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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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    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 humans2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S279-S280Artikel i tidskrift (Övrigt vetenskapligt)
  • 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    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 secretion2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, nr 9, s. 1928-1937Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    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)2009Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, nr Suppl 1, s. S25-S25Artikel i tidskrift (Refereegranskat)
  • 4. Afghahi, H
    et al.
    Hadimeri, H
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Eliasson, Björn
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    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)2010Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, nr Suppl 1, s. 110-Artikel i tidskrift (Refereegranskat)
  • 5.
    Ahlqvist, E.
    et al.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Karajamaki, A.
    Vaasa Cent Hosp, Primary Hlth Care, Vaasa, Finland..
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    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 outcome2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, s. S117-S117Artikel i tidskrift (Övrigt vetenskapligt)
  • 6.
    Alskar, Oskar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Karlsson, Mats O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Kjellsson, Maria C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Interspecies scaling of dynamic glucose and insulin using a mathematical model approach2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S306-S307Artikel i tidskrift (Övrigt vetenskapligt)
  • 7. Ambegaonkar, B
    et al.
    Pettersson, B
    Sazonov, V
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    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)2009Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, nr Suppl. 1, s. S495-S495Artikel i tidskrift (Refereegranskat)
  • 8.
    Andersson, Arne
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Eriksson, Ulf J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Jansson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sandler, Stellan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Welsh, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Welsh, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Claes Hellerström: a friendly islet explorer2007Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, nr 2, s. 4 p following 496-Artikel i tidskrift (Refereegranskat)
  • 9. Auro, K.
    et al.
    Kristiansson, K.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Taskinen, M-R.
    Jauhiainen, M.
    Perola, M.
    Peltonen, Leena
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study2008Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, nr 3, s. 464-472Artikel i tidskrift (Refereegranskat)
    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.

  • 10. Bakhtadze, E
    et al.
    Borg, H
    Stenström, G
    Fernlund, P
    Arnqvist, H J
    Ekbom-Schnell, A
    Bolinder, J
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och 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 Sweden2006Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, nr 8, s. 1785-1794Artikel i tidskrift (Refereegranskat)
    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.

  • 11. 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 patients2008Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, nr 12, s. 2224-2232Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    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 Cohort2019Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, nr 1, s. 78-86Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    Barbu, Andreea R.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Bodin, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Welsh, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Jansson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Welsh, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    A perfusion protocol for highly efficient transduction of intact pancreatic islets of Langerhans2006Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, nr 10, s. 2388-2391Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Barg, Sebastian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Gandasi, Nikhil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Quantitative analysis of t-SNARE and Ca2+-channel clusters near secretory granules2010Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, nr Suppl. 1, s. S46-S46Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Beijer, Kristina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Nowak, Christoph
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    In search of causal pathways in diabetes: a study using proteomics and genotyping data from a cross-sectional study2019Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, nr 11, s. 1998-2006Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: The pathogenesis of type 2 diabetes is not fully understood. We investigated whether circulating levels of preselected proteins were associated with the outcome 'diabetes' and whether these associations were causal.

    Methods: In 2467 individuals of the population-based, cross-sectional EpiHealth study (45-75 years, 50% women), 249 plasma proteins were analysed by the proximity extension assay technique. DNA was genotyped using the Illumina HumanCoreExome-12 v1.0 BeadChip. Diabetes was defined as taking glucose-lowering treatment or having a fasting plasma glucose of >= 7.0 mmol/l. The associations between proteins and diabetes were assessed using logistic regression. To investigate causal relationships between proteins and diabetes, a bidirectional two-sample Mendelian randomisation was performed based on large, genome-wide association studies belonging to the DIAGRAM and MAGIC consortia, and a genome-wide association study in the EpiHealth study.

    Results: Twenty-six proteins were positively associated with diabetes, including cathepsin D, retinal dehydrogenase 1, alpha-l-iduronidase, hydroxyacid oxidase 1 and galectin-4 (top five findings). Three proteins, lipoprotein lipase, IGF-binding protein 2 and paraoxonase 3 (PON-3), were inversely associated with diabetes. Fourteen of the proteins are novel discoveries. The Mendelian randomisation study did not disclose any significant causal effects between the proteins and diabetes in either direction that were consistent with the relationships found between the protein levels and diabetes.

