Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events

BACKGROUNDThe ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown.METHODSIn a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardi...

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Published in:New England Journal of Medicine
Main Authors: Holman, Rury R., Haffner, Steven M., McMurray, John J., Bethel, M. Angelyn, Holzhauer, Bjoern, Hua, Tsushung A., Belenkov, Yuri, Boolell, Mitradev, Buse, John B., Buckley, Brendan M., Chacra, Antonio R., Chiang, Fu-Tien, Charbonnel, Bernard, Chow, Chun-Chung, Davies, Melanie J., Deedwania, Prakash, Diem, Peter, Einhorn, Daniel, Fonseca, Vivian, Fulcher, Gregory R., Gaciong, Zbigniew, Gaztambide, Sonia, Giles, Thomas, Horton, Edward, Ilkova, Hasan, Jenssen, Trond, Kahn, Steven E., Krum, Henry, Laakso, Markku, Leiter, Lawrence A., Levitt, Naomi S., Mareev, Viacheslav, Martinez, Felipe, Masson, Chantal, Mazzone, Theodore, Meaney, Eduardo, Nesto, Richard, Pan, Changyu, Prager, Rudolf, Raptis, Sotirios A., Rutten, Guy E. H. M., Sandstroem, Herbert, Schaper, Frank, Scheen, Andre, Schmitz, Ole, Sinay, Isaac, Soska, Vladimir, Stender, Steen, Tamas, Gyula, Tognoni, Gianni, Tuomilehto, Jaako, Villamil, Alberto S., Vozar, Juraj, Califf, Robert M., NAVIGATOR Study Grp
Other Authors: Univ Oxford, Univ Glasgow, Univ Leicester, Univ Texas Hlth Sci Ctr San Antonio, Duke Univ, Univ N Carolina, Novartis Pharmaceut, Univ Hosp Bern, Univ Bern, Moscow MV Lomonosov State Univ, Natl Univ Ireland Univ Coll Cork, Universidade Federal de São Paulo (UNIFESP), Natl Taiwan Univ Hosp, Univ Hosp, Chinese Univ Hong Kong, 301 Hosp, Calif State Univ Fresno, VA Cent Calif Hlth Care Syst, Univ Calif San Diego, Scripps Whittier Diabet Inst, Tulane Univ, Univ Sydney, Monash Univ, Warsaw Med Univ, Hosp Univ Cruces, Joslin Diabet Ctr, Istanbul Univ, Oslo Univ Hosp, Univ Tromso, VA Puget Sound Hlth Care Syst, Univ Washington, Univ Kuopio, Kuopio Univ Hosp, Univ Helsinki, S Ostrobothnia Cent Hosp, Univ Toronto, Univ Cape Town, Natl Univ Cordoba, Univ Buenos Aires, Univ Illinois, Hosp 10 Octubre, Lahey Clin Fdn, Krankenhaus Hietzing Neurolog, Attikon Univ Hosp, Univ Med Ctr, Umea Univ, Tech Univ Dresden, Univ Liege, Aarhus Univ, Univ Copenhagen
Format: Article in Journal/Newspaper
Language:English
Published: Massachusetts Medical Soc 2010
Subjects:
Online Access:http://repositorio.unifesp.br/handle/11600/32480
https://doi.org/10.1056/NEJMoa1001122
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description BACKGROUNDThe ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown.METHODSIn a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization.RESULTSAfter adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P = 0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P = 0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P = 0.16). Nateglinide did, however, increase the risk of hypoglycemia.CONCLUSIONSAmong persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.) Novartis Pharma Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA Duke Univ, Duke Translat Med Inst, Durham, NC 27706 USA Univ N Carolina, Sch Med, Div Gen Med, Chapel Hill, NC USA Univ N Carolina, Sch Med, Clin Epidemiol & Diabet Care Ctr, Chapel Hill, NC USA Novartis Pharmaceut, Basel, Switzerland Univ Hosp Bern, Inselspital, Div Endocrinol Diabet & Clin Nutr, CH-3010 Bern, Switzerland Univ Bern, Bern, Switzerland Novartis Pharmaceut, E Hanover, NJ USA Moscow MV Lomonosov State Univ, Moscow 117234, Russia Natl Univ Ireland Univ Coll Cork, Cork, Ireland Universidade Federal de São Paulo, São Paulo, Brazil Natl Taiwan Univ Hosp, Dept Cardiol, Taipei, Taiwan Univ Hosp, Dept Endocrinol, Nantes, France Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China 301 Hosp, Dept Endocrinol, Beijing, Peoples R China Calif State Univ Fresno, San Francisco Program Fresno, Div Cardiol, Fresno, CA 93740 USA VA Cent Calif Hlth Care Syst, Fresno, CA USA Univ Calif San Diego, La Jolla, CA 92093 USA Scripps Whittier Diabet Inst, La Jolla, CA USA Tulane Univ, Sch Med, Dept Endocrinol, New Orleans, LA 70112 USA Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia Monash Univ, Alfred Hosp, Clin Pharmacol Unit, Dept Epidemiol & Prevent Med, Prahran, Vic, Australia Warsaw Med Univ, Dept Internal Med Hypertens & Vasc Dis, Warsaw, Poland Hosp Univ Cruces, Dept Endocrinol, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Baracaldo, Spain Joslin Diabet Ctr, Boston, MA 02215 USA Istanbul Univ, Dept Diabet Endocrinol & Metab, Istanbul, Turkey Oslo Univ Hosp, Rikshosp, Oslo Inst Clin Med, Tromso, Norway Univ Tromso, Tromso, Norway VA Puget Sound Hlth Care Syst, Seattle, WA USA Univ Washington, Seattle, WA 98195 USA Univ Kuopio, FIN-70211 Kuopio, Finland Kuopio Univ Hosp, SF-70210 Kuopio, Finland Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland S Ostrobothnia Cent Hosp, Seinajoki, Finland Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada Univ Cape Town, Dept Med, Endocrine Unit, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa Natl Univ Cordoba, Cordoba, Spain Univ Buenos Aires, Inst Cardiovasc Buenos Aires, Buenos Aires, DF, Argentina Univ Buenos Aires, Hypertens Unit, Div Cardiol, Argerich Hosp, Buenos Aires, DF, Argentina Univ Illinois, Dept Diabet & Metab, Chicago, IL USA Hosp 10 Octubre, Inst Seguridad & Serv Sociales Trabajadores Estad, Mexico City, DF, Mexico Lahey Clin Fdn, Burlington, MA USA Krankenhaus Hietzing Neurolog, Zentrum Rosenhugel, Hietzig Hosp, Vienna, Austria Attikon Univ Hosp, Hellen Natl Diabet Ctr, Dept Internal Med Endocrinol & Diabetol 2, Athens, Greece Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden Tech Univ Dresden, Ctr Clin Studies Metab & Endocrinol Knowledge & T, D-8027 Dresden, Germany Univ Liege, Div Diabet, Liege, Belgium Univ Liege, Clin Pharmacol Unit, Ctr Hosp Univ Liege, Liege, Belgium Aarhus Univ, Med Dept Endocrinol & Diabet M, Arhus Univ Hosp, Aarhus, Denmark Aarhus Univ, Dept Clin Pharmacol, Aarhus, Denmark Univ Copenhagen, Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark Fac Hosp St Anna, Clin Internal Med 2, Brno, Czech Republic Fac Hosp St Anna, Dept Clin Biochem, Brno, Czech Republic Semmelweis Univ, Diabet Unit, Dept Med 1, H-1085 Budapest, Hungary Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, I-66030 Santa Maria Imbaro, Italy Diabetol Outpatient Clin, Jesenius Samaria, Samorin, Slovakia Universidade Federal de São Paulo, São Paulo, Brazil Web of Science
author2 Univ Oxford
Univ Glasgow
Univ Leicester
Univ Texas Hlth Sci Ctr San Antonio
Duke Univ
Univ N Carolina
Novartis Pharmaceut
Univ Hosp Bern
Univ Bern
Moscow MV Lomonosov State Univ
Natl Univ Ireland Univ Coll Cork
Universidade Federal de São Paulo (UNIFESP)
Natl Taiwan Univ Hosp
Univ Hosp
Chinese Univ Hong Kong
301 Hosp
Calif State Univ Fresno
VA Cent Calif Hlth Care Syst
Univ Calif San Diego
Scripps Whittier Diabet Inst
Tulane Univ
Univ Sydney
Monash Univ
Warsaw Med Univ
Hosp Univ Cruces
Joslin Diabet Ctr
Istanbul Univ
Oslo Univ Hosp
Univ Tromso
VA Puget Sound Hlth Care Syst
Univ Washington
Univ Kuopio
Kuopio Univ Hosp
Univ Helsinki
S Ostrobothnia Cent Hosp
Univ Toronto
Univ Cape Town
Natl Univ Cordoba
Univ Buenos Aires
Univ Illinois
Hosp 10 Octubre
Lahey Clin Fdn
Krankenhaus Hietzing Neurolog
Attikon Univ Hosp
Univ Med Ctr
Umea Univ
Tech Univ Dresden
Univ Liege
Aarhus Univ
Univ Copenhagen
format Article in Journal/Newspaper
author Holman, Rury R.
Haffner, Steven M.
McMurray, John J.
Bethel, M. Angelyn
Holzhauer, Bjoern
Hua, Tsushung A.
Belenkov, Yuri
Boolell, Mitradev
Buse, John B.
Buckley, Brendan M.
Chacra, Antonio R.
Chiang, Fu-Tien
Charbonnel, Bernard
Chow, Chun-Chung
Davies, Melanie J.
Deedwania, Prakash
Diem, Peter
Einhorn, Daniel
Fonseca, Vivian
Fulcher, Gregory R.
Gaciong, Zbigniew
Gaztambide, Sonia
Giles, Thomas
Horton, Edward
Ilkova, Hasan
Jenssen, Trond
Kahn, Steven E.
Krum, Henry
Laakso, Markku
Leiter, Lawrence A.
Levitt, Naomi S.
Mareev, Viacheslav
Martinez, Felipe
Masson, Chantal
Mazzone, Theodore
Meaney, Eduardo
Nesto, Richard
Pan, Changyu
Prager, Rudolf
Raptis, Sotirios A.
Rutten, Guy E. H. M.
Sandstroem, Herbert
Schaper, Frank
Scheen, Andre
Schmitz, Ole
Sinay, Isaac
Soska, Vladimir
Stender, Steen
Tamas, Gyula
Tognoni, Gianni
Tuomilehto, Jaako
Villamil, Alberto S.
Vozar, Juraj
Califf, Robert M.
NAVIGATOR Study Grp
spellingShingle Holman, Rury R.
Haffner, Steven M.
McMurray, John J.
Bethel, M. Angelyn
Holzhauer, Bjoern
Hua, Tsushung A.
Belenkov, Yuri
Boolell, Mitradev
Buse, John B.
Buckley, Brendan M.
Chacra, Antonio R.
Chiang, Fu-Tien
Charbonnel, Bernard
Chow, Chun-Chung
Davies, Melanie J.
Deedwania, Prakash
Diem, Peter
Einhorn, Daniel
Fonseca, Vivian
Fulcher, Gregory R.
Gaciong, Zbigniew
Gaztambide, Sonia
Giles, Thomas
Horton, Edward
Ilkova, Hasan
Jenssen, Trond
Kahn, Steven E.
Krum, Henry
Laakso, Markku
Leiter, Lawrence A.
