Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. When administering melatonin, the proximity to meal timing may need to be considered, particularly in those at risk for glucose intolerance.

Aims The common MTNR1B genetic variant rs10830963 is associated with an increased risk of type 2 diabetes (T2D). To date, no experimental study has tested the effect of the MTNR1B variant on glucose metabolism in humans during exposure of the melatonin receptors to their ligand. The aim of this study was to investigate whether this MTNR1B variant influenced the effect of melatonin (5 mg) on glucose tolerance assessed by an oral glucose tolerance-test (OGTT; 75 g) at different times of the day (morning and evening) as compared to a placebo. Methods Seventeen normoglycemic women (24±6 y; BMI 23.0±3.3 kg/m2) completed the study (11 carriers of the risk allele [CG] and 6 noncarriers [CC]). Results The effect of melatonin on glucose tolerance depended on the genotype. In the morning, the effect of melatonin (melatonin-placebo) on the glucose area-under-the-curve (AUC) above baseline differed significantly (P=0.036) between the carriers and noncarriers. This effect of melatonin on the carriers was six times as large as that on the noncarriers. The MTNR1B SNP explained over one-quarter (26%) of the inter-individual differences in the effect of melatonin on glucose AUC. However, in the evening, the effect of melatonin on glucose AUC of the carriers and noncarriers did not differ significantly (P>0.05). Conclusions MTNR1B rs10830963 risk variant worsens the effect of melatonin on glucose tolerance, suggesting the importance of genotyping and personalized recommendations, especially in people consuming food when melatonin levels are elevated. Large-scale studies in vulnerable populations are necessary to translate these results into real-world, clinically-relevant recommendations.

The adequate time to perform physical activity (PA) to maintain optimal circadian system health has not been defined. We studied the influence of morning and evening PA on circadian rhythmicity in 16 women with wrist temperature (WT). Participants performed controlled PA (45 min continuous-running) during 7 days in the morning (MPA) and evening (EPA) and results were compared with a no-exercise-week (C). EPA was characterized by a lower amplitude (evening: 0.028 ± 0.01 °C versus control: 0.038 ± 0.016 °C; p<0.05) less pronounced second-harmonic (power) (evening: 0.41 ± 0.47 versus morning: 1.04 ± 0.59); and achrophase delay (evening: 06:35 ± 02:14 h versus morning: 04:51 ± 01:11 h; p>0.05) as compared to MPA and C. Performing PA in the late evening might not be as beneficial as in the morning.