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  • 1.
    Abels, M.
    et al.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Riva, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Poon, W.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Bennet, H.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Nagaraj, V.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Dyachok, Oleg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Isomaa, B.
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Jacobstad, Finland..
    Tuomi, T.
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Med, Helsinki, Finland..
    Ahren, B.
    Lund Univ, Ctr Diabet, Lund, Sweden..
    Tengholm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fex, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Renstrom, E.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Groop, L.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Lyssenko, V.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Wierup, N.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    CART is a novel glucose-dependent peptide with antidiabetic actions in humans2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S279-S280Article in journal (Other academic)
  • 2.
    Abels, Mia
    et al.
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Riva, Matteo
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Bennet, Hedvig
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Ahlqvist, Emma
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Dyachok, Oleg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Nagaraj, Vini
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Shcherbina, Liliya
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Fred, Rikard G.
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Poon, Wenny
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Sorhede-Winzell, Maria
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Lindqvist, Andreas
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Kask, Lena
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Sathanoori, Ramasri
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Dekker-Nitert, Marloes
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Kuhar, Michael J.
    Emory Univ, Yerkes Res Ctr, Atlanta, GA 30322 USA..
    Ahren, Bo
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Wollheim, Claes B.
    Univ Med Ctr, Dept Cell Physiol & Metab, Geneva, Switzerland..
    Hansson, Ola
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Tengholm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fex, Malin
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Renström, Erik
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Groop, Leif
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Lyssenko, Valeriya
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden.;Steno Diabet Ctr AS, Gentofte, Denmark..
    Wierup, Nils
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden.;Lund Univ, Clin Res Ctr 91 12, Ctr Diabet, Skane Univ Hosp,Dept Clin Sci Malmo,Unit Neuroend, Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden..
    CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 9, p. 1928-1937Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart(-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice. Methods CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and rodent models of diabetes. Insulin and glucagon secretion was examined in isolated islets and in vivo in mice. Ca2+ oscillation patterns and exocytosis were studied in mouse islets. Results We report an important role of CART in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. CART increased insulin secretion in vivo in mice and in human and mouse islets. Furthermore, CART increased beta cell exocytosis, altered the glucose-induced Ca2+ signalling pattern in mouse islets from fast to slow oscillations and improved synchronisation of the oscillations between different islet regions. Finally, CART reduced glucagon secretion in human and mouse islets, as well as in vivo in mice via diminished alpha cell exocytosis. Conclusions/interpretation We conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes.

  • 3. Afghahi, H
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eliasson, B
    Nilsson, PM
    Eeg-Olofsson, K
    Gudbjornsdottir, S
    Svensson, MK
    Different sets of risk factors for the development of albuminuria and renal impairment in type 2 diabetes: the Swedish National Diabetes register (NDR)2009In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no Suppl 1, p. S25-S25Article in journal (Refereed)
  • 4. Afghahi, H
    et al.
    Hadimeri, H
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eliasson, Björn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjornsdottir, S
    Svensson, MK
    The majority of type 2 diabetic patients with renal impairment have non-albuminuric renal disease: the Swedish National Diabetes register (NDR)2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, no Suppl 1, p. 110-Article in journal (Refereed)
  • 5.
    Ahlqvist, E.
    et al.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Karajamaki, A.
    Vaasa Cent Hosp, Primary Hlth Care, Vaasa, Finland..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Storm, P.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Dorkhan, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Vikman, P.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Prasad, R. B.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Aly, D. Mansour
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Shaat, N.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Lindholm, E.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Rosengren, A. H.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Groop, L.
    Lund Univ, Ctr Diabet, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Clustering of diabetes into novel subgroups provides improved prediction of outcome2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S117-S117Article in journal (Other academic)
  • 6. Albrechtsen, A.
    et al.
    Grarup, N.
    Li, Y.
    Sparso, T.
    Tian, G.
    Cao, H.
    Jiang, T.
    Kim, S. Y.
    Korneliussen, T.
    Li, Q.
    Nie, C.
    Wu, R.
    Skotte, L.
    Morris, A. P.
    Ladenvall, C.
    Cauchi, S.
    Stancakova, A.
    Andersen, G.
    Astrup, A.
    Banasik, K.
    Bennett, A. J.
    Bolund, L.
    Charpentier, G.
    Chen, Y.
    Dekker, J. M.
    Doney, A. S. F.
    Dorkhan, M.
    Forsen, T.
    Frayling, T. M.
    Groves, C. J.
    Gui, Y.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hattersley, A. T.
    He, K.
    Hitman, G. A.
    Holmkvist, J.
    Huang, S.
    Jiang, H.
    Jin, X.
    Justesen, J. M.
    Kristiansen, K.
    Kuusisto, J.
    Lajer, M.
    Lantieri, O.
    Li, W.
    Liang, H.
    Liao, Q.
    Liu, X.
    Ma, T.
    Ma, X.
    Manijak, M. P.
    Marre, M.
    Mokrosinski, J.
    Morris, A. D.
    Mu, B.
    Nielsen, A. A.
    Nijpels, G.
    Nilsson, P.
    Palmer, C. N. A.
    Rayner, N. W.
    Renstrom, F.
    Ribel-Madsen, R.
    Robertson, N.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rossing, P.
    Schwartz, T. W.
    Slagboom, P. E.
    Sterner, M.
    Tang, M.
    Tarnow, L.
    Tuomi, T.
    van't Riet, E.
    van Leeuwen, N.
    Varga, T. V.
    Vestmar, M. A.
    Walker, M.
    Wang, B.
    Wang, Y.
    Wu, H.
    Xi, F.
    Yengo, L.
    Yu, C.
    Zhang, X.
    Zhang, J.
    Zhang, Q.
    Zhang, W.
    Zheng, H.
    Zhou, Y.
    Altshuler, D.
    't Hart, L. M.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Balkau, B.
    Froguel, P.
    McCarthy, M. I.
    Laakso, M.
    Groop, L.
    Christensen, C.
    Brandslund, I.
    Lauritzen, T.
    Witte, D. R.
    Linneberg, A.
    Jorgensen, T.
    Hansen, T.
    Wang, J.
    Nielsen, R.
    Pedersen, O.
    Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 2, p. 298-310Article in journal (Refereed)
    Abstract [en]

    Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

  • 7. Ali, Yusuf
    et al.
    Diez, Juan
    Selander, Lars
    Zheng, Xiaofeng
    Edlund, Helena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
    Berggren, Per-Olof
    The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 5, p. 1007-1011Article in journal (Refereed)
    Abstract [en]

    In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time. The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.

  • 8. Allin, Kristine H.
    et al.
    Tremaroli, Valentina
    Caesar, Robert
    Jensen, Benjamin A. H.
    Damgaard, Mads T. F.
    Bahl, Martin I.
    Licht, Tine R.
    Hansen, Tue H.
    Nielsen, Trine
    Dantoft, Thomas M.
    Linneberg, Allan
    Jørgensen, Torben
    Vestergaard, Henrik
    Kristiansen, Karsten
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hansen, Torben
    Bäckhed, Fredrik
    Pedersen, Oluf
    Aberrant intestinal microbiota in individuals with prediabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 4, p. 810-820Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0 mmol/l or HbA1c of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers of poor metabolic health.

    Methods: In the present case-control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age-and sex-matched individuals with normal glucose regulation.

    Results: We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change -0.64 (SEM 0.23), p adj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), p adj = 5 x 10-4; 0.51 (SEM 0.11), p adj = 1 x 10-4; 0.60 (SEM 0.21), p adj = 0.0497; and 0.92 (SEM0.21), p adj = 4 x 10-4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log2 fold change -1.74 (SEM0.41), p adj = 2 x 10-3 and -1.65 (SEM0.34), p adj = 4 x 10-4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice.

    Conclusions/interpretation: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

  • 9. Almby, K. E.
    et al.
    Abrahamsson, N.
    Lundqvist, M. H.
    Hammar, U.
    Thombare, K.
    Panagiotou, A.
    Karlsson, F. A.
    Sundbom, M.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eriksson, J. W.
    Effects of GLP-1 receptor activation on counterregulatory responses during hypoglycaemia after gastric bypass surgery: no evidence for GLP-1 as a counterregulatory hormone2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, p. S416-S416Article in journal (Other academic)
  • 10. Almby, K. E.
    et al.
    Abrahamsson, N.
    Lundqvist, M. H.
    Hammar, U.
    Thombare, K.
    Panagiotou, A.
    Karlsson, F. A.
    Sundbom, M.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eriksson, J. W.
    Effects of GLP-1 receptor activation on counterregulatory responses during hypoglycaemia after gastric bypass surgery: no evidence for GLP-1 as a counterregulatory hormone2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, p. S416-S416Article in journal (Refereed)
  • 11.
    Alskar, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kjellsson, Maria C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Interspecies scaling of dynamic glucose and insulin using a mathematical model approach2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S306-S307Article in journal (Other academic)
  • 12. Alssema, M
    et al.
    Vistisen, D
    Heymans, M W
    Nijpels, G
    Glümer, C
    Zimmet, P Z
    Shaw, J E
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stehouwer, C D A
    Tabák, A G
    Colagiuri, S
    Borch-Johnsen, K
    Dekker, J M
    Risk scores for predicting type 2 diabetes: using the optimal tool2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 9, p. 2468-2470Article in journal (Refereed)
  • 13. Alssema, M
    et al.
    Vistisen, D
    Heymans, MW
    Nijpels, G
    Glümer, C
    Zimmet, PZ
    Shaw, JE
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stehouwer, CDA
    Tabák, AG
    Colagiuri, S
    Borch-Johnsen, K
    Dekker, JM
    The evaluation of screening and early detection strategies for type 2 diabetes and impaired glucose tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 5, p. 1004-1012Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors.

    METHODS: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques.

    RESULTS: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726-0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity.

    CONCLUSIONS/INTERPRETATION: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.

  • 14. Alvarsson, M
    et al.
    Sundkvist, G
    Lager, I
    Henricsson, M
    Berntorp, K
    Forbes, E
    Steen, L
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Orn, T
    Grill, V
    Different effects of withdrawal of insulin or glibenclamide treatment on beta cell function in recently diagnosed Type 2 diabetic patients.2003In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, p. 798-Conference paper (Other academic)
  • 15. Ambegaonkar, B
    et al.
    Pettersson, B
    Sazonov, V
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Prevalence of lipid abnormalities before and after the introduction of lipid modifying therapy among Swedish patients with type 2 diabetes and/or coronary heart disease (PRIMULA Sweden)2009In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no Suppl. 1, p. S495-S495Article in journal (Refereed)
  • 16.
    Andersen, C. D.
    et al.
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Bennet, L.
    Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lindblad, U.
    Department of Primary Health Care, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Lindholm, E.
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Groop, L.
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 2, p. 252-258Article in journal (Refereed)
    Abstract [en]