    Conclusions/interpretation: The 29 proteins associated with diabetes are involved in several physiological pathways, but given the power of the study no causal link was identified for those proteins tested in Mendelian randomisation. Therefore, the identified proteins are likely to be biomarkers for type 2 diabetes, rather than representing causal pathways.

  • 16.
    Beijer, Kristina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala Univ, Med Sci, Uppsala, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Arnlöv, J.
    Karolinska Inst, Stockholm, Sweden.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, E.
    Stanford Univ, Palo Alto, CA 94304 USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    A targeted proteomic profile of prevalent diabetes in a population-based sample2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S252-S252Artikel i tidskrift (Övrigt vetenskapligt)
  • 17.
    Benedict, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Antihypertensive medication prior to nocturnal sleep reduces the risk of new-onset type 2 diabetes in hypertensive patients: a role for slow-wave sleep?2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, nr 2, s. 390-391Artikel i tidskrift (Refereegranskat)
  • 18.
    Berg, Anna-Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Frisk, Gun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Induction of the chemokine interferon-gamma-inducible protein-10 in human pancreatic islets during enterovirus infection2006Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, nr 11, s. 2697-2703Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    Berne, Christian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Flyvbjerg, A.
    Gronbaek, H.
    Jensevik, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    The association between IGFBP-1 and type 2 diabetes is modified by degrees of insulin sensitivity and early insulin response2010Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53Artikel i tidskrift (Övrigt vetenskapligt)
  • 20. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Roche, H. M.
    Drevon, C. A.
    The relationship between vitamin D status and markers of oxidation and inflammation in subjects with the metabolic syndrome2010Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53Artikel i tidskrift (Övrigt vetenskapligt)
  • 21.
    Bodegard, J.
    et al.
    AstraZeneca, Sodertalje, Sweden..
    Nathanson, D.
    Karolinska Inst, Dept Clin Sci & Educa, Stockholm, Sweden..
    Nystrom, T.
    Karolinska Inst, Stockholm, Sweden..
    Thuresson, M.
    Statisticon AB, Uppsala, Sweden..
    Norhammar, A.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Second-line treatment with sulfonylurea compared to DPP4 inhibitors demonstrated associations with earlier treatment intensification with insulin2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S189-S189Artikel i tidskrift (Övrigt vetenskapligt)
  • 22.
    Boersma, Greta J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Heurling, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Johansson, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lau Börjesson, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Katsogiannos, Petros
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;AstraZeneca, Dept Med, Gothenburg, Sweden..
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, s. S80-S80Artikel i tidskrift (Övrigt vetenskapligt)
  • 23.
    Boersma, Greta J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Johansson, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Pereira, Maria J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;Univ Gothenburg, Dept Med, Gothenburg, Sweden..
    Lau Börjesson, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Katsogiannos, Petros
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Panagiotou, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Skeletal muscle and liver, but not brain, account for impaired glucose utilisation in type 2 diabetes: whole-body PET/MR during hyperinsulinaemic euglycaemic clamp2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, s. S33-S33Artikel i tidskrift (Refereegranskat)
  • 24. Borg, H
    et al.
    Arnqvist, H J
    Björk, E
    Bolinder, J
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och 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).2003Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, nr 2, s. 173-81Artikel i tidskrift (Refereegranskat)
    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.

  • 25. Brandt, A. -S
    et al.
    de Portu, S.
    Medtron Int Sarl, Tolochenaz, Switzerland..
    Hellman, Jarl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Cost savings associated with CSII therapy compared to MDI in a Swedish setting2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S477-S477Artikel i tidskrift (Övrigt vetenskapligt)
  • 26.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    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 womenM2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S16-S17Artikel i tidskrift (Övrigt vetenskapligt)
  • 27. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sandboge, Samuel
    Iozzo, Patricia
    Eriksson, Johan G
    Nuutila, Pirjo
    Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers.2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, nr 1, s. 77-86Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    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 probes2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, s. S170-S171Artikel i tidskrift (Refereegranskat)
  • 29.
    Byberg, Liisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Zethelius, B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    McKeigue, P.M.
    Lithell, H.O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Changes in physical activity are associated with changes in metabolic cardiovascular risk factors2001Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, nr 12, s. 2134-2139Artikel i tidskrift (Refereegranskat)
    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.

