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  • 101.
    Rolandsson, Olov
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Allmänmedicin.
    Hasselström, Jan
    Oien, Rut
    Säwe, Juliette
    [Peripheral arterial disease in primary health care. Occurrence and care]2006Inngår i: Lakartidningen, ISSN 0023-7205, Vol. 103, nr 37, s. 2645-6, 2648Artikkel i tidsskrift (Fagfellevurdert)
  • 102.
    Rolandsson, Olov
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Ågren, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hägg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hemoglobin A1c can be analyzed in blood kept frozen at -80 degrees C and is not commonly affected by hemolysis in the general population.2004Inngår i: Metabolism, ISSN 0026-0495, Vol. 53, nr 11, s. 1496-9Artikkel i tidsskrift (Fagfellevurdert)
  • 103.
    Rolandsson, Olov
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Nyström, Lennarth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Svensson, Maria
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    How to diagnose and classify diabetes in primary health care: Lessons learned from the Diabetes Register in Northern Sweden (DiabNorth)2012Inngår i: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 30, nr 2, s. 81-87Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. The objective was to create a diabetes register and to evaluate the validity of the clinical diabetes diagnosis and its classification. Design. The diabetes register was created by linkage of databases in primary and secondary care, the pharmaceutical database, and ongoing population-based health surveys in the county. Diagnosis and classification were validated by specialists in diabetology or general practitioners with special competence in diabetology. Analysis of autoantibodies associated with type 1 diabetes was used for classification. Setting. Primary and secondary health care in the county of V sterbotten, Sweden. Patients. Patients with diabetes (median age at diagnosis 56 years, inter quartile range 50-60 years) who had participated in the V sterbotten Intervention Programme (VIP) and accepted participation in a diabetes register. Results. Of all individuals with diabetes in VIP, 70% accepted to participate in the register. The register included 3256 (M/F 1894/1362) diabetes patients. The vast majority (95%) had data confirming the diabetes diagnoses according to WHO recommendations. Unspecified diabetes was the most common (54.6%) classification by the general practitioners. After assessment by specialists and analysis of autoantibodies the majority were classified as type 2 diabetes (76.8%). Type 1 diabetes was the second largest group (7.2%), including a sub-group of patients with latent autoimmune diabetes (4.8%). Conclusion. It was concluded that it is feasible to create a diabetes register based on information in medical records in general practice. However, special attention should be paid to the validity of the diabetes diagnosis and its classification.

  • 104.
    Rolandsson, Olov
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Palmer, JP
    Latent autoimmune diabetes in adults (LADA) is dead: long live autoimmune diabetes!2010Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, nr 7, s. 1250-1253Artikkel i tidsskrift (Fagfellevurdert)
  • 105.
    Rolandsson, Olov
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Allmänmedicin.
    Risborg, M
    Rasmark, S
    Distal symmetric polyneuropathy is uncommon in impaired glucose tolerance.2008Inngår i: 67th Annual Meeting of the American-Diabetes-AssociationJune 06-10, 2008, San Francisco, 2008Konferansepaper (Annet vitenskapelig)
  • 106.
    Rolandsson, Olov
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Stigbrand, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eary, J
    Greenbaum, C
    Accumulation of(125)iodine labeled interleukin-2 in the pancreas of NOD mice.2001Inngår i: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 17, nr 4, s. 281-287Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Interleukin-2 (IL-2) is an important cytokine in the autoimmune process proceeding Type 1 diabetes. Our aim was to investigate, in two previously used animal models, the NOD mouse and the BB/W rat, the in vivo tissue distribution of radio-labeled IL-2. If the radio-labeled IL-2 accumulated significantly in the pancreas compared to surrounding organs it could allow imaging of lymphocyte infiltration of the islets of Langerhans by scintigraphic methods. IL-2 was labeled enzymatically with(125)Iodine. Radio-labeled IL-2 was injected iv in prediabetic NOD mice, diabetic NOD mice and Balb/c mice in the first animal model and in BB rats in the second model. Animals were sacrificed at different time points and the activity in different organs was measured. It was found that the mean activity in the pancreas in both diabetic and prediabetic NOD mice was significantly higher compared to pancreas from Balb/c mice (P< 0.001 and P=0.005, respectively). However, the mean activity in the pancreas was at the lower range of the surrounding organs in both animal models, thereby excluding the possibility of imaging the autoimmune process by scintigraphic methods. It is concluded that radio-labeled IL-2 did accumulate significantly in the pancreas of NOD mice compared to control mice but there is a need to develop new techniques in order to visualize the localized activity.

  • 107. Romaguera, D.
    et al.
    Norat, T.
    Wark, P. A.
    Vergnaud, A. C.
    Schulze, M. B.
    van Woudenbergh, G. J.
    Drogan, D.
    Amiano, P.
    Molina-Montes, E.
    Sanchez, M. J.
    Balkau, B.
    Barricarte, A.
    Beulens, J. W. J.
    Clavel-Chapelon, F.
    Crispim, S. P.
    Fagherazzi, G.
    Franks, P. W.
    Grote, V. A.
    Huybrechts, I.
    Kaaks, R.
    Key, T. J.
    Khaw, K. T.
    Nilsson, P.
    Overvad, K.
    Palli, D.
    Panico, S.
    Quiros, J. R.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, C.
    Sieri, S.
    Slimani, N.
    Spijkerman, A. M. W.
    Tjonneland, A.
    Tormo, M. J.
    Tumino, R.
    van den Berg, S. W.
    Wermeling, P. R.
    Zamora-Ros, R.
    Feskens, E. J. M.
    Langenberg, C.
    Sharp, S. J.
    Forouhi, N. G.
    Riboli, E.
    Wareham, N. J.
    Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct2013Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, nr 7, s. 1520-1530Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.

  • 108.
    Ruge, Toralph
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Nyström, Lennarth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Recruiting high-risk individuals to a diabetes prevention program: how hard can it be?2007Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, nr 7, s. e61-Artikkel i tidsskrift (Fagfellevurdert)
  • 109. Sacerdote, Carlotta
    et al.
    Ricceri, Fulvio
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Baldi, Ileana
    Chirlaque, Maria-Dolores
    Feskens, Edith
    Bendinelli, Benedetta
    Ardanaz, Eva
    Arriola, Larraitz
    Balkau, Beverley
    Bergmann, Manuela
    Beulens, Joline W. J.
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Crowe, Francesca
    de Lauzon-Guillain, Blandine
    Forouhi, Nita
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gallo, Valentina
    Gonzalez, Carlos
    Halkjaer, Jytte
    Illner, Anne-Kathrin
    Kaaks, Rudolf
    Key, Timothy
    Khaw, Kay-Tee
    Navarro, Carmen
    Nilsson, Peter M.
    Dalton, Susanne Oksbjerg
    Overvad, Kim
    Pala, Valeria
    Palli, Domenico
    Panico, Salvatore
    Polidoro, Silvia
    Ramon Quiros, J.
    Romieu, Isabelle
    Sanchez, Maria-Jose
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne
    Vergnaud, Anne-Claire
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sharp, Stephen
    Langenberg, Claudia
    Riboli, Elio
    Vineis, Paolo
    Wareham, Nicholas
    Lower educational level is a predictor of incident type 2 diabetes in European countries: The EPIC-InterAct study2012Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 41, nr 4, s. 1162-1173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Type 2 diabetes mellitus ( T2DM) is one of the most common chronic diseases worldwide. In high- income countries, low socioeconomic status seems to be related to a high incidence of T2DM, but very little is known about the intermediate factors of this relationship.

    Method We performed a case-cohort study in eight Western European countries nested in the EPIC study (n = 340 234, 3.99 million person-years of follow-up). A random sub-cohort of 16 835 individuals and a total of 12 403 incident cases of T2DM were identified. Crude and multivariate-adjusted hazard ratios (HR) were estimated for each country and pooled across countries using meta-analytical methods. Age-, gender- and country-specific relative indices of inequality (RII) were used as the measure of educational level and RII tertiles were analysed.

    Results Compared with participants with a high educational level (RII tertile 1), participants with a low educational level (RII tertile 3) had a higher risk of T2DM [HR: 1.77, 95% confidence interval (CI): 1.69-1.85; P-trend < 0.01]. The HRs adjusted for physical activity, smoking status and propensity score according to macronutrient intake were very similar to the crude HR (adjusted HR: 1.67, 95% CI: 1.52-1.83 in men; HR: 1.88, 95% CI: 1.73-2.05 in women). The HRs were attenuated only when they were further adjusted for BMI (BMI-adjusted HR: 1.36, 95% CI: 1.23-1.51 in men; HR: 1.32, 95% CI: 1.20-1.45 in women).

    Conclusion This study demonstrates the inequalities in the risk of T2DM in Western European countries, with an inverse relationship between educational level and risk of T2DM that is only partially explained by variations in BMI.

  • 110. Schlesinger, S
    et al.
    Aleksandrova, K
    Pischon, T
    Jenab, M
    Fedirko, V
    Trepo, E
    Overvad, K
    Roswall, N
    Tjønneland, A
    Boutron-Ruault, M C
    Fagherazzi, G
    Racine, A
    Kaaks, R
    Grote, V A
    Boeing, H
    Trichopoulou, A
    Pantzalis, M
    Kritikou, M
    Mattiello, A
    Sieri, S
    Sacerdote, C
    Palli, D
    Tumino, R
    Peeters, P H
    Bueno-de-Mesquita, H B
    Weiderpass, E
    Quirós, J R
    Zamora-Ros, R
    Sánchez, M J
    Arriola, L
    Ardanaz, E
    Tormo, M J
    Nilsson, P
    Lindkvist, B
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Khaw, K T
    Wareham, N
    Travis, R C
    Riboli, E
    Nöthlings, U
    Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort2013Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, nr 9, s. 2449-2455Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.

