32 results on '"Spijkerman, Annemieke MW"'
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2. Cohort Profile Update: The Doetinchem Cohort Study 1987-2017: lifestyle, health and chronic diseases in a life course and ageing perspective
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Picavet, H SJ, Blokstra, Anneke, Spijkerman, Annemieke MW, and Verschuren, Monique WM
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- 2017
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3. Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study
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Forouhi, Nita G, Koulman, Albert, Sharp, Stephen J, Imamura, Fumiaki, Kröger, Janine, Schulze, Matthias B, Crowe, Francesca L, Huerta, José María, Guevara, Marcela, Beulens, Joline WJ, van Woudenbergh, Geertruida J, Wang, Laura, Summerhill, Keith, Griffin, Julian L, Feskens, Edith JM, Amiano, Pilar, Boeing, Heiner, Clavel-Chapelon, Françoise, Dartois, Laureen, Fagherazzi, Guy, Franks, Paul W, Gonzalez, Carlos, Jakobsen, Marianne Uhre, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Kühn, Tilman, Mattiello, Amalia, Nilsson, Peter M, Overvad, Kim, Pala, Valeria, Palli, Domenico, Quirós, J Ramón, Rolandsson, Olov, Roswall, Nina, Sacerdote, Carlotta, Sánchez, María-José, Slimani, Nadia, Spijkerman, Annemieke MW, Tjonneland, Anne, Tormo, Maria-José, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Langenberg, Claudia, Riboli, Elio, and Wareham, Nicholas J
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- 2014
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4. Non-invasive risk scores for prediction of type 2 diabetes (EPIC-InterAct): a validation of existing models
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Kengne, Andre Pascal, Beulens, Joline WJ, Peelen, Linda M, Moons, Karel GM, van der Schouw, Yvonne T, Schulze, Matthias B, Spijkerman, Annemieke MW, Griffin, Simon J, Grobbee, Diederick E, Palla, Luigi, Tormo, Maria-Jose, Arriola, Larraitz, Barengo, Noël C, Barricarte, Aurelio, Boeing, Heiner, Bonet, Catalina, Clavel-Chapelon, Françoise, Dartois, Laureen, Fagherazzi, Guy, Franks, Paul W, Huerta, José María, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Li, Kuanrong, Mühlenbruch, Kristin, Nilsson, Peter M, Overvad, Kim, Overvad, Thure F, Palli, Domenico, Panico, Salvatore, Quirós, J Ramón, Rolandsson, Olov, Roswall, Nina, Sacerdote, Carlotta, Sánchez, María-José, Slimani, Nadia, Tagliabue, Giovanna, Tjønneland, Anne, Tumino, Rosario, van der A, Daphne L, Forouhi, Nita G, Sharp, Stephen J, Langenberg, Claudia, Riboli, Elio, and Wareham, Nicholas J
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- 2014
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5. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study
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Sluijs, Ivonne, 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, Françoise, Crowe, Francesca L, de Lauzon-Guillain, Blandine, Drogan, Dagmar, Franks, Paul W, Gavrila, Diana, Gonzalez, Carlos, Halkjær, Jytte, Kaaks, Rudolf, Moskal, Aurelie, Nilsson, Peter, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, José R, Ricceri, Fulvio, Rinaldi, Sabina, Rolandsson, Olov, Sacerdote, Carlotta, Sánchez, María-José, Slimani, Nadia, Spijkerman, Annemieke MW, Teucher, Birgit, Tjonneland, Anne, Tormo, María-José, Tumino, Rosario, van der A, Daphne L, Sharp, Stephen J, Langenberg, Claudia, Feskens, Edith JM, Riboli, Elio, and Wareham, Nicholas J
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- 2012
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6. The prospective association between total and type of fish intake and type 2 diabetes in 8 European countries: EPIC-InterAct Study
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Patel, Pinal S, Forouhi, Nita G, Kuijsten, Anneleen, Schulze, Matthias B, van Woudenbergh, Geertruida J, Ardanaz, Eva, Amiano, Pilar, Arriola, Larraitz, Balkau, Beverley, Barricarte, Aurelio, Beulens, Joline WJ, Boeing, Heiner, Buijsse, Brian, Crowe, Francesca L, de Lauzon-Guillan, Blandine, Fagherazzi, Guy, Franks, Paul W, Gonzalez, Carlos, Grioni, Sara, Halkjaer, Jytte, Huerta, José María, Key, Timothy J, Kühn, Tilman, Masala, Giovanna, Nilsson, Peter, Overvad, Kim, Panico, Salvatore, Quirós, Jose Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Sánchez, María-José, Schmidt, Erik B, Slimani, Nadia, Spijkerman, Annemieke MW, Teucher, Birgit, Tjonneland, Anne, Tormo, Maria-Jose, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Sharp, Stephen J, Langenberg, Claudia, Feskens, Edith JM, Riboli, Elio, and Wareham, Nicholas J
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- 2012
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7. Coffee and tea consumption in relation to estimated glomerular filtration rate: results from the population-based longitudinal Doetinchem Cohort Study1
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Herber-Gast, Gerrie-Cor M, van Essen, Hanneke, Verschuren, Monique WM, Stehouwer, Coen DA, Gansevoort, Ron T, Bakker, Stephan JL, and Spijkerman, Annemieke MW
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- 2016
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8. Effect of change in physical activity on body fatness over a 10-y period in the Doetinchem Cohort Study
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May, Anne M, Bueno-de-Mesquita, H Bas, Boshuizen, Hendriek, Spijkerman, Annemieke MW, Peeters, Petra HM, and Verschuren, WM Monique