  • 30.
    Börjesson, J. Lau
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Henriksnäs, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Berggren, P. -O
    Kohler, M.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Pancreatic islets transplanted intraportally into the liver in mice have a substantially lower blood flow than native islets2010Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53Artikel i tidskrift (Övrigt vetenskapligt)
  • 31. Campbell-Thompson, M. L.
    et al.
    Atkinson, M. A.
    Butler, A. E.
    Chapman, N. M.
    Frisk, Gun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Gianani, R.
    Giepmans, B. N.
    von Herrath, M. G.
    Hyoty, H.
    Kay, T. W.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Morgan, N. G.
    Powers, A. C.
    Pugliese, A.
    Richardson, S. J.
    Rowe, P. A.
    Tracy, S.
    Veld, P. A. In't
    The diagnosis of insulitis in human type 1 diabetes2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, nr 11, s. 2541-2543Artikel i tidskrift (Refereegranskat)
  • 32.
    Carlbom, Lina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Espes, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Jansson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, nr 9, s. 1968-1972Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: The aim of this study was to investigate pancreatic perfusion and its response to a glucose load in patients with type 1 diabetes mellitus compared with non-diabetic ('healthy') individuals.

    METHODS: Eight individuals with longstanding type 1 diabetes and ten sex-, age- and BMI-matched healthy controls underwent dynamic positron emission tomography scanning with (15)O-labelled water before and after intravenous administration of glucose. Perfusion in the pancreas was measured. Portal and arterial hepatic perfusion were recorded as references.

    RESULTS: Under fasting conditions, total pancreatic perfusion was on average 23% lower in the individuals with diabetes compared with healthy individuals. Glucose increased total pancreatic and portal hepatic blood perfusion in healthy individuals by 48% and 38%, respectively. In individuals with diabetes there was no significant increase in either total pancreatic or portal hepatic perfusion.

    CONCLUSIONS/INTERPRETATION: Individuals with type 1 diabetes have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.

  • 33. Carlsson, S.
    et al.
    Andersson, T.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Dorkhan, M.
    Groop, L.
    Lofvenborg, J. Edwall
    Hjort, R.
    Martinell, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Rasouli, B.
    Storm, P.
    Tuomi, T.
    Family history of type 1 and type 2 diabetes and the risk of LADA-results from a population-based study of incident cases2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr S1, s. S80-S80Artikel i tidskrift (Övrigt vetenskapligt)
  • 34.
    Castillejo-Lopez, Casimiro
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Abalo, Xesus M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sidibeh, Cherno O
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Kamble, Prasad G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    FKBP51 ablation using CRISPR/Cas-9 impairs adipocyte differentiation2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S11-S12Artikel i tidskrift (Övrigt vetenskapligt)
  • 35.
    Cen, Jing
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sargsyan, Ernest
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Metformin restores insulin secretion from palmitate-treated human islets by normalising mitochondrial metabolism and reducing ER stress and apoptosis2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, s. S47-S47Artikel i tidskrift (Övrigt vetenskapligt)
  • 36. Cervin, C
    et al.
    Orho-Melander, M
    Ridderstråle, M
    Lehto, M
    Barg, S
    Groop, L
    Cilio, C M
    Characterization of a naturally occurring mutation (L107I) in the HNF1 alpha (MODY3) gene.2002Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 45, nr 12, s. 1703-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: Maturity onset diabetes of the young type 3 (MODY3) is a monogenic form of diabetes mellitus caused by mutations in the gene encoding for hepatocyte nuclear factor 1 alpha, HNF1 alpha. In this study we have examined the in vivo and in vitro effects of a mutation (L107I) outside the DNA binding and dimerization domains in the N terminal part of the HNF1 alpha gene.

    METHODS: Beta-cell function of the affected family members was assessed by an oral glucose tolerance test. Functional tests were carried out to explain the role of the mutation in vitro by transcriptional activity assay, Western blotting, DNA-binding assays and subcellular localization experiments.

