONCLUSIONS: The instrument 'Check your Health' by proxy showed acceptable psychometric characteristics in parents to young people (8-17 years of age) with diabetes. We also concluded that parents reported that their children had lower health and higher burden of diabetes than the children did, and it correlated to reported disease severity.

  • 13.
    Brorsson, Anna Lena
    et al.
    Karolinska Institutet.
    Viklund, Gunnel
    Karolinska Institutet.
    Örtqvist, Eva
    Karolinska Institutet.
    Lindholm Olinder, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Does treatment with an insulin pump improve glycaemic control in children and adolescents with type 1 diabetes?: A retrospective case-control study2014In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, no 7, p. 546-553Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate long-term effects on glycaemic control, ketoacidosis, serious hypoglycaemic events, insulin requirements, and body mass index standard deviation scores (BMI-SDS) in children and adolescents with type 1 diabetes starting on continuous subcutaneous insulin infusion (CSII) compared with children and adolescents treated with multiple daily injections (MDI).

    METHODS: This retrospective case-control study compares 216 patients starting CSII with a control group on MDI (n = 215), matched for glycated hemoglobin (HbA1c), sex, and age during a 2-yr period. Variables collected were gender, age, HbA1c, insulin requirement, BMI, BMI-SDS, ketoacidosis, and serious hypoglycaemic events.

    RESULTS: In the CSII group there was an improvement in HbA1c after 6 and 12 months compared with the MDI group. For boys and girls separately the same effect was detected after 6 months, but only for boys after 12 months. The incidence of ketoacidosis was higher in the CSII group compared with the MDI group (2.8 vs. 0.5/100 person-yr). The incidences of severe hypoglycaemic episodes per 100 person-yr were three in the CSII group and six in the MDI group (p < 0.05). After 6, 12, and 24 months, the insulin requirement was higher in the MDI group.

    CONCLUSIONS: This study shows that treatment with CSII resulted in an improvement in HbA1c levels up to 1 yr and decreased the number of severe hypoglycaemic events, but the frequency of ketoacidosis increased. The major challenge is to identify methods to maintain the HbA1c improvement, especially among older children and teenagers, and reduce the frequency of ketoacidosis.

  • 14.
    Burman, Pia
    et al.
    Lund Univ, Skane Univ Hosp Malmo, Dept Endocrinol, S-20502 Malmo, Sweden..
    Edén-Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ekman, Bertil
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Schwarcz, Erik
    Univ Orebro, Fac Med & Hlth, Dept Internal Med, SE-70182 Orebro, Sweden..
    Wahlberg, Jeanette
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Limited value of cabergoline in Cushing's disease: a prospective study of a 6-week treatment in 20 patients2016In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 174, no 1, p. 17-24Article in journal (Refereed)
    Abstract [en]

    Context and objective: The role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after >= 1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD. Design: Twenty patients (19 naive and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks. Methods: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end. Results: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study. Conclusions: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

  • 15.
    Chawla, Anjali
    et al.
    Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA..
    Cordner, Zachary A.
    Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA..
    Boersma, Greta J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA.
    Moran, Timothy H.
    Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA..
    Cognitive impairment and gene expression alterations in a rodent model of binge eating disorder2017In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 180, p. 78-90Article in journal (Refereed)
    Abstract [en]

    Binge eating disorder (BED) is defined as recurrent, distressing over-consumption of palatable food (PF) in a short time period. Clinical studies suggest that individuals with BED may have impairments in cognitive processes, executive functioning, impulse control, and decision-making, which may play a role in sustaining binge eating behavior. These clinical reports, however, are limited and often conflicting. In this study, we used a limited access rat model of binge-like behavior in order to further explore the effects of binge eating on cognition. In binge eating prone (BEP) rats, we found novel object recognition (NOR) as well as Barnes maze reversal learning (BM-RL) deficits. Aberrant gene expression of brain derived neurotrophic factor (Bdnf) and tropomyosin receptor kinase B (TrkB) in the hippocampus (HPC)-prefrontal cortex (PFC) network was observed in BEP rats. Additionally, the NOR deficits were correlated with reductions in the expression of TrkB and insulin receptor (Ir) in the CA3 region of the hippocampus. Furthermore, up-regulation of serotonin-2C (5-HT2C) receptors in the orbitoprefrontal cortex (OFC) was associated with BM-RL deficit. Finally, in the nucleus accumbens (NAc), we found decreased dopamine receptor 2 (Drd2) expression among BEP rats. Taken together, these data suggest that binge eating vegetable shortening may induce contextual and reversal learning deficits which may be mediated, at least in part, by the altered expression of genes in the CA3-OFC-NAc neural network.

  • 16. Denison, H
    et al.
    Nilsson, C
    Kujacic, M
    Löfgren, L
    Karlsson, C
    Knutsson, M
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Proof of mechanism for the DGAT1 inhibitor AZD7687: results from a first-time-in-human single-dose study2013In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 15, no 2, p. 136-143Article in journal (Refereed)
    Abstract [en]

    AIMS: Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which catalyses the final step in triacylglycerol (TAG) assembly, is suggested as a treatment for type 2 diabetes and obesity based on animal data indicating insulin sensitization and weight reduction. This first-time-in-human single ascending dose study explored the safety, tolerability, pharmacokinetics and pharmacodynamics of the selective DGAT1 inhibitor AZD7687.

    METHODS: Eighty healthy male subjects were enrolled. In each of 10 cohorts, six subjects received the same dose of AZD7687 orally (range across cohorts 1-60 mg) and two placebo. Plasma AZD7687 exposure was measured repeatedly. Postprandial serum TAG excursion was measured during 8 h after a standardized mixed meal with fat energy content of 60% (SMM 60%; five cohorts, 1-20 mg), before (baseline) and after dosing, to assess effects on gut DGAT1 activity.

    RESULTS: AZD7687 markedly reduced postprandial TAG excursion with a steep concentration-effect relationship. Incremental TAG AUC (area under the serum concentration vs. time curve) following SMM 60% was decreased >75% from baseline at doses ≥5 mg (p < 0.0001 vs. placebo). Serum levels of diacylglycerol, specifically measured with mass spectrometry, did not increase after AZD7687 administration. Nausea, vomiting and diarrhoea were reported with increasing doses and they limited dose escalation. Lowering of SMM fat content to 45 or 30% in five cohorts gradually reduced the frequency of gastrointestinal symptoms at a given dose of AZD7687.

    CONCLUSIONS: The attenuating effect of AZD7687 on postprandial TAG excursion provides proof of mechanism with respect to gut DGAT1 inhibition. However, dose and diet-related gastrointestinal side effects may impact further development of DGAT1 inhibitors.

