Influences of Breakfast on Clock Gene Expression and Postprandial Glycemia in Healthy Individuals and Individuals With Diabetes: A Randomized Clinical Trial

Diabetes Care. 2017 Nov;40(11):1573-1579. doi: 10.2337/dc16-2753. Epub 2017 Aug 22.


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, and HbA1c 7.6 ± 0.1% (59.6 ± 0.8 mmol/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 Rorα increased (P < 0.05) after breakfast. In healthy individuals, the expression level of Bmal1, Rorα, and Sirt1 was 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-erbα, 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 clock-controlled gene expression and is correlated with increased postprandial glycemic response in both healthy individuals and individuals with diabetes.

Trial registration: NCT01939782.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Breakfast*
  • Circadian Clocks / genetics*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Gene Expression Regulation
  • Glucagon-Like Peptide 1 / blood
  • Glycated Hemoglobin A / metabolism
  • Homeostasis
  • Humans
  • Insulin / blood
  • Middle Aged
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • Postprandial Period / genetics*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism


  • ARNTL Transcription Factors
  • ARNTL protein, human
  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • PER1 protein, human
  • PER2 protein, human
  • Period Circadian Proteins
  • Glucagon-Like Peptide 1
  • AMP-Activated Protein Kinases
  • SIRT1 protein, human
  • Sirtuin 1

Associated data