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- 2010
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9. Anti-Müllerian hormone levels and risk of type 2 diabetes in women
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Verdiesen, Renee MG, primary, Onland-Moret, N Charlotte, additional, van, Gils Carla H, additional, Stellato, Rebecca K, additional, Spijkerman, Annemieke MW, additional, Picavet, H Susan J, additional, Broekmans, Frank JM, additional, Verschuren, WM Monique, additional, and van, der Schouw Yvonne T, additional
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- 2021
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10. Sufficient sleep duration contributes to lower cardiovascular disease risk in addition to four traditional lifestyle factors: the MORGEN study
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Hoevenaar-Blom, Marieke P, Spijkerman, Annemieke MW, Kromhout, Daan, and Verschuren, Monique WM
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- 2014
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11. Todayʼs adult generations are less healthy than their predecessors: generation shifts in metabolic risk factors: the Doetinchem Cohort Study
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Hulsegge, Gerben, J Picavet, Susan H, Blokstra, Anneke, Nooyens, Astrid CJ, Spijkerman, Annemieke MW, van der Schouw, Yvonne T, Smit, Henriëtte A, and Monique Verschuren, W M
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- 2014
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12. Plasma vitamin C and type 2 diabetes: genome-wide association study and Mendelian randomization analysis in European populations
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Zheng, Ju-Sheng, primary, Luan, Jian’an, primary, Sofianopoulou, Eleni, primary, Imamura, Fumiaki, primary, Stewart, Isobel D, primary, Day, Felix R, primary, Pietzner, Maik, primary, Wheeler, Eleanor, primary, Lotta, Luca A, primary, Gundersen, Thomas E., primary, Amiano, Pilar, primary, Ardanaz, Eva, primary, Chirlaque, María-Dolores, primary, Fagherazzi, Guy, primary, Franks, Paul W, primary, Kaaks, Rudolf, primary, Laouali, Nasser, primary, Mancini, Francesca Romana, primary, Nilsson, Peter M, primary, Onland-Moret, N. Charlotte, primary, Olsen, Anja, primary, Overvad, Kim, primary, Panico, Salvatore, primary, Palli, Domenico, primary, Ricceri, Fulvio, primary, Rolandsson, Olov, primary, Spijkerman, Annemieke MW, primary, Sánchez, María-José, primary, Schulze, Matthias B, primary, Sala, Núria, primary, Sieri, Sabina, primary, Tjønneland, Anne, primary, Tumino, Rosario, primary, Schouw, Yvonne T van der, primary, Weiderpass, Elisabete, primary, Riboli, Elio, primary, Danesh, John, primary, Butterworth, Adam S, primary, Sharp, Stephen J, primary, Langenberg, Claudia, primary, Forouhi, Nita G, primary, and Wareham, Nicholas J, primary
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- 2020
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13. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-Inter Act Study1-3
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Sluijs, Ivonne, Forouhi, Nita G, Beulens, Joline WJ, van der Schouw, Yvonne T, Agnoli, Claudia, Arriola, Larraitz, Balkau, Beverley, Barricarte, Aurelio, Boeing, Heiner, Bueno-de-Mesquita, Bas H, Clavel-Chapelon, Françoise, Crowe, Francesca L, de Lauzon-Guillain, Blandine, Drogan, Dagmar, Franks, Paul W, Gavrila, Diana, Gonzalez, Carlos, Halkjær, Jytte, Kaaks, Rudolf, Moskal, Aurelie, Nilsson, Peter, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, José R, Ricceri, Fulvio, Rinaldi, Sabina, Rolandsson, Olov, Sacerdote, Carlotta, Sánchez, María-José, Slimani, Nadia, Spijkerman, Annemieke MW, Teucher, Birgit, Tjonneland, Anne, Tormo, María-José, Tumino, Rosario, van der A, Daphne L, Sharp, Stephen J, Langenberg, Claudia, Feskens, Edith JM, Riboli, Elio, and Wareham, Nicholas J
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- 2012
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14. Erratum. Dietary protein intake and incidence of type 2 diabetes in europe: the EPIC-InterAct case-cohort study. Diabetes Care 2014;37:1854-1862
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Van Nielen, Monique, Feskens, Edith JM, Mensink, Marco, Sluijs, Ivonne, Molina, Esther, Amiano, Pilar, Ardanaz, Eva, Balkau, Beverly, Beulens, Joline WJ, Boeing, Heiner, Clavel-Chapelon, Françoise, Fagherazzi, Guy, Franks, Paul W, Halkjaer, Jytte, Huerta, José Maria, Katzke, Verena, Key, Timothy J, Khaw, Kay Tee, Krogh, Vittorio, Kühn, Tilman, Menéndez, Virginia VM, Nilsson, Peter, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Rolandsson, Olov, Romieu, Isabelle, Sacerdote, Carlotta, Sánchez, Maria-José, Schulze, Matthias B, Spijkerman, Annemieke MW, Tjonneland, Anne, Tumino, Rosario, Van Der A, Daphne L, Würtz, Anne ML, Zamora-Ros, Raul, Langenberg, Claudia, Sharp, Stephen J, Forouhi, Nita G, Riboli, Elio, Wareham, Nicholas J, InterAct Consortium, Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Sharp, Stephen [0000-0003-2375-1440], Forouhi, Nita [0000-0002-5041-248X], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
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InterAct Consortium - Published
- 2018