  • 17. Denison, H.
    et al.
    Nilsson, C.
    Lofgren, L.
    Al-Shurbaji, A.
    Himmelmann, A.
    Martensson, G.
    Tornqvist, H.
    Knutsson, M.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    A one-week phase 1 trial with the DGAT1 inhibitor AZD7687: lipid handling, hormone secretion and adverse effects in the gut2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, p. S407-S407Article in journal (Other academic)
  • 18.
    Edholm, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Karlsson, F Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Haenni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Changes in liver volume and body composition during 4 weeks of low calorie diet before laparoscopic gastric bypass2015In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 11, no 3, p. 602-606Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Weight loss before laparoscopic Roux-en-Y gastric bypass (LRYGB) is desirable, because it can reduce liver volume and thereby facilitate the procedure. The optimal duration of a low-calorie diet (LCD) has not been established. The objective of this study was to assess changes in liver volume and body composition during 4 weeks of LCD.

    METHODS:

    Ten women (aged 43±8.9 years, 114±12.1 kg, and body mass index 42±2.6 kg/m2) were examined on days 0, 3, 7, 14, and 28 after commencing the LCD. At each evaluation, body composition was assessed through bioelectric impedance analysis, and liver volume and intrahepatic fat content were assessed by magnetic resonance imaging. Serum and urine samples were obtained. Questionnaires regarding quality of life and LCD-related symptoms were administered.

    RESULTS:

    In total, mean weight decreased by 7.4±1.2 kg (range 5.7-9.1 kg), and 71% of the weight loss consisted of fat mass according to bioelectric impedance analysis. From day 0 to day 3, the weight loss (2.0 kg) consisted mainly of water. Liver volume decreased by 18%±6.2%, from 2.1 to 1.7 liters (P<.01), during the first 2 weeks with no further change thereafter. A continuous 51%±16% decrease was seen in intrahepatic fat content. Systolic blood pressure, insulin, and lipids improved, while liver enzymes, glucose levels, and quality of life were unaffected.

    CONCLUSION:

    A significant decrease in liver volume (18%) occurred during the first 2 weeks of LCD treatment, and intrahepatic fat gradually decreased throughout the study period. A preoperative 2-week LCD treatment seems sufficient in similar patients.

  • 19.
    Edholm, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Näslund, Ingmar
    Karlsson, Anders F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Rask, Eva
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Twelve-year results for revisional gastric bypass after failed restrictive surgery in 131 patients2014In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 10, no 1, p. 44-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gastric banding (GB) and vertical banded gastroplasty (VBG) may result in unsatisfactory weight loss or intolerable side effects. Such outcomes are potential indications for additional bariatric surgery, and Roux-en-Y gastric bypass is frequently used at such revisions (rRYGB). The present study examined long-term results of rRYGB.

    METHODS: In total, 175 patients who had undergone rRYGB between 1993 and 2003 at 2 university hospitals received a questionnaire regarding their current status. The questionnaire was returned by 131 patients (75% follow-up rate, 66 VBG and 65 GB patients). Blood samples were obtained and medical charts studied. The reason for conversion was mainly unsatisfactory weight loss among the VBG patients and intolerable side effects among GB patients.

    RESULTS: The 131 patients (112 women), mean age 41.8 years at rRYGB, were evaluated at mean 11.9 years (range 7-17) after rRYGB. Mean body mass index of those with prior unsatisfactory weight loss was reduced from 40.1 kg/m(2) (range 28.7-52.2) to 32.6 kg/m(2) (range 19.1-50.2) (P<.01). Only 2 patients (2%) underwent additional bariatric surgery after rRYGB. The overall result was satisfactory for 74% of the patients. Only 21% of the patients adhered to the recommendation of lifelong multivitamin supplements while 76% took vitamin B12. Anemia was present in 18%.

    CONCLUSIONS: rRYGB results in sustained weight loss and satisfied patients when VBG or GB have failed. Subsequent bariatric surgery was rare but micronutrient deficiencies were frequent.

  • 20.
    Engström, Maria Svedbo
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg; Dalarna Univ, Sch Educ Hlth & Social Studies, Falun.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun.
    Johansson, Unn-Britt
    Sophiahemmet Univ, Stockholm; Karolinska Inst, Dept Clin Sci & Educ, Södersjukhuset, Stockholm.
    Eeg-Olofsson, Katarina
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg; Sahlgrens Univ Hosp, Gothenburg.
    Borg, Sixten
    Lund Univ, Dept Clin Sci Malmo, Hlth Econ Unit, Lund.
    Palaszewski, Bo
    Dept Data Management & Anal, Region Västra Götaland, Gothenburg.
    Gudbjornsdottir, Soffia
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg; Register Ctr Västra Götaland, Gothenburg, Sweden..
    A disease-specific questionnaire for measuring patient-reported outcomes and experiences in the Swedish National Diabetes Register: Development and evaluation of content validity, face validity, and test-retest reliability2018In: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 101, no 1, p. 139-146Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the development and evaluation of the content and face validity and test-retest reliability of a disease-specific questionnaire that measures patient-reported outcomes and experiences for the Swedish National Diabetes Register for adult patients who have type 1 or type 2 diabetes.

    Methods: In this methodological study, a questionnaire was developed over four phases using an iterative process. Expert reviews and cognitive interviews were conducted to evaluate content and face validity, and a postal survey was administered to evaluate test-retest reliability.

    Results: The expert reviews and cognitive interviews found the disease-specific questionnaire to be understandable, with relevant content and value for diabetes care. An item-level content validity index ranged from 0.6-1.0 and a scale content validity/average ranged from 0.7-1.0. The fourth version, with 33 items, two main parts and seven dimensions, was answered by 972 adults with type 1 and type 2 diabetes (response rate 61%). Weighted Kappa values ranged from 0.31-0.78 for type 1 diabetes and 0.27-0.74 for type 2 diabetes.

    Conclusions: This study describes the initial development of a disease-specific questionnaire in conjunction with the NDR. Content and face validity were confirmed and test-retest reliability was satisfactory. Practice implications: With the development of this questionnaire, the NDR becomes a clinical tool that contributes to further understanding the perspectives of adult individuals with diabetes.

  • 21.
    Engström, Maria Svedbo
    et al.
    Gothenburg Univ, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.;Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Johansson, Unn-Britt
    Sophiahemmet Univ, Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden..
    Gudbjörnsdottir, Soffia
    Gothenburg Univ, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.;Register Ctr Vastra Gotaland, Gothenburg, Sweden..
    What is important for you?: A qualitative interview study of living with diabetes and experiences of diabetes care to establish a basis for a tailored Patient-Reported Outcome Measure for the Swedish National Diabetes Register2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 3, article id e010249Article in journal (Refereed)
    Abstract [en]

    Objectives There is a growing emphasis on the perspective of individuals living with diabetes and the need for a more person-centred diabetes care. At present, the Swedish National Diabetes Register (NDR) lacks patient-reported outcome measures (PROMs) based on the perspective of the patient. As a basis for a new PROM, the aim of this study was to describe important aspects in life for adult individuals with diabetes. Design Semistructured qualitative interviews analysed using content analysis. Setting Hospital-based outpatient clinics and primary healthcare clinics in Sweden. Participants 29 adults with type 1 diabetes mellitus (DM) (n=15) and type 2 DM (n=14). Inclusion criteria: Swedish adults (18years) living with type 1 DM or type 2 DM (duration 5years) able to describe their situation in Swedish. Purposive sampling generated heterogeneous characteristics. Results To live a good life with diabetes is demanding for the individual, but experienced barriers can be eased by support from others in the personal sphere, and by professional support from diabetes care. Diabetes care was a crucial resource to nurture the individual's ability and knowledge to manage diabetes, and to facilitate life with diabetes by supplying support, guidance, medical treatment and technical devices tailored to individual needs. The analysis resulted in the overarching theme To live a good life with diabetes' constituting the two main categories How I feel and how things are going with my diabetes' and Support from diabetes care in managing diabetes' including five different categories. Conclusions Common aspects were identified including the experience of living with diabetes and support from diabetes care. These will be used to establish a basis for a tailored PROM for the NDR.