  • 111. Scott, Robert A.
    et al.
    Fall, Tove
    Pasko, Dorota
    Barker, Adam
    Sharp, Stephen J.
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Barroso, Ines
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Crowe, Francesca L.
    Dekker, Jacqueline M.
    Fagherazzi, Guy
    Ferrannini, Ele
    Forouhi, Nita G.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gavrila, Diana
    Giedraitis, Vilmantas
    Grioni, Sara
    Groop, Leif C.
    Kaaks, Rudolf
    Key, Timothy J.
    Kuehn, Tilman
    Lotta, Luca A.
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Roswall, Nina
    Sacerdote, Carlotta
    Sala, Nuria
    Sanchez, Maria-Jose
    Schulze, Matthias B.
    Siddiq, Afshan
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    Yaghootkar, Hanieh
    McCarthy, Mark I.
    Semple, Robert K.
    Riboli, Elio
    Walker, Mark
    Ingelsson, Erik
    Frayling, Tim M.
    Savage, David B.
    Langenberg, Claudia
    Wareham, Nicholas J.
    Common Genetic Variants Highlight the Role of Insulin Resistance and Body Fat Distribution in Type 2 Diabetes, Independent of Obesity2014Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, nr 12, s. 4378-4387Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp- and oral glucose tolerance test-based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (beta in SDs per allele [95% CI], -0.03 [-0.04, -0.01]; P = 0.004). This score was associated with lower BMI (-0.01 [-0.01, -0.0]; P = 0.02) and gluteofemoral fat mass (-0.03 [-0.05,-0.02; P = 1.4x10(-6) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and gamma-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (P-interaction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (P-interaction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.

  • 112. Scott, Robert A.
    et al.
    Freitag, Daniel F.
    Li, Li
    Chu, Audrey Y.
    Surendran, Praveen
    Young, Robin
    Grarup, Niels
    Stancakova, Alena
    Chen, Yuning
    Varga, Tibor V.
    Yaghootkar, Hanieh
    Luan, Jian'an
    Zhao, Jing Hua
    Willems, Sara M.
    Wessel, Jennifer
    Wang, Shuai
    Maruthur, Nisa
    Michailidou, Kyriaki
    Pirie, Ailith
    van der Lee, Sven J.
    Gillson, Christopher
    Al Olama, Ali Amin
    Amouyel, Philippe
    Arriola, Larraitz
    Arveiler, Dominique
    Aviles-Olmos, Iciar
    Balkau, Beverley
    Barricarte, Aurelio
    Barroso, Ines
    Garcia, Sara Benlloch
    Bis, Joshua C.
    Blankenberg, Stefan
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Borecki, Ingrid B.
    Bork-Jensen, Jette
    Bowden, Sarah
    Caldas, Carlos
    Caslake, Muriel
    Cupples, L. Adrienne
    Cruchaga, Carlos
    Czajkowski, Jacek
    den Hoed, Marcel
    Dunn, Janet A.
    Earl, Helena M.
    Ehret, Georg B.
    Ferrannini, Ele
    Ferrieres, Jean
    Foltynie, Thomas
    Ford, Ian
    Forouhi, Nita G.
    Gianfagna, Francesco
    Gonzalez, Carlos
    Grioni, Sara
    Hiller, Louise
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Research Unit, 931 41 Skellefteå, Sweden.
    Jorgensen, Marit E.
    Jukema, J. Wouter
    Kaaks, Rudolf
    Kee, Frank
    Kerrison, Nicola D.
    Key, Timothy J.
    Kontto, Jukka
    Kote-Jarai, Zsofia
    Kraja, Aldi T.
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Linneberg, Allan
    Liu, Chunyu
    Marenne, Galle
    Mohlke, Karen L.
    Morris, Andrew P.
    Muir, Kenneth
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Navarro, Carmen
    Nielsen, Sune F.
    Nilsson, Peter M.
    Nordestgaard, Borge G.
    Packard, Chris J.
    Palli, Domenico
    Panico, Salvatore
    Peloso, Gina M.
    Perola, Markus
    Peters, Annette
    Poole, Christopher J.
    Quiros, J. Ramn
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Salomaa, Veikko
    Sanchez, Mara-Jose
    Sattar, Naveed
    Sharp, Stephen J.
    Sims, Rebecca
    Slimani, Nadia
    Smith, Jennifer A.
    Thompson, Deborah J.
    Trompet, Stella
    Tumino, Rosario
    van der A, Daphne L.
    van der Schouw, Yvonne T.
    Virtamo, Jarmo
    Walker, Mark
    Walter, Klaudia
    Abraham, Jean E.
    Amundadottir, Laufey T.
    Aponte, Jennifer L.
    Butterworth, Adams.
    Dupuis, Josee
    Easton, Douglas F.
    Eeles, Rosalind A.
    Erdmann, Jeanette
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, SE-205 Malmö, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
    Frayling, Timothy M.
    Hansen, Torben
    Howson, Joanna M. M.
    Jorgensen, Torben
    Kooner, Jaspal
    Laakso, Markku
    Langenberg, Claudia
    McCarthy, Mark I.
    Pankow, James S.
    Pedersen, Oluf
    Riboli, Elio
    Rotter, Jerome I.
    Saleheen, Danish
    Samani, Nilesh J.
    Schunkert, Heribert
    Vollenweider, Peter
    O'Rahilly, Stephen
    Deloukas, Panos
    Danesh, John
    Goodarzi, Mark O.
    Kathiresan, Sekar
    Meigs, James B.
    Ehm, Margaret G.
    Wareham, Nicholas J.
    Waterworth, Dawn M.
    A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease2016Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 8, nr 341, artikkel-id 341ra76Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

  • 113.
    Shi, Lin
    et al.
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden..
    Brunius, Carl
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden..
    Bergdahl, Ingvar
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Donat Vargas, Carolina
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden..
    Kiviranta, Hannu
    Environmental Health Unit, National Institute for Health and Welfare, Kuopio, Finland..
    Hanhineva, Kati
    LC-MS Metabolomics Center, Kuopio, Finland. Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland..
    Åkesson, Agneta
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden..
    Landberg, Rikard
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden..
    Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults2019Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 149, nr 8, s. 1413-1423Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish.

    OBJECTIVE: The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults.

    METHODS: In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression.

    RESULTS: We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P < 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake.

    CONCLUSIONS: Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence.

  • 114. Shi, Lin
    et al.
    Brunius, Carl
    Lehtonen, Marko
    Auriola, Seppo
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Hanhineva, Kati
    Landberg, Rikard
    Plasma metabolites associated with type 2 diabetes in a Swedish population: a case-control study nested in a prospective cohort2018Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 4, s. 849-861Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis: The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction.

    Methods: We established a nested case-control study within the Swedish prospective population-based Vasterbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case-control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case-control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index.

    Results: We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19: 1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed intermediate to high reproducibility among healthy individuals. Moreover, PCs with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric acid and glutamate changed over time along with disease progression among diabetes cases. Importantly, we found that a combination of five of the most robustly predictive metabolites significantly improved risk prediction if added to models with an a priori defined set of traditional risk factors, but only a marginal improvement was achieved when using models based on optimally selected traditional risk factors.

    Conclusions/interpretation: Predictive metabolites may improve understanding of the pathophysiology of type 2 diabetes and reflect disease progression, but they provide limited incremental value in risk prediction beyond optimal use of traditional risk factors.

  • 115. Sigvant, Birgitta
    et al.
    Wiberg-Hedman, Katarina
    Bergqvist, David
    Rolandsson, Olov
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Allmänmedicin.
    Andersson, Bob
    Persson, Elisabeth
    Wahlberg, Eric
    A population-based study of peripheral arterial disease prevalence with special focus on critical limb ischemia and sex differences.2007Inngår i: Journal of Vascular Surgery, ISSN 0741-5214, Vol. 45, nr 6, s. 1185-91Artikkel i tidsskrift (Fagfellevurdert)
  • 116. Sigvant, Birgitta
    et al.
    Wiberg-Hedman, Katarina
    Bergqvist, David
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Wahlberg, Eric
    Risk factor profile and use of cardiovascular drugprevention in women and men with peripheral artery disease2009Inngår i: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, nr 1, s. 39-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To determine cardiovascular comorbidities and use of cardiovascular disease preventive drugs in patients with peripheral arterial disease (PAD), with special attention to sex differences.

    Design A cross-sectional point-prevalence study.

    Patients A population sample of patients that are 60-90 years old.

    Setting Primary care areas in four Swedish regions.

    Main outcome measures Prevalence of PAD stages, comorbidities and medication use.

    Results The prevalence of any type of PAD was 18.0% (range 16-20), of asymptomatic peripheral arterial disease (APAD) was 11.1% (range 9-13), intermittent claudication was 6.8% (range 6.5-7.1), and of critical limb ischemia (CLI) was 1.2% (range 1.0-1.5). APAD and CLI were more common in women. Statins were used by 17.5% (range 16.9-18.2), 29.4% (range 29.0-30.1), and 30.3% (range 29.9-30.8) of the patients with APAD, intermittent claudication, and CLI, respectively, and antiplatelet therapy was reported by 34.1% (range 33.7-34.3), 47.6% (range 47.3-47.9), and 60.2% (range 59.1-60.7). The odds ratio for having APAD was 1.7 (range 1.2-2.4) for women with a smoking history of 10 years in relation to nonsmokers. This association was observed only in men who had smoked for at least 30 years or more. Preventive drug use was more common in men with PAD. Compared with women they had an odds ratio of 1.3 (range 1.1-1.5) for lipid-lowering therapy, 1.3 (range 1.0-1.7) for β-blockers or angiotensin-converting enzyme inhibitors, and 1.5 (range 1.2-1.9) for antiplatelet therapy.

    Conclusion The patients' risk factor profiles differed among the PAD stages. Smoking duration already seemed to be a risk factor for women with PAD after 10 years of smoking, as compared with 30 years for men, and fewer women reported use of preventive medication. These observations may partly explain the sex differences in prevalence that were observed.

