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  • 201.
    Wigren, Jane
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Surapureddi, Sailesh
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Olsson, Anders
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Glass, C. K.
    University of California, San Diego, La Jolla, CA, USA.
    Hammarström, Sven
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Söderström, Mats
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Differential recruitment of the coactivator proteins CREB-binding protein and steroid receptor coactivator-1 to peroxisome proliferator-activated receptor gamma/9-cis-retinoic acid receptor heterodimers by ligands present in oxidized low-density lipoprotein2003Inngår i: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 177, nr 2, s. 207-214Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peroxisome proliferator-activated receptor gamma (PPAR?) colocalizes with oxidized low-density lipoprotein (LDL) in foam cells in atherosclerotic lesions. We have explored a potential role of oxidized fatty acids in LDL as PPAR? activators. LDL from patients suffering from intermittent claudication due to atherosclerosis was analyzed using HPLC and gas chromatography/mass spectrophotometry and found to contain 9-hydroxy-and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), as well as 5-hydroxy-, 12-hydroxy- and 15-hydroxyeicosatetraenoic acid (5-, 12- and 15-HETE respectively). PPAR? was potently activated by 13(S)-HODE and 15(S)-HETE, as judged by transient transfection assays in macrophages or CV-1 cells. 5(S)- and 12(S)-HETE as well as 15-deoxy-?12,14 -prostaglandin J2 also activated PPAR? but were less potent. Interestingly, the effect of the lipoxygenase products 13(S -HODE and 15(S)-HETE as well as of the drug rosiglitazone were preferentially enhanced by the coactivator CREB-binding protein, whereas the effect of the cyclooxygenase product 15-deoxy-?12,14-prostaglandin J2 was preferentially enhanced by steroid receptor coactivator-1. We interpret these results, which may have relevance to the pathogenesis of atherosclerosis, to indicate that the lipoxygenase products on the one hand and the cyclooxygenase product on the other exert specific effects on the transcription of target genes through differential coactivator recruitment by PPAR?/9-cis retinoic acid receptor heterodimer complexes.

  • 202.
    Wijkman, Magnus
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Fysiologi.
    Länne, Toste
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Engvall, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Lindström, Torbjörn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Östgren, Carl-Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Allmänmedicin. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland.
    Arterial stiffness in patients with type 2 diabetes correlates with both ambulatory and central blood pressure but not with glycemic control2007Inngår i: 17th meeting on Hypertension,2007, 2007Konferansepaper (Annet vitenskapelig)
  • 203.
    Wijkman, Magnus
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Fysiologi.
    Länne, Toste
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Engvall, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Lindström, Torbjörn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Östgren, Carl-Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Allmänmedicin. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland.
    Correlations between left ventricular mass and conventional, ambulatory and central blood pressure in patients with type 2 diabetes.2007Inngår i: 17th meeting on Hypertension,2007, 2007Konferansepaper (Annet vitenskapelig)
  • 204.
    Wilsson, Åsa
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lundqvist, Helen
    Department of Medical Microbiology and Immunology, University of Göteborg.
    Gustafsson, Mikael
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Stendahl, Olle
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Killing of phagocytosed Staphylococcus aureus by human neutrophils requires intracellular free calcium1996Inngår i: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 59, nr 6, s. 902-907Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The mobilization of intracellular calcium plays an important role in regulating neutrophil activation. With this in mind we investigated the effect of intra- and extracellular calcium on the ability of human neutrophils to kill complement-opsonized Staphylococcus aureus. We found that a rise in intracellular calcium is necessary for efficient killing of phagocytosed S. aureus. In the presence of extracellular calcium, killing of ingested bacteria in calcium-buffered neutrophils compared with normal cells was slightly reduced. Calcium buffering had no effect on phagocytic uptake by the neutrophils, but did decrease the generation of toxic oxygen metabolites, measured as chemiluminescence (CL). In nondepleted and calcium-depleted cells, removal of extracellular calcium did not affect ingestion but did cause a marked decrease in the ability to kill the bacteria. In parallel, the CL response was substantially reduced or completely blocked. These data show that calcium is not a prerequisite for phagocytosis of S. aureus by human neutrophils, but does play a vital role in the post-ingestion killing of the bacteria by regulating the generation of toxic oxygen metabolites.