  • 22.
    Eriksson, Jan W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Bodegard, J.
    AstraZeneca, Sodertalje, Sweden..
    Norhammar, A.
    Karolinska Inst, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Nathanson, D.
    Karolinska Inst, Stockholm, Sweden..
    Thuresson, M.
    Statisticon, Uppsala, Sweden..
    Nystrom, T.
    Karolinska Inst, Stockholm, Sweden..
    Second-line treatment with sulfonylurea compared to DPP4 inhibitors is associated with risk of cardiovascular disease, all-cause mortality and severe hypoglycaemia2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S64-S64Article in journal (Other academic)
  • 23.
    Eriksson, Jan W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Bodegard, Johan
    AstraZeneca Nordic Baltic, Sodertalje, Sweden..
    Nathanson, David
    Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Nyström, Thomas
    Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
    Norhammare, Anna
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Sulphonylurea compared to DPP-4 inhibitors in combination with metformin carries increased risk of severe hypoglycemia, cardiovascular events, and all-cause mortality2016In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 117, p. 39-47Article in journal (Refereed)
    Abstract [en]

    Aims: There are safety concerns related to sulphonylurea treatment. The objective of this nationwide study was to compare the risk of cardiovascular disease (CVD), all-cause mortality and severe hypoglycemia in patients with type 2 diabetes (T2D) starting second-line treatment with either metformin + sulphonylurea or metformin + dipeptidyl peptidase-4 inhibitor (DPP-4i). Methods: All patients with T2D in Sweden who initiated second-line treatment with metformin + sulphonylurea or metformin + DPP-4i during 2006-2013 (n = 40,736 and 12,024, respectively) were identified in this nationwide study. The Swedish Prescribed Drug Register and the Cause of Death and National Patient Registers were used, and Cox survival models adjusted for age, sex, fragility, prior CVD, and CVD-preventing drugs were applied to estimate risks of events. Propensity score adjustments and matching methods were used to test the results. Results: Of 52,760 patients; 77% started metformin + SU and 23% metformin + DPP-4i. Crude incidences for severe hypoglycemia, CVD, and all-cause mortality in the SU cohort were 2.0, 19.6, and 24.6 per 1000 patient-years and in the DPP-4i cohort were 0.8, 7.6, and 14.9 per 1000 patient-years, respectively. Sulphonylurea compared with DPP4i was associated with higher risk of subsequent severe hypoglycemia, fatal and nonfatal CVD, and all-cause mortality; adjusted HR (95% CI): 2.07 (1.11-3.86); 1.17 (1.01-1.37); and 1.25 (1.02-1.54), respectively. Results were confirmed by additional propensity-adjusted and matched analyses. Among the SU drugs, glibenclamide had the highest risks. Conclusions: Metformin + SU treatment was associated with an increased risk of subsequent severe hypoglycemia, cardiovascular events, and all-cause mortality compared with metformin + DPP4i. Results from randomized trials will be important to elucidate causal relationships.

  • 24.
    Eriksson, Jan W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lundkvist, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sjöström, C.
    AstraZeneca, Gothenburg, Sweden..
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johnsson, E.
    AstraZeneca, Gothenburg, Sweden..
    One year of treatment with dapagliflozin QD plus exenatide QW in obese adults without diabetes: results of an open-label extension study2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S332-S333Article in journal (Refereed)
  • 25.
    Eriksson, Jan W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Norhammar, A.
    Karolinska Inst, Stockholm, Sweden..
    Bodegard, J.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Thuresson, M.
    Statisticon AB, Uppsala, Sweden..
    Fenici, P.
    AstraZeneca, Cambridge, England..
    Nathanson, D.
    Soder Sjukhuset, Stockholm, Sweden..
    Kosiborod, M.
    St Lukes Mid Amer Heart Inst, Kansas City, MO USA..
    Gulseth, H. L.
    Oslo Univ Hosp, Oslo, Norway..
    Nystrom, T.
    Soder Sjukhuset, Stockholm, Sweden..
    Birkeland, K. I.
    Oslo Univ Hosp, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Dapagliflozin compared to DPP4i treatment is associated with lower risk of kidney disease, heart failure and all-cause death: CVD-REAL Nordic2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no S1, p. S401-S402, article id 868Article in journal (Other academic)
  • 26.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Selvaraju, Ram K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Jansson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 10, p. 3428-3437Article in journal (Refereed)
    Abstract [en]

    In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.

  • 27.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Selvaraju, Ram K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas2014In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, no 3, p. 460-465Article in journal (Refereed)
    Abstract [en]

    Serotonergic biosynthesis in the endocrine pancreas, of which the islets of Langerhans is the major constituent, has been implicated in insulin release and β cell proliferation. In this study, we investigated the feasibility of quantitative noninvasive imaging of the serotonergic metabolism in the pancreas using the PET tracer (11)C-5-hydroxy-l-tryptophan ((11)C-5-HTP).

    METHODS: Uptake of (11)C-5-HTP, and its specificity for key enzymes in the serotonergic metabolic pathway, was assessed in vitro (INS-1 and PANC1 cells and human islet and exocrine preparations) and in vivo (nonhuman primates and healthy and diabetic rats).

    RESULTS: In vitro tracer uptake in endocrine cells (INS-1 and human islets), but not PANC1 and exocrine cells, was mediated specifically by intracellular conversion into serotonin. Pancreatic uptake of (11)C-5-HTP in nonhuman primates was markedly decreased by inhibition of the enzyme dopa decarboxylase, which converts (11)C-5-HTP to (11)C-serotonin and increased after inhibition of monoamine oxidase-A, the main enzyme responsible for serotonin degradation. Uptake in the rat pancreas was similarly modulated by inhibition of monoamine oxidase-A and was reduced in animals with induced diabetes.

    CONCLUSION: The PET tracer (11)C-5-HTP can be used for quantitative imaging of the serotonergic system in the endocrine pancreas.

