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  • 1.
    Abrahamsson, Niclas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Engström, Britt Edén
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Karlsson, Anders F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?2013Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 169, nr 6, s. 885-889Artikkel i tidsskrift (Fagfellevurdert)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Engström, Britt Edén
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Karlsson, Anders F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Hypoglycemia in everyday life after gastric bypass and duodenal switch2015Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, nr 1, s. 91-100Artikkel i tidsskrift (Fagfellevurdert)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lau Börjesson, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Wiklund, Urban
    Umea Univ, Biomed Engn, Dept Radiat Sci, Umea, Sweden.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Gastric bypass reduces symptoms and hormonal responses to hypoglycemia2016Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, nr 9, s. 2667-2675Artikkel i tidsskrift (Fagfellevurdert)
    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.
    Aldenbratt, Annika
    et al.
    Sahlgrens Univ Hosp, Dept Nephrol, Gothenburg, Sweden.
    Lindberg, Christopher
    Sahlgrens Univ Hosp, Dept Neurol, Neuromuscular Ctr, Gothenburg, Sweden.
    Svensson, Maria K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Reduced renal function in patients with Myotonic Dystrophy type 1 and the association to CTG expansion and other potential risk factors for chronic kidney disease2017Inngår i: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, nr 11, s. 1038-1042Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Myotonic dystrophy type 1 (DM1) affects several organs. Disease severity and age at onset are correlated to the CTG repeat expansion. The aim of this study was to assess renal function and the association to numbers of CTG repeat expansion in patients with DM1. Ninety-eight patients with DM1 were included. Glomerular filtration rate (measured GFR) was measured using iohexol clearance. Data on CTG repeats were available in 83/98 (85%) patients. The overall mGFR was 74 (16) ml/min/1.73 m(2) (range 38-134). Sixty-four patients (69%) had a mild and sixteen patients (17%) a moderate decrease in renal function (mGFR 60-89 and 30-59 ml/min/1.73 m(2), respectively). No correlations were found between CTG repeats and mGFR (r = 0.10, p = 0.4) or between CTG repeats and serum cystatin C (r = 0.12, p = 0.29). CTG repeats was positively correlated to creatinine-based estimates of GFR (eGFR) (modified diet in renal disease r = 0.49, p < 0.001, CKD-EPI creatinine equation; r = 0.50, p < 0.001), but analyses using Structural Equation Modeling showed no correlation. The correlation was explained by an indirect effect via serum creatinine and skeletal muscle mass index. In conclusion, patients with DM1 seem to have a slight decrease in renal function but there is no association between renal function and the number of CTG repeats, a marker of disease severity.

  • 5.
    Almby, Kristina E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Abrahamsson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lundqvist, Martin H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Hammar, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Thombare, Ketan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Panagiotou, Amalia
    Uppsala Univ Hosp, Dept Internal Med, Uppsala, Sweden.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Wiklund, Urban
    Umea Univ, Dept Radiat Sci, Biomed Engn, Umea, Sweden.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery2019Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, nr 2, s. 161-171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

    Design: Experimental hyperinsulinemic-hypoglycemic clamp study.

    Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

    Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

    Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

  • 6.
    Almby, Kristina E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Akademiska Sjukhuset.
    Edholm, David
    Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Anastomotic Strictures After Roux-en-Y Gastric Bypass: a Cohort Study from the Scandinavian Obesity Surgery Registry2019Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, nr 1, s. 172-177Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure worldwide. Anastomotic stricture is a known complication of RYGB. The aim was to explore the incidence and outcomes of strictures within the Scandinavian Obesity Surgery Registry (SOReg).

    Method

    SOReg included prospective data from 36,362 patients undergoing bariatric surgery in the years 2007–2013. Outcomes were recorded at 30-day and at 1-year follow-up according to the standard SOReg routine. The medical charts of patients suffering from stricture after RYGB were requested and assessed.