    RESULTS: Affected family members showed an 86% decreased insulin response to glucose when compared to age-matched healthy control subjects. In vitro the mutation showed a 79% decrease in transcriptional activity as compared to wild type HNF1 alpha in HeLa cells lacking HNF1 alpha. The transcriptional activity was not suppressed when the mutant was co-expressed with wild type HNF1 alpha suggesting that the decreased activity was not mediated by a dominant negative mechanism. The L107I/HNF1alpha protein showed normal nuclear targeting but impaired binding to an HNF1 alpha consensus sequence.

    CONCLUSION/INTERPRETATION: Our results suggest that the L107I substitution represents a MODY3 mutation which impairs beta-cell function by a loss-of-function mechanism.

  • 37.
    Chowdhury, Azazul Islam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Dyachok, Oleg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Tengholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sandler, Stellan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Functional differences between aggregated and dispersed insulin-producing cells2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, nr 7, s. 1557-1568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Beta cells situated in the islet of Langerhans respond more vigorously to glucose than do dissociated beta cells. Mechanisms for this discrepancy were studied by comparing insulin-producing MIN6 cells aggregated into pseudoislets with MIN6 monolayer cells and mouse and human islets. MIN6 monolayers, pseudoislets and mouse and human islets were exposed to glucose, alpha-ketoisocaproic acid (KIC), pyruvate, KIC plus glutamine and the phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin. Insulin secretion (ELISA), cytoplasmic Ca2+ concentration ([Ca2+](c); microfluorometry), glucose oxidation (radiolabelling), the expression of genes involved in mitochondrial metabolism (PCR) and the phosphorylation of insulin receptor signalling proteins (western blotting) were measured. Insulin secretory responses to glucose, pyruvate, KIC and glutamine were higher in pseudoislets than monolayers and comparable to those of human islets. Glucose oxidation and genes for mitochondrial metabolism were upregulated in pseudoislets compared with single cells and monolayers, respectively. Phosphorylation at the inhibitory S636/639 site of IRS-1 was significantly higher in monolayers and dispersed human and mouse cells than pseudoislets and intact human and mouse islets. PI3K inhibition only slightly attenuated glucose-stimulated insulin secretion from monolayers, but substantially reduced that from pseudoislets and human and mouse islets without suppressing the glucose-induced [Ca2+](c) response. We propose that islet architecture is critical for proper beta cell mitochondrial metabolism and IRS-1 signalling, and that PI3K regulates insulin secretion at a step distal to the elevation of [Ca2+](c).

  • 38.
    Chowdhury, Azazul Islam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hörnaeus, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala Univ, Med Cell Biol, Uppsala, Sweden..
    Role of PIAS1 in palmitate mediated beta cell dysfunction2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S230-S230Artikel i tidskrift (Övrigt vetenskapligt)
  • 39.
    Cunha, D. A.
    et al.
    Univ Libre Bruxelles, ULB Ctr Diabet Res, Brussels, Belgium..
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Molkentin, J. D.
    Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA..
    Bugliani, M.
    Univ Pisa, Dept Endocrinol & Metab, I-56100 Pisa, Italy..
    Marchetti, P.
    Univ Pisa, Dept Endocrinol & Metab, I-56100 Pisa, Italy..
    Eizirik, D. L.
    Univ Libre Bruxelles, ULB Ctr Diabet Res, Brussels, Belgium..
    Cnop, M.
    Univ Libre Bruxelles, ULB Ctr Diabet Res, Brussels, Belgium..
    Thrombospondin 1: a master regulator of the anti-oxidant defence in pancreatic beta cells2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S46-S46Artikel i tidskrift (Övrigt vetenskapligt)
  • 40.
    Dahlgren, Andreas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Jensevik, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Variants of the TCF7L2 gene are associated with beta cell dysfunction and confer an increased risk of type 2 diabetes mellitus in the ULSAM cohort of Swedish elderly men2007Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, nr 9, s. 1852-1857Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis:

    In a population-based cohort of elderly men with well-defined phenotypes and biochemical markers related to type 2 diabetes mellitus, we analysed two single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, in the transcription factor 7-like 2 gene (TCF7L2), which are associated with an increased risk of type 2 diabetes mellitus.