  • 28.
    Evers, Simon S.
    et al.
    Univ Groningen, Dept Behav Neurosci, Nijenborgh, Netherlands.;Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA..
    Boersma, Greta J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
    Tamashiro, Kellie L. K.
    Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA..
    Scheurink, Anton J. W.
    Univ Groningen, Dept Behav Neurosci, Nijenborgh, Netherlands..
    van Dijk, Gertjan
    Univ Groningen, Dept Behav Neurosci, Nijenborgh, Netherlands..
    Roman high and low avoidance rats differ in their response to chronic olanzapine treatment at the level of body weight regulation, glucose homeostasis, and cortico-mesolimbic gene expression2017In: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 31, no 11, p. 1437-1452Article in journal (Refereed)
    Abstract [en]

    Olanzapine, an antipsychotic agent mainly used for treating schizophrenia, is frequently associated with body weight gain and diabetes mellitus. Nonetheless, studies have shown that not every individual is equally susceptible to olanzapine's weight-gaining effect. Therefore, Roman high and low avoidance rat strains were examined on their responsiveness to olanzapine treatment. The Roman high avoidance rat shares many behavioral and physiological characteristics with human schizophrenia, such as increased central dopaminergic sensitivity, whereas the Roman low avoidance rat has been shown to be prone to diet-induced obesity and insulin resistance. The data revealed that only the Roman high avoidance rats are susceptible to olanzapine-induced weight gain and attenuated glucose tolerance. Here it is suggested that the specific olanzapine-induced weight gain in Roman high avoidance rats could be related to augmented dopaminergic sensitivity at baseline through increased expression of prefrontal cortex dopamine receptor D1 mRNA and nucleus accumbens dopamine receptor D2 mRNA expression. Regression analyses revealed that olanzapine-induced weight gain in the Roman high avoidance rat is above all related to increased prolactin levels, whereas changes in glucose homeostasis is best explained by differences in central dopaminergic receptor expressions between strains and treatment. Our data indicates that individual differences in dopaminergic receptor expression in the cortico-mesolimbic system are related to susceptibility to olanzapine-induced weight gain.

  • 29.
    Fall, Tove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Brandmaier, Stefan
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Nowak, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA..
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.;Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA..
    Kastenmueller, Gabi
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Bioinformat & Syst Biol, Neuherberg, Germany..
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.;German Ctr Diabet Res DZD, Munich, Germany..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Wang-Sattler, Rui
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 10, p. 2114-2124Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Identification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction. Methods In this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n = 970; TwinGene, n = 1630). Metabolites associated with impaired fasting glucose (IFG) and/or prevalent type 2 diabetes were assessed for associations with incident type 2 diabetes in the three cohorts followed by replication attempts in the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort (n = 855). Assessment of the association of metabolite-regulating genetic variants with type 2 diabetes was done using data from a meta-analysis of genome-wide association studies. Results Out of 5961 investigated metabolic features, 1120 were associated with prevalent type 2 diabetes and IFG and 70 were annotated to metabolites and replicated in the three cohorts. Fifteen metabolites were associated with incident type 2 diabetes in the four cohorts combined (358 events) following adjustment for age, sex, BMI, waist circumference and fasting glucose. Novel findings included associations of higher values of the bile acid deoxycholic acid and monoacylglyceride 18:2 and lower concentrations of cortisol with type 2 diabetes risk. However, adding metabolites to an existing risk score improved model fit only marginally. A genetic variant within the CYP7A1 locus, encoding the rate-limiting enzyme in bile acid synthesis, was found to be associated with lower concentrations of deoxycholic acid, higher concentrations of LDL-cholesterol and lower type 2 diabetes risk. Variants in or near SGPP1, GCKR and FADS1/2 were associated with diabetes-associated phospholipids and type 2 diabetes. Conclusions/interpretation We found evidence that the metabolism of bile acids and phospholipids shares some common genetic origin with type 2 diabetes. Access to research materials Metabolomics data have been deposited in the Metabolights database, with accession numbers MTBLS93 (TwinGene), MTBLS124 (ULSAM) and MTBLS90 (PIVUS).

  • 30.
    Fonseca, Ana R. G.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Ctr Neurosci & Cell Biol, Coimbra, Portugal.
    Carvalho, E.
    Ctr Neurosci & Cell Biol, Coimbra, Portugal.;Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA..
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Calcineurin is involved in the regulation of human adipocyte glucose uptake2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S227-S227Article in journal (Other academic)
  • 31.
    Forsner, Maria
    et al.
    Dalarna University.
    Berggren,, Jenny
    Masaba, Jennipher
    Ekbladh, Annelie
    Lindholm Olinder, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Parents' experiences of caring for a child younger than two years of age treated with continuous subcutaneous insulin infusion2014In: European Diabetes Nursing, ISSN 1551-7853, E-ISSN 1551-7861, Vol. 11, no 1, p. 7-12Article in journal (Refereed)
    Abstract [en]

    Diabetes during infancy is uncommon and continuous subcutaneous insulin infusion (CSII) is the recommended treatment with such young children. However, this form of treatment has not been investigated previously from the perspective of the parents.

    The aim of this study was to determine parents' experiences of caring for a child less than two years old who had diabetes mellitus and was being treated with CSII therapy.

    Three pairs of parents were interviewed twice to elucidate their views on the initial period and on daily living. Data were submitted to qualitative content analysis and resulted in seven categories and one theme, the latter being: ‘The diabetes disease was threatening our baby's life, but then the insulin pump came as a rescuing, though challenging, angel’. Parents initially felt life had been turned upside down, but later they felt in control nearly all the time.

    It was concluded that parents of infants with diabetes are in great need of support in order to manage the disease and CSII technology. The fear of losing control and the lack of relief lead to social isolation. Educating someone close to the family could be a valuable intervention.

  • 32.
    Fryk, E.
    et al.
    Gothenburg Univ, Med, Mol & Clin Med, S-41124 Gothenburg, Sweden..
    Sundelin, J. Perman
    Gothenburg Univ, Med, Mol & Clin Med, S-41124 Gothenburg, Sweden..
    Strindberg, L.
    Gothenburg Univ, Med, Mol & Clin Med, S-41124 Gothenburg, Sweden..
    Pereira, Maria João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Federici, M.
    Univ Roma Tor Vergata, Med, Syst Med, Rome, Italy..
    Marx, N.
    Univ Hosp RWTH Aachen, Div Cardiol, Med, Aachen, Germany..
    Svensson, P. -A
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Boren, J.
    Gothenburg Univ, Med, Mol & Clin Med, S-41124 Gothenburg, Sweden..
    Jansson, P. -A
    Microdialysis and proteomics of the subcutaneous interstitial fluid reveals abundance of galectin-1 in type 2 diabetes patients2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S320-S320Article in journal (Other academic)
  • 33.
    Fryk, Emanuel
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden..
    Sundelin, Jeanna Perman
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden..
    Strindberg, Lena
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Federici, Massimo
    Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy..
    Marx, Nikolaus
    Univ Hosp RWTH Aachen, Div Cardiol, Aachen, Germany..
    Nystrom, Fredrik H.
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Linkoping, Sweden..
    Schmelz, Martin
    Heidelberg Univ, Dept Anesthesiol & Intens Care Med Mannheim, Heidelberg, Germany..
    Svensson, Per-Arne
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Boren, Jan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden..
    Jansson, Per-Anders
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden..
    Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients2016In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, no 7, p. 998-1006Article in journal (Refereed)
    Abstract [en]

    Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p < 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p < 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p < 0.05) and increased by overfeeding (p < 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p < 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes.