    Our aim was to study whether glycaemic control differs between individuals with latent autoimmune diabetes in adults (LADA) and patients with type 2 diabetes, and whether it is influenced by time on insulin therapy. We performed a retrospective study of 372 patients with LADA (205 men and 167 women; median age 54 years, range 35-80 years) from Swedish cohorts from SkAyenne (n = 272) and Vasterbotten (n = 100). Age- and sex-matched patients with type 2 diabetes were included as controls. Data on the use of oral hypoglycaemic agents (OHAs), insulin and insulin-OHA combination therapy was retrieved from the medical records. Poor glycaemic control was defined as HbA(1c) a parts per thousand yen7.0% (a parts per thousand yen53 mmol/mol) at follow-up. The individuals with LADA and with type 2 diabetes were followed for an average of 107 months. LADA patients were leaner than type 2 diabetes patients at diagnosis (BMI 27.7 vs 31.0 kg/m(2); p < 0.001) and follow-up (BMI 27.9 vs 30.2 kg/m(2); p < 0.001). Patients with LADA had been treated with insulin for longer than those with type 2 diabetes (53.3 vs 28.8 months; p < 0.001). There was no significant difference between the patient groups with regard to poor glycaemic control at diagnosis, but more patients with LADA (67.8%) than type 2 diabetes patients (53.0%; p < 0.001) had poor glycaemic control at follow-up. Patients with LADA had worse glycaemic control at follow-up compared with participants with type 2 diabetes (OR = 1.8, 95% CI 1.2, 2.7), adjusted for age at diagnosis, HbA(1c), BMI at diagnosis, follow-up time and duration of insulin treatment. Individuals with LADA have worse glycaemic control than patients with type 2 diabetes despite a longer time on insulin therapy.

  • 17. Andersen, Mette K.
    et al.
    Sterner, Maria
    Forsen, Tom
    Käräjämäki, Annemari
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Forsblom, Carol
    Groop, Per-Henrik
    Lahti, Kaj
    Nilsson, Peter M.
    Groop, Leif
    Tuomi, Tiinamaija
    Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 9, p. 1859-1868Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA). Methods We assessed 41 type 2 diabetes-associated gene variants in Finnish (phase I) and Swedish (phase II) patients with LADA (n=911) or type 1 diabetes (n=406), all diagnosed after the age of 35 years, as well as in non-diabetic control individuals 40 years or older (n=4,002). Results Variants in the ZMIZ1 (rs12571751, p=4.1 x 10(-5)) and TCF7L2 (rs7903146, p=5.8 x 10(-4)) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p=0.0012), HHEX (rs1111875, p=0.0024 in Finns) and MTNR1B (rs10830963, p=0.0039) loci showed the strongest association in patients with low GADA, supporting the hypothesis that the disease in these patients is more like type 2 diabetes. In contrast, variants in the KLHDC5 (rs10842994, p=9.5 x 10(-4) in Finns), TP53INP1 (rs896854, p=0.005), CDKAL1 (rs7756992, p=7.0 x 10(-4); rs7754840, p=8.8 x 10(-4)) and PROX1 (rs340874, p=0.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p=3.2 x 10(-6)) and HNF1A (rs2650000, p=0.0012). Conclusions/interpretation LADA and adult-onset type 1 diabetes share genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form of diabetes and distinguishing them from patients with classical young-onset type 1 diabetes.

  • 18.
    Andersson, Arne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Eriksson, Ulf J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Claes Hellerström: a friendly islet explorer2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 2, p. 4 p following 496-Article in journal (Refereed)
  • 19. Auro, K.
    et al.
    Kristiansson, K.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Taskinen, M-R.
    Jauhiainen, M.
    Perola, M.
    Peltonen, Leena
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study2008In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, no 3, p. 464-472Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS:

    Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up.

    METHODS:

    Participants, born in 1920-1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1.

    RESULTS:

    SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p=0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades.

    CONCLUSIONS/INTERPRETATION:

    Our results suggest that USF1 variants associate with the metabolic syndrome at population level and influence the cardiovascular risk factors throughout adulthood in a consistent, longitudinal manner.

  • 20. Bakhtadze, E
    et al.
    Borg, H
    Stenström, G
    Fernlund, P
    Arnqvist, H J
    Ekbom-Schnell, A
    Bolinder, J
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gudbjörnsdottir, S
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Groop, L C
    Sundkvist, G
    HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden.2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 8, p. 1785-1794Article in journal (Refereed)
  • 21. Bakhtadze, E
    et al.
    Borg, H
    Stenström, G
    Fernlund, P
    Arnqvist, H J
    Ekbom-Schnell, A
    Bolinder, J
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Gudbjörnsdottir, S
    Nyström, L
    Groop, L C
    Sundkvist, G
    HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 8, p. 1785-1794Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients.

    SUBJECTS AND METHODS: Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743.

    RESULTS: Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003).

    CONCLUSIONS/INTERPRETATION: Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes.

  • 22. Bakhtadze, E
    et al.
    Borg, H
    Stenström, G
    Fernlund, P
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ekbom-Schnell, A
    Bolinder, J
    Eriksson, JW
    Gudbjörnsdottir, S
    Nyström, L
    Groop, LC
    Sundkvist, G
    HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 8, p. 1785-1794Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients. Subjects and methods: Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743. Results: Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003). Conclusions/ interpretation: Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes. © Springer-Verlag 2006.

