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  • 1. Dawed, A. Y.
    et al.
    Mari, A.
    McDonald, T. J.
    Hong, Mun-Gwan
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sharma, S.
    Robertson, N. R.
    Mahajan, A.
    Walker, M.
    Gough, S.
    Zhou, K.
    Forgie, I.
    Ruetten, H.
    Jones, A. G.
    Pearson, E. R.
    GLP-1 receptor variants markedly differentiate glycaemic response to GLP-1 receptor agonists: a DIRECT study2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S393-S393Article in journal (Refereed)
  • 2. Ferrari, A.
    et al.
    Fiorino, E.
    Longo, R.
    Barilla, S.
    Mitro, N.
    Cermenati, G.
    Giudici, Marco
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Caruso, D.
    Mai, A.
    Guerrini, U.
    De Fabiani, E.
    Crestani, M.
    Attenuation of diet-induced obesity and induction of white fat browning with a chemical inhibitor of histone deacetylases2017In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 2, p. 289-298Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: In the last decade, a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high-fat diet (HFD). METHODS: C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups, treated intraperitoneally with vehicle dimethylsulfoxide (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days. Glucose tolerance test and measurement of body temperature during cold exposure were performed. Adipose tissues and liver were phenotypically characterized through histological analysis. Gene and protein expression analysis of brown and white adipose tissues (WATs) were performed. RESULTS: MS-275 treated mice showed 10% reduction of body weight, lower adipocyte size and improved glucose tolerance. Inhibition of class I HDAC determined reduction of adipocyte size and of fat mass, paralleled by higher expression of adipose functionality markers and by increased rate of lipolysis and fatty acid beta-oxidation. MS-275 also promoted thermogenic capacity, related to `browning' of visceral and subcutaneous WAT, showing increased expression of uncoupling protein 1. In brown adipose tissue, we observed limited effects on gene expression and only reduction of brown adipocyte size. CONCLUSIONS: This study provides evidence that class I HDAC inhibition stimulated functionality and oxidative potential of adipose tissue, improving glucose tolerance and ameliorating the metabolic profile in diet-induced obese mice.

  • 3.
    Govind, Satish C.
    et al.
    BMJ Heart Center, Bangalore, India.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Nowak, J.
    Karolinska Institute, Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Arvind, S. R.
    BMJ Heart Center, Bangalore, India.
    Ramesh, S. S.
    BMJ Heart Center, Bangalore, India.
    Netyö, A.
    Karolinska Institute, Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Prasad, K.Y.M.
    BMJ Heart Center, Bangalore, India.
    Saha, S.
    Karolinska Institute, Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Microalbuminuria and Left Ventricular Functions in Type 2 Diabetes: A Quantitative Assessment by Stress Echocardiography in the Myocardial Doppler in Diabetes (MYDID) Study III2007In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 41, no 6, p. 363-369Article in journal (Refereed)
    Abstract [en]

    Background. Left ventricular (LV) function might be altered in type 2 diabetes (DM) and microalbuminuria (MA) may accentuate the abnormalities. We sought to investigate whether additional LV dysfunction could be unmasked using tissue Doppler (TVE)-enhanced dobutamine stress echocardiography (TVE-DSE) in patients with DM+MA. Methods. Twenty seven DM subjects with MA, (DM+MA), 31 DM subjects without MA (DM-MA), and 13 Controls were evaluated using TVE-DSE. LV basal peak systolic (PSV), early (E') and late (A') diastolic velocities (cm/sec) at rest and peak stress were post-processed. LV filling pressure was assessed using E/E'ratio. Results. PSV and E'velocity at peak stress in the respective three groups were 13.7±1.0, 10.1±1.1, 10.0±1.2 for PSV; and 10.0±1.6, 5.0±1.4, 4.8±1.4 for E' (p < 0.001 for controls vs. both groups). E/E' at rest was 7.9±0.7 in the controls, 10.8±2.4 in DM-MA, and 11.0±2.2 in DM+MA (p < 0.01 Controls vs. both the DM groups). Conclusions. Patients with DM+MA do not have additional LV regional systolic and diastolic dysfunctions compared with DM-MA, as revealed by TVE-DSE, when controlled for glycemia levels, lipids, and treatment strategies.

