Lower nocturnal urinary 6-sulfatoxymelatonin is associated with more severe insulin resistance in patients with prediabetes

Objective: Melatonin, a neurohormone secreted by the pineal gland, controls circadian rhythmicity, modulates sleep and plays a role in glucose metabolism. Low secretion of nocturnal urinary 6-sulfatoxymelatonin (aMT6S) was associated with incident diabetes. Sleep disturbances have also been shown to be risk factors for diabetes. In this study, we explored the relationship between nocturnal urinary aMT6s and markers of glucose metabolism in prediabetes patients, considering sleep related factors. Methods: Sixty two non-shift working patients with prediabetes [hemoglobin A1c (HbA1c) 5.7–6.49%] who were not on beta-blockers participated. Sleep duration and efficiency was recorded using 7-day actigraphy. Obstructive sleep apnea was evaluated using an overnight in-home monitoring device. Nocturnal urinary aMT6s/creatinine ratio was measured from an overnight urine sample. Oral glucose tolerance test (OGTT, 75-grams glucose) was performed, with measurements of insulin and glucose levels. Results: Mean (SD) age was 55.3 (8.2) years and mean HbA1c level was 6.01 (0.2)%. Mean (SD) sleep duration 6.0 (0.9) h, sleep efficiency was 83.4 (6.6)% and a median (interquartile rage) apnea hypopnea index was 10.3 (3.6, 16.4). Median nocturnal urinary aMT6s was 17.4 (9.4, 28.2) ng/mg creatinine. Higher nocturnal urinary aMT6s significantly correlated with lower fasting insulin (p = 0.004), lower insulin response to OGTT (p = 0.027), and lower fasting and whole body insulin resistance as indicated by lower HOMA-IR and higher Matsuda insulin sensitivity index (p = 0.006 and p = 0.011, respectively), but it was not correlated with fasting glucose, glucose response to OGTT, or HbA1c. Sleep duration inversely correlated with HbA1c but no other correlations were found between other sleep variables and markers of glucose metabolism or nocturnal urinary aMT6s. After adjusting for body mass index, higher nocturnal urinary aMT6s significantly correlated with lower HOMA-IR (p = 0.025) and fasting insulin levels (p = 0.014). Conclusion: Nocturnal urinary aMT6s inversely correlated with fasting insulin resistance and insulin levels in patients with prediabetes. These results support the role of melatonin in glucose metabolism. Keywords: Melatonin, Glucose metabolism, Insulin resistance, Insulin, Prediabete