  • 23. Bakhtadze, E
    et al.
    Cervin, C
    Lindholm, E
    Borg, H
    Nilsson, P
    Arnqvist, H J
    Bolinder, J
    Eriksson, Jan W
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Gudbjörnsdottir, S
    Nyström, L
    Agardh, C-D
    Landin-Olsson, M
    Sundkvist, G
    Groop, L C
    Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients2008In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, no 12, p. 2224-2232Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis

    Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15–34 years) and middle-aged (40–59 years) diabetic patients.

    Methods

    In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide.

    Results

    Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p= 9.4×10−34; 45% vs 18%, p= 1.4 × 10−16), PTPN22 CT/TT (34% vs 26%, p= 0.0023; 31% vs 23%, p= 0.034), INS VNTR class I/I (69% vs 53%, p= 1.3 × 10−8; 69% vs 51%, p= 8.5 × 10−5) and INS VNTR class IIIA/IIIA (75% vs 63%, p=  4.3 × 10−6; 73% vs 60%, p= 0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p= 0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%).

    Conclusions/interpretation

    Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.

  • 24.
    Bakhtadze, E
    et al.
    Lund University.
    Cervin, C
    Lund University.
    Lindholm, E
    Lund University.
    Borg, H
    Lund University.
    Nilsson, P
    Lund University.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Bolinder, J
    Karolinska University.
    Eriksson, J W
    Umeå University Hospital.
    Gudbjornsdottir, S
    Sahlgrens University Hospital.
    Nystrom, L
    Umeå University Hospital.
    Agardh, C D
    Lund University.
    Landin-Olsson, M
    Lund University Hospital.
    Sundkvist, G
    Lund University Hospital.
    C Groop , L C
    Lund University Hospital.
    Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients2008In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, no 12, p. 2224-2232Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients.

    In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide.

    Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p =9.4x10(-34); 45% vs 18%, p= 1.4x10(-16)), PTPN22 CT/TT (34% vs 26%, p=0.0023; 31% vs 23%, p=0.034), INS VNTR class I/I (69% vs 53%, p=1.3x10(-8); 69% vs 51%, p=8.5x10(-5)) and INS VNTR class IIIA/IIIA (75% vs 63%, p=4.3x10(-6); 73% vs 60%, p=0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p=0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%).

    Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.

  • 25.
    Bao, Xue
    et al.
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China;Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Borne, Yan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Muhammad, Iram Faqir
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Nilsson, Jan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Melander, Olle
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Niu, Kaijun
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 1, p. 78-86Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor- superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population.

    Methods: Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.45.96years, 38.6% men) who were participants in the Malmo Diet and Cancer-Cardiovascular Cohort. After a follow-up of 19.05.16years (mean +/- SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP).

    Results: During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p<0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n=3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged 55, 56-60 (>55 and 60) and >60years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p=0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061).

    Conclusions/interpretation: GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are 60years old.

  • 26.
    Barbu, Andreea R.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bodin, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    A perfusion protocol for highly efficient transduction of intact pancreatic islets of Langerhans2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 10, p. 2388-2391Article in journal (Refereed)
    Abstract [en]

    Successful gene transfer to pancreatic islets might be a powerful tool for dissecting the biological pathways involved in the functional impairment and destruction of beta cells in type 1 diabetes. In the long run, such an approach may also prove useful for promoting islet graft survival after transplantation in diabetic patients. However, efficient genetic modification of primary insulin-producing cells is limited by the specific compact structure of the pancreatic islet. We present here a whole-pancreas perfusion-based transduction procedure for genetic modification of intact pancreatic islets.

    We used flow cytometry analysis and confocal microscopy to evaluate the efficiency of in vitro and perfusion-based transduction protocols that use adenoviral and lentiviral vectors expressing green fluorescent protein. Islet cell viability was assessed by fluorescence microscopy and beta cell function was determined via glucose-stimulated insulin secretion.

    In intact rat and human pancreatic islets, adenoviral and lentiviral vectors mediated gene transfer to about 30% of cells, but they did not reach the inner cellular mass within the islet core. Using the whole-pancreas perfusion protocol, we demonstrate that at least in rodent models the centrally located insulin-producing cells can be transduced with high efficiency, while preserving the structural integrity of the islet. Moreover, islet cell viability and function are not impaired by this procedure.

    These results support the view that perfusion-based transduction protocols may significantly improve the yield of successfully engineered primary insulin-producing cells for diabetes research.

  • 27.
    Barg, Sebastian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gandasi, Nikhil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quantitative analysis of t-SNARE and Ca2+-channel clusters near secretory granules2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, no Suppl. 1, p. S46-S46Article in journal (Other academic)
  • 28.
    Beam, Craig A.
    et al.
    Western Michigan University, MI 49008 USA.
    MacCallum, Colleen
    Western Michigan University, MI 49008 USA.
    Herold, Kevan C.
    Yale University, CT USA; Yale University, CT USA.
    Wherrett, Diane K.
    Hospital Sick Children, Canada; University of Toronto, Canada.
    Palmer, Jerry
    University of Washington, WA 98195 USA; VA Puget Sound Health Care Syst, WA USA.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 1, p. 43-49Article in journal (Refereed)
    Abstract [en]

    GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

  • 29. Beijer, K.
    et al.
    Nowak, C.
    Sundström, J.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska Institutet.
    Fall, T.
    Lind, L.
    In search of causal pathways in diabetes: a study using proteomics and genotyping data from a cross-sectional study2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428Article in journal (Refereed)
  • 30.
    Beijer, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala Univ, Med Sci, Uppsala, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arnlöv, J.
    Karolinska Inst, Stockholm, Sweden.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, E.
    Stanford Univ, Palo Alto, CA 94304 USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    A targeted proteomic profile of prevalent diabetes in a population-based sample2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S252-S252Article in journal (Other academic)
  • 31. Bendinelli, B.
    et al.
    Palli, D.
    Masala, G.
    Sharp, S. J.
    Schulze, M. B.
    Guevara, M.
    van der A, D. L.
    Sera, F.
    Amiano, P.
    Balkau, B.
    Barricarte, A.
    Boeing, H.
    Crowe, F. L.
    Dahm, C. C.
    Dalmeijer, G.
    de Lauzon-Guillain, B.
    Egeberg, R.
    Fagherazzi, G.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
    Krogh, V.
    Huerta, J. M.
    Jakszyn, P.
    Khaw, K. T.
    Li, K.
    Mattiello, A.
    Nilsson, P. M.
    Overvad, K.
    Ricceri, F.
    Rodríguez-Suárez, L.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sánchez, M. J.
    Slimani, N.
    Sluijs, I.
    Spijkerman, A. M. W.
    Teucher, B.
    Tjonneland, A.
    Tumino, R.
    van den Berg, S. W.
    Forouhi, N. G.
    Langenberg, C.
    Feskens, E. J. M.
    Riboli, E.
    Wareham, N. J.
    Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 1, p. 47-59Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    Methods: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption.

    Results: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants.

    Conclusions/interpretation: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.

  • 32.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Antihypertensive medication prior to nocturnal sleep reduces the risk of new-onset type 2 diabetes in hypertensive patients: a role for slow-wave sleep?2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 2, p. 390-391Article in journal (Refereed)
  • 33.
    Berg, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Frisk, Gun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Induction of the chemokine interferon-gamma-inducible protein-10 in human pancreatic islets during enterovirus infection2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 11, p. 2697-2703Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Enterovirus infections have long been suspected to be environmental factors that may cause type 1 diabetes, but the pathways leading from infection to beta cell destruction are still unknown. We therefore examined whether enterovirus infection of human islets leads to upregulation of interferon-gamma-inducible protein (IP-10, now known as chemokine [C-X-C motif] ligand 10 [CXCL10]), a chemokine important for the induction of insulitis. Methods: Isolated human islets were infected with three different strains of Coxsackie B4 virus. IP-10 expression and secretion from the infected human islets were then measured using RT-PCR and ELISA at several time points. Results: IP-10 was clearly upregulated in and secreted from human islets during enterovirus infection. This was demonstrated with three different strains of Coxsackie B4 virus, two of which are lytic to islets and one which is non-lytic and can establish a persistent infection in human islets. Conclusions/interpretation: We propose that enterovirus-induced upregulation of IP-10 during infection of the islets in vivo is the first step towards destructive insulitis. Our findings support the idea that enterovirus infection triggers immune-mediated beta cell destruction, and for the first time suggest a possible mechanism behind enterovirus-induced diabetes.

  • 34.
    Bergman, Marie-Louise
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Penha-Gonçalves, Carlos
    Gulbenkian Institute for Science, Oeiras, Portugal, PT.
    Lejon, Kristina
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Holmberg, Dan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Low rate of proliferation in immature thymocytes of the non-obese diabetic mouse maps to the Idd6 diabetes susceptibility region2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, no 8, p. 1054-1061Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: The non-obese diabetic (NOD) mouse spontaneously develops T-cell-dependent autoimmune diabetes. This mouse strain has a number of immune dysfunctions related to T-cell development but so far there are no available data on the proliferation of NOD immature thymocytes. We therefore studied the thymocyte proliferation in the NOD mouse in discrete stages of T-cell development.

    Methods: We depleted thymocytes in vivo and analysed thymocyte proliferation during the thymus recovery from depletion. We used co-segregation analysis and quantitative loci trait analysis to investigate the genetic control of proliferation impairments in NOD thymocytes.

    Results: Immature thymocytes of female NOD mice proliferate with a relatively low rate compared to non-autoimmune C57Bl/6 mice. This aberrant proliferation was most pronounced in CD4 /loCD8+ cells differentiating from the CD4CD8 to the CD4+CD8+ stage. A genetic mapping study using an F2 intercross between the NOD and the C57BL/6 strains showed that a major locus controlling this trait is linked to the insulin-dependent diabetes susceptibility locus Idd6.

    Conclusion/interpretation: Our results suggest that impairment of proliferation of immature thymocytes is one possible mechanism through which the Idd6 locus contributes to the pathogenesis of diabetes.

