Diurnal variation in insulin sensitivity of glucose metabolism is associated with diurnal variations in whole-body and cellular fatty acid metabolism in metabolically normal women

J Clin Endocrinol Metab. 2014 Sep;99(9):E1666-70. doi: 10.1210/jc.2014-1579. Epub 2014 May 30.


Context: The mechanism(s) responsible for diurnal variations in insulin sensitivity of glucose metabolism in healthy people are unclear.

Objective: The objective of the study was to evaluate whether diurnal variations in whole-body and cellular fatty acid metabolism could contribute to evening insulin resistance in metabolically normal people.

Subjects and design: We measured plasma the free fatty acid (FFA) concentration, palmitate kinetics, and skeletal muscle expression of genes involved in fatty acid metabolism at breakfast (7:00 am) and dinner (7:00 pm) in 13 overweight (body mass index 27.8 ± 1.2 kg/m(2)) but metabolically normal, women.

Results: Plasma FFA concentration was approximately 30% greater just before consuming dinner than breakfast (P < .05) and remained greater after dinner than breakfast (FFA areas under the curve: 0.88 ± 0.33 and 0.51 ± 0.09 μmol/mL × 4 h, P = .001). However, adipose tissue lipolytic activity was not different in the evening and in the morning. Skeletal muscle expression of genes that regulate fatty acid oxidation were 38-82% lower, whereas genes involved in de novo lipogenesis were 51%-87 % higher before dinner than before breakfast (all P < .05), and these changes were associated with diurnal variation in the muscle expression of core clock genes that regulate fatty acid metabolism.

Conclusion: Metabolically normal women demonstrate diurnal variations in fatty acid metabolism, manifested by an increase in circulating FFAs, presumably derived from previous meal consumption rather than lipolysis of adipose tissue triglycerides, and a shift in muscle fatty acid metabolism from oxidation to lipogenesis. These metabolic alterations could be responsible for the known evening decline in insulin sensitivity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / metabolism
  • Adult
  • Blood Glucose / metabolism*
  • Circadian Rhythm / physiology*
  • Eating / physiology
  • Fatty Acids, Nonesterified / metabolism*
  • Female
  • Humans
  • Hydrocortisone / blood
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Lipogenesis / physiology
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Overweight / metabolism*
  • Palmitates / pharmacokinetics
  • Reference Values


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Palmitates
  • Hydrocortisone