  • 117. Sluijs, I.
    et al.
    Beulens, J. W. J.
    Van Der Schouw, Y. T.
    Van Der A, D. L.
    Buckland, G.
    Kuijsten, A.
    Schulze, M. B.
    Amiano, P.
    Ardanaz, E.
    Balkau, B.
    Boeing, H.
    Gavrila, D.
    Grote, V. A.
    Key, T. J.
    Li, K.
    Nilsson, P.
    Overvad, K.
    Palli, D.
    Panico, S.
    Quiŕos, J. R.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Roswall, N.
    Sacerdote, C.
    Śanchez, M.-J.
    Sieri, S.
    Slimani, N.
    Spijkerman, A. M. W.
    Tjønneland, A.
    Tumino, R.
    Sharp, S. J.
    Langenberg, C.
    Feskens, E. J. M.
    Forouhi, N. G.
    Riboli, E.
    Wareham, N. J.
    Dietary glycemic index, glycemic load, and digestible carbohydrate intake are not associated with risk of type 2 diabetes in eight European countries2013Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 143, nr 1, s. 93-99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The association of glycemic index (GI) and glycemic load (GL) with the risk of type 2 diabetes remains unclear. We investigated associations of dietary GI, GL, and digestible carbohydrate with incident type 2 diabetes.We performed a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition Study, including a random subcohort (n = 16,835) and incident type 2 diabetes cases (n = 12,403). The median follow-up time was 12 y. Baseline dietary intakes were assessed using countryspecific dietary questionnaires. Country-specific HR were calculated and pooled using random effects meta-analysis. Dietary GI, GL,and digestible carbohydrate in the subcohortwere (mean± SD) 56± 4, 127± 23, and 226± 36 g/d, respectively. After adjustment for confounders, GI and GL were not associated with incident diabetes [HR highest vs. lowest quartile (HRQ4) forGI: 1.05 (95%CI=0.96, 1.16); HRQ4 for GL: 1.07 (95%CI = 0.95, 1.20)]. Digestible carbohydrate intake was not associated with incident diabetes[HRQ4: 0.98 (95% CI = 0.86, 1.10)]. In additional analyses, we found that discrepancies in the GI value assignment to foods possibly explain differences in GI associationswith diabeteswithin the same study population. In conclusion, an expansion of the GI tables and systematic GI value assignment to foods may be needed to improve the validity of GI values derived in such studies, after which GI associations may need reevaluation. Our study shows that digestible carbohydrate intake is not associated with diabetes risk and suggests that diabetes risk with high-GI and -GL diets may be more modest than initial studies suggested.

  • 118. Sluijs, Ivonne
    et al.
    Forouhi, Nita G
    Beulens, Joline WJ
    van der Schouw, Yvonne T
    Agnoli, Claudia
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Boeing, Heiner
    Bueno-de-Mesquita, H Bas
    Clavel-Chapelon, Francoise
    Crowe, Francesca L
    de Lauzon-Guillain, Blandine
    Drogan, Dagmar
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gavrila, Diana
    Gonzalez, Carlos
    Halkjaer, Jytte
    Kaaks, Rudolf
    Moskal, Aurelie
    Nilsson, Peter
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, Jose R
    Ricceri, Fulvio
    Rinaldi, Sabina
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Spijkerman, Annemieke MW
    Teucher, Birgit
    Tjonneland, Anne
    Tormo, Maria-Jose
    Tumino, Rosario
    van der A, Daphne L
    Sharp, Stephen J
    Langenberg, Claudia
    Feskens, Edith JM
    Riboli, Elio
    Wareham, Nicholas J
    The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study2012Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, nr 2, s. 382-390Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Dairy product intake may be inversely associated with risk of type 2 diabetes, but the evidence is inconclusive for total dairy products and sparse for types of dairy products.

    Objective: The objective was to investigate the prospective association of total dairy products and different dairy subtypes with incidence of diabetes in populations with marked variation of intake of these food groups.

    Design: A nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) included a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403). Baseline dairy product intake was assessed by using dietary questionnaires. Country-specific Prentice-weighted Cox regression HRs were calculated and pooled by using a random-effects meta-analysis.

    Results: Intake of total dairy products was not associated with diabetes (HR for the comparison of the highest with the lowest quintile of total dairy products: 1.01; 95% CI: 0.83, 1.34; P-trend = 0.92) in an analysis adjusted for age, sex, BMI, diabetes risk factors, education, and dietary factors. Of the dairy subtypes, cheese intake tended to have an inverse association with diabetes (HR: 0.88; 95% CI: 0.76, 1.02; P-trend = 0.01), and a higher combined intake of fermented dairy products (cheese, yogurt, and thick fermented milk) was inversely associated with diabetes (HR: 0.88; 95% CI: 0.78, 0.99; P-trend = 0.02) in adjusted analyses that compared extreme quintiles.

    Conclusions: This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study. Ant J Clin Nutr 2012;96:382-90.

  • 119. Sluijs, Ivonne
    et al.
    Holmes, Michael V.
    van der Schouw, Yvonne T.
    Beulens, Joline W. J.
    Asselbergs, Folkert W.
    Maria Huerta, Jose
    Palmer, Tom M.
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gavrila, Diana
    Kaaks, Rudolf
    Khaw, Kay Tee
    Kuehn, Tilman
    Molina-Montes, Esther
    Mortensen, Lotte Maxild
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Ramon Quiros, J.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sala, Nuria
    Schmidt, Julie A.
    Scott, Robert A.
    Sieri, Sabina
    Slimani, Nadia
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Travis, Ruth C.
    Tumino, Rosario
    Daphne, L. van der A.
    Sharp, Stephen J.
    Forouhi, Nita G.
    Langenberg, Claudia
    Riboli, Elio
    Wareham, Nicholas J.
    A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes2015Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, nr 8, s. 3028-3036Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (HR) of 1.20 (95% CI 1.11, 1.30) per 59.48 mu mol/L (1mg/dL) uric acid. The genetic score raised uric acid by 17 mu mol/L (95% CI 15, 18) per SD increase and explained 4% of uric acid variation. By using the genetic score to estimate the unconfounded effect, we found that a 59.48 mu mol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01 [95% CI 0.87, 1.16]). Including data from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio estimate was 0.99 (95% CI 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid-lowering therapies may therefore not be beneficial in reducing diabetes risk.

  • 120. Sluik, D.
    et al.
    Jankovic, N.
    Hughes, M.
    O'Doherty, M. G.
    Schoettker, B.
    Drygas, W.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Maennistoe, S.
    Ordonez-Mena, J. M.
    Ferrieres, J.
    Bamia, C.
    De Gaetano, G.
    Kiefte-De Jong, J. C.
    Franco, O. H.
    Sluijs, I.
    Spijkerman, A. M. W.
    Sans, S.
    Eriksson, S.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Kromhout, D.
    Trichopoulou, A.
    Wilsgaard, T.
    Brenner, H.
    Kuulasmaa, K.
    Laatikainen, T.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Iacoviello, L.
    Boffetta, P.
    Kee, F.
    Feskens, E. J. M.
    Alcoholic beverage preference and diabetes incidence across Europe: the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project2017Inngår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 71, nr 5, s. 659-668Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND/OBJECTIVES: It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol. SUBJECTS/METHODS: Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when. >= 70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis. RESULTS: Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases. CONCLUSIONS: This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.

  • 121. Sluik, Diewertje
    et al.
    Boeing, Heiner
    Bergmann, Manuela M
    Schütze, Madlen
    Teucher, Birgit
    Kaaks, Rudolf
    Tjønneland, Anne
    Overvad, Kim
    Arriola, Larraitz
    Ardanaz, Eva
    Bendinelli, Benedetta
    Agnoli, Claudia
    Tumino, Rosario
    Ricceri, Fulvio
    Mattiello, Amalia
    Spijkerman, Annemieke M W
    Beulens, Joline W J
    Grobbee, Diederick E
    Nilsson, Peter M
    Melander, Olle
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Riboli, Elio
    Gallo, Valentina
    Romaguera, Dora
    Nöthlings, Ute
    Alcohol consumption and mortality in individuals with diabetes mellitus2012Inngår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 108, nr 7, s. 1307-1315Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies have suggested that moderate alcohol consumption is associated with a reduced risk of CVD and premature mortality in individuals with diabetes mellitus. However, history of alcohol consumption has hardly been taken into account. We investigated the association between current alcohol consumption and mortality in men and women with diabetes mellitus accounting for past alcohol consumption. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was defined of 4797 participants with a confirmed diagnosis of diabetes mellitus. Men and women were assigned to categories of baseline and past alcohol consumption. Hazard ratios (HR) and 95 % CI for total mortality were estimated with multivariable Cox regression models, using light alcohol consumption (>0-6 g/d) as the reference category. Compared with light alcohol consumption, no relationship was observed between consumption of 6 g/d or more and total mortality. HR for >6-12 g/d was 0·89 (95 % CI 0·61, 1·30) in men and 0·86 (95 % CI 0·46, 1·60) in women. Adjustment for past alcohol consumption did not change the estimates substantially. In individuals who at baseline reported abstaining from alcohol, mortality rates were increased relative to light consumers: HR was 1·52 (95 % CI 0·99, 2·35) in men and 1·81 (95 % CI 1·04, 3·17) in women. The present study in diabetic individuals showed no association between current alcohol consumption >6 g/d and mortality risk compared with light consumption. The increased mortality risk among non-consumers appeared to be affected by their past alcohol consumption rather than their current abstinence.

  • 122. Sluik, Diewertje
    et al.
    Boeing, Heiner
    Li, Kuanrong
    Kaaks, Rudolf
    Johnsen, Nina Fons
    Tjonneland, Anne
    Arriola, Larraitz
    Barricarte, Aurelio
    Masala, Giovanna
    Grioni, Sara
    Tumino, Rosario
    Ricceri, Fulvio
    Mattiello, Amalia
    Spijkerman, Annemieke M. W.
    van der A, Daphne L.
    Sluijs, Ivonne
    Franks, Paul W.
    Nilsson, Peter M.
    Orho-Melander, Marju
    Fhärm, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Riboli, Elio
    Romaguera, Dora
    Weiderpass, Elisabete
    Sanchez-Cantalejo, Emilio
    Noethlings, Ute
    Lifestyle factors and mortality risk in individuals with diabetes mellitus: are the associations different from those in individuals without diabetes?2014Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr 1, s. 63-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis Thus far, it is unclear whether lifestyle recommendations for people with diabetes should be different from those for the general public. We investigated whether the associations between lifestyle factors and mortality risk differ between individuals with and without diabetes. Methods Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was formed of 6,384 persons with diabetes and 258,911 EPIC participants without known diabetes. Joint Cox proportional hazard regression models of people with and without diabetes were built for the following lifestyle factors in relation to overall mortality risk: BMI, waist/height ratio, 26 food groups, alcohol consumption, leisure-time physical activity, smoking. Likelihood ratio tests for heterogeneity assessed statistical differences in regression coefficients. Results Multivariable adjusted mortality risk among individuals with diabetes compared with those without was increased, with an HR of 1.62 (95% CI 1.51, 1.75). Intake of fruit, legumes, nuts, seeds, pasta, poultry and vegetable oil was related to a lower mortality risk, and intake of butter and margarine was related to an increased mortality risk. These associations were significantly different in magnitude from those in diabetes-free individuals, but directions were similar. No differences between people with and without diabetes were detected for the other lifestyle factors. Conclusions/interpretation Diabetes status did not substantially influence the associations between lifestyle and mortality risk. People with diabetes may benefit more from a healthy diet, but the directions of association were similar. Thus, our study suggests that lifestyle advice with respect to mortality for patients with diabetes should not differ from recommendations for the general population.