Levitt, Naomi S.
Mareev, Viacheslav
Martinez, Felipe
Masson, Chantal
Mazzone, Theodore
Meaney, Eduardo
Nesto, Richard
Pan, Changyu
Prager, Rudolf
Raptis, Sotirios A.
Rutten, Guy E. H. M.
Sandstroem, Herbert
Schaper, Frank
Scheen, Andre
Schmitz, Ole
Sinay, Isaac
Soska, Vladimir
Stender, Steen
Tamas, Gyula
Tognoni, Gianni
Tuomilehto, Jaako
Villamil, Alberto S.
Vozar, Juraj
Califf, Robert M.
NAVIGATOR Study Grp
Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
author_facet Holman, Rury R.
Haffner, Steven M.
McMurray, John J.
Bethel, M. Angelyn
Holzhauer, Bjoern
Hua, Tsushung A.
Belenkov, Yuri
Boolell, Mitradev
Buse, John B.
Buckley, Brendan M.
Chacra, Antonio R.
Chiang, Fu-Tien
Charbonnel, Bernard
Chow, Chun-Chung
Davies, Melanie J.
Deedwania, Prakash
Diem, Peter
Einhorn, Daniel
Fonseca, Vivian
Fulcher, Gregory R.
Gaciong, Zbigniew
Gaztambide, Sonia
Giles, Thomas
Horton, Edward
Ilkova, Hasan
Jenssen, Trond
Kahn, Steven E.
Krum, Henry
Laakso, Markku
Leiter, Lawrence A.
Levitt, Naomi S.
Mareev, Viacheslav
Martinez, Felipe
Masson, Chantal
Mazzone, Theodore
Meaney, Eduardo
Nesto, Richard
Pan, Changyu
Prager, Rudolf
Raptis, Sotirios A.
Rutten, Guy E. H. M.
Sandstroem, Herbert
Schaper, Frank
Scheen, Andre
Schmitz, Ole
Sinay, Isaac
Soska, Vladimir
Stender, Steen
Tamas, Gyula
Tognoni, Gianni
Tuomilehto, Jaako
Villamil, Alberto S.
Vozar, Juraj
Califf, Robert M.
NAVIGATOR Study Grp
author_sort Holman, Rury R.
title Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
title_short Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
title_full Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
title_fullStr Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
title_full_unstemmed Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
title_sort effect of nateglinide on the incidence of diabetes and cardiovascular events
publisher Massachusetts Medical Soc
publishDate 2010
url http://repositorio.unifesp.br/handle/11600/32480
https://doi.org/10.1056/NEJMoa1001122
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op_relation New England Journal of Medicine
http://dx.doi.org/10.1056/NEJMoa1001122
New England Journal of Medicine. Waltham: Massachusetts Medical Soc, v. 362, n. 16, p. 1463-1476, 2010.