    Setting

    National bariatric surgery registry

    Results

    Anastomotic stricture within 1 year of surgery was confirmed in 101 patients representing an incidence of 0.3%. Risk factors for stricture were patient age above 60 years (odds ratio (OR), 6.2 95% confidence interval (CI) 2.7–14.3), circular stapled gastrojejunostomy (OR 2.7, 95% CI 1.4–5.5), postoperative anastomotic leak (OR 8.9 95%, CI 4.7–17.0), and marginal ulcer (OR 30.0, 95% CI 19.2–47.0). Seventy-five percent of the strictures were diagnosed within 70 days of surgery. Two dilatations or less was sufficient to successfully treat 50% of patients. Ten pecent of patients developed perforation during dilatation, and the risk of perforating at each dilatation was 3.8%. Perforation required surgery in six cases but there was no mortality. Strictures in SOReg may be underreported, which could explain the low incidence in the study.

    Conclusion

    Most strictures present within 2 months and are successfully treated with two dilatations or less. Dilating a strictured gastrojejunostomy entails a risk of perforation (3.8%).

  • 7.
    Biglarnia, Ali-Reza
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Nilsson, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    von Zur-Mühlen, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Wagner, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Wanders, Alkwin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Tufveson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation2011Inngår i: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, nr 8, s. e61-e66Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 8.
    Billing, Ewa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    McKenna, S. P.
    Staun, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Lindqvist, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Adaptation of the Psoriatic Arthritis Quality of Life (PsAQoL) instrument for Sweden2010Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 39, nr 3, s. 223-228Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 9.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Second-line treatment with sulfonylurea compared to DPP4 inhibitors demonstrated associations with earlier treatment intensification with insulin2015Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S189-S189Artikkel i tidsskrift (Annet vitenskapelig)
  • 10.
    Boersma, Greta J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Heurling, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Johansson, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lau Börjesson, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Katsogiannos, Petros
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;AstraZeneca, Dept Med, Gothenburg, Sweden..
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia2017Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, s. S80-S80Artikkel i tidsskrift (Annet vitenskapelig)
  • 11.
    Boersma, Greta J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Johansson, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Heurling, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Sweden.
    Skrtic, Stanko
    Lau, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Katsogiannos, Petros
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Panagiotou, Grigorios
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Antaros Medical, Mölndal, Sweden.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Antaros Medical, Mölndal, Sweden.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study2018Inngår i: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 50, nr 8, s. 627-639Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=-0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