  • 205.
    Yamaguchi, M.
    et al.
    Faculty of Engineering Toyama University, Japan.
    Kawabata, Y.
    Faculty of Engineering Toyama University, Japan.
    Kambe, S.
    Faculty of Engineering Toyama University, Japan.
    Wårdell, Karin
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Nyström, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Naitoh, K.
    Suzuken Co. Ltd. Nagoya, Japan.
    Yoshida, H.
    Nipro Co. Shiga, Japan.
    Non-invasive monitoring of gingival crevicular fluid for estimation of blood glucose level2004Inngår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 42, nr 3, s. 322-327Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Development of a non-invasive method for measuring the blood glucose level is an urgent necessity, and putting such a method into practical use will enable some of the physical and mental stress that patients with diabetes have to endure to be removed. To realise a non-invasive blood glucose monitor, the gingival crevicular fluid (GCF) was measured. A GCF-collecting device was developed that was designed to be disposable, biocompatible and small enough to be inserted in the gingival crevice for collection of a sub-microlitre sample of GCF. Also, a high-sensitivity glucose testing tape incorporated in the device was developed. Red laser light in a portable optical device measured the colour density of the testing tape. Standard glucose solutions were used to investigate the measurement accuracy of the GCF glucose monitor and showed a correlation coefficient of R=0.99 (n=20) between the optical density and the glucose levels. The GCF glucose monitor was evaluated on healthy Swedish and Japanese adults (n=10) and both GCF glucose levels (GCFLs) and blood glucose levels (BGLs) were measured in conjunction with meal loads. The GCFLs were about 1/10-1/560 lower than the BGLs. No difference in the range of GCFLs between the Swedish and the Japanese subjects was observed. Therefore it was concluded that physique, body mass index and life-style, such as dietary habit, did not significantly influence the GCFLs. Further, the correlation coefficients of all the subjects were 0.70 and 0.88 with each group. It was suggested that GCF could be used as a method of non-invasive blood glucose measurement.

  • 206.
    Yuan, Xi Ming
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Iron and macrophages in atherogenesis1995Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Oxidation of low density lipoprotein (LDL) may result in its uptake by macrophages and ensuing foam cell formation. Thus, oxidised LDL may play an important role in atherogenesis. Extensive in vitro evidences are in favour of the notion that LDL oxidation by cells present in atherosclerotic plaques requires the presence of transition metals. It has been confirmed repeatedly that atherosclerotic lesions contain significant amounts of copper and iron. The mechanism by which LDL becomes oxidised in vivo, though, remains unknown.

    In the first part of the present study we wanted to learn about how iron is involved in the process of LDL oxidation by human macrophages; whether iron may be exocytosed after cellular exposure to different iron compounds; and if such exocytosis would affect LDL oxidation and its uptake by macrophages. Human monocyte-derived macrophages (HMDMs) were firstly exposed to different iron compounds (100μM), or haemoglobin (25 or 50 μg/ml) for 24 hours. Following rinsing LDL (50 or 150 µg/ml) was added in fresh culture medium without serum. After another 24 hours the concentrations of iron and thiobarbituric acid-reactive substances (TBARS), as well as the electrophoretic mobility of LDL in medium, were found increased, while the cells showed only minimal signs of decreased viability. Neutral lipids and phospholipids accumulated in a granular, lysosome-like, pattern and the cells acquired a foam cell-like morphology.