  • 4.
    Govind, Satish C.
    et al.
    BMJ Heart Center, Bangalore, India.
    Brodin, Lars-Åke
    Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Nowak, J.
    Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Quintana, M.
    Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Raumina, S.
    Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Ramesh, S.S.
    BMJ Heart Center, Bangalore, India.
    Keshava, R.
    BMJ Heart Center, Bangalore, India.
    Saha, S.
    Department of Clinical Physiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Isolated Type 2 Diabetes mellitus Causes Myocardial Dysfunction That Becomes Worse in the Presence of Cardiovascular Diseases: Results of the Myocardial Doppler in Diabetes (MYDID): Study 12005In: Cardiology, ISSN 0008-6312, E-ISSN 1421-9751, Vol. 103, no 4, p. 189-195Article in journal (Refereed)
    Abstract [en]

    Aims: Patients with type 2 diabetes mellitus (DM) often suffer disproportionately and have a worse outcome when burdened with cardiovascular complications compared with those without DM. A specific heart muscle disease reportedly caused by DM per se may explain this. We sought to investigate whether an echo Doppler diagnosis of such a myocardial disease is clinically relevant in DM with or without coexistent coronary artery disease (CAD) and/or hypertension ( HTN). Subjects and Methods: Two hundred subjects (127 males, 73 females, 56 +/- 10 years) including controls (n=23), patients with HTN (n=20), CAD (n=35), uncomplicated DM (n=59), DM+HTN (n=27), DM+ CAD (n=16) and DM+CAD+HTN (n=20) underwent tissue Doppler-enhanced dobutamine stress echocardiography. Myocardial function was assessed by measuring left ventricular myocardial peak systolic velocity (PSV) and early diastolic velocity at rest and during peak stress, besides measurements of standard Doppler variables. Results: Average left ventricular PSV at rest was significantly lower in CAD (4.7 +/- 1.5) compared with controls (5.7 center dot +/- 1.2) and in DM+CAD+HTN (4.6 +/- 1.4) compared with DM (5.6 +/- 1.3; all p < 0.05). During peak stress, lower PSV persisted in CAD (9.5 +/- 3.1) and DM+CAD+HTN (8.1 +/- 2.7), while appearing de novo in DM (11.3 +/- 2.6) and HTN (11.0 +/- 2.3) unlike in the controls (12.5 +/- 2.5; all p < 0.001). When pooled together, DM subjects with CAD and/or HTN or both had significantly lower PSV (9.1 +/- 2.7) than those without (10.0 +/- 2.8; p < 0.001). Early diastolic velocity response was equally lower in both groups compared with the controls. Conclusion: The results suggest that dobutamine stress unmasks myocardial functional disturbances caused by uncomplicated DM. The discrete disturbances become quantitatively more pronounced in the presence of coexistent cardiovascular diseases.

  • 5.
    Govind, Satish C.
    et al.
    Bhagwan Mahavir Jain Heart Center, Bangalore, India.
    Roumina, S.
    Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Nowak, J.
    Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Ramesh, S. S.
    Bhagwan Mahavir Jain Heart Center, Bangalore, India.
    Saha, S. K.
    Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Differing myocardial response to a single session of hemodialysis in end-stage renal disease with and without type 2 diabetes mellitus and coronary artery disease2006In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 4, no 9Article in journal (Refereed)
    Abstract [en]

    Background: Though hemodialysis (HD) acutely improves cardiac function, the impact of background diseases like coronary artery disease (CAD) and Type 2 diabetes (DM) in the setting of end-stage renal disease (ESRD) is not known. Tissue velocity echocardiography (TVE) offers a fast choice to follow changes in myocardial function after HD in ESRD with concomitant DM and/or CAD. Methods: 46 subjects (17 with ESRD, Group 1; 15 with DM, Group 2; 14 with DM+CAD, Group 3) underwent standard and TVE prior to and shortly after HD. Besides standard Doppler variables, regional myocardial systolic and diastolic velocities, as well as systolic strain rate were post processed. Results: Compared with pre-HD, post-HD body weight (kg) significantly decreased in all the three groups (51 ± 9 vs. 48 ± 8, 62 ± 10 vs.59 ± 10, and 61 ± 9 vs. 58 ± 9 respectively; all p < 0.01). Left ventricular end diastolic dimensions (mm) also decreased post- HD (46 ± 5 vs. 42 ± 7, 53 ± 7 vs. 50 ± 7, 51 ± 7 vs. 47 ± 8 respectively; all p < 0.01). Regional longitudinal peak systolic velocity in septum (cm/s) significantly increased post-HD in Group 1(5.7 ± 1.6 vs. 7.2 ± 2.3; p < 0.001) while remained unchanged in the other two groups. Similar trends were noted in other left ventricular walls. When the myocardial velocities (cm/s) were computed globally, the improvement was seen only in Group 1 (6.3 ± 1.5 vs. 7.9 ± 2.0; p < 0.001). Global early regional diastolic velocity (cm/s) improved in Group 1, remained unchanged in Group 2, while significantly decreased in Group 3(-5.9 ± 1.3 vs. -4.1 ± 1.8; p < 0.01). Global systolic strain rate (1/sec) increased in the first 2 Groups but remained unchanged (-0.87 ± 0.4 vs. -0.94 ± 0.3; p = ns) in Group 3. Conclusion: A single HD session improves LV function only in ESRD without coexistent DM and/or CAD. The present data suggest that not only dialysis-dependent changes in loading conditions but also co-existent background diseases determine the myocardial response to HD.