0028-4793
http://repositorio.unifesp.br/handle/11600/32480
doi:10.1056/NEJMoa1001122
WOS:000276894700006
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spelling ftunivfsaopaulo:oai:repositorio.unifesp.br:11600/32480 2023-05-15T18:33:53+02:00 Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events Holman, Rury R. Haffner, Steven M. McMurray, John J. Bethel, M. Angelyn Holzhauer, Bjoern Hua, Tsushung A. Belenkov, Yuri Boolell, Mitradev Buse, John B. Buckley, Brendan M. Chacra, Antonio R. Chiang, Fu-Tien Charbonnel, Bernard Chow, Chun-Chung Davies, Melanie J. Deedwania, Prakash Diem, Peter Einhorn, Daniel Fonseca, Vivian Fulcher, Gregory R. Gaciong, Zbigniew Gaztambide, Sonia Giles, Thomas Horton, Edward Ilkova, Hasan Jenssen, Trond Kahn, Steven E. Krum, Henry Laakso, Markku Leiter, Lawrence A. Levitt, Naomi S. Mareev, Viacheslav Martinez, Felipe Masson, Chantal Mazzone, Theodore Meaney, Eduardo Nesto, Richard Pan, Changyu Prager, Rudolf Raptis, Sotirios A. Rutten, Guy E. H. M. Sandstroem, Herbert Schaper, Frank Scheen, Andre Schmitz, Ole Sinay, Isaac Soska, Vladimir Stender, Steen Tamas, Gyula Tognoni, Gianni Tuomilehto, Jaako Villamil, Alberto S. Vozar, Juraj Califf, Robert M. NAVIGATOR Study Grp Univ Oxford Univ Glasgow Univ Leicester Univ Texas Hlth Sci Ctr San Antonio Duke Univ Univ N Carolina Novartis Pharmaceut Univ Hosp Bern Univ Bern Moscow MV Lomonosov State Univ Natl Univ Ireland Univ Coll Cork Universidade Federal de São Paulo (UNIFESP) Natl Taiwan Univ Hosp Univ Hosp Chinese Univ Hong Kong 301 Hosp Calif State Univ Fresno VA Cent Calif Hlth Care Syst Univ Calif San Diego Scripps Whittier Diabet Inst Tulane Univ Univ Sydney Monash Univ Warsaw Med Univ Hosp Univ Cruces Joslin Diabet Ctr Istanbul Univ Oslo Univ Hosp Univ Tromso VA Puget Sound Hlth Care Syst Univ Washington Univ Kuopio Kuopio Univ Hosp Univ Helsinki S Ostrobothnia Cent Hosp Univ Toronto Univ Cape Town Natl Univ Cordoba Univ Buenos Aires Univ Illinois Hosp 10 Octubre Lahey Clin Fdn Krankenhaus Hietzing Neurolog Attikon Univ Hosp Univ Med Ctr Umea Univ Tech Univ Dresden Univ Liege Aarhus Univ Univ Copenhagen 2010-04-22 1463-1476 http://repositorio.unifesp.br/handle/11600/32480 https://doi.org/10.1056/NEJMoa1001122 eng eng Massachusetts Medical Soc New England Journal of Medicine http://dx.doi.org/10.1056/NEJMoa1001122 New England Journal of Medicine. Waltham: Massachusetts Medical Soc, v. 362, n. 16, p. 1463-1476, 2010. 0028-4793 http://repositorio.unifesp.br/handle/11600/32480 doi:10.1056/NEJMoa1001122 WOS:000276894700006 Acesso restrito Artigo 2010 ftunivfsaopaulo https://doi.org/10.1056/NEJMoa1001122 2020-12-09T07:39:10Z BACKGROUNDThe ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown.METHODSIn a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization.RESULTSAfter adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P = 0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P = 0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P = 0.16). Nateglinide did, however, increase the risk of hypoglycemia.CONCLUSIONSAmong persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.) Novartis Pharma Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA Duke Univ, Duke Translat Med Inst, Durham, NC 27706 USA Univ N Carolina, Sch Med, Div Gen Med, Chapel Hill, NC USA Univ N Carolina, Sch Med, Clin Epidemiol & Diabet Care Ctr, Chapel Hill, NC USA Novartis Pharmaceut, Basel, Switzerland Univ Hosp Bern, Inselspital, Div Endocrinol Diabet & Clin Nutr, CH-3010 Bern, Switzerland Univ Bern, Bern, Switzerland