OBJECTIVE The circadian clock regulates glucose metabolism by mediating the activity of metabolic enzymes, hormones, and transport systems. Breakfast skipping and night eating have been associated with high HbA1c and postprandial hyperglycemia after lunch and dinner. Our aim was to explore the acute effect of breakfast consumption or omission on glucose homeostasis and clock gene expression in healthy individuals and individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In a crossover design, 18 healthy volunteers and 18 volunteers with 14.5 ± 1.5 years diabetes, BMI 30.7 ± 1.1 kg/m2, andHbA1c 7.6 ± 0.1% (59.6 ± 0.8mmol/mol) were randomly assigned to a test day with breakfast and lunch (YesB) and a test day with only lunch (NoB). Postprandial clock and clock-controlled gene expression, plasma glucose, insulin, intact glucagon-like peptide 1 (iGLP-1), and dipeptidyl peptidase IV (DPP-IV) plasma activity were assessed after breakfast and lunch. RESULTS In healthy individuals, the expression level of Per1, Cry1, Rorα, and Sirt1 was lower (P < 0.05) but Clock was higher (P < 0.05) after breakfast. In contrast, in individuals with type 2 diabetes, Per1, Per2, and Sirt1 only slightly, but significantly, decreased and Rora increased (P < 0.05) after breakfast. In healthy individuals, the expression level ofBmal1, Rora, andSirt1was higher (P < 0.05) after lunch on YesB day,whereas the other clock genes remained unchanged. In individuals with type 2 diabetes, Bmal1, Per1, Per2, Rev-erba, and Ampk increased (P < 0.05) after lunch on the YesB day. Omission of breakfast altered clock and metabolic gene expression in both healthy and individuals with type 2 diabetes. CONCLUSIONS Breakfast consumption acutely affects clock and clock-controlled gene expression leading to normal oscillation. Breakfast skipping adversely affects clock and clockcontrolled gene expression and is correlated with increased postprandial glycemic response in both healthy individuals and individuals with diabetes.
Bibliographical noteFunding Information:
Funding. This study was funded by D-Cure and the Ministry of Health, Israel (grant 3-0000-11406). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. D.J. and O.F. contributed to the conception and design of the study; acquired, analyzed, and interpreted data; and drafted and revised the manuscript. J.W. contributed to the conception and design of the study, acquired and interpreted data, and drafted the manuscript. Z.L., N.C., T.G., M.M., and Y.B.-D. contributed to the conception and designofthestudy,acquiredandinterpreteddata, organized the randomization, and drafted the manuscript. I.R. and B.A. researched data, contributed to the interpretation of the data, and drafted and revised the manuscript. M.B. analyzed and interpreted data. D.J. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. This study was presented orally at the 77th Scientific Sessions of the American Diabetes Association, San Diego, CA, 9–13 June 2017.
© 2017 by the American Diabetes Association.