IMPORTANCE: Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance. OBJECTIVE: To study the association between melatonin secretion and the risk of developing type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Case-control study nested within the Nurses' Health Study cohort. Among participants without diabetes who provided urine and blood samples at baseline in 2000, we identified 370 women who developed type 2 diabetes from 2000-2012 and matched 370 controls using risk-set sampling. MAIN OUTCOME MEASURES: Associations between melatonin secretion at baseline and incidence of type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction. RESULTS: The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg (5%-95% range, 5.5-84.2 ng/mg) among cases and 36.3 ng/mg (5%-95% range, 6.9-110.8 ng/mg) among controls. Women with lower ratios of 6-sulfatoxymelatonin to creatinine had increased risk of diabetes (multivariable odds ratio, 1.48 [95% CI, 1.11-1.98] per unit decrease in the estimated log ratio of 6-sulfatoxymelatonin to creatinine). Compared with women in the highest ratio category of 6-sulfatoxymelatonin to creatinine, those in the lowest category had a multivariable odds ratio of 2.17 (95% CI, 1.18-3.98) of developing type 2 diabetes. Women in the highest category of melatonin secretion had an estimated diabetes incidence rate of 4.27 cases/1000 person-years compared with 9.27 cases/1000 person-years in the lowest category. CONCLUSIONS AND RELEVANCE: Lower melatonin secretion was independently associated with a higher risk of developing type 2 diabetes. Further research is warranted to assess if melatonin secretion is a modifiable risk factor for diabetes within the general population.
IMPORTANCE: Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance. OBJECTIVE: To study the association between melatonin secretion and the risk of developing type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Case-control study nested within the Nurses' Health Study cohort. Among participants without diabetes who provided urine and blood samples at baseline in 2000, we identified 370 women who developed type 2 diabetes from 2000-2012 and matched 370 controls using risk-set sampling. MAIN OUTCOME MEASURES: Associations between melatonin secretion at baseline and incidence of type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction. RESULTS: The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg (5%-95% range, 5.5-84.2 ng/mg) among cases and 36.3 ng/mg (5%-95% range, 6.9-110.8 ng/mg) among controls. Women with lower ratios of 6-sulfatoxymelatonin to creatinine had increased risk of diabetes (multivariable odds ratio, 1.48 [95% CI, 1.11-1.98] per unit decrease in the estimated log ratio of 6-sulfatoxymelatonin to creatinine). Compared with women in the highest ratio category of 6-sulfatoxymelatonin to creatinine, those in the lowest category had a multivariable odds ratio of 2.17 (95% CI, 1.18-3.98) of developing type 2 diabetes. Women in the highest category of melatonin secretion had an estimated diabetes incidence rate of 4.27 cases/1000 person-years compared with 9.27 cases/1000 person-years in the lowest category. CONCLUSIONS AND RELEVANCE: Lower melatonin secretion was independently associated with a higher risk of developing type 2 diabetes. Further research is warranted to assess if melatonin secretion is a modifiable risk factor for diabetes within the general population.
Authors: F B Hu; E Rimm; S A Smith-Warner; D Feskanich; M J Stampfer; A Ascherio; L Sampson; W C Willett Journal: Am J Clin Nutr Date: 1999-02 Impact factor: 7.045
Authors: E R Bertone; W C Willett; B A Rosner; D J Hunter; C S Fuchs; F E Speizer; G A Colditz; S E Hankinson Journal: J Natl Cancer Inst Date: 2001-06-20 Impact factor: 13.506