  • 35.
    Berne, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Flyvbjerg, A.
    Gronbaek, H.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The association between IGFBP-1 and type 2 diabetes is modified by degrees of insulin sensitivity and early insulin response2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53Article in journal (Other academic)
  • 36. Birkeland, K. I.
    et al.
    Gulseth, H. L.
    Gjelstad, I. M. F.
    Lovegrove, J. A.
    Defoort, C.
    Blaak, E. E.
    Lopez-Miranda, J.
    Dembinska-Kiec, A.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Roche, H. M.
    Drevon, C. A.
    The relationship between vitamin D status and markers of oxidation and inflammation in subjects with the metabolic syndrome2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53Article in journal (Other academic)
  • 37.
    Bodegard, J.
    et al.
    AstraZeneca, Sodertalje, Sweden..
    Nathanson, D.
    Karolinska Inst, Dept Clin Sci & Educa, Stockholm, Sweden..
    Nystrom, T.
    Karolinska Inst, Stockholm, Sweden..
    Thuresson, M.
    Statisticon AB, Uppsala, Sweden..
    Norhammar, A.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Second-line treatment with sulfonylurea compared to DPP4 inhibitors demonstrated associations with earlier treatment intensification with insulin2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S189-S189Article in journal (Other academic)
  • 38.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;AstraZeneca, Dept Med, Gothenburg, Sweden..
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S80-S80Article in journal (Other academic)
  • 39.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;Univ Gothenburg, Dept Med, Gothenburg, Sweden..
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Panagiotou, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skeletal muscle and liver, but not brain, account for impaired glucose utilisation in type 2 diabetes: whole-body PET/MR during hyperinsulinaemic euglycaemic clamp2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S33-S33Article in journal (Refereed)
  • 40.
    Boon, Hanneke
    et al.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.
    Blaak, E. E.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands.
    Saris, W. H.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands.
    Keizer, H. A.
    Department of Movement Sciences, NUTRIM, Maastricht University, Maastricht, Netherlands & Department of Human Physiology and Sportsmedicine, Free University of Brussels, Brussels, Belgium.
    Wagenmakers, A. J.
    School of Sport and Exercise Science, University of Birmingham, Birmingham, United Kingdom.
    van Loon, L. J. C.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands & Department of Movement Sciences, NUTRIM, Maastricht University, Maastricht, Netherlands.
    Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 1, p. 103-112Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Disturbances in substrate source metabolism and, more particularly, in fatty acid metabolism, play an important role in the aetiology and progression of type 2 diabetes. However, data on substrate source utilisation in type 2 diabetes are inconclusive. METHODS: [U-(13)C]palmitate and [6,6-(2)H(2)]glucose tracers were used to assess plasma NEFA and glucose oxidation rates and to estimate the use of muscle- and/or lipoprotein-derived triacylglycerol and muscle glycogen. Subjects were ten male patients who had a long-term (7 +/- 1 years) diagnosis of type 2 diabetes and were overweight, and ten matched healthy, male control subjects. Muscle biopsy samples were collected before and after exercise to assess muscle fibre type-specific intramyocellular lipid and glycogen content. RESULTS: At rest and during exercise, the diabetes patients had greater values than the controls for palmitate rate of appearance (Ra) (rest, 2.46 +/- 0.18 and 1.85 +/- 0.20 respectively; exercise, 3.71 +/- 0.36 and 2.84 +/- 0.20 micromol kg(-1) min(-1)) and rate of disappearance (Rd) (rest, 2.45 +/- 0.18 and 1.83 +/- 0.20; exercise, 3.64 +/- 0.35 and 2.80 +/- 0.20 micromol kg(-1) min(-1) respectively). This was accompanied by significantly higher fat oxidation rates at rest and during recovery in the diabetes patients (rest, 0.11 +/- 0.01 in diabetes patients and 0.09 +/- 0.01 in controls; recovery, 0.13 +/- 0.01 and 0.11 +/- 0.01 g/min respectively), despite significantly greater plasma glucose Ra, Rd and circulating plasma glucose concentrations. Furthermore, exercise significantly lowered plasma glucose concentrations in the diabetes patients, as a result of increased blood glucose disposal. CONCLUSION: This study demonstrates that substrate source utilisation in long-term-diagnosed type 2 diabetes patients, in whom compensatory hyperinsulinaemia is no longer present, shifts towards an increase in whole-body fat oxidation rate and is accompanied by disturbances in fat and carbohydrate handling. © 2006 Springer-Verlag.

  • 41.
    Boon, Hanneke
    et al.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands.
    Bosselaar, M.
    Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
    Praet, S. F. E.
    Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands.
    Blaak, E. E.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands.
    Saris, W. H.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands.
    Wagenmakers, A. J.
    School of Sport and Exercise Sciences, University of Birmingham, Birmingham, United Kingdom.
    McGee, S. L.
    Department of Physiology, University of Melbourne, Melbourne, VIC, Australia.
    Tack, C. J.
    Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
    Smits, P.
    Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands & Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
    Hargreaves, M.
    Department of Physiology, University of Melbourne, Melbourne, VIC, Australia.
    van Loon, L. J.
    Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands & Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands.
    Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients2008In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, no 10, p. 1893-1900Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The 5'-AMP-activated protein kinase (AMPK) pathway is intact in type 2 diabetic patients and is seen as a target for diabetes treatment. In this study, we aimed to assess the impact of the AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) on both glucose and fatty acid metabolism in vivo in type 2 diabetic patients. METHODS: Stable isotope methodology and blood and muscle biopsy sampling were applied to assess blood glucose and fatty acid kinetics following continuous i.v. infusion of AICAR (0.75 mg kg(-1) min(-1)) and/or NaCl (0.9%) in ten male type 2 diabetic patients (age 64 +/- 2 years; BMI 28 +/- 1 kg/m(2)). RESULTS: Plasma glucose rate of appearance (R (a)) was reduced following AICAR administration, while plasma glucose rate of disappearance (R (d)) was similar in the AICAR and control test. Consequently, blood glucose disposal (R (d) expressed as a percentage of R (a)) was increased following AICAR infusion (p < 0.001). Accordingly, a greater decline in plasma glucose concentration was observed following AICAR infusion (p < 0.001). Plasma NEFA R (a) and R (d) were both significantly reduced in response to AICAR infusion, and were accompanied by a significant decline in plasma NEFA concentration. Although AMPK phosphorylation in skeletal muscle was not increased, we observed a significant increase in acetyl-CoA carboxylase phosphorylation (p < 0.001). CONCLUSIONS/INTERPRETATION: The i.v. administration of AICAR reduces hepatic glucose output, thereby lowering blood glucose concentrations in vivo in type 2 diabetic patients. Furthermore, AICAR administration stimulates hepatic fatty acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA concentration. © 2008 The Author(s).