  • 12.
    Boersma, Greta J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Johansson, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Pereira, Maria J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;Univ Gothenburg, Dept Med, Gothenburg, Sweden..
    Lau Börjesson, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Katsogiannos, Petros
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Panagiotou, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Skeletal muscle and liver, but not brain, account for impaired glucose utilisation in type 2 diabetes: whole-body PET/MR during hyperinsulinaemic euglycaemic clamp2016Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, s. S33-S33Artikkel i tidsskrift (Fagfellevurdert)
  • 13.
    Boersma, Greta J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 stress2017Inngår i: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 178, s. 126-133Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 14.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 trial2016Inngår i: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 18, nr Suppl. 1, s. A104-A104Artikkel i tidsskrift (Annet vitenskapelig)
  • 15. Brorsson, Anna Lena
    et al.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Viklund, Gunnel
    Olinder, Anna Lindholm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    A multicentre randomized controlled trial of an empowerment-inspired intervention for adolescents starting continuous subcutaneous insulin infusion: a study protocol2013Inngår i: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 13, s. 212-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 16.
    Brorsson, Anna Lena
    et al.
    Karolinska Inst & Hosp, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Olinder, Anna Lindholm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.
    Wikblad, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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.2017Inngår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 31, nr 3, s. 497-504Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 17.
    Brorsson, Anna Lena
    et al.
    Karolinska Institutet.
    Viklund, Gunnel
    Karolinska Institutet.
    Örtqvist, Eva
    Karolinska Institutet.
    Lindholm Olinder, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Does treatment with an insulin pump improve glycaemic control in children and adolescents with type 1 diabetes?: A retrospective case-control study2014Inngår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, nr 7, s. 546-553Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 18.
    Burman, Pia
    et al.
    Lund Univ, Skane Univ Hosp Malmo, Dept Endocrinol, S-20502 Malmo, Sweden..
    Edén-Engström, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Ekman, Bertil
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Karlsson, Anders F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 patients2016Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 174, nr 1, s. 17-24Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 19.
    Castillejo-Lopez, Casimiro
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Abalo, Xesus M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sidibeh, Cherno O
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Kamble, Prasad G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    FKBP51 ablation using CRISPR/Cas-9 impairs adipocyte differentiation2018Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S11-S12Artikkel i tidsskrift (Annet vitenskapelig)
  • 20.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 disorder2017Inngår i: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 180, s. 78-90Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 21. Denison, H
    et al.
    Nilsson, C
    Kujacic, M
    Löfgren, L
    Karlsson, C
    Knutsson, M
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 study2013Inngår i: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 15, nr 2, s. 136-143Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 22. Denison, H.
    et al.
    Nilsson, C.
    Lofgren, L.
    Al-Shurbaji, A.
    Himmelmann, A.
    Martensson, G.
    Tornqvist, H.
    Knutsson, M.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    A one-week phase 1 trial with the DGAT1 inhibitor AZD7687: lipid handling, hormone secretion and adverse effects in the gut2013Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S407-S407Artikkel i tidsskrift (Annet vitenskapelig)
  • 23.
    Diamanti, Klev
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Cavalli, Marco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Kumar, Chanchal
    AstraZeneca, R&D BioPharmaceut, Translat Sci & Expt Med, Early Cardiovasc Renal & Metab, Gothenburg, Sweden;Karolinska Inst, AstraZeneca Integrated CardioMetab Ctr KI AZ ICMC, Dept Med, Huddinge, Sweden.
    Skrtic, Stanko
    AstraZeneca AB, Pharmaceut Technol & Dev, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.
    Grabherr, Manfred
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Komorowski, Jan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik. Polish Acad Sci, Inst Comp Sci, Warsaw, Poland.
    Wadelius, Claes
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 9653Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Type 2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from 43 multi-organ donors. The intra-individual analysis was assessed across five key metabolic tissues (serum, visceral adipose tissue, liver, pancreatic islets and skeletal muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. In diabetes cases, carnitines were significantly higher in liver, while lysophosphatidylcholines were significantly lower in muscle and serum. We tracked the primary tissue of origin for multiple metabolites whose alterations were reflected in serum. An investigation of three major stages spanning from controls, to pre-diabetes and to overt T2D indicated that a subset of lysophosphatidylcholines was significantly lower in the muscle of pre-diabetes subjects. Moreover, glycodeoxycholic acid was significantly higher in liver of pre-diabetes subjects while additional increase in T2D was insignificant. We confirmed many previously reported findings and substantially expanded on them with altered markers for early and overt T2D. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

  • 24.
    Diamanti, Klev
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Visvanathar, Robin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Cavalli, Marco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Kumar, Chanchal
    Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca; Karolinska Institute/AstraZeneca Integrated CardioMetabolic Centre (KI/AZ ICMC), Department of Medicine.
    Stanko, Stanko
    Pharmaceutical Technology & Development, AstraZeneca AB; Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lind, Lars
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wadelius, Claes
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Komorowski, Jan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissuesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.

    Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.

    Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.

    Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.