  • 34. Fuhrmann, A.
    et al.
    Lopes, P. C.
    Sereno, J.
    Pedro, J.
    Espinoza, D. O.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Reis, F.
    Eriksson, J. W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carvalho, E.
    Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on glucose and lipid metabolism in liver, skeletal muscle and adipose tissue in an in vivo rat model2014In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 88, no 2, p. 216-228Article in journal (Refereed)
    Abstract [en]

    Cyclosporin A (CsA) and sirolimus (SRL) are immunosuppressive agents (IAs) associated with dyslipidemia, insulin resistance and new onset diabetes after transplantation (NODAT). However, the molecular mechanisms involved are not fully understood. We investigated the effects of six-week treatment of either CsA or SRL on glucose and lipid metabolism in Wistar rats. The results show that, compared with vehicle-treated rats, SRL-treated rats were significantly lighter starting at week 5. CsA or SRL caused glucose intolerance, increased storage of lipids in the liver and skeletal muscle, and decreased the insulin-stimulated glucose uptake in isolated adipocytes. Furthermore, these agents significantly decreased genes involved in insulin action and glucose uptake, such as, IRS-1, Glut4 and Glut1, and increased genes and/or proteins involved in hepatic lipogenesis and gluconeogenesis, while decreasing them in adipose tissue. After either treatment PGC1 alpha gene expression was down regulated in skeletal muscle, an important player in fatty acid oxidation. Moreover, there was an increase in IL-6 gene expression in adipose tissue in the SRL-treated rats, suggesting stimulation of lipolysis. The results of the present study suggest that CsA and SRL lead to metabolic alterations in liver, muscle and adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy. (C) 2014 Elsevier Inc. All rights reserved.

  • 35.
    Gardulf, Ann
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Immunol,Unit Clin Nursing Res & Clin Res, SE-14186 Stockholm, Sweden.;Japanese Red Cross Inst Humanitarian Studies, Tokyo, Japan..
    Nilsson, Jan
    Japanese Red Cross Inst Humanitarian Studies, Tokyo, Japan.;Karlstad Univ, Dept Hlth Sci, Fac Hlth Sci & Technol, Karlstad, Sweden..
    Florin, Jan
    Dalama Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalama Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Lepp, Margret
    Univ Gothenburg, Sahlgrenska Acad, Inst Hlth & Care Sci, Gothenburg, Sweden.;Ostfold Univ Coll, Holden, Norway..
    Lindholm, Christina
    Sophiahemmet Univ, Stockholm, Sweden..
    Nordström, Gun
    Karlstad Univ, Dept Hlth Sci, Fac Hlth Sci & Technol, Karlstad, Sweden.;Hedmark Univ Coll, Hedmark, Norway..
    Theander, Kersti
    Karlstad Univ, Dept Hlth Sci, Fac Hlth Sci & Technol, Karlstad, Sweden.;Cty Council Varmland, Primary Care Res Unit, Karlstad, Sweden..
    Wilde-Larsson, Bodil
    Karlstad Univ, Dept Hlth Sci, Fac Hlth Sci & Technol, Karlstad, Sweden.;Hedmark Univ Coll, Hedmark, Norway..
    Carlsson, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Fac Hlth & Occupat Studies, Gavle, Sweden..
    Johansson, Eva
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Dept Nursing, Stockholm, Sweden..
    The Nurse Professional Competence (NPC) Scale: Self-reported competence among nursing students on the point of graduation2016In: Nurse Education Today, ISSN 0260-6917, E-ISSN 1532-2793, Vol. 36, p. 165-171Article in journal (Refereed)
    Abstract [en]

    Background: International organisations, e.g. WHO, stress the importance of competent registered nurses (RN) for the safety and quality of healthcare systems. Low competence among RNs has been shown to increase the morbidity and mortality of inpatients. Objectives: To investigate self-reported competence among nursing students on the point of graduation (NSPGs), using the Nurse Professional Competence (NPC) Scale, and to relate the findings to background factors. Methods and participants; The NPC Scale consists of 88 items within eight competence areas (CAs) and two overarching themes. Questions about socio-economic background and perceived overall quality of the degree programme were added. In total, 1086 NSPGs (mean age, 28.1[20-56] years, 87.3% women) from 11 universities/university colleges participated. Results: NSPGs reported significantly higher scores for Theme I "Patient-Related Nursing" than for Theme II "Organisation and Development of Nursing Care". Younger NSPGs (20-27 years) reported significantly higher scores for the CAs "Medical and Technical Care" and "Documentation and Information Technology". Female NSPGs scored significantly higher for "Value-Based Nursing". Those who had taken the nursing care programme at upper secondary school before the Bachelor of Science in Nursing (BSN) programme scored significantly higher on "Nursing Care", "Medical and Technical Care", "Teaching/Learning and Support", "Legislation in Nursing and Safety Planning" and on Theme I. Working extra paid hours in healthcare alongside the BSN programme contributed to significantly higher self-reported scores for four CAs and both themes. Clinical courses within the BSN programme contributed to perceived competence to a significantly higher degree than theoretical courses (932% vs 875% of NSPGs). Summary and conclusion: Mean scores reported by NSPGs were highest for the four CAs connected with patient-related nursing and lowest for CAs relating to organisation and development of nursing care. We conclude that the NPC Scale can be used to identify and measure aspects of self-reported competence among NSPGs.

  • 36.
    Granström, Therese
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Falun, Sweden..
    Forsman, Henrietta
    Dalarna Univ, Falun, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Granstam, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Univ Cty Council Vastmanland, Uppsala, Sweden..
    Patient reported outcomes and visual function among patients with diabetes related macular edema2016In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 25, p. 130-131Article in journal (Refereed)
  • 37.
    Granström, Therese
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Forsman, Henrietta
    Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Jani, Siba
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Raghib, Aseel Modher
    Dalarna Cty Hosp, Dept Ophthalmol, Falun, Sweden..
    Granstam, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Department of Ophthalmology, Västmanland County Hospital, Västerås, Sweden.
    Visual functioning and health-related quality of life in diabetic patients about to undergo anti-vascular endothelial growth factor treatment for sight-threatening macular edema2015In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 29, no 8, p. 1183-1190Article in journal (Refereed)
    Abstract [en]

    Purpose: To examine patient-reported outcome (PRO) in a selected group of Swedish patients about to receive anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). Material and methods: In this cross-sectional study, 59 patients with diabetes mellitus, who regularly visited the outpatient eye-clinics, were included. Sociodemographic and clinical data were collected and the patients completed PRO measures before starting anti-VEGF treatment. PRO measures assessed eye-specific outcomes (NEI-VFQ-25) and generic health-related quality of life (SF-36). Results: The participants consisted of 30 men and 29 women (mean age, 68.5 years); 54 (92%) patients had type 2 diabetes; 5 (9%) patients had moderate or severe visual impairment; 28 (47%) were classified as having mild visual impairment. Some of the patients reported overall problems in their daily lives, such as with social relationships, as well as problems with impaired sight as a result of reduced distance vision. Conclusions: Further studies are needed to investigate PRO factors related to low perceived general health in this patient population. It is important to increase our understanding of such underlying mechanisms to promote improvements in the quality of patient care.