    The second part of the study was designed (i) to establish a model of erythrophagocytosis by macrophages, and (ii) to study iron-sequestration within secondary lysosomes, and exocytosis by these cells following the degradation of erythrocytes. The binding and uptake of UV-irradiated red blood cells (UV-RBC) by human macrophages and J-774 cells were greatly stimulated compared to that of native erythrocytes. The uptake resulted in lysosomal accumulation of iron in a low-molecular-weight form, as shown by autometallography. Following the exposure to UV-RBC and ferric iron a much enhanced amount of cytosolic ferritin was demonstrated in macrophages by immunocytochemistry. Ensuing exocytosis of iron to the culture medium was demonstrated by atomic absorption spectroscopy.

    The third part of the study aimed to investigate oxidative stress-induced lipofuscinogenesis in human macrophages as well as in a test-tube system of mitochondria and lysosomes from rat liver. Firstly, control HMDMs, and HMDMs exposed to different iron compounds (100 µM Fe3+) or Hb (25 or 50 µg/ml), were incubated for 48 hours with LDL. Lipofuscin-specific autofluorescence was markedly increased in all LDL-exposed cells. A linear correlation was found between lipofuscin formation and the concentration of FeCl3 to which the HMDMs earlier had been pre-exposed. Secondly, endogenous iron in lysosomal-mitochondrial fraction (LMF) homogenates (545 µg/1, about 10 µM) was detected by atomic absorption spectrophotometry. After incubation of LMF with different concentrations of cystein for different periods of time a time- and dose-dependent TBARS-yield was observed. The peroxidation was completely inhibited by the addition of desferrioxamine or butylated hydroxytoluen (BHT). Under the same conditions the carbonyls of the trichloroacetic acid (TCA) precipitable protein of LMF were analysed. They were found increased, but only after a slight initial decrease. Following a sharp initial decrease, the normal tryptophan-tyrosine (protein) autofluorescence remained stable. In contrast, after a lag period of a few days, a lipofuscin-type autofluorescence was also observed.

    In conclusion: A. Lysosomal iron may be exocytosed from HMDMs, following a previous uptake of simple iron compounds or Hb promoting oxidation and uptake of LDL and thus induce foam cell formation. B. Macrophage erythrophagocytosis is a useful model for the study of the lysosomal sequestration of iron. Iron is accumulated within the macrophage acidic vacuolar apparatus arid subsequently exocytosed. C. Lipofuscin forms in secondary lysosomes as a result of iron-catalyzed oxidative reactions involving autophagocytosed materials D. LDL and iron may both play important roles in lipofuscinogenesis within atherosclerotic lesions.