  • 25.
    Edholm, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Karlsson, F Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Changes in liver volume and body composition during 4 weeks of low calorie diet before laparoscopic gastric bypass2015Inngår i: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 11, nr 3, s. 602-606Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 26.
    Edholm, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Näslund, Ingmar
    Karlsson, Anders F
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Rask, Eva
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Twelve-year results for revisional gastric bypass after failed restrictive surgery in 131 patients2014Inngår i: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 10, nr 1, s. 44-48Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 27.
    Edén, Desireé
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mokhtari, Dariush
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Åberg, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Adipocytes are coagulant active in a TF/FVIIa dependent manner but lipolysis is unaffected by TF/FVIIa2018Inngår i: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 114, s. S131-S131Artikkel i tidsskrift (Annet vitenskapelig)
  • 28.
    Ellegård, L.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Aldenbratt, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Svensson, Maria K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lindberg, C.
    Sahlgrens Univ Hosp, Neuromuscular Ctr, Dept Neurol, Gothenburg, Sweden.
    Body composition in patients with primary neuromuscular disease assessed by dual energy X-ray absorptiometry (DXA) and three different bioimpedance devices2019Inngår i: Clinical Nutrition ESPEN, ISSN 2405-4577, Vol. 29, s. 142-148Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Patients with primary neuromuscular disease have reduced muscle mass, and use of body mass index to assess nutritional status and body composition can therefore be questioned. Dual emission X-ray absorptiometry (DXA) can estimate muscle mass, but is not always readily available. Bioimpedance is a simple, portable and "easy to use" method for the assessment of body composition.

    Objectives: To assess muscle mass by DXA in 143 patients with primary neuromuscular disease and validate three bioimpedance devices; Impedimed SFB7, (BISIMPEDIMED), Xitron4200 (BISXITRON) and Tanita MC180MA (MFBIATANITA).

    Methods: Body composition was assessed by DXA in 143, by BISIMPEDIMED in 116, by MFBIATANITA in 104 and by BISXITRON in 35 patients.

    Results: Muscle mass assessed by DXA, and phase angle (PhA) were below reference values in all female and 96% of male patients. BISIMPEDIMED underestimated muscle mass by 6.5±14.2 kg (p < 0.001), but this could be corrected after exclusion of resistance (Ri) values > 3500 Ohm (p = 0.84). MFBIATANITA over-estimated muscle mass by 30.8±9.1 kg (p < 0.001) with systematic bias, whereas BISXITRON was in agreement with DXA, and without systematic bias. Muscle mass was strongly correlated to PhA (rPEARSON = 0.75, p < 0.01).

    Conclusion: Patients with primary neuromuscular disease have proportionally more fat and less muscle mass than the population in general, despite normal BMI. Muscle mass can be assessed by bioimpedance in these patients, but performance and bias depends on device. Phase angle by bioimpedance correlates to muscle mass, and could therefore potentially be used a surrogate measure of muscle mass during follow up.

  • 29.
    Engström, Maria Svedbo
    et al.
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden;Dalarna Univ, Sch Educ Hlth & Social Studies, SE-79188 Falun, Sweden.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, SE-79188 Falun, Sweden.
    Johansson, Unn-Britt
    Sophiahemmet Univ, SE-11486 Stockholm, Sweden;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, SE-11883 Stockholm, Sweden.
    Borg, Sixten
    Lund Univ, Dept Clin Sci Malmo, Hlth Econ Unit, SE-22381 Lund, Sweden.
    Palaszewski, Bo
    Reg Vastra Gotaland, Dept Data Management & Anal, Gothenburg, Sweden.
    Franzén, Stefan
    Register Ctr Vastra Gotaland, SE-41345 Gothenburg, Sweden.
    Gudbjörnsdottir, Soffia
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden;Register Ctr Vastra Gotaland, SE-41345 Gothenburg, Sweden.
    Eeg-Olofsson, Katarina
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden;Sahlgrens Univ Hosp, SE-41345 Gothenburg, Sweden.
    Health-related quality of life and glycaemic control among adults with type 1 and type 2 diabetes - a nationwide cross-sectional study2019Inngår i: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 17, nr 1, artikkel-id 141Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Health-related quality of life and glycaemic control are some of the central outcomes in clinical diabetes care and research. The purpose of this study was to describe the health-related quality of life and assess its association with glycaemic control in adults with type 1 and type 2 diabetes in a nationwide setting.