  • 38.
    Granström, Therese
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Forsman, Henrietta
    Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Söder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden.;Söder Sjukhuset, Karolinska Inst, Dept Clin Res & Educ, Stockholm, Sweden..
    Gkretsis, Dimitrios
    Dalarna Cty Hosp, Dept Ophthalmol, Falun, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Granstam, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Ophthalmol, Vasteras, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Patient-reported outcomes and visual acuity after 12 months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting2016In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 121, p. 157-165Article in journal (Refereed)
    Abstract [en]

    Aims: To examine objective visual acuity measured with ETDRS, retinal thickness (OCT), patient reported outcome and describe levels of glycated hemoglobin and its association with the effects on visual acuity in patients treated with anti-VEGF for visual impairment due to diabetic macular edema (DME) during 12 months in a real world setting.

    Methods: In this cross-sectional study, 58 patients (29 females and 29 males; mean age, 68 years) with type 1 and type 2 diabetes diagnosed with DME were included. Medical data and two questionnaires were collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of life questionnaire (SF-36) were used.

    Results: The total patient group had significantly improved visual acuity and reduced retinal thickness at 4 months and remains at 12 months follow up. Thirty patients had significantly improved visual acuity, and 27 patients had no improved visual acuity at 12 months. The patients with improved visual acuity had significantly improved scores for NEI VFQ-25 subscales including general health, general vision, near activities, distance activities, and composite score, but no significant changes in scores were found in the group without improvements in visual acuity.

    Conclusions: Our study revealed that anti-VEGF treatment improved visual acuity and central retinal thickness as well as patient-reported outcome in real world 12 months after treatment start.

  • 39. Graue, M
    et al.
    Iversen, M
    Sigurdardottir, AK
    Zoffman, V
    Smide, Bibbi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Leksell, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Diabetes nursing research in the Nordic countries2013In: European Diabetes Nursing, ISSN 1551-7853, E-ISSN 1551-7861, Vol. 10, no 2, p. 46-51Article in journal (Refereed)
    Abstract [en]

    New knowledge from research studies is important as a foundation for high-quality care in practice as well as crucial to further stimulate research in the future.

    The aims of this study were to determine the total number of peer-reviewed articles on diabetes research reported by nurses in four Nordic countries (Denmark, Iceland, Norway and Sweden) from 1979–2009, and to identify the time periods in which they had been published, different study designs and the number of publications related to nurse authors.

    We performed an electronic search for potentially relevant scientific articles between 1 January 1979 and 31 December 2009 using the MEDLINE, Medline in process, EMBASE, CINAHL, PsycINFO and Cochrane databases. The studies focused either on the diabetes population or on diabetes health care professionals.

    We included 164 scientific articles; 132 resulting from electronic search and 32 from manual search. They were published in 63 different scientific journals, with 52 (32%) published in nursing journals and typically by authors with university degrees. Only one in four authors had published five or more articles. The majority of the studies originated from a single country, with 23 (14%) including co-authors from another country.

    It was concluded that research in diabetes reported by nurses has increased considerably after the year 2000. Further action is needed to build stronger national groups of researchers. International collaborative research networks facilitate funding opportunities and contribute to further development of professional research competence.

  • 40.
    Gutierrez, P. Morentin
    et al.
    AstraZeneca R&D, Mereside, Macclesfield SK10 4TG, Cheshire, England..
    Gyte, A.
    AstraZeneca R&D, Mereside, Macclesfield SK10 4TG, Cheshire, England..
    deSchoolmeester, J.
    AstraZeneca R&D, Mereside, Macclesfield SK10 4TG, Cheshire, England..
    Ceuppens, P.
    AstraZeneca R&D, Mereside, Macclesfield SK10 4TG, Cheshire, England..
    Swales, J.
    AstraZeneca R&D, Mereside, Macclesfield SK10 4TG, Cheshire, England..
    Stacey, C.
    AstraZeneca R&D, Mereside, Macclesfield SK10 4TG, Cheshire, England..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. AstraZeneca R&D, Molndal, Sweden..
    Sjostrand, M.
    AstraZeneca R&D, Molndal, Sweden..
    Nilsson, C.
    AstraZeneca R&D, Molndal, Sweden..
    Leighton, B.
    AstraZeneca R&D, Mereside, Macclesfield SK10 4TG, Cheshire, England..
    Continuous inhibition of 11 beta-hydroxysteroid dehydrogenase type I in adipose tissue leads to tachyphylaxis in humans and rats but not in mice2015In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 172, no 20, p. 4806-4816Article in journal (Refereed)
    Abstract [en]

    Background and Purpose11-hydroxysteroid dehydrogenase type I (11-HSD1), a target for Type 2 diabetes mellitus, converts inactive glucocorticoids into bioactive forms, increasing tissue concentrations. We have compared the pharmacokinetic-pharmacodynamic (PK/PD) relationship of target inhibition after acute and repeat administration of inhibitors of 11-HSD1 activity in human, rat and mouse adipose tissue (AT). Experimental ApproachStudies included abdominally obese human volunteers, rats and mice. Two specific 11-HSD1 inhibitors (AZD8329 and COMPOUND-20) were administered as single oral doses or repeat daily doses for 7-9days. 11-HSD1 activity in AT was measured ex vivo by conversion of H-3-cortisone to H-3-cortisol. Key ResultsIn human and rat AT, inhibition of 11-HSD1 activity was lost after repeat dosing of AZD8329, compared with acute administration. Similarly, in rat AT, there was loss of inhibition of 11-HSD1 activity after repeat dosing with COMPOUND-20 with continuous drug cover, but effects were substantially reduced if a drug holiday' period was maintained daily. Inhibition of 11-HSD1 activity was not lost in mouse AT after continuous cover with COMPOUND-20 for 7days. Conclusions and ImplicationsHuman and rat AT, but not mouse AT, exhibited tachyphylaxis for inhibition of 11-HSD1 activity after repeat dosing. Translation of observed efficacy in murine disease models to human for 11-HSD1 inhibitors may be misleading. Investigators of the effects of 11-HSD1 inhibitors should confirm that desired levels of enzyme inhibition in AT can be maintained over time after repeat dosing and not rely on results following a single dose.