  • 123. Sluik, Diewertje
    et al.
    Boeing, Heiner
    Montonen, Jukka
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Sandbaek, Annelli
    Overvad, Kim
    Arriola, Larraitz
    Ardanaz, Eva
    Saieva, Calogero
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Spijkerman, Annemieke M. W.
    van der A, Daphne L.
    Beulens, Joline W. J.
    van Dieren, Susan
    Nilsson, Peter M.
    Groop, Leif C.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Bueno-de-Mesquita, Bas
    Noethlings, Ute
    HbA(1c) Measured in Stored Erythrocytes Is Positively Linearly Associated with Mortality in Individuals with Diabetes Mellitus2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 6, s. e38877-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Observational studies have shown that glycated haemoglobin (HbA(1c)) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA(1c) measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods: Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA(1c) was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA(1c) in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results: After a median follow-up of 9.3 years, 460 participants died. Higher HbA(1c) was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity = 0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA(1c) and medication. Conclusion: This prospective study showed that persons with lower HbA(1c) had better survival than those with higher HbA(1c). The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA(1c) appears to be associated with reduced mortality risk.

  • 124. Sluik, Diewertje
    et al.
    Boeing, Heiner
    Montonen, Jukka
    Pischon, Tobias
    Kaaks, Rudolf
    Teucher, Birgit
    Tjønneland, Anne
    Halkjaer, Jytte
    Berentzen, Tina L
    Overvad, Kim
    Arriola, Larraitz
    Ardanaz, Eva
    Bendinelli, Benedetta
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Spijkerman, Annemieke MW
    van der A, Daphne L
    Beulens, Joline W
    van der Schouw, Yvonne T
    Nilsson, Peter M
    Hedblad, Bo
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nöthlings, Ute
    Associations between general and abdominal adiposity and mortality in individuals with diabetes mellitus2011Inngår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 174, nr 1, s. 22-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models.

  • 125. Sluik, Diewertje
    et al.
    Buijsse, Brian
    Muckelbauer, Rebecca
    Kaaks, Rudolf
    Teucher, Birgit
    Johnsen, Nina Fons
    Tjonneland, Anne
    Overvad, Kim
    Ostergaard, Jane Nautrup
    Amiano, Pilar
    Ardanaz, Eva
    Bendinelli, Benedetta
    Pala, Valeria
    Tumino, Rosario
    Ricceri, Fulvio
    Mattiello, Amalia
    Spijkerman, Annemieke M. W.
    Monninkhof, Evelyn M.
    May, Anne M.
    Franks, Paul W.
    Nilsson, Peter M.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Fagherazzi, Guy
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Huerta Castano, Jose Maria
    Gallo, Valentina
    Boeing, Heiner
    Nothlings, Ute
    Physical Activity and Mortality in Individuals With Diabetes Mellitus A Prospective Study and Meta-analysis2012Inngår i: Archives of Internal Medicine, ISSN 0003-9926, E-ISSN 1538-3679, Vol. 172, nr 17, s. 1285-1295Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Background: Physical activity (PA) is considered a cornerstone of diabetes mellitus management to prevent complications, but conclusive evidence is lacking. Methods: This prospective cohort study and meta-analysis of existing studies investigated the association between PA and mortality in individuals with diabetes. In the EPIC study (European Prospective Investigation Into Cancer and Nutrition), a cohort was defined of 5859 individuals with diabetes at baseline. Associations of leisure-time and total PA and walking with cardiovascular disease (CVD) and total mortality were studied using multivariable Cox proportional hazards regression models. Fixed-and random-effects meta-analyses of prospective studies published up to December 2010 were pooled with inverse variance weighting. Results: In the prospective analysis, total PA was associated with lower risk of CVD and total mortality. Compared with physically inactive persons, the lowest mortality risk was observed in moderately active persons: hazard ratios were 0.62 (95% CI, 0.49-0.78) for total mortality and 0.51 (95% CI, 0.32-0.81) for CVD mortality. Leisure-time PA was associated with lower total mortality risk, and walking was associated with lower CVD mortality risk. In the meta-analysis, the pooled random-effects hazard ratio from 5 studies for high vs low total PA and all-cause mortality was 0.60 (95% CI, 0.49-0.73). Conclusions: Higher levels of PA were associated with lower mortality risk in individuals with diabetes. Even those undertaking moderate amounts of activity were at appreciably lower risk for early death compared with inactive persons. These findings provide empirical evidence supporting the widely shared view that persons with diabetes should engage in regular PA.

  • 126. Sluik, Diewertje
    et al.
    Jankovic, Nicole
    O'Doherty, Mark G.
    Geelen, Anouk
    Schöttker, Ben
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Kiefte-de Jong, Jessica C.
    Ferrieres, Jean
    Bamia, Christina
    Fransen, Heidi P.
    Boer, Jolanda M. A.
    Eriksson, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Martinez, Begoña
    María Huerta, José
    Kromhout, Daan
    de Groot, Lisette C. P. G. M.
    Franco, Oscar H.
    Trichopoulou, Antonia
    Boffetta, Paolo
    Kee, Frank
    Feskens, Edith J. M.
    Alcoholic Beverage Preference and Dietary Habits in Elderly across Europe: Analyses within the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) Project2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 8, artikkel-id e0161603Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: The differential associations of beer, wine, and spirit consumption on cardiovascular risk found in observational studies may be confounded by diet. We described and compared dietary intake and diet quality according to alcoholic beverage preference in European elderly. Methods: From the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES), seven European cohorts were included, i.e. four sub-cohorts from EPIC-Elderly, the SENECA Study, the Zutphen Elderly Study, and the Rotterdam Study. Harmonized data of 29,423 elderly participants from 14 European countries were analyzed. Baseline data on consumption of beer, wine, and spirits, and dietary intake were collected with questionnaires. Diet quality was assessed using the Healthy Diet Indicator (HDI). Intakes and scores across categories of alcoholic beverage preference (beer, wine, spirit, no preference, non-consumers) were adjusted for age, sex, socio-economic status, self-reported prevalent diseases, and lifestyle factors. Cohort-specific mean intakes and scores were calculated as well as weighted means combining all cohorts. Results: In 5 of 7 cohorts, persons with a wine preference formed the largest group. After multivariate adjustment, persons with a wine preference tended to have a higher HDI score and intake of healthy foods in most cohorts, but differences were small. The weighted estimates of all cohorts combined revealed that non-consumers had the highest fruit and vegetable intake, followed by wine consumers. Non-consumers and persons with no specific preference had a higher HDI score, spirit consumers the lowest. However, overall diet quality as measured by HDI did not differ greatly across alcoholic beverage preference categories. Discussion: This study using harmonized data from ~30,000 elderly from 14 European countries showed that, after multivariate adjustment, dietary habits and diet quality did not differ greatly according to alcoholic beverage preference.

  • 127. Spijkerman, Annemieke M. W.
    et al.
    van der A, Daphne L.
    Nilsson, Peter M.
    Ardanaz, Eva
    Gavrila, Diana
    Agudo, Antonio
    Arriola, Larraitz
    Balkau, Beverley
    Beulens, Joline W.
    Boeing, Heiner
    de Lauzon-Guillain, Blandine
    Fagherazzi, Guy
    Feskens, Edith J. M.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Grioni, Sara
    Huerta, Jose Maria
    Kaaks, Rudolf
    Key, Timothy J.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Redondo, M. Luisa
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Roswal, Nina
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schulze, Matthias B.
    Slimani, Nadia
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Langenberg, Claudia
    Sharp, Stephen J.
    Forouhi, Nita G.
    Riboli, Elio
    Wareham, Nicholas J.
    Smoking and Long-Term Risk of Type 2 Diabetes: The EPIC-InterAct Study in European Populations2014Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, nr 12, s. 3164-3171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE

    The aims of this study were to investigate the association between smoking and incident type 2 diabetes, accounting for a large number of potential confounding factors, and to explore potential effect modifiers and intermediate factors.

    RESEARCH DESIGN AND METHODS

    The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct is a prospective case-cohort study within eight European countries, including 12,403 cases of incident type 2 diabetes and a random subcohort of 16,835 individuals. After exclusion of individuals with missing data, the analyses included 10,327 cases and 13,863 subcohort individuals. Smoking status was used (never, former, current), with never smokers as the reference. Country-specific Prentice-weighted Cox regression models and random-effects meta-analysis were used to estimate hazard ratios (HRs) for type 2 diabetes.

    RESULTS

    In men, the HRs (95% CI) of type 2 diabetes were 1.40 (1.26, 1.55) for former smokers and 1.43 (1.27, 1.61) for current smokers, independent of age, education, center, physical activity, and alcohol, coffee, and meat consumption. In women, associations were weaker, with HRs (95% CI) of 1.18 (1.07, 1.30) and 1.13 (1.03, 1.25) for former and current smokers, respectively. There was some evidence of effect modification by BMI. The association tended to be slightly stronger in normal weight men compared with those with overall adiposity.

    CONCLUSIONS

    Former and current smoking was associated with a higher risk of incident type 2 diabetes compared with never smoking in men and women, independent of educational level, physical activity, alcohol consumption, and diet. Smoking may be regarded as a modifiable risk factor for type 2 diabetes, and smoking cessation should be encouraged for diabetes prevention.