  • 42. Borg, H
    et al.
    Arnqvist, H J
    Björk, E
    Bolinder, J
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Nyström, L
    Jeppsson, J-O
    Sundkvist, G
    Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS).2003In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, no 2, p. 173-81Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years.

    METHODS: During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide.

    RESULTS: In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up.

    CONCLUSION/INTERPRETATION: Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.

  • 43. Borg, H
    et al.
    Björk, E
    Bolinder, J
    Eriksson, JW
    Nyström, L
    Jeppsson, J-O
    Sundkvist, G
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS)2003In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, no 2, p. 173-181Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis. We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. Methods. During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. Results. In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. Conclusion/interpretation. Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.

  • 44. Brandt, A. -S
    et al.
    de Portu, S.
    Medtron Int Sarl, Tolochenaz, Switzerland..
    Hellman, Jarl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cost savings associated with CSII therapy compared to MDI in a Swedish setting2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S477-S477Article in journal (Other academic)
  • 45.
    Brito, Ema C
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Vimaleswaran, K S
    Brage, S
    Andersen, L B
    Sardinha, L B
    Wareham, N J
    Ekelund, U
    Loos, R J F
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    PPARGC1A sequence variation and cardiovascular risk-factor levels: a study of the main genetic effects and gene x environment interactions in children from the European youth heart study2009In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no 4, p. 609-613Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The PPARGC1A gene coactivates multiple nuclear transcription factors involved in cellular energy metabolism and vascular stasis. In the present study, we genotyped 35 tagging polymorphisms to capture all common PPARGC1A nucleotide sequence variations and tested for association with metabolic and cardiovascular traits in 2,101 Danish and Estonian boys and girls from the European Youth Heart Study, a multicentre school-based cross-sectional cohort study. METHODS: Fasting plasma glucose concentrations, anthropometric variables and blood pressure were measured. Habitual physical activity and aerobic fitness were objectively assessed using uniaxial accelerometry and a maximal aerobic exercise stress test on a bicycle ergometer, respectively. RESULTS: In adjusted models, nominally significant associations were observed for BMI (rs10018239, p = 0.039), waist circumference (rs7656250, p = 0.012; rs8192678 [Gly482Ser], p = 0.015; rs3755863, p = 0.02; rs10018239, beta = -0.01 cm per minor allele copy, p = 0.043), systolic blood pressure (rs2970869, p = 0.018) and fasting glucose concentrations (rs11724368, p = 0.045). Stronger associations were observed for aerobic fitness (rs7656250, p = 0.005; rs13117172, p = 0.008) and fasting glucose concentrations (rs7657071, p = 0.002). None remained significant after correcting for the number of statistical comparisons. We proceeded by testing for gene x physical activity interactions for the polymorphisms that showed nominal evidence of association in the main effect models. None of these tests was statistically significant. CONCLUSIONS/INTERPRETATION: Variants at PPARGC1A may influence several metabolic traits in this European paediatric cohort. However, variation at PPARGC1A is unlikely to have a major impact on cardiovascular or metabolic health in these children.

  • 46.
    Brunner, G. A.
    et al.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Balent, B.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Ellmerer, M.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Schaupp, L.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Siebenhofer, A.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Jendle, Johan
    Novo Nordisk A/S, Copenhagen, Denmark.
    Okikawa, J.
    Aradigm Corp., Hayward, California, USA.
    Pieber, T. R.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Dose-response relation of liquid aerosol inhaled insulin in type I diabetic patients.2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, no 3, p. 305-308Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 47.
    Bucci, M.
    et al.
    Turku Univ, Turku Pet Ctr, Turku, Finland..
    Huovinen, V.
    Turku Univ, Turku Pet Ctr, Turku, Finland.;Turku Univ, Dept Radiol Med Imaging Ctr Southwest Finland, Turku, Finland. Turku Univ Hosp, Turku, Finland..
    Guzzardi, M. A.
    CNR, Inst Clin Physiol, PET Ctr, Pisa, Italy..
    Koskinen, S.
    Turku Univ, Turku Pet Ctr, Turku, Finland..
    Raiko, J.
    Turku Univ, Turku Pet Ctr, Turku, Finland..
    Lipponen, H.
    Turku Univ, Turku Pet Ctr, Turku, Finland..
    Badeau, R. M.
    Turku Univ, Turku Pet Ctr, Turku, Finland..
    Sarja, N.
    Turku Univ, Turku Pet Ctr, Turku, Finland..
    Salonen, M.
    Folkhalsan Res Ctr, Helsinki, Finland..
    Andersson, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sandboge, S.
    Folkhalsan Res Ctr, Helsinki, Finland..
    Iozzo, P.
    CNR, Inst Clin Physiol, PET Ctr, Pisa, Italy..
    Eriksson, J. G.
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, FIN-00014 Helsinki, Finland..
    Nuutila, P.
    Turku Univ, Turku Pet Ctr, Turku, Finland.;Univ Turku, Dept Med, SF-20500 Turku, Finland.;Turku Univ Hosp, Turku, Finland..
    Maternal obesity and telomere length associate with skeletal muscle insulin resistance which is reversed by exercise training in elderly womenM2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S16-S17Article in journal (Other academic)
  • 48. Bucci, Marco
    et al.
    Huovinen, Ville
    Guzzardi, Maria Angela
    Koskinen, Suvi
    Raiko, Juho R
    Lipponen, Heta
    Ahsan, Shaila
    Badeau, Robert M
    Honka, Miikka-Juhani
    Koffert, Jukka
    Savisto, Nina
    Salonen, Minna K
    Andersson, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sandboge, Samuel
    Iozzo, Patricia
    Eriksson, Johan G
    Nuutila, Pirjo
    Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers.2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 1, p. 77-86Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Maternal obesity predisposes offspring to adulthood morbidities, including type 2 diabetes. Type 2 diabetes and insulin resistance have been associated with shortened telomere length. First, we aimed to investigate whether or not maternal obesity influences insulin sensitivity and its relationship with leucocyte telomere length (LTL) in elderly women. Second, we tested whether or not resistance exercise training improves insulin sensitivity in elderly frail women.

