Background: Melatonin modulates circadian rhythms in physiology and sleep initiation.
Genetic variants of the MTNR1B locus, encoding the melatonin MT2 receptor, have
been associated with increased type 2 diabetes (T2D) risk. Carriers of the common
intronic MTNR1B rs10830963 T2D risk variant have modified sleep and circadian traits
such as changes of the melatonin profile. However, it is currently unknown whether rare
variants in the MT2 coding region are also associated with altered sleep and circadian
phenotypes, including meal timing.
Materials and Methods: In this pilot study, 28 individuals [50% male; 46–82 years
old; 50% with rare MT2 mutations (T2D MT2)] wore actigraphy devices and filled
out daily food logs for 4 weeks. We computed circadian, sleep, and caloric intake
phenotypes, including sleep duration, timing, and regularity [assessed by the Sleep
Regularity Index (SRI)]; composite phase deviations (CPD) as well a sleep timing-based
proxy for circadian misalignment; and caloric intake patterns throughout the day. Using
regression analyses, we estimated age- and sex-adjusted mean differences (MD) and
95% confidence intervals (95%CI) between the two patient groups. Secondary analyses
also compare T2D MT2 to 15 healthy controls.
Results: Patients with rare MT2 mutations had a later sleep onset (MD = 1.23,
95%CI = 0.42;2.04), and midsleep time (MD = 0.91, 95%CI = 0.12;1.70), slept more
irregularly (MD in SRI = −8.98, 95%CI = −16.36;−1.60), had higher levels of behavioral
circadian misalignment (MD in CPD = 1.21, 95%CI = 0.51;1.92), were more variable in regard to duration between first caloric intake and average sleep offset (MD = 1.08,
95%CI = 0.07;2.08), and had more caloric episodes in a 24 h day (MD = 1.08,
95%CI = 0.26;1.90), in comparison to T2D controls. Secondary analyses showed similar
patterns between T2D MT2 and non-diabetic controls.
Conclusion: This pilot study suggests that compared to diabetic controls, T2D MT2
patients display a number of adverse sleep, circadian, and caloric intake phenotypes,
including more irregular behavioral timing. A prospective study is needed to determine
the role of these behavioral phenotypes in T2D onset and severity, especially in view of
rare MT2 mutations.