  • 207. Zeng, G
    et al.
    Nyström, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ravichandran, L V
    Cong, L
    Kirby, M
    Mostowski, H
    Quon, M J
    Roles for Inuslin receptor, PI3-kinase, and AKT in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells.2000Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 101, s. 1539-1545Artikkel i tidsskrift (Fagfellevurdert)
  • 208.
    Zidén, Bo
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Kaminkas, A
    Kristensson, Margareta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö. Östergötlands Läns Landsting, FHVC - Folkhälsovetenskapligt centrum, Förebygg.med.
    Kucinskiene, Z
    Vessby, B
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Diczfaluzy, U
    Increased plasma 7B-hydroxycholesterol concentrations in a population with high risk for cardiovascular disease.1999Inngår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 19, s. 967-971Artikkel i tidsskrift (Fagfellevurdert)
  • 209. Zieden, B
    et al.
    Kaminskas, A
    Kristenson, M
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Kucinskiene, Z
    Long chain polyunsaturated fatty acids may account for higher low-density lipoprotein oxidation susceptibility in Lithuanian compared to Swedish men2002Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 62, nr 4, s. 307-314Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Mortality in coronary heart disease among middle-aged men is four times higher in Lithuania than in Sweden. Traditional risk factors cannot account for this difference. We earlier reported that low-density lipoprotein (LDL) in Lithuanian men showed a lower resistance to oxidation, measured as LDL lag time during copper oxidation, than that in Swedish men. Serum concentrations of several fat-soluble antioxidant vitamins were lower among Lithuanian men. The aim of this study was to investigate whether differences in LDL fatty acid composition could account for the difference in LDL oxidation susceptibility between men in the two countries. Methods: This cross-sectional study included randomly selected healthy 50-year-old men from Vilnius, Lithuania (n = 50) and Link÷ping, Sweden (n = 50). Main outcome measures were fatty acids in LDL, phospholipid (PL) and cholesterol ester (CE) fractions of LDL and LDL oxidation susceptibility. Results: The mean proportions of PL 20:5n3 (eicosapentaenoic acid, EPA) were higher in Vilnius men (2.09▒1.05 vs. 1.53▒0.58%, p = 0.004). LDL lag time was shorter in Vilnius men, mean▒SD (75.4▒13.6 vs. 89.5▒13.1 mins, p<0.0001) than in Link÷ping men. Mean serum ?-tocopherol was lower in Vilnius men (0.07▒0.05 vs. 0.12▒0.04 ╡g/mmol, p<0.0001) but a-tocopherol did not differ. In a multiple regression analysis controlled for city, high PL-EPA, low a-tocopherol, and high plasma triglycerides significantly contributed to a short LDL lag time, r2 = 0.53. Conclusions: Fat quality, i.e. poly unsaturated fatty acids especially LDL-EPA, plasma triglycerides and antioxidative vitamins may partly account for the increased LDL oxidation susceptibility found in Vilnius men compared with Link÷ping men.

  • 210.
    Ziedén, Bo
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    LDL Oxidation Susceptibility and Its Relation To Antioxidants and Fatty Acids: A Clinical and Experimental Study1999Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Atherosclerosis is an arterial disease characterized by lipid deposits in the artery wall. These lipid deposits partly consist of oxidatively modified low density lipoprotein (LDL). Several lines of evidence indicate a role of oxidized LDL in atherogenesis. The susceptibility of human circulating LDL towards oxidation was therefore considered to be of interest.

    The LDL oxidation susceptibility was followed spectrophotometrically after addition of copper and was expressed as LDL lag time. We also investigated the plasma concentrations of oxidized cholesterol, lipophilic antioxidative vitamins and fatty acids to get a better understanding of the mechanisms governing LDL oxidation.

    We compared 50-54 year old men from Vilnius, Lithuania who have a four fold higher coronary heart disease (CHD) mortality compared to men from Link6ping, Sweden. Plasma or LDL cholesterol, blood pressure and smoking could not account for this difference. We found a significantly shorter Jag time in Vilnius men, higher serum concentrations of 7-ß hydroxycholesterol, lower concentrations of y-tocopherol, ß-carotene and lycopene and also higher amount of easily oxidized highly unsaturated fatty acids, such as eicosapentaenioc acid ( EPA). Important determinants of the LDL lag time were found to be EPA (negative), a-tocopherol (positive), but also LDL cholesterol and plasma triglyceride concentrations were associated with a shorter LDL lag time.

    The effect of ω-3 fatty acid compared to corn oil supplementation was investigated in patients with severe hypertriglyceridernia. Plasma triglyceride concentrations decreased by 48% in the ω-3 group. In both groups the LDL lag time shortened after 12 weeks of supplementation.

    In vitro addition of the antihypertensive drug captopril to LDL was investigated. Captopril prolonged the LDL lag time, decreased other oxidation products such as thiobarbituric acid reactive substances (TBARS) and lipid peroxides in a dose dependent manner.

    These studies show that the LDL oxidation susceptibility differs between two groups of healthy men from two populations with a marked difference in CHD mortality. Supplementation with ω-3 fatty acids shortened the LDL lag time. LDL oxidation susceptibility is related to low serum concentrations of lipophilic antioxidative vitamins and high content of long chain highly unsaturated fatty acids.