Authors: Orfeu M Buxton; Sean W Cain; Shawn P O'Connor; James H Porter; Jeanne F Duffy; Wei Wang; Charles A Czeisler; Steven A Shea Journal: Sci Transl Med Date: 2012-04-11 Impact factor: 17.956
Authors: Nicole Soranzo; Serena Sanna; Eleanor Wheeler; Christian Gieger; Dörte Radke; Josée Dupuis; Nabila Bouatia-Naji; Claudia Langenberg; Inga Prokopenko; Elliot Stolerman; Manjinder S Sandhu; Matthew M Heeney; Joseph M Devaney; Muredach P Reilly; Sally L Ricketts; Alexandre F R Stewart; Benjamin F Voight; Christina Willenborg; Benjamin Wright; David Altshuler; Dan Arking; Beverley Balkau; Daniel Barnes; Eric Boerwinkle; Bernhard Böhm; Amélie Bonnefond; Lori L Bonnycastle; Dorret I Boomsma; Stefan R Bornstein; Yvonne Böttcher; Suzannah Bumpstead; Mary Susan Burnett-Miller; Harry Campbell; Antonio Cao; John Chambers; Robert Clark; Francis S Collins; Josef Coresh; Eco J C de Geus; Mariano Dei; Panos Deloukas; Angela Döring; Josephine M Egan; Roberto Elosua; Luigi Ferrucci; Nita Forouhi; Caroline S Fox; Christopher Franklin; Maria Grazia Franzosi; Sophie Gallina; Anuj Goel; Jürgen Graessler; Harald Grallert; Andreas Greinacher; David Hadley; Alistair Hall; Anders Hamsten; Caroline Hayward; Simon Heath; Christian Herder; Georg Homuth; Jouke-Jan Hottenga; Rachel Hunter-Merrill; Thomas Illig; Anne U Jackson; Antti Jula; Marcus Kleber; Christopher W Knouff; Augustine Kong; Jaspal Kooner; Anna Köttgen; Peter Kovacs; Knut Krohn; Brigitte Kühnel; Johanna Kuusisto; Markku Laakso; Mark Lathrop; Cécile Lecoeur; Man Li; Mingyao Li; Ruth J F Loos; Jian'an Luan; Valeriya Lyssenko; Reedik Mägi; Patrik K E Magnusson; Anders Mälarstig; Massimo Mangino; María Teresa Martínez-Larrad; Winfried März; Wendy L McArdle; Ruth McPherson; Christa Meisinger; Thomas Meitinger; Olle Melander; Karen L Mohlke; Vincent E Mooser; Mario A Morken; Narisu Narisu; David M Nathan; Matthias Nauck; Chris O'Donnell; Konrad Oexle; Nazario Olla; James S Pankow; Felicity Payne; John F Peden; Nancy L Pedersen; Leena Peltonen; Markus Perola; Ozren Polasek; Eleonora Porcu; Daniel J Rader; Wolfgang Rathmann; Samuli Ripatti; Ghislain Rocheleau; Michael Roden; Igor Rudan; Veikko Salomaa; Richa Saxena; David Schlessinger; Heribert Schunkert; Peter Schwarz; Udo Seedorf; Elizabeth Selvin; Manuel Serrano-Ríos; Peter Shrader; Angela Silveira; David Siscovick; Kjioung Song; Timothy D Spector; Kari Stefansson; Valgerdur Steinthorsdottir; David P Strachan; Rona Strawbridge; Michael Stumvoll; Ida Surakka; Amy J Swift; Toshiko Tanaka; Alexander Teumer; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Anke Tönjes; Gianluca Usala; Veronique Vitart; Henry Völzke; Henri Wallaschofski; Dawn M Waterworth; Hugh Watkins; H-Erich Wichmann; Sarah H Wild; Gonneke Willemsen; Gordon H Williams; James F Wilson; Juliane Winkelmann; Alan F Wright; Carina Zabena; Jing Hua Zhao; Stephen E Epstein; Jeanette Erdmann; Hakon H Hakonarson; Sekar Kathiresan; Kay-Tee Khaw; Robert Roberts; Nilesh J Samani; Mark D Fleming; Robert Sladek; Gonçalo Abecasis; Michael Boehnke; Philippe Froguel; Leif Groop; Mark I McCarthy; W H Linda Kao; Jose C Florez; Manuela Uda; Nicholas J Wareham; Inês Barroso; James B Meigs Journal: Diabetes Date: 2010-09-21 Impact factor: 9.461
Authors: Timothy I Morgenthaler; Janet B Croft; Leslie C Dort; Lauren D Loeding; Janet M Mullington; Sherene M Thomas Journal: J Clin Sleep Med Date: 2015-09-15 Impact factor: 4.062
Authors: Garth R Swanson; Annika Gorenz; Maliha Shaikh; Vishal Desai; Thomas Kaminsky; Jolice Van Den Berg; Terrence Murphy; Shohreh Raeisi; Louis Fogg; Martha Hotz Vitaterna; Christopher Forsyth; Fred Turek; Helen J Burgess; Ali Keshavarzian Journal: Am J Physiol Gastrointest Liver Physiol Date: 2016-05-19 Impact factor: 4.052