    Materials and methods:

    The 1,142 subjects were from the population-based Uppsala Longitudinal Study of Adult Men cohort study (see http://www.pubcare.uu.se/ULSAM/ , last accessed in May 2007). Insulin sensitivity was assessed using a euglycaemic-hyperinsulinaemic clamp; fasting intact and 32-33 split proinsulin, immunoreactive insulin and specific insulin were measured in plasma samples. The SNPs rs7903146 and rs12255372 were genotyped using a fluorescent homogeneous single base extension assay. The SNP genotypes were analysed against diabetes prevalence at age 70 using logistic regression and against quantitative biochemical measures using linear regression analysis.

    Results:

    We replicated the association with type 2 diabetes mellitus for both SNPs in this cohort of elderly males. The highest significant odds ratio (2.15, 95% CI 1.20-3.85) was found for SNP rs7903146. The odds ratio for SNP rs12255372 was 1.69 (95% CI 1.20-2.39). Both TCF7L2 SNPs were found to be significantly associated with plasma proinsulin when adjusting for insulin sensitivity, both in the whole cohort and when the diabetic subjects were excluded. Analysis for fasting plasma insulin or insulin sensitivity did not give significant results.

    Conclusions/interpretation:

    The association between the risk alleles of the two SNPs studied and levels of proinsulin in plasma, identified when adjusting for insulin sensitivity using euglycaemic-hyperinsulinaemic clamp measurements in this study, is an important novel finding.

  • 41. Denison, H.
    et al.
    Nilsson, C.
    Lofgren, L.
    Al-Shurbaji, A.
    Himmelmann, A.
    Martensson, G.
    Tornqvist, H.
    Knutsson, M.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    A one-week phase 1 trial with the DGAT1 inhibitor AZD7687: lipid handling, hormone secretion and adverse effects in the gut2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S407-S407Artikel i tidskrift (Övrigt vetenskapligt)
  • 42.
    Drott, Carl Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Franzén, Petra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Ghrelin in rat pancreatic islets decreases islet blood flow and impairs insulin secretion2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S218-S218Artikel i tidskrift (Övrigt vetenskapligt)
  • 43.
    Dyachok, Oleg
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Idevall, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Tengholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Gylfe, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Crosstalk between cAMP- and Zn2+-signalling in insulin secretion2010Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53Artikel i tidskrift (Övrigt vetenskapligt)
  • 44.
    Edén, Desireé
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mokhtari, Dariush
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tissue factor/factor VIIa signalling promotes cytokine-induced beta cell death and impairs glucose-stimulated insulin secretion from human pancreatic islets2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr 11, s. 2563-2572Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis Patients diagnosed with type 1 or type 2 diabetes have elevated levels of coagulation factor VIIa (FVIIa) and its receptor tissue factor (TF) in their bloodstream. This may affect the fate of the beta cells. We aimed to study the effects of TF/FVIIa signalling on cytokine-induced beta cell death and islet function in vitro. Methods Human pancreatic islets and MIN-6 beta cells were used to study TF mRNA and protein expression using real-time PCR, immunoblotting and flow cytometry. The effects of TF/FVIIa on cytokine-induced beta cell death were studied in MIN-6 cells and human pancreatic islets using cell-death ELISA and propidium iodide and cleaved caspase-3 staining. Effects of TF/FVIIa on the phosphorylation of p38, extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK) were investigated by immunoblotting. Glucose-stimulated insulin secretion (GSIS) from human islets was measured with an insulin ELISA. Results A combination of the cytokines IL-1 beta, TNF-alpha and IFN-gamma induced TF expression in human pancreatic islets and in beta cells. TF/FVIIa did not affect basal beta cell death but, independently of downstream coagulation activity, augmented beta cell death in response to cytokines. The effect of TF/FVIIa on cytokine-induced beta cell death was found to be dependent on the stress kinase JNK, since FVIIa addition potentiated cytokine-induced JNK activation and JNK inhibition abolished the effect of TF/FVIIa on cytokine-induced beta cell death. Moreover, TF/FVIIa signalling resulted in inhibition of GSIS from human pancreatic islets. Conclusions/interpretation These results indicate that TF/FVIIa signalling has a negative effect on beta cell function and promotes beta cell death in response to cytokines.