  • 128. Surendran, Praveen
    et al.
    Drenos, Fotios
    Young, Robin
    Warren, Helen
    Cook, James P.
    Manning, Alisa K.
    Grarup, Niels
    Sim, Xueling
    Barnes, Daniel R.
    Witkowska, Kate
    Staley, James R.
    Tragante, Vinicius
    Tukiainen, Taru
    Yaghootkar, Hanieh
    Masca, Nicholas
    Freitag, Daniel F.
    Ferreira, Teresa
    Giannakopoulou, Olga
    Tinker, Andrew
    Harakalova, Magdalena
    Mihailov, Evelin
    Liu, Chunyu
    Kraja, Aldi T.
    Nielsen, Sune Fallgaard
    Rasheed, Asif
    Samue, Maria
    Zhao, Wei
    Bonnycastle, Lori L.
    Jackson, Anne U.
    Narisu, Narisu
    Swift, Amy J.
    Southam, Lorraine
    Marten, Jonathan
    Huyghe, Jeroen R.
    Stancakova, Alena
    Fava, Cristiano
    Ohlsson, Therese
    Matchan, Angela
    Stirrups, Kathleen E.
    Bork-Jensen, Jette
    Gjesing, Anette P.
    Kontto, Jukka
    Perola, Markus
    Shaw-Hawkins, Susan
    Havulinna, Aki S.
    Zhang, He
    Donnelly, Louise A.
    Groves, Christopher J.
    Rayner, N. William
    Neville, Matt J.
    Robertson, Neil R.
    Yiorkas, Andrianos M.
    Herzig, Karl-Heinz
    Kajantie, Eero
    Zhang, Weihua
    Willems, Sara M.
    Lannfelt, Lars
    Malerba, Giovanni
    Soranzo, Nicole
    Trabetti, Elisabetta
    Verweij, Niek
    Evangelou, Evangelos
    Moayyeri, Alireza
    Vergnaud, Anne-Claire
    Nelson, Christopher P.
    Poveda, Alaitz
    Varga, Tibor V.
    Caslake, Muriel
    de Craen, Anton J. M.
    Trompet, Stella
    Luan, Jian'an
    Scott, Robert A.
    Harris, Sarah E.
    Liewald, David C. M.
    Marioni, Riccardo
    Menni, Cristina
    Farmaki, Aliki-Eleni
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Huffman, Jennifer E.
    Hassinen, Maija
    Burgess, Stephen
    Vasan, Ramachandran S.
    Felix, Janine F.
    Uria-Nickelsen, Maria
    Malarstign, Anders
    Reilly, Dermot F.
    Hoek, Maarten
    Vogt, Thomas F.
    Lin, Honghuang
    Lieb, Wolfgang
    Traylor, Matthew
    Markus, Hugh S.
    Highland, Heather M.
    Justice, Anne E.
    Marouli, Eirini
    Lindstrom, Jaana
    Uusitupa, Matti
    Komulainen, Pirjo
    Lakka, Timo A.
    Rauramaa, Rainer
    Polasek, Ozren
    Rudan, Igor
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
    Dedoussis, George
    Spector, Timothy D.
    Jousilahti, Pekka
    Mannisto, Satu
    Deary, Ian J.
    Starr, John M.
    Langenberg, Claudia
    Wareham, Nick J.
    Brown, Morris J.
    Dominiczak, Anna F.
    Connell, John M.
    Jukema, J. Wouter
    Sattar, Naveed
    Ford, Ian
    Packard, Chris J.
    Esko, Tonu
    Magi, Reedik
    Metspalu, Andres
    de Boer, Rudolf A.
    van der Meer, Peter
    van der Harst, Pim
    Gambaro, Giovanni
    Ingelsson, Erik
    Lind, Lars
    de Bakker, Paul I. W.
    Numans, Mattijs E.
    Brandslund, Ivan
    Christensen, Cramer
    Petersen, Eva R. B.
    Korpi-Hyovalti, Eeva
    Oksa, Heikki
    Chambers, John C.
    Kooner, Jaspal S.
    Blakemore, Alexandra I. F.
    Franks, Steve
    Jarvelin, Marjo-Riitta
    Husemoen, Lise L.
    Linneberg, Allan
    Skaaby, Tea
    Thuesen, Betina
    Karpe, Fredrik
    Tuomilehto, Jaakko
    Doney, Alex S. F.
    Morris, Andrew D.
    Palmer, Colin N. A.
    Holmen, Oddgeir Lingaas
    Hveem, Kristian
    Willer, Cristen J.
    Tuomi, Tiinamaija
    Groop, Leif
    Karajamaki, AnneMari
    Palotie, Aarno
    Ripatti, Samuli
    Salomaa, Veikko
    Alam, Dewan S.
    Majmnder, Abdulla Al Shafi
    Di Angelantonio, Emanuele
    Chowdhury, Rajiv
    McCarthy, Mark I.
    Poulter, Neil
    Stanton, Alice V.
    Sever, Peter
    Amouyel, Philippe
    Arveiler, Dominique
    Blankenberg, Stefan
    Ferrieres, Jean
    Kee, Frank
    Kuulasmaa, Kari
    Muller-Nurasyid, Martina
    Veronesi, Giovanni
    Virtamo, Jarmo
    Deloukas, Panos
    Elliott, Paul
    Zeggini, Eleftheria
    Kathiresan, Sekar
    Melander, Olle
    Kuusisto, Johanna
    Laakso, Markku
    Padmanabhan, Sandosh
    Porteous, David J.
    Hayward, Caroline
    Scotland, Generation
    Collins, Francis S.
    Mohlke, Karen L.
    Hansen, Torben
    Pedersen, Oluf
    Boehnke, Michael
    Stringham, Heather M.
    Frossard, Philippe
    Newton-Cheh, Christopher
    Tobin, Martin D.
    Nordestgaard, Borge Gronne
    Caulfield, Mark J.
    Mahajan, Anubha
    Morris, Andrew P.
    Tomaszewski, Maciej
    Samani, Nilesh J.
    Saleheen, Danish
    Asselbergs, Folkert W.
    Lindgren, Cecilia M.
    Danesh, John
    Wain, Louise V.
    Butterworth, Adam S.
    Howson, Joanna M. M.
    Munroe, Patricia B.
    Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension2016Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, nr 10, s. 1151-1161Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192,763 individuals and used similar to 155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

  • 129.
    Tornevi, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Sommar, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Rantakokko, Panu
    Åkesson, Agneta
    Donat-Vargas, Carolina
    Kiviranta, Hannu
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rylander, Lars
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Chlorinated persistent organic pollutants and type 2 diabetes - A population-based study with pre- and post- diagnostic plasma samples2019Inngår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 174, s. 35-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Persistent organic pollutants (POPs) have been associated with type 2 diabetes (T2D), but causality is uncertain.

    OBJECTIVE: Within longitudinal population-based data from northern Sweden, we assessed how POPs associated with T2D prospectively and cross-sectionally, and further investigated factors related to individual changes in POP concentrations.

    METHODS: For 129 case-controls pairs matched by age, sex and date of sampling, plasma concentrations of hexachlorobenzene (HCB), dichlorodiphenyl-dichloroethylene (p,p'-DDE), dioxin-like (DL) polychlorinated biphenyl congeners (PCB-118 and PCB-156), and non-dioxin like (NDL-PCB: PCB-74, -99, -138 -153, -170, -180, -183 and PCB-187) were analyzed twice (baseline and follow-up, 9-20 years apart). The cases received their T2D diagnose between baseline and follow-up. Prospective (using baseline data) and cross-sectional (using follow-up data) odds ratios (ORs) for T2D on lipid standardized POPs (HCB, p,p'-DDE, ∑DL-PCBs, ∑NDL-PCBs) were estimated using conditional logistic regression, adjusting for body mass index (BMI) and plasma lipids. The influence of BMI, weight-change, and plasma lipids on longitudinal changes in POP concentrations were evaluated among non-diabetic individuals (n = 306).

    RESULTS: POPs were associated with T2D in both the prospective and cross-sectional assessments. Of a standard deviation increase in POPs, prospective ORs ranged 1.42 (95% CI: 0.99, 2.06) for ∑NDL-PCBs to 1.55 (95% CI: 1.01, 2.38) for HCB (p < 0.05 only for HCB), and cross-sectional ORs ranged 1.62 (95% CI: 1.13; 2.32) for p,p'-DDE to 2.06 (95% CI: 1.29, 3.28) for ∑DL-PCBs (p < 0.05 for all POPs). In analyses of non-diabetic individuals, higher baseline BMI, decreased weight and decreased plasma lipid concentrations were associated with a slower decrease of POPs. Cases had, besides a higher BMI, reduced cholesterol and weight gain at follow-up compared to controls, which can explain the higher ORs in the cross-sectional assessments.

    DISCUSSION: The association between POPs and T2D was confirmed, but an indication that individuals body fat history might influence POP-T2D associations weakens the epidemiological support for a causal association. It also warrants studies based on other exposure metrics than biomonitoring. In addition, we note that a cross-sectional design overestimates the ORs if T2D cases have successfully intervened on weight and/or blood lipids, as changes in these factors cause changes in POPs.