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15. Association of dietary protein and dairy intakes and change in renal function: results from the population-based longitudinal Doetinchem cohort study ,
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Herber-Gast, Gerrie-Cor M, primary, Biesbroek, Sander, additional, Verschuren, WM Monique, additional, Stehouwer, Coen DA, additional, Gansevoort, Ron T, additional, Bakker, Stephan JL, additional, and Spijkerman, Annemieke MW, additional
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- 2016
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16. Alcohol consumption and risk of type 2 diabetes in European men and women:Influence of beverage type and body sizeThe EPIC-InterAct study
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Beulens, Joline Wj, van der Schouw, Yvonne T, Bergmann, Manuela M, Rohrmann, Sabine, Schulze, Matthias B, Buijsse, Brian, Grobbee, Diederick E, Arriola, Larraitz, Cauchi, Stephane, Tormo, Maria-Jose, Allen, Naomi E, van der, Daphne L, Balkau, Beverly, Boeing, Heiner, Clavel-Chapelon, Françoise, de Lauzon-Guillan, Blandine, Franks, Paul, Froguel, Phillipe, Gonzales, Carlos, Halkjaer, Jytte, Huerta, Jose Maria, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Krogh, Vittorio, Molina-Montes, Esther, Nilsson, Peter, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, Jose Ramón, Ronaldsson, Olov, Romieu, Isabelle, Romaguera, Dora, Sacerdote, Carlotta, Sánchez, María-José, Spijkerman, Annemieke Mw, Teucher, Birgit, Tjonneland, Anne, Tumino, Rosario, Sharpe, Stephen, Forouhi, Nita G, Langenberg, Claudia, Feskens, Edith Jm, Riboli, Elio, Wareham, Nicholas J, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, and APH - Health Behaviors & Chronic Diseases
- Abstract
Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective case-cohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16154 participants and 12403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.78-1.05) for 6.1-12.0 versus 0.1-6.0gday-1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.1-96.0gday-1 with an HR of 0.86 (95% CI: 0.75-0.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.72-0.92) for 6.1-12.0gday-1 (P interaction gender
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- 2012
17. Isocaloric substitution of carbohydrates with protein: the association with weight change and mortality among patients with type 2 diabetes
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Campmans-Kuijpers, Marjo JE, primary, Sluijs, Ivonne, additional, Nöthlings, Ute, additional, Freisling, Heinz, additional, Overvad, Kim, additional, Weiderpass, Elisabete, additional, Fagherazzi, Guy, additional, Kühn, Tilman, additional, Katzke, Verena A, additional, Mattiello, Amalia, additional, Sonestedt, Emily, additional, Masala, Giovanna, additional, Agnoli, Claudia, additional, Tumino, Rosario, additional, Spijkerman, Annemieke MW, additional, Barricarte, Aurelio, additional, Ricceri, Fulvio, additional, Chamosa, Saioa, additional, Johansson, Ingegerd, additional, Winkvist, Anna, additional, Tjønneland, Anne, additional, Sluik, Diewertje, additional, Boeing, Heiner, additional, and Beulens, Joline WJ, additional
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- 2015
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18. Sufficient sleep duration contributes to lower cardiovascular disease risk in addition to four traditional lifestyle factors: the MORGEN study
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Hoevenaar-Blom, Marieke P, primary, Spijkerman, Annemieke MW, additional, Kromhout, Daan, additional, and Verschuren, WM Monique, additional
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- 2013
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19. Today's adult generations are less healthy than their predecessors: generation shifts in metabolic risk factors: the Doetinchem Cohort Study
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Hulsegge, Gerben, primary, Picavet, H Susan J, additional, Blokstra, Anneke, additional, Nooyens, Astrid CJ, additional, Spijkerman, Annemieke MW, additional, van der Schouw, Yvonne T, additional, Smit, Henriëtte A, additional, and Verschuren, WM Monique, additional
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- 2013
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20. Cycling and sports, but not walking, are associated with 10-year cardiovascular disease incidence: the MORGEN Study
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Hoevenaar-Blom, Marieke P, primary, Wendel-Vos, GC Wanda, additional, Spijkerman, Annemieke MW, additional, Kromhout, Daan, additional, and Verschuren, WMM, additional
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- 2010
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21. Cycling and sports, but not walking, are associated with 10-year cardiovascular disease incidence: the MORGEN Study
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Hoevenaar-Blom, Marieke P, Wendel-Vos, GC Wanda, Spijkerman, Annemieke MW, Kromhout, Daan, and Verschuren, WMM
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Background:Physical activity is inversely related to cardiovascular diseases. However, the type of activities that contribute most to these beneficial effects remain unclear. For this reason, we investigated self-reported leisure time physical activities in relation to fatal/nonfatal cardiovascular disease incidence.