  • 45. Eeg-Olofsson, K
    et al.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Nilsson, P M
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Nunez, L
    Gudbjörnsdóttir, S
    Eliasson, B
    Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients2009Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, nr 1, s. 65-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: The aim of this study of type 2 diabetic patients in the Swedish National Diabetes Register was to study the associations of BMI, overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI >or= 30 kg/m(2)) with cardiovascular disease in type 2 diabetes, as these associations have not previously been clarified. METHODS: Patients aged 30-74 years with no previous CHD or stroke (N = 13,087) were followed for a mean of 5.6 years until 2003 for fatal or non-fatal CHD, stroke, cardiovascular disease (CHD or stroke) and total mortality. In total, 1,922 cardiovascular-disease events occurred, based on 64,864 person-years. RESULTS: The relative risks of CHD, stroke, cardiovascular disease and total mortality for a 5 unit increase in BMI at baseline were 15%, 11%, 13% and 27%, respectively, using Cox regression analysis, after adjusting for age, sex, diabetes duration, hypoglycaemic treatment and smoking (model 1), and were 9%, 4% (not significant), 7% and 20%, respectively, when adjusting also for HbA(1c), blood pressure, antihypertensive drugs, lipid-reducing drugs and microalbuminuria (model 2). Adjusted hazard ratios (model 1) for CHD, cardiovascular disease and total mortality with overweight were 1.27 (95% CI 1.09-1.48), 1.24 (1.09-1.41) and 1.16 (0.94-1.45), respectively, and 1.49 (1.27-1.76), 1.44 (1.26-1.64) and 1.71 (1.36-2.14) with obesity, as compared with normal weight. Significant hazard ratios were attenuated when adjusted according to model 2. For a 1 unit increase in BMI during follow-up, the relative risk of CHD (model 2) was 1.13 (1.04-1.23; p = 0.005). CONCLUSIONS/INTERPRETATION: Both overweight and obesity independently increased the risk of CHD and cardiovascular disease in patients with type 2 diabetes. The CHD risk was higher with increasing BMI than with stable or decreasing BMI during the study.

  • 46. Eeg-Olofsson, K.
    et al.
    Gudbjornsdottir, S.
    Eliasson, B.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    The triglycerides-to-HDL-cholesterol ratio and cardiovascular disease risk in obese patients with type 2 diabetes: a report from the Swedish national diabetes register2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S185-S186Artikel i tidskrift (Övrigt vetenskapligt)
  • 47. Eeg-Olofsson, K.
    et al.
    Gudbjornsdottir, S.
    Eliasson, B.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Svensson, A. -M
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Multifactorial risk factor control in clinical practice and risk of cardiovascular disease in type 2 diabetes: report from the Swedish national diabetes register2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr S1, s. S493-S493Artikel i tidskrift (Övrigt vetenskapligt)
  • 48.
    Eeg-Olofsson, K.
    et al.
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Med, S-41124 Gothenburg, Sweden..
    Ritsinger, V.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.;Reg Kronoberg, Dept Res & Dev, Vaxjo, Sweden..
    Hero, C.
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Med, S-41124 Gothenburg, Sweden..
    Saleh, N.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Svensson, A. -M
    Norhammar, A.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    Mortality by affected coronary artery vessels in 2776 patients with type 1 diabetes undergoing coronary angiography2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S577-S578Artikel i tidskrift (Övrigt vetenskapligt)
  • 49. Ejskjaer, N.
    et al.
    Wo, J.
    Esfandyari, T.
    Jamal, M.
    Dimcevski, G.
    Tarnow, L.
    Malik, R.
    Hellstrom, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Mondou, E.
    Quinn, J.
    Rousseau, F.
    Richard, M.
    Gastric emptying, glycaemia, and upper GI symptoms are independent factors in diabetic gastroparesis2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S493-S493Artikel i tidskrift (Övrigt vetenskapligt)
  • 50. Ekstrom, N.
    et al.
    Miftaraj, M.
    Svensson, A. -M
    Sundell, K. Andersson
    Eeg-Olofsson, K.
    Cederholm, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gudbjornsdottir, S.
    Eliasson, B.
    Durability of oral hypoglycaemic agents in drug naive patients with type 2 diabetes: observational study from the Swedish National Diabetes Register (NDR)2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S91-S92Artikel i tidskrift (Övrigt vetenskapligt)
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