  • 6.
    Govind, Satish C.
    et al.
    Department of Clinical Physiology, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Saha, S.
    Department of Clinical Physiology, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Brodin, Lars-Åke
    Department of Clinical Physiology, Karolinska Institute, Karolinska University Hospital, Huddinge.
    Ramesh, S. S.
    BMJ Heart Center, Bangalore, India.
    Arvind, S. R.
    BMJ Heart Center, Bangalore, India.
    Quintana, M.
    Department of Clinical Physiology, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Impaired Myocardial Functional Reserve in Hypertension and Diabetes Mellitus Without Coronary Artery Disease: Searching for the Possible Link With Congestive Heart Failure in the Myocardial Doppler in Diabetes (MYDID) Study II2006In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 19, no 8, p. 851-857Article in journal (Refereed)
    Abstract [en]

    Background: Although the impact of type 2 diabetes mellitus (DM) and hypertension (HTN) on myocardial function has recently been studied using tissue Doppler echocardiography (TDE), the independent role of both conditions, and the influence of other risk factors on myocardial function has not been completely defined, particularly in absence of coronary artery disease (CAD). The aim of this study was to assess the myocardial functional reserve in patients with DM or HTN with apparently normal left ventricular (LV) systolic function.

    Methods: Standard and dobutamine stress echocardiography using TDE was performed in 128 subjects: 59 had DM, 20 had HTN, 27 had both DM and HTN (HTN + DM), and 22 subjects were controls (C). Subjects with known CAD and depressed LV function were excluded. In addition, standard two-dimensional and Doppler measurements, LV regional peak systolic (PSV), early (E') and late (A') diastolic velocities, strain (S%) and strain rate (SR), were assessed at rest and peak stress.

    Results: The LV mass did not differ, although relative wall thickness was significantly higher in subjects with HTN + DM and HTN. The PSV did not differ at rest but was lowest in subjects with HTN + DM at peak stress. The E' wave velocity was significantly lower in subjects with HTN + DM both at rest and during peak stress, as were S% and SR.

    Conclusions: The addition of DM to HTN has a negative effect on LV systolic and diastolic functions. A depressed myocardial functional reserve might be postulated as one of the pathophysiologic mechanisms for the excessive occurrence of congestive heart failure in patients with DM or HTN.

  • 7. Haglund, Felix
    et al.
    Hallström, Björn M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Inga-Lena
    Hoog, Anders
    Juhlin, C. Christofer
    Larsson, Catharina
    Inflammatory infiltrates in parathyroid tumors2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 177, no 6, p. 445-453Article in journal (Refereed)
    Abstract [en]

    Context: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias. Objective: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism. Design: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts. Results: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH (P = 0.007) and oxyphilic differentiation (P = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation (P = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium (P = 0.037). Conclusions: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.

