Matthew Maxwell

Introduction: Metabolic syndrome is defined as having 3 out of 5 criteria: insulin resistance, elevated blood glucose, hypertension, dyslipidemia, and obesity¹. It is a potentially life-threatening disease that is associated with an increased risk of developing cardiovascular disease, diabetes, cognitive decline, and even stroke¹. Presently, treatment for metabolic syndrome is primarily focused on treating individual symptoms such as the use of antihypertensives and statins¹. Night shift work is becoming increasingly more common with >20% of workers participating in shift work in industrialized countries². Participation in shift work is associated with a disruption in sleep/wake cycles and mealtimes and results in an increased risk of developing obesity, Type II Diabetes, Cardiovascular disease, and some cancers^2,3. In particular, an 8-year study of hospital workers in Taiwan showed that night shift workers had an increased risk for the development of Metabolic Syndrome (OR 1.47, p<0.01) and an increased waist circumference (OR 1.26, p<0.01)⁴. Methods: Human participants were subjected to a 12-hour circadian misalignment and skeletal muscle biopsies were taken to analyze insulin sensitivity⁵. Blood samples were collected from individuals after two consecutive day shifts and two consecutive night shifts to compare glucose metabolism during different shifts⁶. Syrian Hamsters subjected to Metabolic Syndrome were treated with subcutaneous melatonin⁷. Human participants received a late evening meal and were kept awake overnight and subjected to either 1) light, 2) dark plus exogenous melatonin, or 3) light plus exogenous melatonin⁸. Results: Misalignment leads to decreased insulin sensitivity accompanied by an increase in fasting plasma glucose levels⁵. After two consecutive night shifts there was an increase in postprandial glucose, delayed time to peak insulin and c-peptide concentration, and delayed time to lowest glucagon suppression⁶. Hamsters subjected to metabolic syndrome had all their symptoms ameliorated by treatment with melatonin⁷. Symptoms prevented included elevated triglyceride, cholesterol, and LDL levels⁷. Exogenous melatonin following a late evening meal in participants kept awake overnight results in a decrease in postprandial glucose and insulin vs those only subjected to light at night⁸. Conclusions: Circadian misalignment results in impaired glucose metabolism ^5,6 and an increased risk of developing Metabolic Syndrome^4,5,6. Melatonin decreased symptoms of Metabolic Syndrome in animal models⁷ and decreased the impact of shift work on metabolism in human participants. Melatonin has been shown to have potential ameliorating factors in treatment and/or prevention of Metabolic Syndrome, especially in people subjected to circadian misalignment as in shift work.

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2. Rácz B, Dušková M, Stárka L, Hainer V, Kunešová M. Links between the circadian rhythm, obesity and the microbiome. Physiol Res. 11 28 2018;67(Suppl 3):S409-S420. doi:10.33549/physiolres.934020
3. Li Y, Ma J, Yao K, et al. Circadian rhythms and obesity: Timekeeping governs lipid metabolism. J Pineal Res. Oct 2020;69(3):e12682. doi:10.1111/jpi.12682
4. Cheng WJ, Liu CS, Hu KC, Cheng YF, Karhula K, Härmä M. Night shift work and the risk of metabolic syndrome: Findings from an 8-year hospital cohort. PLoS One. 2021;16(12):e0261349. doi:10.1371/journal.pone.0261349
5. Wefers J, van Moorsel D, Hansen J, et al. Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. Proc Natl Acad Sci U S A. 07 24 2018;115(30):7789-7794. doi:10.1073/pnas.1722295115
6. Sharma A, Laurenti MC, Dalla Man C, et al. Glucose metabolism during rotational shift-work in healthcare workers. Diabetologia. 08 2017;60(8):1483-1490. doi:10.1007/s00125-017-4317-0
7. Santos-Ledo A, Luxán-Delgado B, Caballero B, et al. Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model. Antioxidants (Basel). May 18 2021;10(5)doi:10.3390/antiox10050796
8. Albreiki MS, Middleton B, Hampton SM. The effect of melatonin on glucose tolerance, insulin sensitivity and lipid profiles after a late evening meal in healthy young males. J Pineal Res. Dec 2021;71(4):e12770. doi:10.1111/jpi.12770