    Methods: In this cross-sectional survey, people with type 1 (n = 2479) and type 2 diabetes (n = 2469) were selected at random without replacement from the Swedish National Diabetes Register. Eligibility criteria were being aged 18-80 years with at least one registered test of glycated haemoglobin (HbA(1c)) the last 12 months. The generic 36-item Short Form version 2 (SF-36v2) was answered by 1373 (55.4%) people with type 1 diabetes and 1353 (54.8%) with type 2 diabetes.

    Results: Correlation analyses showed weak correlations between scores on the SF-36v2 and glycaemic control for both diabetes types. After the participants were divided into three groups based on their levels of HbA(1c), multivariate regression analyses adjusted for demographics, other risk factors and diabetes complications showed that among participants with type 1 diabetes, the high-risk group (>= 70 mmol/mol/8.6%) had statistically significantly lower means in five out of eight domains of the SF-36v2 and the mental component summary measure, as compared with the well-controlled group (< 52 mmol/mol/6.9%). Among the participants with type 2 diabetes, the high-risk group had the lowest statistically significantly means in seven domains and both summary measures.

    Conclusions: Among people with type 1 and type 2 diabetes, adults with high-risk HbA(1c) levels have lower levels of health-related quality of life in most but not all domains of the SF-36v2. This finding was not explained by demographics, other risk factors, or diabetes complications. The weak individual-level correlations between HRQOL scores and levels of glycaemic control argues for the need to not focus exclusively on either HbA(1c) levels or HRQOL scores but rather on both because both are important parts of a complex, life-long, challenging condition.