Novartis Pharmaceut, E Hanover, NJ USA Moscow MV Lomonosov State Univ, Moscow 117234, Russia Natl Univ Ireland Univ Coll Cork, Cork, Ireland Universidade Federal de São Paulo, São Paulo, Brazil Natl Taiwan Univ Hosp, Dept Cardiol, Taipei, Taiwan Univ Hosp, Dept Endocrinol, Nantes, France Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China 301 Hosp, Dept Endocrinol, Beijing, Peoples R China Calif State Univ Fresno, San Francisco Program Fresno, Div Cardiol, Fresno, CA 93740 USA VA Cent Calif Hlth Care Syst, Fresno, CA USA Univ Calif San Diego, La Jolla, CA 92093 USA Scripps Whittier Diabet Inst, La Jolla, CA USA Tulane Univ, Sch Med, Dept Endocrinol, New Orleans, LA 70112 USA Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia Monash Univ, Alfred Hosp, Clin Pharmacol Unit, Dept Epidemiol & Prevent Med, Prahran, Vic, Australia Warsaw Med Univ, Dept Internal Med Hypertens & Vasc Dis, Warsaw, Poland Hosp Univ Cruces, Dept Endocrinol, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Baracaldo, Spain Joslin Diabet Ctr, Boston, MA 02215 USA Istanbul Univ, Dept Diabet Endocrinol & Metab, Istanbul, Turkey Oslo Univ Hosp, Rikshosp, Oslo Inst Clin Med, Tromso, Norway Univ Tromso, Tromso, Norway VA Puget Sound Hlth Care Syst, Seattle, WA USA Univ Washington, Seattle, WA 98195 USA Univ Kuopio, FIN-70211 Kuopio, Finland Kuopio Univ Hosp, SF-70210 Kuopio, Finland Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland S Ostrobothnia Cent Hosp, Seinajoki, Finland Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada Univ Cape Town, Dept Med, Endocrine Unit, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa Natl Univ Cordoba, Cordoba, Spain Univ Buenos Aires, Inst Cardiovasc Buenos Aires, Buenos Aires, DF, Argentina Univ Buenos Aires, Hypertens Unit, Div Cardiol, Argerich Hosp, Buenos Aires, DF, Argentina Univ Illinois, Dept Diabet & Metab, Chicago, IL USA Hosp 10 Octubre, Inst Seguridad & Serv Sociales Trabajadores Estad, Mexico City, DF, Mexico Lahey Clin Fdn, Burlington, MA USA Krankenhaus Hietzing Neurolog, Zentrum Rosenhugel, Hietzig Hosp, Vienna, Austria Attikon Univ Hosp, Hellen Natl Diabet Ctr, Dept Internal Med Endocrinol & Diabetol 2, Athens, Greece Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden Tech Univ Dresden, Ctr Clin Studies Metab & Endocrinol Knowledge & T, D-8027 Dresden, Germany Univ Liege, Div Diabet, Liege, Belgium Univ Liege, Clin Pharmacol Unit, Ctr Hosp Univ Liege, Liege, Belgium Aarhus Univ, Med Dept Endocrinol & Diabet M, Arhus Univ Hosp, Aarhus, Denmark Aarhus Univ, Dept Clin Pharmacol, Aarhus, Denmark Univ Copenhagen, Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark Fac Hosp St Anna, Clin Internal Med 2, Brno, Czech Republic Fac Hosp St Anna, Dept Clin Biochem, Brno, Czech Republic Semmelweis Univ, Diabet Unit, Dept Med 1, H-1085 Budapest, Hungary Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, I-66030 Santa Maria Imbaro, Italy Diabetol Outpatient Clin, Jesenius Samaria, Samorin, Slovakia Universidade Federal de São Paulo, São Paulo, Brazil Web of Science Article in Journal/Newspaper Tromso Tromso Universidade Federal de São Paulo (UNIFESP): Repositório Institucional Argentina Burlington ENVELOPE(-56.015,-56.015,49.750,49.750) Canada Chapel Hill ENVELOPE(-57.976,-57.976,-63.685,-63.685) Leicester ENVELOPE(-116.403,-116.403,55.717,55.717) Norway Orleans ENVELOPE(-60.667,-60.667,-63.950,-63.950) Scripps ENVELOPE(-63.783,-63.783,-69.150,-69.150) Tromso ENVELOPE(16.546,16.546,68.801,68.801) New England Journal of Medicine 362 16 1463 1476