  • 130. Turcot, Valerie
    et al.
    Lu, Yingchang
    Highland, Heather M.
    Schurmann, Claudia
    Justice, Anne E.
    Fine, Rebecca S.
    Bradfield, Jonathan P.
    Esko, Tonu
    Giri, Ayush
    Graff, Mariaelisa
    Guo, Xiuqing
    Hendricks, Audrey E.
    Karaderi, Tugce
    Lempradl, Adelheid
    Locke, Adam E.
    Mahajan, Anubha
    Marouli, Eirini
    Sivapalaratnam, Suthesh
    Young, Kristin L.
    Alfred, Tamuno
    Feitosa, Mary F.
    Masca, Nicholas G. D.
    Manning, Alisa K.
    Medina-Gomez, Carolina
    Mudgal, Poorva
    Ng, Maggie C. Y.
    Reiner, Alex P.
    Vedantam, Sailaja
    Willems, Sara M.
    Winkler, Thomas W.
    Abecasis, Goncalo
    Aben, Katja K.
    Alam, Dewan S.
    Alharthi, Sameer E.
    Allison, Matthew
    Amouyel, Philippe
    Asselbergs, Folkert W.
    Auer, Paul L.
    Balkau, Beverley
    Bang, Lia E.
    Barroso, Ines
    Bastarache, Lisa
    Benn, Marianne
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bork-Jensen, Jette
    Bots, Michiel L.
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Breen, Gerome
    Brilliant, Murray H.
    Broer, Linda
    Brumat, Marco
    Burt, Amber A.
    Butterworth, Adam S.
    Campbell, Peter T.
    Cappellani, Stefania
    Carey, David J.
    Catamo, Eulalia
    Caulfield, Mark J.
    Chambers, John C.
    Chasman, Daniel I.
    Chen, Yii-Der I.
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audrey Y.
    Cocca, Massimiliano
    Collins, Francis S.
    Cook, James P.
    Corley, Janie
    Galbany, Jordi Corominas
    Cox, Amanda J.
    Crosslin, David S.
    Cuellar-Partida, Gabriel
    D'Eustacchio, Angela
    Danesh, John
    Davies, Gail
    Bakker, Paul I. W.
    Groot, Mark C. H.
    Mutsert, Renee
    Deary, Ian J.
    Dedoussis, George
    Demerath, Ellen W.
    Heijer, Martin
    Hollander, Anneke I.
    Ruijter, Hester M.
    Dennis, Joe G.
    Denny, Josh C.
    Angelantonio, Emanuele
    Drenos, Fotios
    Du, Mengmeng
    Dube, Marie-Pierre
    Dunning, Alison M.
    Easton, Douglas F.
    Edwards, Todd L.
    Ellinghaus, David
    Ellinor, Patrick T.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Farooqi, I. Sadaf
    Faul, Jessica D.
    Fauser, Sascha
    Feng, Shuang
    Ferrannini, Ele
    Ferrieres, Jean
    Florez, Jose C.
    Ford, Ian
    Fornage, Myriam
    Franco, Oscar H.
    Franke, Andre
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Friedrich, Nele
    Frikke-Schmidt, Ruth
    Galesloot, Tessel E.
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Gibson, Jane
    Giedraitis, Vilmantas
    Gjesing, Anette P.
    Gordon-Larsen, Penny
    Gorski, Mathias
    Grabe, Hans-Joergen
    Grant, Struan F. A.
    Grarup, Niels
    Griffiths, Helen L.
    Grove, Megan L.
    Gudnason, Vilmundur
    Gustafsson, Stefan
    Haessler, Jeff
    Hakonarson, Hakon
    Hammerschlag, Anke R.
    Hansen, Torben
    Harris, Kathleen Mullan
    Harris, Tamara B.
    Hattersley, Andrew T.
    Have, Christian T.
    Hayward, Caroline
    He, Liang
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Heid, Iris M.
    Helgeland, Oyvind
    Hernesniemi, Jussi
    Hewitt, Alex W.
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hu, Yao
    Huang, Paul L.
    Huffman, Jennifer E.
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Research Unit Skellefteå, Skellefteå, Sweden.
    Jarvik, Gail P.
    Jensen, Gorm B.
    Jia, Yucheng
    Johansson, Stefan
    Jorgensen, Marit E.
    Jorgensen, Torben
    Jukema, J. Wouter
    Kahali, Bratati
    Kahn, Rene S.
    Kahonen, Mika
    Kamstrup, Pia R.
    Kanoni, Stavroula
    Kaprio, Jaakko
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kathiresan, Sekar
    Kee, Frank
    Kiemeney, Lambertus A.
    Kim, Eric
    Kitajima, Hidetoshi
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kooperberg, Charles
    Korhonen, Tellervo
    Kovacs, Peter
    Kuivaniemi, Helena
    Kutalik, Zoltan
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo A.
    Lamparter, David
    Lange, Ethan M.
    Lange, Leslie A.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, Nanette R.
    Lehtimaki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    Li-Gao, Ruifang
    Lin, Honghuang
    Lin, Keng-Hung
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstrom, Jaana
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Dajiang J.
    Liu, Yongmei
    Lo, Ken S.
    Lophatananon, Artitaya
    Lotery, Andrew J.
    Loukola, Anu
    Luan, Jian'an
    Lubitz, Steven A.
    Lyytikainen, Leo-Pekka
    Mannisto, Satu
    Marenne, Gaelle
    Mazul, Angela L.
    McCarthy, Mark I.
    McKean-Cowdin, Roberta
    Medland, Sarah E.
    Meidtner, Karina
    Milani, Lili
    Mistry, Vanisha
    Mitchell, Paul
    Mohlke, Karen L.
    Moilanen, Leena
    Moitry, Marie
    Montgomery, Grant W.
    Mook-Kanamori, Dennis O.
    Moore, Carmel
    Mori, Trevor A.
    Morris, Andrew D.
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Nalls, Mike A.
    Narisu, Narisu
    Nelson, Christopher P.
    Neville, Matt
    Nielsen, Sune F.
    Nikus, Kjell
    Njolstad, Pal R.
    Nordestgaard, Borge G.
    Nyholt, Dale R.
    O'Connel, Jeffrey R.
    O'Donoghue, Michelle L.
    Loohuis, Loes M. Olde
    Ophoff, Roel A.
    Owen, Katharine R.
    Packard, Chris J.
    Padmanabhan, Sandosh
    Palmer, Colin N. A.
    Palmer, Nicholette D.
    Pasterkamp, Gerard
    Patel, Aniruddh P.
    Pattie, Alison
    Pedersen, Oluf
    Peissig, Peggy L.
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    Perry, James A.
    Perry, John R. B.
    Pers, Tune H.
    Person, Thomas N.
    Peters, Annette
    Petersen, Eva R. B.
    Peyser, Patricia A.
    Pirie, Ailith
    Polasek, Ozren
    Polderman, Tinca J.
    Puolijoki, Hannu
    Raitakari, Olli T.
    Rasheed, Asif
    Rauramaa, Rainer
    Reilly, Dermot F.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rheinberger, Myriam
    Ridker, Paul M.
    Rioux, John D.
    Rivas, Manuel A.
    Roberts, David J.
    Robertson, Neil R.
    Robino, Antonietta
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Sapkota, Yadav
    Sattar, Naveed
    Schoen, Robert E.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo P.
    Shah, Svati H.
    Sheu, Wayne H. -H.
    Sim, Xueling
    Slater, Andrew J.
    Small, Kerrin S.
    Smith, Albert V.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Starr, John M.
    Stefansson, Kari
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Strauch, Konstantin
    Stringham, Heather M.
    Stumvoll, Michael
    Sun, Liang
    Surendran, Praveen
    Swift, Amy J.
    Tada, Hayato
    Tansey, Katherine E.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Tromp, Gerard
    Trompet, Stella
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Tybjaerg-Hansen, Anne
    Tyrer, Jonathan P.
    Uher, Rudolf
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Laan, Sander W.
    Duijn, Cornelia M.
    Leeuwen, Nienke
    van Setten, Jessica
    Vanhala, Mauno
    Varbo, Anette
    Varga, Tibor V.
    Varma, Rohit
    Edwards, Digna R. Velez
    Vermeulen, Sita H.
    Veronesi, Giovanni
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Voelker, Uwe
    Vuckovic, Dragana
    Wagenknecht, Lynne E.
    Walker, Mark
    Wallentin, Lars
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wang, Yiqin
    Ware, Erin B.
    Wareham, Nicholas J.
    Warren, Helen R.
    Waterworth, Dawn M.
    Wessel, Jennifer
    White, Harvey D.
    Willer, Cristen J.
    Wilson, James G.
    Witte, Daniel R.
    Wood, Andrew R.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Yao, Pang
    Yerges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zhou, Wei
    Zondervan, Krina T.
    Rotter, Jerome I.
    Pospisilik, John A.
    Rivadeneira, Fernando
    Borecki, Ingrid B.
    Deloukas, Panos
    Frayling, Timothy M.
    Lettre, Guillaume
    North, Kari E.
    Lindgren, Cecilia M.
    Hirschhorn, Joel N.
    Loos, Ruth J. F.
    Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity2018Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 1, s. 26-41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

  • 131. van den Berg, Saskia W.
    et al.
    van der A, Daphne L.
    Spijkerman, Annemieke M. W.
    van Woudenbergh, Geertruida J.
    Tijhuis, Mariken J.
    Amiano, Pilar
    Ardanaz, Eva
    Beulens, Joline W. J.
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Crowe, Francesca L.
    de Lauzon-Guillain, Blandine
    Fagherazzi, Guy
    Franks, Paul W.
    Freisling, Heinz
    Gonzalez, Carlos
    Grioni, Sara
    Halkjaer, Jytte
    Maria Huerta, Jose
    Huybrechts, Inge
    Kaaks, Rudolf
    Khaw, Kay Tee
    Masala, Giovanna
    Nilsson, Peter M.
    Overvad, Kim
    Panico, Salvatore
    Ramon Quiros, J.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schulze, Matthias B.
    Slimani, Nadia
    Struijk, Ellen A.
    Tjonneland, Anne
    Tumino, Rosario
    Sharp, Stephen J.
    Langenberg, Claudia
    Forouhi, Nita G.
    Feskens, Edith J. M.
    Riboli, Elio
    Wareham, Nicholas J.
    The Association between Dietary Energy Density and Type 2 Diabetes in Europe: Results from the EPIC-InterAct Study2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 5, s. e59947-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited evidence exists. Therefore, we investigated the association between DED and risk of T2D in a large prospective study with heterogeneity of dietary intake.

    Methodology/Principal Findings: A case-cohort study was nested within the European Prospective Investigation into Cancer (EPIC) study of 340,234 participants contributing 3.99 million person years of follow-up, identifying 12,403 incident diabetes cases and a random subcohort of 16,835 individuals from 8 European countries. DED was calculated as energy (kcal) from foods (except beverages) divided by the weight (gram) of foods estimated from dietary questionnaires. Prentice-weighted Cox proportional hazard regression models were fitted by country. Risk estimates were pooled by random effects meta-analysis and heterogeneity was evaluated. Estimated mean (sd) DED was 1.5 (0.3) kcal/g among cases and subcohort members, varying across countries (range 1.4-1.7 kcal/g). After adjustment for age, sex, smoking, physical activity, alcohol intake, energy intake from beverages and misreporting of dietary intake, no association was observed between DED and T2D (HR 1.02 (95% CI: 0.93-1.13), which was consistent across countries (l(2) = 2.9%).

    Conclusions/Significance: In this large European case-cohort study no association between DED of solid and semi-solid foods and risk of T2D was observed. However, despite the fact that there currently is no conclusive evidence for an association between DED and T2DM risk, choosing low energy dense foods should be promoted as they support current WHO recommendations to prevent chronic diseases.