  • 30.
    Engström, Maria Svedbo
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg; Dalarna Univ, Sch Educ Hlth & Social Studies, Falun.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun.
    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 reliability2018Inngår i: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 101, nr 1, s. 139-146Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 31.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 Register2016Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, nr 3, artikkel-id e010249Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 32.
    Eriksson, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Bodegard, J.
    AstraZeneca Nord Balt, Oslo, Norway.
    Norhammar, A.
    Karolinska Inst, Stockholm, Sweden.
    Thuresson, M.
    Statisticon AB, Uppsala, Sweden.
    Nathanson, D.
    Soder Sjukhuset, Stockholm, Sweden.
    Nyström, T.
    Soder Sjukhuset, Stockholm, Sweden.
    SGLT2i vs bolus insulin as add-on to stable basal insulin treatment in type 2 diabetes and risk of cardiovascular disease and mortality: a nationwide observational study2018Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S58-S59Artikkel i tidsskrift (Annet vitenskapelig)
  • 33.
    Eriksson, Jan W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 hypoglycaemia2015Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S64-S64Artikkel i tidsskrift (Annet vitenskapelig)
  • 34.
    Eriksson, Jan W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 mortality2016Inngår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 117, s. 39-47Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 35.
    Eriksson, Jan W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lundkvist, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Jansson, Per-Anders
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden..
    Johansson, Lars
    Antaros Med AB, Gothenburg, Sweden..
    Kvarnstrom, Mats
    AstraZeneca Gothenburg, Gothenburg, Sweden..
    Moris, Linda
    Karolinska Univ Hosp, ICarolinska Trial Alliance, Stockholm, Sweden..
    Miliotis, Tasso
    AstraZeneca Gothenburg, Gothenburg, Sweden..
    Forsberg, Gun-Britt
    AstraZeneca Gothenburg, Gothenburg, Sweden..
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Oscarsson, Jan
    AstraZeneca Gothenburg, Gothenburg, Sweden..
    Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study2018Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 9, s. 1923-1934Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis The EFFECT-II study aimed to investigate the effects of dapagliflozin and omega-3 (n-3) carboxylic acids (OM-3CA). individually or combined, on liver fat content in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Methods This randomised placebo-controlled double-blind parallel-group study was performed at five clinical research centres at university hospitals in Sweden. 84 participants with type 2 diabetes and NAFLD were randomly assigned 1:1:1:1 to four treatments by a centralised randomisation system, and all participants as well as investigators and staff involved in the study conduct and analyses were blinded to treatments. Each group received oral doses of one of the following: 10 mg dapagliflozin (n = 21). 4 g OM3-CA (n = 20), a combination of both (n = 22) or placebo (n = 21). The primary endpoint was liver fat content assessed by MRI (proton density fat fraction [PDFF]) and, in addition, total liver volume and markers of glucose and lipid metabolism as well as of hepatocyte injury and oxidative stress were assessed at baseline and after 12 weeks of treatment (completion of the trial). Results Participants had a mean age of 65.5 years (SD 5.9), BMI 31.2 kg/m(2) (3.5) and liver PDFF 18% (9.3). All active treatments significantly reduced liver PDFF from baseline, relative changes: OM-3CA, -15%; dapagliflozin, -13%; OM-3CA + dapagliflozin, -21%. Only the combination treatment reduced liver PDFF (p = 0.046) and total liver fat volume (relative change, -24%,p = 0.037) in comparison with placebo. There was an interaction between the PNPLA31148M polymorphism and change in liver PDFF in the active treatment groups (p = 0.03). Dapagliflozin monotherapy, but not the combination with OM-3CA, reduced the levels of hepatocyte injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transfcrase (gamma-GT), cytokeratin (CK) 18-M30 and CK 18-M65 and plasma fibroblast growth factor 21 (FGF21). Changes in gamma-GT correlated with changes in liver PDFF (rho = 0.53, p = 0.02). Dapagliflozin alone and in combination with OM-3CA improved glucose control and reduced body weight and abdominal fat volumes. Fatty acid oxidative stress biomarkers were not affected by treatments. There were no new or unexpected adverse events compared with previous studies with these treatments. Conclusions/interpretation Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content. Dapagliflozin monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD.

  • 36.
    Eriksson, Jan W.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lundkvist, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sjöström, C.
    AstraZeneca, Gothenburg, Sweden..
    Katsogiannos, Petros
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 study2016Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, s. S332-S333Artikkel i tidsskrift (Fagfellevurdert)
  • 37.
    Eriksson, Jan W
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 Nordic2017Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, nr S1, s. S401-S402, artikkel-id 868Artikkel i tidsskrift (Annet vitenskapelig)
  • 38.
    Eriksson, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Espes, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Selvaraju, Ram K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Jansson, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Biglarnia, Alireza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas2014Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, nr 10, s. 3428-3437Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 39.
    Eriksson, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Selvaraju, Ram K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas2014Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, nr 3, s. 460-465Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 40.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 expression2017Inngår i: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 31, nr 11, s. 1437-1452Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 41.
    Ewertzon, Mats
    et al.
    Ersta Skondal Bracke Univ Coll, Dept Hlth Care Sci, POB 11189, SE-10061 Stockholm, Sweden.
    Alvariza, Anette
    Ersta Skondal Bracke Univ Coll, Palliat Res Ctr, Dept Hlth Care Sci, Stockholm, Sweden;Dalen Hosp, Capio Palliat Care, Stockholm, Sweden.
    Winnberg, Elisabeth
    Ersta Skondal Bracke Univ Coll, Dept Hlth Care Sci, POB 11189, SE-10061 Stockholm, Sweden.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden.
    Andershed, Birgitta
    Norwegian Univ Sci & Technol, Fac Hlth Care & Nursing, Gjovik, Norway.
    Goliath, Ida
    Ersta Hosp, Stockholm, Sweden;Karolinska Inst, Med Management Ctr, Learning Informat Management & Eth, Stockholm, Sweden.
    Momeni, Pardis
    Ersta Skondal Bracke Univ Coll, Dept Hlth Care Sci, POB 11189, SE-10061 Stockholm, Sweden.
    Kneck, Åsa
    Ersta Skondal Bracke Univ Coll, Dept Hlth Care Sci, POB 11189, SE-10061 Stockholm, Sweden.
    Skott, Maria
    Stockholm Cty Hosp, Northern Stockholm Psychiat, Stockholm, Sweden;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Årestedt, Kristofer
    Kalmar Cty Hosp, Dept Res, Kalmar, Sweden;Linnaeus Univ, Fac Hlth & Life Sci, Kalmar, Sweden;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Adaptation and evaluation of the Family Involvement and Alienation Questionnaire for use in the care of older people, psychiatric care, palliative care and diabetes care2018Inngår i: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 74, nr 8, s. 1839-1850Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To adapt the Family Involvement and Alienation Questionnaire (FIAQ) for use in the care of older people, psychiatric care, palliative care and diabetes care and to evaluate its validity and reliability.

