Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy

Abstract

The present study has been designed to determine melatonin levels in type 2 diabetic patients and test the relationship between the autonomic nervous system and melatonin dynamics. Thirty-six type 2 diabetic patients and 13 age-matched healthy subjects were recruited for the study. Circadian rhythm of melatonin secretion was assessed by measuring serum melatonin concentrations between 02:00-04:00 and 16:00-18:00 hr. Melatonin dynamics were re-evaluated with respect to autonomic nervous system in diabetic patients with autonomic neuropathy who were diagnosed by the cardiovascular reflex tests, heart rate variability (HRV), and 24-hr blood pressure monitoring. Nocturnal melatonin levels and the nocturnal melatonin surge were low in the diabetic group (P = 0.027 and 0.008 respectively). Patients with autonomic neuropathy revealed decreased melatonin levels both at night and during day when compared with healthy controls (P < 0.001 and 0.004 respectively) while the melatonin dynamics were similar to controls in patients without autonomic neuropathy. Nocturnal melatonin level was positively correlated with nocturnal high and low frequency components of HRV (P = 0.005 and 0.011 respectively) and systolic and diastolic blood pressures at night (P = 0.002 and 0.004 respectively) in patients with autonomic neuropathy. We found a negative correlation between nocturnal melatonin levels and the degree of systolic blood pressure decrease at night (r = -0.478, P = 0.045). As a conclusion this study has shown that circadian rhythm of melatonin secretion is blunted in type 2 diabetic patients and there is a complex relationship between various components of autonomic nervous system and melatonin secretion at night. Among the patients with autonomic neuropathy those with more preserved HRV and the systolic nondippers (<10% reduction in blood pressure during the night relative to daytime values) have more pronounced melatonin surge at night.

Chronomedicine and type 2 diabetes: shining some light on melatonin

“…As with pre-clinical research, data from clinical studies generally support a correlation between reduced night-time melatonin and increased diabetes risk (see text box: Melatonin administration in diabetes). Studies show that normal daily rhythms of melatonin secretion are altered and/or abolished in individuals with type 2 diabetes, particularly those with autonomic neuropathy [147,148]. Similar decrements in plasma melatonin levels during the night were also reported in diabetic patients with proliferative retinopathy relative to individuals without diabetes and diabetic individuals without retinopathy [149].…”

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

“…On the other hand, the high melatonin plasma levels in streptozotocin rats were associated with increased expression of Aanat mRNA [21]. These results are in agreement with observations that administration of melatonin [22][23][24][25][26][27] or pinealectomy [28,29] affect metabolic disturbances related to plasma insulin and diabetes [19]. Using the LEW.1AR1-iddm rat, we analysed the situation in a spontaneous animal model of human type 1 diabetes.…”

“…In this context, recent investigations have analysed the plasma levels of melatonin in slightly hyperinsulinaemic GotoKakizaki (GK) rats, a rat model of type 2 diabetes [16], as well as in a hypoinsulinaemic streptozotocin-induced rat model of type 1 diabetes. GK rats had reduced plasma melatonin levels, whereas these were increased in streptozotocin rats [17][18][19]. Furthermore, it was proved that the reduced plasma melatonin levels were coupled with decreased pineal melatonin synthesis in GK rats [18,20].…”

Pineal gland calcification, lumbar intervertebral disc degeneration and abdominal aorta calcifying atherosclerosis correlate in low back pain subjects: A cross-sectional observational CT study

“…This hypothesis is based on the following observations: (a) MEL secretion decreases with advanced age, a period associated with an increased risk of development of disc degeneration and atherosclerotic calcifications [5,6]; (b) obesity, which is a major risk factor for DDD and atherosclerosis, is associated with impaired circadian MEL secretion [13,14]; (c) diabetes mellitus, which is an additional risk factor for DDD and atherosclerosis, is associated with decreased MEL secretion and an increased rate of pineal calcification [15,16]; and (d) significant difference in the presence as well as severity of degenerated disc, aortic atherosclerosis, and pineal calcification according to ethnicity [8,17,18].To test our hypothesis, we designed a cross-sectional observational radiological study to investigate the correlations between pineal gland calcification, intervertebral disc degeneration and abdominal aorta atherosclerosis in subjects with low back pain to clarify the possible impact of pineal gland calcification.…”