  • 132. van Nielen, Monique
    et al.
    Feskens, Edith J. M.
    Mensink, Marco
    Sluijs, Ivonne
    Molina, Esther
    Amiano, Pilar
    Ardanaz, Eva
    Balkau, Beverly
    Beulens, Joline W. J.
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Franks, Paul W.
    Halkjaer, Jytte
    Maria Huerta, Jose
    Katzke, Verena
    Key, Timothy J.
    Khaw, Kay Tee
    Krogh, Vittorio
    Kuhn, Tilman
    Menendez, Virginia V. M.
    Nilsson, Peter
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Romieu, Isabelle
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schulze, Matthias B.
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tumino, Rosario
    Daphne, L. van der A.
    Wurtz, Anne M. L.
    Zamora-Ros, Raul
    Langenberg, Claudia
    Sharp, Stephen J.
    Forouhi, Nita G.
    Riboli, Elio
    Wareham, Nicholas J.
    Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study2014Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, nr 7, s. 1854-1862Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from eight European countries, with an average follow-up time of 12.0 years. Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake. RESULTS: After adjustment for important diabetes risk factors and dietary factors, the incidence of type 2 diabetes was higher in those with high intake of total protein (per 10 g: HR 1.06 [95% CI 1.02-1.09], P-trend < 0.001) and animal protein (per 10 g: 1.05 [1.02-1.08], P-trend = 0.001). Effect modification by sex (P < 0.001) and BMI among women (P < 0.001) was observed. Compared with the overall analyses, associations were stronger in women, more specifically obese women with a BMI > 30 kg/m(2) (per 10 g animal protein: 1.19 [1.09-1.32]), and nonsignificant in men. Plant protein intake was not associated with type 2 diabetes (per 10 g: 1.04 [0.93-1.16], P-trend = 0.098). CONCLUSIONS: High total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults. In view of the rapidly increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered.

  • 133. van Woudenbergh, Geertruida J.
    et al.
    Kuijsten, Anneleen
    Drogan, Dagmar
    van der A, Daphne L.
    Romaguera, Dora
    Ardanaz, Eva
    Amiano, Pilar
    Barricarte, Aurelio
    Beulens, Joline W. J.
    Boeing, Heiner
    Bueno-de-Mesquita, H. Bas
    Dahm, Christina C.
    Chirlaque, M-Doleres
    Clavel, Fran-coise
    Crowe, Francesca L.
    Eomois, Piia-Piret
    Fagher-azzi, Guy
    Franks, Paul W.
    Halkjaer, Jytte
    Khaw, Kay T.
    Masala, Giovanna
    Mattiello, Amalia
    Nilsson, Peter
    Overvad, Kim
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Romieu, Isabelle
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schulze, Matthias B.
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke M. W.
    Tagliabue, Giovanna
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    Forouhi, Nita G.
    Sharp, Stephen
    Langenberg, Claudia
    Feskens, Edith J. M.
    Riboli, Elio
    Wareham, Nicholas J.
    Tea Consumption and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 5, s. e36910-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In previous meta-analyses, tea consumption has been associated with lower incidence of type 2 diabetes. It is unclear, however, if tea is associated inversely over the entire range of intake. Therefore, we investigated the association between tea consumption and incidence of type 2 diabetes in a European population. Methodology/Principal Findings: The EPIC-InterAct case-cohort study was conducted in 26 centers in 8 European countries and consists of a total of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,835 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Country-specific Hazard Ratios (HR) for incidence of type 2 diabetes were obtained after adjustment for lifestyle and dietary factors using a Cox regression adapted for a case-cohort design. Subsequently, country-specific HR were combined using a random effects meta-analysis. Tea consumption was studied as categorical variable (0, >0-<1, 1-<4, >= 4 cups/day). The dose-response of the association was further explored by restricted cubic spline regression. Country specific medians of tea consumption ranged from 0 cups/day in Spain to 4 cups/day in United Kingdom. Tea consumption was associated inversely with incidence of type 2 diabetes; the HR was 0.84 [95% CI 0.71, 1.00] when participants who drank >= 4 cups of tea per day were compared with non-drinkers (p(linear) (trend) = 0.04). Incidence of type 2 diabetes already tended to be lower with tea consumption of 1-<4 cups/day (HR = 0.93 [95% CI 0.81, 1.05]). Spline regression did not suggest a non-linear association (p(non-linearity) = 0.20). Conclusions/Significance: A linear inverse association was observed between tea consumption and incidence of type 2 diabetes. People who drink at least 4 cups of tea per day may have a 16% lower risk of developing type 2 diabetes than non-tea drinkers.

  • 134. Vissers, Linda E. T.
    et al.
    Sluijs, Ivonne
    van der Schouw, Yvonne T.
    Forouhi, Nita G.
    Imamura, Fumiaki
    Burgess, Stephen
    Barricarte, Aurelio
    Boeing, Heiner
    Bonet, Catalina
    Chirlaque, Maria-Dolores
    Fagherazzi, Guy
    Franks, Paul W.
    Freisling, Heinz
    Gunter, Marc J.
    Ramón Quirós, J.
    Ibsen, Daniel B.
    Kaaks, Rudolf
    Key, Timothy
    Khaw, Kay T.
    Kühn, Tilman
    Mokoroa, Olatz
    Nilsson, Peter M.
    Overvad, Kim
    Pala, Valeria
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tumino, Rosario
    Rodríguez-Barranco, Miguel
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Riboli, Elio
    Sharp, Stephen J.
    Langenberg, Claudia
    Wareham, Nicholas J.
    Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study2019Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, nr 4, s. 568-575Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE To estimate the causal association between intake of dairy products and incident type 2 diabetes.

    RESEARCH DESIGN AND METHODS The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression.

    RESULTS Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6–23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0–4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β −7.0 g/day, 95% CI −12.4 to −1.7 per additional LP allele), nonalcoholic beverages (β −18.0 g/day, 95% CI −34.4 to −1.6), and wine (β −4.8 g/day, 95% CI −9.1 to −0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 15 g/day 0.99, 95% CI 0.93–1.05).

    CONCLUSIONS rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.

  • 135.
    Wennberg, Patrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Jerden, Lars
    Boeing, Heiner
    Sluik, Diewertje
    Kaaks, Rudolf
    Teucher, Birgit
    Spijkerman, Annemieke
    de Mesquita, Bas Bueno
    Dethlefsen, Claus
    Nilsson, Peter
    Noethlings, Ute
    Self-rated health and mortality in individuals with diabetes mellitus: prospective cohort study2012Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, nr 1, s. e000760-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To investigate whether low self-rated health (SRH) is associated with increased mortality in individuals with diabetes.

    Design: Population-based prospective cohort study. Setting: Enrolment took place between 1992 and 2000 in four centres (Bilthoven, Heidelberg, Potsdam, Umea) in a subcohort nested in the European Prospective Investigation into Cancer and Nutrition.

    Participants: 3257 individuals (mean +/- SD age was 55.8 +/- 7.6 years and 42% women) with confirmed diagnosis of diabetes mellitus.

    Primary outcome measure: The authors used Cox proportional hazards modelling to estimate HRs for total mortality controlling for age, centre, sex, educational level, body mass index, physical inactivity, smoking, insulin treatment, hypertension, hyperlipidaemia and history of myocardial infarction, stroke or cancer.

    Results: During follow-up (mean follow-up +/- SD was 8.6 +/- 2.3 years), 344 deaths (241 men/103 women) occurred. In a multivariate model, individuals with low SRH were at higher risk of mortality (HR 1.38, 95% CI 1.10 to 1.73) than those with high SRH. The association was mainly driven by increased 5-year mortality and was stronger among individuals with body mass index of <25 kg/m(2) than among obese individuals. In sex-specific analyses, the association was statistically significant in men only. There was no indication of heterogeneity across centres.

    Conclusions: Low SRH was associated with increased mortality in individuals with diabetes after controlling for established risk factors. In patients with diabetes with low SRH, the physician should consider a more detailed consultation and intensified support.

  • 136.
    Wennberg, Patrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    van der A, Daphne L.
    Spijkerman, Annemieke M. W.
    Kaaks, Rudolf
    Boeing, Heiner
    Feller, Silke
    Bergmann, Manuela M.
    Langenberg, Claudia
    Sharp, Stephen J.
    Forouhi, Nita
    Riboli, Elio
    Wareham, Nicholas
    Self-rated health and type 2 diabetes risk in the European Prospective Investigation into Cancer and Nutrition-InterAct study: a case-cohort study2013Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 3, nr 3, s. e002436-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives:

    To investigate the association between self-rated health and risk of type 2 diabetes and whether the strength of this association is consistent across five European centres.

    Design: Population-based prospective case-cohort study.

    Setting: Enrolment took place between 1992 and 2000 in five European centres (Bilthoven, Cambridge, Heidelberg, Potsdam and Umea).

    Participants: Self-rated health was assessed by a baseline questionnaire in 3399 incident type 2 diabetic case participants and a centre-stratified subcohort of 4619 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study which was drawn from a total cohort of 340 234 participants in the EPIC.

    Primary outcome measure: Prentice-weighted Cox regression was used to estimate centre-specific HRs and 95% CIs for incident type 2 diabetes controlling for age, sex, centre, education, body mass index (BMI), smoking, alcohol consumption, energy intake, physical activity and hypertension. The centre-specific HRs were pooled across centres by random effects meta-analysis.

    Results: Low self-rated health was associated with a higher hazard of type 2 diabetes after adjusting for age and sex (pooled HR 1.67, 95% CI 1.48 to 1.88). After additional adjustment for health-related variables including BMI, the association was attenuated but remained statistically significant (pooled HR 1.29, 95% CI 1.09 to 1.53). I-2 index for heterogeneity across centres was 13.3% (p=0.33).

    Conclusions: Low self-rated health was associated with a higher risk of type 2 diabetes. The association could be only partly explained by other health-related variables, of which obesity was the strongest. We found no indication of heterogeneity in the association between self-rated health and type 2 diabetes mellitus across the European centres.