  • 41.
    Haas, Josephine
    et al.
    Karolinska Institutet Institutionen för klinisk forskning och utbildning Södersjukhuset.
    Persson, Martina
    stitutionen för klinisk forskning och utbildning Södersjukhuset.
    Brorsson, Anna Lena
    stitutionen för klinisk forskning och utbildning Södersjukhuset.
    Toft, Eva Hagström
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Department of Clinical Science and Education, Karolinska Institute; Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm.
    Guided self-determination-young versus standard care in the treatment of young females with type 1 diabetes: study protocol for a multicentre randomized controlled trial2017In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 18, article id 562Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Female adolescents with type 1 diabetes mellitus (T1DM) have the most unsatisfactory glycaemic control of all age groups and report higher disease burden, poorer perceived health, and lower quality of life than their male counterparts. Females with T1DM face an excess risk of all-cause mortality compared with men with T1DM. New methods are needed to help and support young females with T1DM to manage their disease. A prerequisite for successful diabetes management is to offer individualized, person-centred care and support the patient's own motivation. Guided self-determination (GSD) is a person-centred reflection and problem-solving method intended to support the patient's own motivation in the daily care of her diabetes and help develop skills to manage difficulties in diabetes self-management. GSD has been shown to improve glycaemic control and decrease psychosocial stress in young women with T1DM. The method has been adapted for adolescents and their parents, termed GSD-young (GSD-Y). The aim of this study was to evaluate whether an intervention with GSD-Y in female adolescents with T1DM leads to improved glycaemic control, self-management, treatment satisfaction, perceived health and quality of life, fewer diabetes-related family conflicts, and improved psychosocial self-efficacy.

    METHODS/DESIGN: This is a parallel-group randomized controlled superiority trial with an allocation ratio of 1:1. One hundred female adolescents with T1DM, 15-20 years of age, and their parents (if < 18 years of age), will be included. The intervention group will receive seven individual GSD-Y education visits over 3 to 6 months. The control group will receive standard care including regular visits to the diabetes clinic. The primary outcome is level of glycaemic control, measured as glycosylated haemoglobin (HbA1c). Secondary outcomes include diabetes self-management, treatment satisfaction, perceived health and quality of life, diabetes-related family conflicts, and psychosocial self-efficacy. Data will be collected before randomization and at 6 and 12 months.

    DISCUSSION: Poor glycaemic control is common in female adolescents and young adults with T1DM. Long-standing hyperglycaemia increases the risks for severe complications and may also have an adverse impact on the outcome of future pregnancies. In this study, we want to evaluate if the GSD-Y method can be a useful tool in the treatment of female adolescents with T1DM.

    TRIAL REGISTRATION: Current controlled trials, ISRCTN57528404 . Registered on 18 February 2015.

  • 42.
    Hansson, Sara F.
    et al.
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Zhou, Alex-Xianghua
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Vachet, Pauline
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, Stanko
    AstraZeneca, IMED Biotech Unit, Early Clin Dev, Translat Med Unit CVRM, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    Wallin, Helen Jongsma
    Offspring Biosci, Södertälje, Sweden.
    Ericsson-Dahlstrand, Anders
    Offspring Biosci, Södertälje, Sweden.
    Karlsson, Daniel
    AstraZeneca, IMED Biotech Unit, Biosci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Ahnmark, Andrea
    AstraZeneca, IMED Biotech Unit, Biosci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Winzell, Maria Sorhede
    AstraZeneca, IMED Biotech Unit, Biosci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Magnone, Maria Chiara
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Davidsson, Pia
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Secretagogin is increased in plasma from type 2 diabetes patients and potentially reflects stress and islet dysfunction2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196601Article in journal (Refereed)
    Abstract [en]

    Beta cell dysfunction accompanies and drives the progression of type 2 diabetes mellitus (T2D), but there are few clinical biomarkers available to assess islet cell stress in humans. Secretagogin, a protein enriched in pancreatic islets, demonstrates protective effects on beta cell function in animals. However, its potential as a circulating biomarker released from human beta cells and islets has not been studied. In this study primary human islets, beta cells and plasma samples were used to explore secretion and expression of secretagogin in relation to the T2D pathology. Secretagogin was abundantly and specifically expressed and secreted from human islets. Furthermore, T2D patients had an elevated plasma level of secretagogin compared with matched healthy controls, which was confirmed in plasma of diabetic mice transplanted with human islets. Additionally, the plasma secretagogin level of the human cohort had an inverse correlation to clinical assessments of beta cell function. To explore the mechanism of secretagogin release in vitro, human beta cells (EndoC-[beta H1) were exposed to elevated glucose or cellular stress-inducing agents. Secretagogin was not released in parallel with glucose stimulated insulin release, but was markedly elevated in response to endoplasmic reticulum stressors and cytokines. These findings indicate that secretagogin is a potential novel biomarker, reflecting stress and islet cell dysfunction in T2D patients.

  • 43.
    Husdal, Rebecka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    The organisation of diabetes care for persons with type 2 diabetes mellitus: A nationwide cross-sectional study in Swedish primary health care2017Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim To extend the current knowledge about changes in Swedish diabetes care from 2006 to 2013 (Paper I), and to investigate the association between personnel resources and organisational features of primary health care centres (PHCCs) and the individual level of glycated haemoglobin (HbA1c) among persons with type 2 diabetes mellitus (T2DM) (Paper II).

    Methods The longitudinal cross-sectional study described in Paper I included a total of 684 (74.3%) of eligible 921 PHCCs in 2006 and 880 (76.4%) of eligible 1152 PHCCs in 2013. The Swedish National Survey of the Quality and Organisation of Diabetes Care in Primary Healthcare (Swed-QOP) questionnaire was sent to PHCC managers in 2007 and 2014. In Paper II, persons with T2DM (n = 230 958) attending 846 PHCCs were included. The PHCC-level data for 2013 were obtained from the Swed-QOP questionnaire and the individual-level data for 2013 were obtained from the National Diabetes Register. These data were linked to national registers containing individual-level data on socio-economic status and comorbidities.

    Results From 2006 to 2013, the median list size of PHCCs decreased while the median number of persons with T2DM at the PHCC increased (all P < 0.001). The median number of whole time equivalent registered nurses (RNs) per 500 persons with T2DM increased from 0.64 in 2006 to 0.79 in 2013 (P < 0.001). Compared with 2006, 30% percentage points more PHCCs (17.0% in 2006 and 47.5% in 2013) had an RN with at least 16 European Credit Transfer and Accumulation System (ECTS) credits in diabetes-specific education in 2013 (P < 0.001). Access to an in-house psychologist increased from 25.9% in 2006 to 47.1% in 2013 (P < 0.001). No change was found regarding in-house access to dietitians, chiropodists, social workers or physiotherapists. Observed changes in the organisational features of PHCCs from 2006 to 2013 included increased frequency of medical check-ups, use of call–recall systems and use of systems for checking that persons with T2DM participated in annual visits to general practitioners (GPs) and RNs (all P < 0.05). Providing group education remained scarce in both years (Paper I). After adjusting for several important confounders, personnel resources associated with decreasing individual HbA1c levels were the number of ECTS credits in diabetes-specific education among RNs (P < 0.001) and the duration of regular visits to RNs (P < 0.001). However, the opposite effect (i.e., increased HbA1c levels) was found for the duration of visits to GPs (P < 0.001). Organisational features associated with decreased individual HbA1c levels were PHCCs having a diabetes team (P < 0.01) and providing group education (P < 0.01) (Paper II).

    Conclusions The findings presented in this thesis add important knowledge on evaluating changes in diabetes care in Sweden. Some findings can be interpreted as initiatives to focus on increasing the time RNs devote to caring for persons with T2DM, and in ensuring RNs undergo diabetes-specific education. Furthermore, factors such as diabetes-specific education, diabetes teams and group education were associated with lower individual HbA1c levels. These findings could stimulate decision-makers to prioritise these factors for offering high-quality, equitable care to persons with diabetes.

