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

Abstract

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 HbA_1c 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. 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 HbA_1c 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. In healthy individuals, the expression level of <i>Per1</i>, <i>Cry1</i>, <i>Rorα</i>, and <i>Sirt1</i> was lower (<i>P</i> < 0.05) but <i>Clock</i> was higher (<i>P</i> < 0.05) after breakfast. In contrast, in individuals with type 2 diabetes, <i>Per1</i>, <i>Per2</i>, and <i>Sirt1</i> only slightly, but significantly, decreased and <i>Rorα</i> increased (<i>P</i> < 0.05) after breakfast. In healthy individuals, the expression level of <i>Bmal1</i>, <i>Rorα</i>, and <i>Sirt1</i> was higher (<i>P</i> < 0.05) after lunch on YesB day, whereas the other clock genes remained unchanged. In individuals with type 2 diabetes, <i>Bmal1</i>, <i>Per1</i>, <i>Per2</i>, <i>Rev-erbα</i>, and <i>Ampk</i> increased (<i>P</i> < 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. 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.