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- 2011
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22. Autoimmunity plays a role in the onset of diabetes after 40 years of age
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Rolandsson, Olov, Hampe, Christiane S, Sharp, Stephen J, Ardanaz, Eva, Boeing, Heiner, Fagherazzi, Guy, Mancini, Francesca Romana, Nilsson, Peter M, Overvad, Kim, Chirlaque, Maria-Dolores, Dorronsoro, Miren, Gunter, Marc J, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Krogh, Vittorio, Kühn, Tilman, Palli, Domenico, Panico, Salvatore, Sacerdote, Carlotta, Sánchez, Maria-José, Severi, Gianluca, Spijkerman, Annemieke MW, Tumino, Rosario, Van Der Schouw, Yvonne T, Riboli, Elio, Forouhi, Nita G, Langenberg, Claudia, and Wareham, Nicholas J
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Adult ,Male ,Glutamate Decarboxylase ,Autoimmunity ,Type 2 diabetes ,Middle Aged ,Genetic risk score ,Antibodies ,3. Good health ,Autoantibody ,Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Incident diabetes ,Case-Control Studies ,Humans ,Female ,Aged - Abstract
AIMS/HYPOTHESIS: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
23. Estimated Substitution of Tea or Coffee for Sugar-Sweetened Beverages Was Associated with Lower Type 2 Diabetes Incidence in Case-Cohort Analysis across 8 European Countries in the EPIC-InterAct Study
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Imamura, Fumiaki, Schulze, Matthias B, Sharp, Stephen J, Guevara, Marcela, Romaguera, Dora, Bendinelli, Benedetta, Salamanca-Fernández, Elena, Ardanaz, Eva, Arriola, Larraitz, Aune, Dagfinn, Boeing, Heiner, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Freisling, Heinz, Jakszyn, Paula, Kaaks, Rudolf, Khaw, Kay-Tee, Kühn, Tilman, Mancini, Francesca R, Masala, Giovanna, Chirlaque, Maria-Dolores, Nilsson, Peter M, Overvad, Kim, Pala, Valeria M, Panico, Salvatore, Perez-Cornago, Aurora, Quirós, Jose R, Ricceri, Fulvio, Rodríguez-Barranco, Miguel, Rolandsson, Olov, Sluijs, Ivonne, Stepien, Magdalena, Spijkerman, Annemieke MW, Tjønneland, Anne, Tong, Tammy YN, Tumino, Rosario, Vissers, Linda ET, Ward, Heather A, Langenberg, Claudia, Riboli, Elio, Forouhi, Nita G, and Wareham, Nick J
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2. Zero hunger ,Male ,Sugar-Sweetened Beverages ,beverages ,diabetes ,Tea ,Incidence ,Middle Aged ,Coffee ,3. Good health ,Cohort Studies ,Europe ,Diabetes Mellitus, Type 2 ,Risk Factors ,Case-Control Studies ,Humans ,epidemiology ,Female ,Prospective Studies ,dietary guidelines - Abstract
INTRODUCTION: Beverage consumption is a modifiable risk factor for type 2 diabetes (T2D), but there is insufficient evidence to inform the suitability of substituting 1 type of beverage for another. OBJECTIVE: The aim of this study was to estimate the risk of T2D when consumption of sugar-sweetened beverages (SSBs) was replaced with consumption of fruit juice, milk, coffee, or tea. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study of 8 European countries (n = 27,662, with 12,333 cases of incident T2D, 1992-2007), beverage consumption was estimated at baseline by dietary questionnaires. Using Prentice-weighted Cox regression adjusting for other beverages and potential confounders, we estimated associations of substituting 1 type of beverage for another on incident T2D. RESULTS: Mean ± SD of estimated consumption of SSB was 55 ± 105 g/d. Means ± SDs for the other beverages were as follows: fruit juice, 59 ± 101 g/d; milk, 209 ± 203 g/d; coffee, 381 ± 372 g/d; and tea, 152 ± 282 g/d. Substituting coffee for SSBs by 250 g/d was associated with a 21% lower incidence of T2D (95% CI: 12%, 29%). The rate difference was -12.0 (95% CI: -20.0, -5.0) per 10,000 person-years among adults consuming SSBs ≥250 g/d (absolute rate = 48.3/10,000). Substituting tea for SSBs was estimated to lower T2D incidence by 22% (95% CI: 15%, 28%) or -11.0 (95% CI: -20.0, -2.6) per 10,000 person-years, whereas substituting fruit juice or milk was estimated not to alter T2D risk significantly. CONCLUSIONS: These findings indicate a potential benefit of substituting coffee or tea for SSBs for the primary prevention of T2D and may help formulate public health recommendations on beverage consumption in different populations.
24. Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study
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Zheng, Ju-Sheng, Sharp, Stephen J, Imamura, Fumiaki, Koulman, Albert, Schulze, Matthias B, Ye, Zheng, Griffin, Jules, Guevara, Marcela, Huerta, José María, Kröger, Janine, Sluijs, Ivonne, Agudo, Antonio, Barricarte, Aurelio, Boeing, Heiner, Colorado-Yohar, Sandra, Dow, Courtney, Dorronsoro, Miren, Dinesen, Pia T, Fagherazzi, Guy, Franks, Paul W, Feskens, Edith JM, Kühn, Tilman, Katzke, Verena Andrea, Key, Timothy J, Khaw, Kay-Tee, De Magistris, Maria Santucci, Mancini, Francesca Romana, Molina-Portillo, Elena, Nilsson, Peter M, Olsen, Anja, Overvad, Kim, Palli, Domenico, Quirós, Jose Ramón, Rolandsson, Olov, Ricceri, Fulvio, Spijkerman, Annemieke MW, Slimani, Nadia, Tagliabue, Giovanna, Tjonneland, Anne, Tumino, Rosario, Van Der Schouw, Yvonne T, Langenberg, Claudia, Riboli, Elio, Forouhi, Nita G, and Wareham, Nicholas J
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Adult ,Blood Glucose ,Male ,Body Mass Index ,Young Adult ,Hepatic ,Humans ,Saturated fatty acids ,Prospective Studies ,Triglycerides ,Aged ,2. Zero hunger ,Inflammation ,Cholesterol, HDL ,Fatty Acids ,Cholesterol, LDL ,Middle Aged ,Lipids ,Dietary Fats ,3. Good health ,Europe ,Metabolic markers ,Cross-Sectional Studies ,Even-chain ,lipids (amino acids, peptides, and proteins) ,Female ,Very-long-chain ,Glycaemic ,Odd-chain ,Biomarkers - Abstract
BACKGROUND: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. METHODS: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. RESULTS: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. CONCLUSIONS: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.
25. Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study
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Zheng, Ju-Sheng, Imamura, Fumiaki, Sharp, Stephen J, Van Der Schouw, Yvonne T, Sluijs, Ivonne, Gundersen, Thomas E, Ardanaz, Eva, Boeing, Heiner, Bonet, Catalina, Gómez, Jesus Humberto, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Jenab, Mazda, Kühn, 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, Sieri, Sabina, Salamanca-Fernández, Elena, Sacerdote, Carlotta, Spijkerman, Annemieke MW, Stepien, Magdalena, Tjonneland, Anne, Tumino, Rosario, Butterworth, Adam S, Riboli, Elio, Danesh, John, Langenberg, Claudia, Forouhi, Nita G, and Wareham, Nicholas J
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Adult ,Male ,Incidence ,Stereoisomerism ,Middle Aged ,3. Good health ,Europe ,Diabetes Mellitus, Type 2 ,Risk Factors ,Humans ,Female ,Prospective Studies ,Vitamin D ,Biomarkers - Abstract
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.
26. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis
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Zheng, Ju-Sheng, Luan, Jian'an, Sofianopoulou, Eleni, Sharp, Stephen J, Day, Felix R, Imamura, Fumiaki, Gundersen, Thomas E, Lotta, Luca A, Sluijs, Ivonne, Stewart, Isobel D, Shah, Rupal L, Van Der Schouw, Yvonne T, Wheeler, Eleanor, Ardanaz, Eva, Boeing, Heiner, Dorronsoro, Miren, Dahm, Christina C, Dimou, Niki, El-Fatouhi, Douae, Franks, Paul W, Fagherazzi, Guy, Grioni, Sara, Huerta, José María, Heath, Alicia K, Hansen, Louise, Jenab, Mazda, Jakszyn, Paula, Kaaks, Rudolf, Kühn, Tilman, Khaw, Kay-Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M, Overvad, Kim, Olsen, Anja, Panico, Salvatore, Quirós, J Ramón, Rolandsson, Olov, Rodríguez-Barranco, Miguel, Sacerdote, Carlotta, Spijkerman, Annemieke MW, Tong, Tammy YN, Tumino, Rosario, Tsilidis, Konstantinos K, Danesh, John, Riboli, Elio, Butterworth, Adam S, Langenberg, Claudia, Forouhi, Nita G, and Wareham, Nicholas J
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Adult ,Male ,Mendelian Randomization Analysis ,Middle Aged ,White People ,3. Good health ,Diabetes Mellitus, Type 2 ,Risk Factors ,Dietary Supplements ,Humans ,Female ,Prospective Studies ,Vitamin D ,Genome-Wide Association Study - Abstract
BACKGROUND: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND FINDINGS: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. CONCLUSIONS: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
27. Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study
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Langenberg, Claudia, Sharp, Stephen J, Franks, Paul W, Scott, Robert A, Deloukas, Panos, Forouhi, Nita G, Froguel, Philippe, Groop, Leif C, Hansen, Torben, Palla, Luigi, Pedersen, Oluf, Schulze, Matthias B, Tormo, Maria-Jose, Wheeler, Eleanor, Agnoli, Claudia, Arriola, Larraitz, Barricarte, Aurelio, Boeing, Heiner, Clarke, Geraldine M, Clavel-Chapelon, Françoise, Duell, Eric J, Fagherazzi, Guy, Kaaks, Rudolf, Kerrison, Nicola D, Key, Timothy J, Khaw, Kay Tee, Kröger, Janine, Lajous, Martin, Morris, Andrew P, Navarro, Carmen, Nilsson, Peter M, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, J Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Sánchez, María-José, Slimani, Nadia, Spijkerman, Annemieke MW, Tumino, Rosario, Van Der A, Daphne L, Van Der Schouw, Yvonne T, Barroso, Inês, McCarthy, Mark I, Riboli, Elio, and Wareham, Nicholas J
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2. Zero hunger ,Male ,Middle Aged ,Motor Activity ,Diet, Mediterranean ,Polymorphism, Single Nucleotide ,3. Good health ,Body Mass Index ,Cohort Studies ,Diabetes Mellitus, Type 2 ,Risk Factors ,Humans ,Female ,Genetic Predisposition to Disease ,Waist Circumference ,Life Style ,Alleles ,Proportional Hazards Models - Abstract
BACKGROUND: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS: The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.50×10-3) and waist circumference (p for interaction = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.
28. Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations
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Zheng, Ju-Sheng, Luan, Jian'an, Sofianopoulou, Eleni, Imamura, Fumiaki, Stewart, Isobel D, Day, Felix R, Pietzner, Maik, Wheeler, Eleanor, Lotta, Luca A, Gundersen, Thomas E, Amiano, Pilar, Ardanaz, Eva, Chirlaque, María-Dolores, Fagherazzi, Guy, Franks, Paul W, Kaaks, Rudolf, Laouali, Nasser, Mancini, Francesca Romana, Nilsson, Peter M, Onland-Moret, N Charlotte, Olsen, Anja, Overvad, Kim, Panico, Salvatore, Palli, Domenico, Ricceri, Fulvio, Rolandsson, Olov, Spijkerman, Annemieke MW, Sánchez, María-José, Schulze, Matthias B, Sala, Núria, Sieri, Sabina, Tjønneland, Anne, Tumino, Rosario, Van Der Schouw, Yvonne T, Weiderpass, Elisabete, Riboli, Elio, Danesh, John, Butterworth, Adam S, Sharp, Stephen J, Langenberg, Claudia, Forouhi, Nita G, and Wareham, Nicholas J
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Delta-5 Fatty Acid Desaturase ,Diabetes Mellitus, Type 2 ,Risk Factors ,Humans ,Ascorbic Acid ,Mendelian Randomization Analysis ,Polymorphism, Single Nucleotide ,3. Good health ,Genome-Wide Association Study - Abstract
OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
29. Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations
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Jannasch, Franziska, Kröger, Janine, Agnoli, Claudia, Barricarte, Aurelio, Boeing, Heiner, Cayssials, Valerie, Colorado-Yohar, Sandra, Dahm, Christina C, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Freisling, Heinz, Gunter, Marc J, Kerrison, Nicola D, Key, Timothy J, Khaw, Kay-Tee, Kühn, Tilman, Kyro, Cecilie, Mancini, Francesca Romana, Mokoroa, Olatz, Nilsson, Peter, Overvad, Kim, Palli, Domenico, Panico, Salvatore, García, Jose Ramón Quirós, Rolandsson, Olov, Sacerdote, Carlotta, Sánchez, Mariá-José, Sahrai, Mohammad Sediq, Schübel, Ruth, Sluijs, Ivonne, Spijkerman, Annemieke MW, Tjonneland, Anne, Tong, Tammy YN, Tumino, Rosario, Riboli, Elio, Langenberg, Claudia, Sharp, Stephen J, Forouhi, Nita G, Schulze, Matthias B, and Wareham, Nicholas J
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2. Zero hunger ,Adult ,Male ,replication ,Principal Component Analysis ,diet-disease association ,type 2 diabetes mellitus ,Incidence ,dietary patterns ,Middle Aged ,3. Good health ,Diet ,meta-analysis ,Cohort Studies ,Europe ,Diabetes Mellitus, Type 2 ,Risk Factors ,Case-Control Studies ,Feasibility Studies ,Humans ,Female ,Disease Susceptibility ,Aged - Abstract
BACKGROUND: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. OBJECTIVE: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. METHODS: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. RESULTS: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. CONCLUSIONS: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.