    List of papers
    1. Resource allocation and organisational features in Swedish primary diabetes care: Changes from 2006 to 2013
    Open this publication in new window or tab >>Resource allocation and organisational features in Swedish primary diabetes care: Changes from 2006 to 2013
    Show others...
    2017 (English)In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 11, no 1, p. 20-28Article in journal (Refereed) Epub ahead of print
    Abstract [en]

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

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

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

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

    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-304779 (URN)10.1016/j.pcd.2016.08.002 (DOI)000392679200003 ()27578488 (PubMedID)
    Available from: 2016-10-10 Created: 2016-10-10 Last updated: 2018-04-10Bibliographically approved
    2. Resources and organisation in primary health care are associated with HbA1c level: A nationwide study of 230958 people with Type 2 diabetes mellitus.
    Open this publication in new window or tab >>Resources and organisation in primary health care are associated with HbA1c level: A nationwide study of 230958 people with Type 2 diabetes mellitus.
    Show others...
    2018 (English)In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 12, no 1, p. 23-33Article in journal (Refereed) Published
    Abstract [en]

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

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

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

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

    Keywords
    HbA(1c), Organisation, Personnel resources, Primary health care system, Type 2 diabetes mellitus
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-332689 (URN)10.1016/j.pcd.2017.09.003 (DOI)000423008800003 ()28964673 (PubMedID)
    Available from: 2017-10-31 Created: 2017-10-31 Last updated: 2018-04-10Bibliographically approved
  • 44.
    Husdal, Rebecka
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Karlsson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eliasson, Björn
    Jansson, Stefan
    Jerden, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Steen, Lars
    Wallman, Thorne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Svensson, Ann-Marie
    Thors Adolfsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Resources and organisation in primary health care are associated with HbA1c level: A nationwide study of 230958 people with Type 2 diabetes mellitus.2018In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 12, no 1, p. 23-33Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 45.
    Husdal, Rebecka
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eliasson, Björn
    Jansson, Stefan
    Jerdén, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Steen, Lars
    Wallman, Thorne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Adolfsson, Eva Thors
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Resource allocation and organisational features in Swedish primary diabetes care: Changes from 2006 to 20132017In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 11, no 1, p. 20-28Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 46.
    Husdal, Rebecka
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden..
    Thors Adolfsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Hosp Vastmanland, Dept Primary Hlth Care, Reg Vastmanland, Vasteras, Sweden..
    Organisation of diabetes care is associated with systolic blood pressure level: a cross-sectional study of 230,958 people with type 2 diabetes2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no S1, p. S298-S299, article id 657Article in journal (Other academic)
  • 47.
    Iversen, Marjolein M.
    et al.
    Bergen Univ Coll, Fac Hlth & Social Sci, Ctr Evidence Based Practice, Bergen, Norway.;Stavanger Univ Hosp, Endocrinol Sect, Dept Med, Stavanger, Norway..
    Graue, Marit
    Bergen Univ Coll, Fac Hlth & Social Sci, Ctr Evidence Based Practice, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Smide, Bibbi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Zoffmann, Vibeke
    Rigshosp, Univ Copenhagen Hosp, Juliane Marie Ctr, Res Womens & Childrens Hlth, Copenhagen, Denmark..
    Sigurdardottir, Arun K.
    Univ Akureyri, Sch Hlth Sci, Akureyri, Iceland..
    Characteristics of nursing studies in diabetes research published over three decades in Sweden, Norway, Denmark and Iceland: a narrative review of the literature2016In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 30, no 2, p. 241-249Article, review/survey (Refereed)
    Abstract [en]

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

  • 48.
    Jansson, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Barbu, Andreea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bodin, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Drott, Carl Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gao, Xiang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Grapensparr, Liza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kallskog, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lau, Joey Börjesson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Liljebäck, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Strömberg, Victoria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ullsten, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Pancreatic islet blood flow and its measurement2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 2, p. 81-95Article, review/survey (Refereed)
    Abstract [en]

    Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting beta-cells, endothelium derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.

  • 49.
    Jansson, Rolf
    et al.
    Västerås sjukhus.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Otillräcklig kunskap om lindrig TSH-stegring under graviditet Ännu för tidigt för screening inom mödravårdsprogrammet: Insufficient knowledge about mild TSH elevatin during pregnancy. Still too early for screening with the Swedish maternity health system2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, ISSN 0023-7205, Vol. 113, article id DU36Article in journal (Refereed)
    Abstract [sv]

    Övertygande bevis saknas för att subklinisk hypotyreos innebär ökad risk för graviditetskomplikationer och skadlig fosterutveckling.

    Gravida kvinnor kan vid provtagning felaktigt bibringas uppfattningen att de lider av sköldkörtelsjukdom som kan äventyra graviditeten.

    I väntan på att kunskapsläget förbättras kan inte bred screening för sköldkörtelsjukdom under graviditet rekommenderas. 

  • 50.
    Johansson, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala Örebro-Reg Res Council, Uppsala.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, Stanko
    AstraZeneca R&D, Gothenburg; Sahlgrenska Academy at Gothenburg University, Gothenburg.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal.
    Whole-Body Imaging of Tissue-specific Insulin Sensitivity and Body Composition by Using an Integrated PET/MR System: A Feasibility Study.2018In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 286, no 1, p. 271-278Article in journal (Refereed)
    Abstract [en]

    Purpose

    To develop, evaluate, and demonstrate the feasibility of a whole-body protocol for simultaneous assessment of tissue-specific insulin-mediated fluorine 18 (18F) fluorodeoxyglucose (FDG) influx rates, tissue depots, and whole-body insulin sensitivity (referred to as the M value).

    Materials and Methods

    An integrated positron emission tomography (PET)/magnetic resonance (MR) imaging system combined with hyperinsulinemic euglycemic clamp (HEC) was used. Dynamic whole-body PET imaging was used to determine the insulin-mediated 18F-FDG tissue influx rate (Ki) in the whole-body region by using the Patlak method. M value was determined with the HEC method at PET imaging. Tissue depots were quantified by using water-fat separated MR imaging and manual segmentations. Feasibility of the imaging protocol was demonstrated by using five healthy control participants and five patients with type 2 diabetes. Associations between M value and Ki were studied in multiple tissues by using the Pearson correlation.

    Results

    Positive correlations were found between M value and Ki in multiple tissues: the gluteus muscle (r = 0.875; P = .001), thigh muscle (r = 0.903; P , .001), calf muscle (r = 0.825; P = .003), and abdominal visceral adipose tissue (r = 0.820; P = .004). A negative correlation was found in the brain (r = 20.798; P = .006). The MR imaging–based method for quantification of tissue depots was feasible for determining adipose tissue volumes and fat fractions.

    Conclusion

    This PET/MR imaging protocol may be feasible for simultaneous assessment of tissue-specific insulin-mediated 18F-FDG influx rates, tissue depots, and M value.

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