  • 211.
    Örtegren Kugelberg, Unn
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Yin, Lan
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Öst, Anita
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Helen
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Nyström, Fredrik
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Strålfors, Peter
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes: segregation of specific proteins and functions2006Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, nr 14, s. 3381-3392Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary in size between 25 and 150 nm. They constitute sites of entry into the cell as well as platforms for cell signalling. We have previously reported that plasma membrane-associated caveolae that lack cell surface access can be identified by electron microscopy. We now report the identification, after density gradient ultracentrifugation, of a subclass of very high-density apparently closed caveolae that were not labelled by cell surface protein labelling of intact cells. These caveolae contained caveolin-1 and caveolin-2. Another class of high-density caveolae contained caveolin-1, caveolin-2 and specifically fatty acid transport protein-1, fatty acid transport protein-4, fatty acyl-CoA synthetase, hormone-sensitive lipase, perilipin, and insulin-regulated glucose transporter-4. This class of caveolae was specialized in fatty acid uptake and conversion to triacylglycerol. A third class of low-density caveolae contained the insulin receptor, class B scavenger receptor-1, and insulin-regulated glucose transporter-4. Small amounts of these proteins were also detected in the high-density caveolae. In response to insulin, the insulin receptor autophosphorylation and the amount of insulin-regulated glucose transporter-4 increased in these caveolae. The molar ratio of cholesterol to phospholipid in the three caveolae classes varied considerably, from 0.4 in very high-density caveolae to 0.9 in low-density caveolae. There was no correlation between the caveolar contents of caveolin and cholesterol. The low-density caveolae, with the highest cholesterol concentration, were particularly enriched with the cholesterol-rich lipoprotein receptor class B scavenger receptor-1, which mediated cholesteryl ester uptake from high-density lipoprotein and generation of free cholesterol in these caveolae, suggesting a specific role in cholesterol uptake/metabolism. These findings demonstrate a segregation of functions in caveolae subclasses.

  • 212. Östman, J
    et al.
    Landin-Olsson, M
    Törn, C
    Palmer, J
    Lernmark, Å
    Arnqvist, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Björk, E
    Bolinder, J
    Blohmé, G
    Eriksson, J
    Littorin, B
    Nyström, L
    Scherstén, B
    Sundkvist, G
    Wibell, L
    Ketoacidosis in young adults is not related to the islet antibodies at the diagnosis of Type 1 diabetes mellitus - A nationwide study2000Inngår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 17, nr 4, s. 269-274Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: To test the hypothesis that there is lower prevalence of islet antibodies in subjects with newly diagnosed Type 1 diabetes mellitus in young adulthood than in children is associated with less severe diabetes at time of diagnosis. Methods: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of 15-34-year-old newly diagnosed diabetic subjects. During 1992-1993, all diabetic subjects (excluding secondary and gestational diabetes) were reported on standardized forms, with information about clinical characteristics at diagnosis. The study examined islet cell antibodies (ICA) by indirect immunofluorescence, and autoantibodies to glutamic acid decarboxylase (GADA), tyrosine phosphatase- like antigen (IA-2A) and insulin (IAA) as well as C-peptide by radioimmunoassay. Results: Blood samples were available from 78 patients with diabetic ketoacidosis (DKA) and 517 non-acidotic patients. The prevalence of ICA (63% vs. 57%), GADA (63% vs. 66%), IA-2A (35% vs. 44%) and IAA (20% vs. 15%) were very similar in patients with or without DKA. The median levels of the four autoantibodies did not differ between the two groups. High blood glucose (P < 0.001) and low C-peptide levels (P < 0.001) were the only parameters found to be related to DKA. Conclusions: The similarities in findings of newly diagnosed diabetic patients with or without DKA regarding ICA, GADA, IA-2A and IAA suggest that there is no relationship between the expression of antigenicity and the severity of ▀-cell dysfunction. The lower prevalence of the four autoantibodies in 15-34-year-old diabetic subjects compared with previous findings in children is not explained by misclassification of diabetes type.

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