    Background: Involvement in the professional care has proven to be important for family members. However, they have described feelings of alienation in relation to how they experienced the professionals' approach. To explore this issue, a broad instrument that can be used in different care contexts is needed.

    Design: A psychometric evaluation study, with a cross-sectional design.

    Method: The content validity of the FIAQ was evaluated during 2014 by cognitive interviews with 15 family members to adults in different care contexts. Psychometric evaluation was then conducted (2015-2016). A sample of 325 family members participated, 103 of whom in a test-retest evaluation. Both parametric and non-parametric methods were used.

    Results: The content validity revealed that the questionnaire was generally understood and considered to be relevant and retrievable by family members in the contexts of the care of older people, psychiatric care, palliative care and diabetes care. Furthermore, the FIAQ (Revised), demonstrated satisfactory psychometric properties in terms of data quality, homogeneity, unidimensionality (factor structure), internal consistency and test-retest reliability.

    Conclusion: The study provides evidence that the FIAQ (Revised) is reliable and valid for use in further research and in quality assessment in the contexts of the care of older people, psychiatric care, palliative care and diabetes care.

  • 42.
    Fall, Tove
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes2016Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, nr 10, s. 2114-2124Artikkel i tidsskrift (Fagfellevurdert)
    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).

  • 43.
    Fonseca, Ana Catarina R. G.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal.
    Carvalho, Eugenia
    Arkansas Childrens Res Inst, Little Rock, AR 72202 USA;Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72202 USA;Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal;Portuguese Diabet Assoc APDP, P-1250203 Lisbon, Portugal.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Calcineurin is an important factor involved in glucose uptake in human adipocytes2018Inngår i: Molecular and Cellular Biochemistry, ISSN 0300-8177, E-ISSN 1573-4919, Vol. 445, nr 1-2, s. 157-168Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Calcineurin inhibitors are used in immunosuppressive therapy applied after transplantation, but they are associated with major metabolic side effects including the development of new onset diabetes. Previously, we have shown that the calcineurin inhibiting drugs tacrolimus and cyclosporin A reduce adipocyte and myocyte glucose uptakes by reducing the amount of glucose transporter type 4 (GLUT4) at the cell surface, due to an increased internalization rate. However, this happens without alteration in total protein and phosphorylation levels of key proteins involved in insulin signalling or in the total amount of GLUT4. The present study evaluates possible pathways involved in the altered internalization of GLUT4 and consequent reduction of glucose uptake provoked by calcineurin inhibitors in human subcutaneous adipose tissue. Short- and long-term treatments with tacrolimus, cyclosporin A or another CNI deltamethrin (herbicide) decreased basal and insulin-dependent glucose uptake in adipocytes, without any additive effects observed when added together. However, no tacrolimus effects were observed on glucose uptake when gene transcription and protein translation were inhibited. Investigation of genes potentially involved in GLUT4 trafficking showed only a small effect on ARHGEF11 gene expression (p < 0.05). In conlusion, the specific inhibition of calcineurin, but not that of protein phosphatases, decreases glucose uptake in human subcutaneous adipocytes, suggesting that calcineurin is an important regulator of glucose transport. This inhibitory effect is mediated via gene transcription or protein translation; however, expression of genes potentially involved in GLUT4 trafficking and endocytosis appears not to be involved in these effects.