  • 8. Heinonen, Sini
    et al.
    Muniandy, Maheswary
    Buzkova, Jana
    Mardinoglu, Adil
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Rodriguez, Amaia
    Fruhbeck, Gema
    Hakkarainen, Antti
    Lundbom, Jesper
    Lundbom, Nina
    Kaprio, Jaakko
    Rissanen, Aila
    Pietilainen, Kirsi H.
    Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity: a study of young healthy MZ twins2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 1, p. 169-181Article in journal (Refereed)
    Abstract [en]

    Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference Delta BMI ae<yen> 3 kg/m(2)) and concordant (n = 5, Delta BMI < 3 kg/m(2)) for BMI, identified from ten birth cohorts of 22- to 36-year-old Finnish twins. Abdominal body fat distribution (MRI), liver fat content (magnetic resonance spectroscopy), insulin sensitivity (OGTT), high-sensitivity C-reactive protein, serum lipids and adipokines were measured. Subcutaneous abdominal adipose tissue biopsies were obtained to analyse the transcriptomics patterns of the isolated adipocytes as well as of the whole adipose tissue. Mitochondrial DNA transcript levels in adipocytes were measured by quantitative real-time PCR. Western blots of oxidative phosphorylation (OXPHOS) protein levels in adipocytes were performed in obese and lean unrelated individuals. The heavier (BMI 29.9 +/- 1.0 kg/m(2)) co-twins of the discordant twin pairs had more subcutaneous, intra-abdominal and liver fat and were more insulin resistant (p < 0.01 for all measures) than the lighter (24.1 +/- 0.9 kg/m(2)) co-twins. Altogether, 2538 genes in adipocytes and 2135 in adipose tissue were significantly differentially expressed (nominal p < 0.05) between the co-twins. Pathway analysis of these transcripts in both isolated adipocytes and adipose tissue revealed that the heavier co-twins displayed reduced expression of genes relating to mitochondrial pathways, a result that was replicated when analysing the pathways behind the most consistently downregulated genes in the heavier co-twins (in at least 12 out of 14 pairs). Consistently upregulated genes in adipocytes were related to inflammation. We confirmed that mitochondrial DNA transcript levels (12S RNA, 16S RNA, COX1, ND5, CYTB), expression of mitochondrial ribosomal protein transcripts and a major mitochondrial regulator PGC-1 alpha (also known as PPARGC1A) were reduced in the heavier co-twins' adipocytes (p < 0.05). OXPHOS protein levels of complexes I and III in adipocytes were lower in obese than in lean individuals. Subcutaneous abdominal adipocytes in obesity show global expressional downregulation of oxidative pathways, mitochondrial transcripts and OXPHOS protein levels and upregulation of inflammatory pathways. The datasets analysed and generated during the current study are available in the figshare repository.

  • 9. Johansson, I.
    et al.
    Edner, M.
    Ryden, L.
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Centres, Centre for Traffic Research, CTR.
    Dahlstrom, U.
    Norhammar, A.
    Impact of diabetes mellitus on long-term prognosis in patients with preserved heart failure: a report from the Swedish Heart Failure Registry (S-HFR)2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, p. S25-S25Article in journal (Other academic)
  • 10.
    Koivula, Robert W.
    et al.
    Lund Univ, Skane Univ Hosp Malmo, Genet & Mol Epidemiol Unit, Dept Clin Sci,Diabet Ctr,CRC, Bldg 91,Level 10,Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Sci Life Lab, Stockholm, Sweden..
    Franks, Paul W.
    Lund Univ, Skane Univ Hosp Malmo, Genet & Mol Epidemiol Unit, Dept Clin Sci,Diabet Ctr,CRC, Bldg 91,Level 10,Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Sect Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 9, p. 1601-1615Article in journal (Refereed)
    Abstract [en]

    Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up). Methods From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at similar to 18 months (both cohorts) and at similar to 48 months (cohort 1) or similar to 36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe. Results Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean +/- SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m(2); fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m(2); fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l. Conclusions/interpretation The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.

  • 11.
    Matzaroglou, C.
    et al.
    Technol Univ Western Greece, Human Assessment & Rehabil Lab, Aigio, Greece. egas, P.; Gliatis, J.; Tyllianakis, M..
    Angelopoulos, V.
    Gkrilias, P.
    Megas, P.
    Aikateriniadis, C. Menos
    KTH.
    Gliatis, J.
    Tyllianakis, M.
    ARE THE OTTAWA RULES HELPFUL TO PREDICT ANKLE AND FOOT FRACTURES IN2019In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 30, p. S414-S415Article in journal (Other academic)
  • 12. Meyer, C.
    et al.
    Carlqvist, Håkan
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.).
    Vorgerd, M.
    Schöls, L.
    Östenson, C. -G
    Ristow, M.
    Regular insulin secretory oscillations despite impaired ATP synthesis in Friedreich Ataxia patients2006In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 38, no 10, p. 683-687Article in journal (Refereed)
    Abstract [en]