30. Association of plasma vitamin D metabolites with incident type 2 diabetes: EPIC-InterAct case-cohort study
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Courtney Dow, Olatz Mokoroa, Catalina Bonet, Claudia Langenberg, Tilman Kühn, Ivonne Sluijs, Anne Tjønneland, Elena Salamanca-Fernández, Cristina Lasheras, Olov Rolandsson, Jesús Humberto Gómez, Timothy J. Key, Domenico Palli, Rosario Tumino, Nicholas J. Wareham, Ju-Sheng Zheng, Francesca Mancini, Annemieke M.W. Spijkerman, Kay-Tee Khaw, Nita G. Forouhi, Kim Overvad, Peter M. Nilsson, John Danesh, Carlotta Sacerdote, Thomas E. Gundersen, Sabina Sieri, Stephen J. Sharp, Salvatore Panico, Yvonne T. van der Schouw, Eva Ardanaz, Fumiaki Imamura, Magdalena Stepien, Guy Fagherazzi, Mazda Jenab, Adam S. Butterworth, Elio Riboli, Rudolf Kaaks, Paul W. Franks, Heiner Boeing, Zheng, Ju-Sheng, Imamura, Fumiaki, Sharp, Stephen J, van der Schouw, Yvonne T, Sluijs, Ivonne, Gundersen, Thomas E, Ardanaz, Eva, Boeing, Heiner, Bonet, Catalina, Gómez, Jesus Humberto, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Jenab, Mazda, Kühn, 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, Sieri, Sabina, Salamanca-Fernández, Elena, Sacerdote, Carlotta, Spijkerman, Annemieke Mw, Stepien, Magdalena, Tjonneland, Anne, Tumino, Rosario, Butterworth, Adam S, Riboli, Elio, Danesh, John, Langenberg, Claudia, Forouhi, Nita G, Wareham, Nicholas J, Zheng, Jusheng [0000-0001-6560-4890], Imamura, Fumiaki [0000-0002-6841-8396], Sharp, Stephen [0000-0003-2375-1440], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Langenberg, Claudia [0000-0002-5017-7344], Forouhi, Nita [0000-0002-5041-248X], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
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Male ,Metabolite ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Type 2 diabetes ,DETERMINANTS ,Biochemistry ,medical ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Risk Factors ,030212 general & internal medicine ,Prospective Studies ,Vitamin D ,Prospective cohort study ,POPULATION ,RISK ,education.field_of_study ,Nutrition and Dietetics ,Incidence ,Stereoisomerism ,Middle Aged ,CANCER ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Näringslära ,Europe ,Diabetes and Metabolism ,Vitamin D/blood ,Endokrinologi och diabetes ,LIFE-STYLE ,NUTRITION ,Female ,C-3 EPIMER ,Diabetes Mellitus, Type 2/blood ,Life Sciences & Biomedicine ,Cohort study ,Adult ,medicine.medical_specialty ,Diabetes, Pancreatic and Gastrointestinal Hormones ,Population ,030209 endocrinology & metabolism ,Endocrinology and Diabetes ,Europe/epidemiology ,03 medical and health sciences ,Endocrinology & Metabolism ,Internal medicine ,Diabetes mellitus ,medicine ,Vitamin D and neurology ,Humans ,education ,Clinical Research Articles ,METAANALYSIS ,Biochemistry, medical ,Science & Technology ,D-3 ,Biochemistry (medical) ,1103 Clinical Sciences ,medicine.disease ,chemistry ,Diabetes Mellitus, Type 2 ,1114 Paediatrics and Reproductive Medicine ,SERUM 25-HYDROXYVITAMIN D ,Biomarkers/blood ,Biomarkers - Abstract
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., We examined the prospective association of plasma vitamin D metabolites with type 2 diabetes and found that the epimeric form of plasma 25(OH)D3 was positively associated with type 2 diabetes risk.
