Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes.

Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.

Ambulatory blood pressure and its variability in adults born preterm.

Adults born preterm have higher blood pressure (BP) than those born at term. Most studies have focused on preterm birth, and few have assessed BP variability, an independent risk factor of cardiovascular disease. We studied the association of preterm birth with 24-hour ambulatory BP, measured by an oscillometric device, in 42 young adults born early preterm (<34 weeks), 72 born late preterm (34-36 weeks), and 103 controls (≥37 weeks). Sleep was confirmed with accelerometry in 72.4% of subjects. The 24-hour systolic BP of adults born early preterm was 5.5 mm Hg higher (95% confidence interval, 1.9-9.3), awake systolic BP was 6.4 mm Hg higher (95% confidence interval, 2.8-10.1), and sleeping systolic BP was 2.9 mm Hg higher (95% confidence interval 0.3-7.5) when adjusted for age, sex, and use of accelerometry. The differences remained similar when adjusted for height, body mass index, physical activity, smoking, parental education, maternal body mass index, smoking during pregnancy, and gestational diabetes mellitus and attenuated slightly when adjusted for maternal hypertensive pregnancy disorders. Adults born early preterm also had higher BP variability as indicated by higher individual standard deviations of systolic BP and diastolic BP. Although our results were consistent with a dose-response relationship between shorter gestation and higher BP, the difference between the late preterm and term groups was not statistically significant. Our results suggest that the higher BP in adults born early preterm is present during both waking and sleeping hours, may be more pronounced during waking hours, and is accompanied by higher individual BP variability.