    Friedreich Ataxia is an inherited disorder caused by decreased expression of a mitochondrial protein called frataxin. Deficiency of this protein causes reduced biogenesis of iron-sulfur clusters, and subsequently impaired synthesis and replenishment of ATP in vivo. Basal secretion of insulin occurs in an oscillating manner presumably triggered by ATP-dependent feedback inhibition of glycolytic flux. Hence, individuals with reduced ATP synthesis rates should possibly exhibit impaired insulin secretory oscillations if these were solely dependent on ATP. In the present study Friedreich Ataxia patients with a presumptive impairment of ATP synthesis in pancreatic beta-cells were evaluated for regularity of basal secretory oscillations of insulin. Healthy siblings were employed as controls. in conflict with the initial hypothesis, no differences in regards to oscillation patterns were observed between patients and controls. Supported by ex vivo evidence, these findings tentatively suggest that pulsatile insulin secretion might not be exclusively dependent on ATP feedback inhibition in humans.

  • 13. Nagaraj, V.
    et al.
    Kazim, A. S.
    Helgeson, J.
    Lewold, C.
    Barik, S.
    Buda, P.
    Reinbothe, T. M.
    Wennmalm, Stefan
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zhang, E.
    Renström, E.
    Elevated basal insulin secretion in type 2 diabetes caused by reduced plasma membrane cholesterol2016In: Molecular Endocrinology, ISSN 0888-8809, E-ISSN 1944-9917, Vol. 30, no 10, p. 1059-1069Article in journal (Refereed)
    Abstract [en]

    Elevated basal insulin secretion under fasting conditions together with insufficient stimulated insulin release is an important hallmark of type 2 diabetes, but the mechanisms controlling basal insulin secretion remain unclear. Membrane rafts exist in pancreatic islet cells and spatially organize membrane ion channels and proteins controlling exocytosis, which may contribute to the regulation of insulin secretion. Membrane rafts (cholesterol and sphingolipid containing microdomains) were dramatically reduced in human type 2 diabetic and diabetic Goto-Kakizaki (GK) rat islets when compared with healthy islets. Oxidation of membrane cholesterol markedly reduced microdomain staining intensity in healthy human islets, but was without effect in type 2 diabetic islets. Intriguingly, oxidation of cholesterol affected glucose-stimulated insulin secretion only modestly, whereas basal insulin release was elevated. This was accompanied by increased intracellular Ca2+ spike frequency and Ca2+ influx and explained by enhanced single Ca2+ channel activity. These results suggest that the reduced presence of membrane rafts could contribute to the elevated basal insulin secretion seen in type 2 diabetes.