  • 44.
    Fonseca, Ana R. G.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Calcineurin is involved in the regulation of human adipocyte glucose uptake2017Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, s. S227-S227Artikkel i tidsskrift (Annet vitenskapelig)
  • 45.
    Forsner, Maria
    et al.
    Dalarna University.
    Berggren,, Jenny
    Masaba, Jennipher
    Ekbladh, Annelie
    Lindholm Olinder, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Parents' experiences of caring for a child younger than two years of age treated with continuous subcutaneous insulin infusion2014Inngår i: European Diabetes Nursing, ISSN 1551-7853, E-ISSN 1551-7861, Vol. 11, nr 1, s. 7-12Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 46.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 patients2015Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S320-S320Artikkel i tidsskrift (Annet vitenskapelig)
  • 47.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 patients2016Inngår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, nr 7, s. 998-1006Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 48. Fuhrmann, A.
    et al.
    Lopes, P. C.
    Sereno, J.
    Pedro, J.
    Espinoza, D. O.
    Pereira, Maria J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Reis, F.
    Eriksson, J. W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    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 model2014Inngår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 88, nr 2, s. 216-228Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 49.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap. 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 graduation2016Inngår i: Nurse Education Today, ISSN 0260-6917, E-ISSN 1532-2793, Vol. 36, s. 165-171Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 50.
    Ghandour, Rula
    et al.
    Birzeit Univ, ICPH, Birzeit, Palestine.
    Mikki, Nahed
    Birzeit Univ, ICPH, Birzeit, Palestine.
    Abu Rmeileh, Niveen M. E.
    Birzeit Univ, ICPH, Birzeit, Palestine.
    Jerden, Lars
    Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Norberg, Margareta
    Umea Univ, Dept Publ Hlth & Clin Med, Unit Epidemiol & Global Hlth, Umea, Sweden.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Husseini, Abdullatif
    Birzeit Univ, ICPH, Birzeit, Palestine.
    Complications of type 2 diabetes mellitus in Ramallah and al-Bireh: The Palestinian Diabetes Complications and Control Study (PDCCS)2018Inngår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 12, nr 6, s. 547-557Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Type 2 diabetes mellitus (T2DM) is a growing pandemic that will lead, if not managed and controlled, to frequent complications, poor quality of life, and high rates of disability and death. Little is known about T2DM complications in Palestine. The aim of this study is to estimate the prevalence of T2DM complications in Ramallah and al-Bireh governorate of Palestine. Methods: The study was conducted in eleven primary healthcare clinics offering services for persons with T2DM. Macrovascular complications were assessed using the Diabetes complication index. Microvascular complications were measured by physical examinations and laboratory tests. Questionnaires, laboratory tests, and physical examinations were used to assess socio-demographic characteristics, co-morbidities and other risk factors. Results: 517 adult men and nonpregnant women participated in the study (166 men, 351 women). The response rate was 84%. Mean age and mean duration of diabetes were 58.1 and 9.4 years respectively. Prevalence of diagnosed microvascular and macrovascular complications was 67.2% and 28.6% respectively. 78.2% of the participants had poor glycemic control (HbA1c >= 7.0%). Conclusion: Significant proportions of persons with T2DM had macro- and microvascular complications and poor metabolic control. These findings are important for policy development and the planning of health services.

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