    METHODS: Forty-six elderly women, of whom 20 were frail offspring of lean/normal weight mothers (OLM, BMI ≤26.3 kg/m(2)) and 17 were frail offspring of overweight/obese mothers (OOM, BMI ≥28.1 kg/m(2)), were studied before and after a 4 month resistance training (RT) intervention. Muscle insulin sensitivity of glucose uptake was measured using (18)F-fluoro-2-deoxyglucose and positron emission tomography with computed tomography during a hyperinsulinaemic-euglycaemic clamp. Muscle mass and lipid content were measured using magnetic resonance and LTL was measured using real-time PCR.

    RESULTS: The OOM group had lower thigh muscle insulin sensitivity compared with the OLM group (p = 0.048) but similar whole body insulin sensitivity. RT improved whole body and skeletal muscle insulin sensitivity in the OOM group only (p = 0.004 and p = 0.013, respectively), and increased muscle mass in both groups (p < 0.01). In addition, in the OOM group, LTL correlated with different thigh muscle groups insulin sensitivity (ρ ≥ 0.53; p ≤ 0.05). Individuals with shorter LTL showed a higher increase in skeletal muscle insulin sensitivity after training (ρ ≥ -0.61; p ≤ 0.05).

    CONCLUSIONS/INTERPRETATION: Maternal obesity and having telomere shortening were associated with insulin resistance in adult offspring. A resistance exercise training programme may reverse this disadvantage among offspring of obese mothers.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT01931540.

  • 49.
    Busse, N.
    et al.
    Univ Bremen, Islet Biol Lab, Bremen, Germany..
    Paroni, F.
    Richardson, S. J.
    Univ Exeter, Sch Med, Islet Biol Exeter IBEx, Exeter, Devon, England..
    Frisk, Gun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Laiho, J. E.
    Univ Tampere, Dept Virol, Tampere, Finland..
    Oikarinen, M.
    Univ Tampere, Dept Virol, Tampere, Finland..
    Hyoty, H.
    Univ Tampere, Dept Virol, Tampere, Finland..
    Morgan, N. G.
    Univ Exeter, Sch Med, Islet Biol Exeter IBEx, Exeter, Devon, England..
    Maedler, K.
    Univ Bremen, Islet Biol Lab, Bremen, Germany..
    Detection of beta cell virus infection in type 1 diabetes by short fluorescently labelled oligonucleotide probes2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S170-S171Article in journal (Refereed)
  • 50.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    McKeigue, P.M.
    Lithell, H.O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Changes in physical activity are associated with changes in metabolic cardiovascular risk factors2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, no 12, p. 2134-2139Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis

    To investigate the effect of changes in physical activity on changes in metabolic cardiovascular risk factors and to investigate what factors affect the association between physical activity and cardiovascular mortality.

    Methods

    Of the 1860 men who were 50 years of age and who were without pre-existing cardiovascular disease participating in a population-based study, 898 were re-examined 20 years later. Altogether 231 died from cardiovascular diseases during the follow-up (mean = 22.6 years). The examinations which the men underwent at 50 and 70 years of age included assessment of physical activity (self-reported at four alternative levels), anthropometry, measurements of fasting concentrations of glucose, specific insulin, proinsulin, split proinsulin and lipids.

    Results

    During the 20 years, 31 % increased their amount of physical activity while 51 % continued the same amount of exercise. Increased physical activity was associated with significant changes in several important metabolic variables, including fasting glucose, proinsulin and HDL cholesterol, independent of body weight changes. The risk of cardiovascular disease for men performing moderate, regular and athletic physical activity was 25 % (p = 0.127), 34 % (p = 0.022) and 71 % (p = 0.009) lower, respectively, compared with sedentary men. The association was attenuated by adjustment for baseline measurements of insulin, proinsulin and split proinsulin. Additional adjustment for other cardiovascular risk factors did not further attenuate the association.

    Conclusion/interpretation

    Increased leisure time physical activity between the ages of 50 and 70 years, in the absence of active intervention, is associated with improved glucose, insulin and lipid metabolism in men. The concentrations of insulin, proinsulin and split proinsulin could mediate much of the association between a sedentary lifestyle and increased risk of cardiovascular mortality.

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