  • 14. Norhammar, A.
    et al.
    Johansson, I.
    Edner, M.
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Centres, Centre for Traffic Research, CTR.
    Dahlstrom, U.
    Ryden, L.
    Impact of diabetes mellitus on long-term prognosis in patients with ischaemic heart failure: a report from the Swedish Heart Failure Registry (S-HFR)2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, p. S24-S25Article in journal (Other academic)
  • 15. Norhammar, A.
    et al.
    Kjellstrom, B.
    Habib, N.
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Transport Science, Transport planning, economics and engineering.
    Gustafsson, A.
    Karolinska Inst, Dent Med, Stockholm, Sweden..
    Ryden, L.
    Karolinska Inst, Dept Med, Cardiol Unit, Karolinska Univ Hosp, Stockholm, Sweden..
    Previously unknown glucose abnormalities are common in individuals with periodontitis, especially in those with a previous myocardial infarction2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, p. S564-S565Article in journal (Other academic)
  • 16.
    Norhammar, Anna
    et al.
    Karolinska Inst, Dept Med K2, Stockholm, Sweden. orhammar, Anna.
    Kjellström, Barbro
    Habib, Natalie
    Gustafsson, Anders
    Klinge, Björn
    Nygren, Åke
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Centres, Centre for Transport Studies, CTS.
    Svenungsson, Elisabet
    Rydén, Lars
    Undetected Dysglycemia Is an Important Risk Factor for Two Common Diseases, Myocardial Infarction and Periodontitis: A Report From the PAROKRANK Study2019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 8, p. 1504-1511Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Information on the relationship among dysglycemia (prediabetes or diabetes), myocardial infarction (MI), and periodontitis (PD) is limited. This study tests the hypothesis that undetected dysglycemia is associated with both conditions. RESEARCH DESIGN AND METHODS: The PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study included 805 patients with a first MI and 805 matched control subjects. All participants without diabetes (91%) were examined with an oral glucose tolerance test. Abnormal glucose tolerance (AGT) (impaired glucose tolerance or diabetes) was categorized according to the World Health Organization. Periodontal status was categorized from dental X-rays as healthy (≥80% remaining alveolar bone height), moderate (79-66%), or severe (<66%) PD. Odds ratios (ORs) and 95% CIs were calculated by logistic regression and were adjusted for age, sex, smoking, education, marital status, and explored associated risks of dysglycemia to PD and MI, respectively. RESULTS: AGT was more common in patients than in control subjects (32% vs. 19%; P < 0.001) and was associated with MI (OR 2.03; 95% CI 1.58-2.60). Undetected diabetes was associated with severe PD (2.50; 1.36-4.63) and more strongly in patients (2.35; 1.15-4.80) than in control subjects (1.80; 0.48-6.78), but not when categorized as AGT (total cohort: 1.07; 0.67-1.72). Severe PD was most frequent in subjects with undetected diabetes, and reversely undetected diabetes was most frequent in patients with severe PD. CONCLUSIONS: In this large case-control study previously undetected dysglycemia was independently associated to both MI and severe PD. In principal, it doubled the risk of a first MI and of severe PD. This supports the hypothesis that dysglycemia drives two common diseases, MI and PD.

  • 17. Ritsinger, Viveca
    et al.
    Tanoglidi, Eleni
    Malmberg, Klas
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Transport Science, Transport planning, economics and engineering.
    Ryden, Lars
    Tenerz, Ake
    Norhammar, Anna
    Sustained prognostic implications of newly detected glucose abnormalities in patients with acute myocardial infarction: Longterm follow-up of the Glucose Tolerance in Patients with Acute Myocardial Infarction cohort2015In: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 12, no 1, p. 23-32Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate long-term prognostic importance of newly discovered glucose disturbances in patients with acute myocardial infarction (AMI). Methods: During 1998-2001, consecutive patients with AMI (n=167) and healthy controls (n=184) with no previously known diabetes were investigated with an oral glucose tolerance test (OGTT). Patients and controls were separately followed up for cardiovascular events (first of cardiovascular mortality/AMI/stroke/heart failure) during a decade. Results: In all, 68% of the patients and 35% of the controls had newly detected abnormal glucose tolerance (AGT). Cardiovascular event (n=72, p=0.0019) and cardiovascular mortality (n=31, p=0.031) were more frequent in patients with newly detected AGT. Regarding patients, a Cox proportional-hazard regression analysis identified AGT (hazard ratio (HR): 2.30; 95% confidence interval (CI): 1.24-4.25; p=0.008) and previous AMI (HR: 2.39; CI: 1.31-4.35; p=0.004) as prognostically important. Conclusion: An OGTT at discharge after AMI disclosed a high proportion of patients with previously unknown AGT which had a significant and independent association with long-term prognosis.