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- 2019
31. Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes: A Meta-analysis.
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Lotta LA, Sharp SJ, Burgess S, Perry JRB, Stewart ID, Willems SM, Luan J, Ardanaz E, Arriola L, Balkau B, Boeing H, Deloukas P, Forouhi NG, Franks PW, Grioni S, Kaaks R, Key TJ, Navarro C, Nilsson PM, Overvad K, Palli D, Panico S, Quirós JR, Riboli E, Rolandsson O, Sacerdote C, Salamanca EC, Slimani N, Spijkerman AM, Tjonneland A, Tumino R, van der A DL, van der Schouw YT, McCarthy MI, Barroso I, O'Rahilly S, Savage DB, Sattar N, Langenberg C, Scott RA, and Wareham NJ
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- ATP Binding Cassette Transporter, Subfamily G, Member 5 genetics, Adult, Aged, Cholesterol, LDL blood, Cohort Studies, Diabetes Mellitus, Type 2 blood, Drug Therapy, Combination adverse effects, Ezetimibe administration & dosage, Ezetimibe adverse effects, Genetic Association Studies, Humans, Hydroxymethylglutaryl CoA Reductases genetics, Lipoproteins genetics, Membrane Transport Proteins, Middle Aged, Odds Ratio, Polymorphism, Genetic, Proprotein Convertase 9 genetics, Receptors, LDL genetics, Risk, Simvastatin administration & dosage, Simvastatin adverse effects, Cholesterol, LDL genetics, Coronary Artery Disease genetics, Diabetes Mellitus, Type 2 genetics, Genetic Variation, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Membrane Proteins genetics
- Abstract
Importance: Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near NPC1L1 are associated with the risk of type 2 diabetes., Objective: To investigate whether LDL-C-lowering alleles in or near NPC1L1 and other genes encoding current or prospective molecular targets of lipid-lowering therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2 diabetes., Design, Setting, and Participants: The associations with type 2 diabetes and coronary artery disease of LDL-C-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801 individuals with coronary artery disease and 123 504 controls. Data collection took place in Europe and the United States between 1991 and 2016., Exposures: Low-density lipoprotein cholesterol-lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, and LDLR., Main Outcomes and Measures: Odds ratios (ORs) for type 2 diabetes and coronary artery disease., Results: Low-density lipoprotein cholesterol-lowering genetic variants at NPC1L1 were inversely associated with coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61 [95% CI, 0.42-0.88]; P = .008) and directly associated with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42 [95% CI, 1.70-3.43]; P < .001). For PCSK9 genetic variants, the OR for type 2 diabetes per 1-mmol/L genetically predicted reduction in LDL-C was 1.19 (95% CI, 1.02-1.38; P = .03). For a given reduction in LDL-C, genetic variants were associated with a similar reduction in coronary artery disease risk (I2 = 0% for heterogeneity in genetic associations; P = .93). However, associations with type 2 diabetes were heterogeneous (I2 = 77.2%; P = .002), indicating gene-specific associations with metabolic risk of LDL-C-lowering alleles., Conclusions and Relevance: In this meta-analysis, exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other genes was associated with a higher risk of type 2 diabetes. These data provide insights into potential adverse effects of LDL-C-lowering therapy.
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- 2016
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32. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity.
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Scott RA, Fall T, Pasko D, Barker A, Sharp SJ, Arriola L, Balkau B, Barricarte A, Barroso I, Boeing H, Clavel-Chapelon F, Crowe FL, Dekker JM, Fagherazzi G, Ferrannini E, Forouhi NG, Franks PW, Gavrila D, Giedraitis V, Grioni S, Groop LC, Kaaks R, Key TJ, Kühn T, Lotta LA, Nilsson PM, Overvad K, Palli D, Panico S, Quirós JR, Rolandsson O, Roswall N, Sacerdote C, Sala N, Sánchez MJ, Schulze MB, Siddiq A, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, van der A DL, Yaghootkar H, McCarthy MI, Semple RK, Riboli E, Walker M, Ingelsson E, Frayling TM, Savage DB, Langenberg C, and Wareham NJ
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- Adult, Aged, Alanine Transaminase metabolism, Body Fat Distribution, Body Mass Index, Cohort Studies, Diabetes Mellitus, Type 2 metabolism, Female, Genetic Predisposition to Disease, Genetic Variation, Glucose Clamp Technique, Glucose Tolerance Test, Humans, Insulin Secretion, Male, Middle Aged, Overweight metabolism, Polymorphism, Single Nucleotide, Waist Circumference genetics, gamma-Glutamyltransferase metabolism, Body Composition genetics, Diabetes Mellitus, Type 2 genetics, Insulin metabolism, Insulin Resistance genetics, Obesity metabolism
- Abstract
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 (β 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 = 1.4 × 10(-6)) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and γ-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (Pinteraction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (Pinteraction > 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., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
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- 2014
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