  • 137. Wessel, Jennifer
    et al.
    Chu, Audrey Y.
    Willems, Sara M.
    Wang, Shuai
    Yaghootkar, Hanieh
    Brody, Jennifer A.
    Dauriz, Marco
    Hivert, Marie-France
    Raghavan, Sridharan
    Lipovich, Leonard
    Hidalgo, Bertha
    Fox, Keolu
    Huffman, Jennifer E.
    An, Ping
    Lu, Yingchang
    Rasmussen-Torvik, Laura J.
    Grarup, Niels
    Ehm, Margaret G.
    Li, Li
    Baldridge, Abigail S.
    Stancakova, Alena
    Abrol, Ravinder
    Besse, Celine
    Boland, Anne
    Bork-Jensen, Jette
    Fornage, Myriam
    Freitag, Daniel F.
    Garcia, Melissa E.
    Guo, Xiuqing
    Hara, Kazuo
    Isaacs, Aaron
    Jakobsdottir, Johanna
    Lange, Leslie A.
    Layton, Jill C.
    Li, Man
    Zhao, Jing Hua
    Meidtner, Karina
    Morrison, Alanna C.
    Nalls, Mike A.
    Peters, Marjolein J.
    Sabater-Lleal, Maria
    Schurmann, Claudia
    Silveira, Angela
    Smith, Albert V.
    Southam, Lorraine
    Stoiber, Marcus H.
    Strawbridge, Rona J.
    Taylor, Kent D.
    Varga, Tibor V.
    Allin, Kristine H.
    Amin, Najaf
    Aponte, Jennifer L.
    Aung, Tin
    Barbieri, Caterina
    Bihlmeyer, Nathan A.
    Boehnke, Michael
    Bombieri, Cristina
    Bowden, Donald W.
    Burns, Sean M.
    Chen, Yuning
    Chen, Yii-Deri
    Cheng, Ching-Yu
    Correa, Adolfo
    Czajkowski, Jacek
    Dehghan, Abbas
    Ehret, Georg B.
    Eiriksdottir, Gudny
    Andersson Escher, Stefan
    Farmaki, Aliki-Eleni
    Franberg, Mattias
    Gambaro, Giovanni
    Giulianini, Franco
    Goddard, William A., III
    Goel, Anuj
    Gottesman, Omri
    Grove, Megan L.
    Gustafsson, Stefan
    Hai, Yang
    Hallmans, Goeran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Heo, Jiyoung
    Hoffmann, Per
    Ikram, Mohammad K.
    Jensen, Richard A.
    Jorgensen, Marit E.
    Jorgensen, Torben
    Karaleftheri, Maria
    Khor, Chiea C.
    Kirkpatrick, Andrea
    Kraja, Aldi T.
    Kuusisto, Johanna
    Lange, Ethan M.
    Lee, I. T.
    Lee, Wen-Jane
    Leong, Aaron
    Liao, Jiemin
    Liu, Chunyu
    Liu, Yongmei
    Lindgren, Cecilia M.
    Linneberg, Allan
    Malerba, Giovanni
    Mamakou, Vasiliki
    Marouli, Eirini
    Maruthur, Nisa M.
    Matchan, Angela
    McKean-Cowdin, Roberta
    McLeod, Olga
    Metcalf, Ginger A.
    Mohlke, Karen L.
    Muzny, Donna M.
    Ntalla, Ioanna
    Palmer, Nicholette D.
    Pasko, Dorota
    Peter, Andreas
    Rayner, Nigel W.
    Renstroem, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Rice, Ken
    Sala, Cinzia F.
    Sennblad, Bengt
    Serafetinidis, Ioannis
    Smith, Jennifer A.
    Soranzo, Nicole
    Speliotes, Elizabeth K.
    Stahl, Eli A.
    Stirrups, Kathleen
    Tentolouris, Nikos
    Thanopoulou, Anastasia
    Torres, Mina
    Traglia, Michela
    Tsafantakis, Emmanouil
    Javad, Sundas
    Yanek, Lisa R.
    Zengini, Eleni
    Becker, Diane M.
    Bis, Joshua C.
    Brown, James B.
    Cupples, L. Adrienne
    Hansen, Torben
    Ingelsson, Erik
    Karter, Andrew J.
    Lorenzo, Carlos
    Mathias, Rasika A.
    Norris, Jill M.
    Peloso, Gina M.
    Sheu, Wayne H. -H.
    Toniolo, Daniela
    Vaidya, Dhananjay
    Varma, Rohit
    Wagenknecht, Lynne E.
    Boeing, Heiner
    Bottinger, Erwin P.
    Dedoussis, George
    Deloukas, Panos
    Ferrannini, Ele
    Franco, Oscar H.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gibbs, Richard A.
    Gudnason, Vilmundur
    Hamsten, Anders
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hayward, Caroline
    Hofman, Albert
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Langenberg, Claudia
    Launer, Lenore J.
    Levy, Daniel
    Oostra, Ben A.
    O'Donnell, Christopher J.
    O'Rahilly, Stephen
    Padmanabhan, Sandosh
    Pankow, James S.
    Polasek, Ozren
    Province, Michael A.
    Rich, Stephen S.
    Ridker, Paul M.
    Rudan, Igor
    Schulze, Matthias B.
    Smith, Blair H.
    Uitterlinden, Andre G.
    Walker, Mark
    Watkins, Hugh
    Wong, Tien Y.
    Zeggini, Eleftheria
    Laakso, Markku
    Borecki, Ingrid B.
    Chasman, Daniel I.
    Pedersen, Oluf
    Psaty, Bruce M.
    Tai, E. Shyong
    van Duijn, Cornelia M.
    Wareham, Nicholas J.
    Waterworth, Dawn M.
    Boerwinkle, Eric
    Kao, W. H. Linda
    Florez, Jose C.
    Loos, Ruth J. F.
    Wilson, James G.
    Frayling, Timothy M.
    Siscovick, David S.
    Dupuis, Josee
    Rotter, Jerome I.
    Meigs, James B.
    Scott, Robert A.
    Goodarzi, Mark O.
    Sharp, Stephen J.
    Forouhi, Nita G.
    Kerrison, Nicola D.
    Lucarelli, Debora M. E.
    Sims, Matt
    Barroso, Ines
    McCarthy, Mark I.
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Gonzalez, Carlos
    Grioni, Sara
    Kaaks, Rudolf
    Key, Timothy J.
    Navarro, Carmen
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    van der Schouw, Yvonne T.
    Riboli, Elio
    Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility2015Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikkel-id 5897Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

  • 138. Zamora-Ros, Raul
    et al.
    Forouhi, Nita G.
    Sharp, Stephen J.
    Gonzalez, Carlos A.
    Buijsse, Brian
    Guevara, Marcela
    van der Schouw, Yvonne T.
    Amiano, Pilar
    Boeing, Heiner
    Bredsdorff, Lea
    Fagherazzi, Guy
    Feskens, Edith J.
    Franks, Paul W.
    Grioni, Sara
    Katzke, Verena
    Key, Timothy J.
    Khaw, Kay-Tee
    Kuehn, Tilman
    Masala, Giovanna
    Mattiello, Amalia
    Molina-Montes, Esther
    Nilsson, Peter M.
    Overvad, Kim
    Perquier, Florence
    Luisa Redondo, M.
    Ricceri, Fulvio
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Romieu, Isabelle
    Roswall, Nina
    Scalbert, Augustin
    Schulze, Matthias
    Slimani, Nadia
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Jose Tormo, Maria
    Touillaud, Marina
    Tumino, Rosario
    van der A, Daphne L.
    van Woudenbergh, Geertruida J.
    Langenberg, Claudia
    Riboli, Elio
    Wareham, Nicholas J.
    Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in european populations2014Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 144, nr 3, s. 335-343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile. 0.81; 95% Cl: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% Cl: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% Cl: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.

  • 139. Zheng, Ju-Sheng
    et al.
    Imamura, Fumiaki
    Sharp, Stephen J.
    van der Schouw, Yvonne T.
    Sluijs, Ivonne
    Gundersen, Thomas E.
    Ardanaz, Eva
    Boeing, Heiner
    Bonet, Catalina
    Humberto Gomez, Jesus
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Jenab, Mazda
    Kuehn, Tilman
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay-Tee
    Lasheras, Cristina
    Mokoroa, Olatz
    Mancini, Francesca Romana
    Nilsson, Peter M.
    Overvad, Kim
    Panico, Salvatore
    Palli, Domenico
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sieri, Sabina
    Salamanca-Fernandez, Elena
    Sacerdote, Carlotta
    Spijkerman, Annemieke M. W.
    Stepien, Magdalena
    Tjonneland, Anne
    Tumino, Rosario
    Butterworth, Adam S.
    Riboli, Elio
    Danesh, John
    Langenberg, Claudia
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study2019Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, nr 4, s. 1293-1303Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D.

    Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)–InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography–mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis.

    Results: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)].

    Conclusions: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.

  • 140. Zimmerman, Malin
    et al.
    Enes, Sara Rolandsson
    Skarstrand, Hanna
    Pourhamidi, Kaveh
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Gottsater, Anders
    Wollmer, Per
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Westergren-Thorsson, Gunilla
    Dahlin, Lars B.
    Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes2017Inngår i: Journal of clinical and translational endocrinology, ISSN 2214-6237, Vol. 8, s. 15-21Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system.

    Methods: Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed.

    Results: Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio.

    Conclusions: Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.

  • 141. Zimmerman, Malin
    et al.
    Pourhamidi, Kaveh
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Dahlin, Lars B.
    Autonomic Neuropathy: a Prospective Cohort Study of Symptoms and E/I Ratio in Normal Glucose Tolerance, Impaired Glucose Tolerance, and Type 2 Diabetes2018Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, artikkel-id 154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Autonomic neuropathy in diabetes, in addition to causing a range of symptoms originating from the autonomic nervous system, may increase cardiovascular morbidity. Our aim was to study the progression of autonomic neuropathy, based on symptom score and evaluation of an autonomic test, in persons with normal and impaired glucose tolerance and in patients with type 2 diabetes (T2D).

    Methods: Participants were recruited in 2003/2004 with a follow-up in 2014. The participants' glucose tolerance was categorized using oral glucose tolerance tests. Symptoms were evaluated using an autonomic symptom score (ASS), ECG was used to test cardiac autonomic function based on the expiration/inspiration ratio (E/I ratio), and blood samples were taken on both occasions.

    Results: ASSs were higher at follow-up in the T2D patients than in the normal glucose tolerance group (mean 1.21 +/- 1.30 vs. 0.79 +/- 0.7; p < 0.05). E/I ratio did not deteriorate more than could be expected as an aging effect in well-controlled T2D. No relationship was found between E/I ratio and HbA1c or ASS.

    Conclusion: The presence of autonomic symptoms increased over time in T2D patients, but the symptoms did not correlate with the Ell ratio in this metabolically well-controlled cohort. ASSs can be a useful clinical tool when assessing the progression of autonomic dysfunction in patients with abnormal glucose metabolism.

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