  • 18. Rubin, C
    et al.
    Fredriksson, R
    Savolainen, P
    Gunnarsson, U
    Lundeberg, Joakim
    KTH, Superseded Departments, Biotechnology.
    Andersson, L
    Kindmark, A
    Gene expression in femoral bone from two divergent chicken populations, differing markedly in bone phenotypes2004In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 19, p. S242-S242Article in journal (Other academic)
  • 19.
    Ryden, Mikael
    et al.
    Karolinska Inst, Dept Med H7, S-14186 Stockholm, Sweden..
    Uzunel, Mehmet
    Karolinska Inst, Dept Clin Immunol, S-14186 Stockholm, Sweden..
    Hard, Joanna L.
    Karolinska Inst, Dept Cell & Mol Biol C5, S-17177 Stockholm, Sweden..
    Borgström, Erik
    KTH, School of Biotechnology (BIO), Gene Technology.
    Mold, Jeff E.
    Karolinska Inst, Dept Cell & Mol Biol C5, S-17177 Stockholm, Sweden..
    Arner, Erik
    Karolinska Inst, Dept Med H7, S-14186 Stockholm, Sweden..
    Mejhert, Niklas
    Karolinska Inst, Dept Med H7, S-14186 Stockholm, Sweden..
    Andersson, Daniel P.
    Karolinska Inst, Dept Med H7, S-14186 Stockholm, Sweden..
    Widlund, Yvonne
    Karolinska Inst, Dept Med H7, S-14186 Stockholm, Sweden..
    Hassan, Moustapha
    Karolinska Inst, Dept Lab Med H5, S-14186 Stockholm, Sweden..
    Jones, Christina V.
    Karolinska Inst, Dept Cell & Mol Biol C5, S-17177 Stockholm, Sweden..
    Spalding, Kirsty L.
    Karolinska Inst, Dept Cell & Mol Biol C5, S-17177 Stockholm, Sweden..
    Svahn, Britt-Marie
    Karolinska Inst, Dept Clin Immunol, S-14186 Stockholm, Sweden..
    Ahmadian, Afshin
    KTH, School of Biotechnology (BIO), Gene Technology.
    Frisen, Jonas
    Karolinska Inst, Dept Cell & Mol Biol C5, S-17177 Stockholm, Sweden..
    Bernard, Samuel
    Univ Lyon, CNRS UMR 5208, Inst Camille Jordan, F-69622 Villeurbanne, France..
    Mattsson, Jonas
    Karolinska Inst, Dept Clin Immunol, S-14186 Stockholm, Sweden..
    Arner, Peter
    Karolinska Inst, Dept Med H7, S-14186 Stockholm, Sweden..
    Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis2015In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 22, no 3, p. 408-417Article in journal (Refereed)
    Abstract [en]

    Because human white adipocytes display a high turnover throughout adulthood, a continuous supply of precursor cells is required to maintain adipogenesis. Bone marrow (BM)-derived progenitor cells may contribute to mammalian adipogenesis; however, results in animal models are conflicting. Here we demonstrate in 65 subjects who underwent allogeneic BM or peripheral blood stem cell (PBSC) transplantation that, over the entire lifespan, BM/PBSC-derived progenitor cells contribute similar to 10% to the subcutaneous adipocyte population. While this is independent of gender, age, and different transplantation-related parameters, body fat mass exerts a strong influence, with up to 2.5-fold increased donor cell contribution in obese individuals. Exome and whole-genome sequencing of single adipocytes suggests that BM/PBSC-derived progenitors contribute to adipose tissue via both differentiation and cell fusion. Thus, at least in the setting of transplantation, BM serves as a reservoir for adipocyte progenitors, particularly in obese subjects.

  • 20. Sigurgeirsson, Benjamín
    et al.
    Åmark, Hanna
    Jemt, Anders
    KTH, School of Biotechnology (BIO), Gene Technology.
    Ujvari, Dorina
    Westgren, Magnus
    Lundeberg, Joakim
    Gidlöf, Sebastian
    Comprehensive RNA sequencing of healthy human endometrium at two time points of the menstrual cycle2016Manuscript (preprint) (Other academic)
    Abstract [en]

    Endometrial receptivity is crucial for implantation and establishment of a normal pregnancy. The shift from proliferative to receptive endometrium is still far from understood. In this paper we comprehensively present the transcriptome of the human endometrium by comparing endometrial biopsies from proliferative phase with consecutive biopsies 7-9 days after ovulation. The results show a clear difference in expression between the two time points using both total and small RNA sequencing.  3297 mRNAs, 516 long non-coding RNAs and 102 small non-coding RNAs were identified as statistically differentially expressed between the two time points. We show a thorough description of the change in mRNA between the two time points and display lncRNAs, snoRNAs and snRNAs not previously reported in the healthy human endometrium. In conclusion this paper reports in detail the shift in RNA expression from the proliferative to receptive endometrium.

  • 21. Wang, A.
    et al.
    Arver, S.
    Flanagan, J.
    Mellbin, L. G.
    Gyberg, V.
    Malmberg, K.
    Norhammar, A.
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Transport Science, Transport planning, economics and engineering.
    Ritsinger, V.
    Ryden, L.
    Testosterone in patients with acute myocardial infarction and glucose abnormalities and in matched controls: a report from the GAMI study2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, p. S556-S557Article in journal (Other academic)
1 - 21 of 21
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