Abnormal Circadian Rhythm of Melatonin in Diabetic Autonomic Neuropathy

Abstract

The circadian rhythm of melatonin secretion from the pineal body is entrained to the light-dark cycle and is controlled via sympathetic fibres originating from the superior cervical ganglia. We have therefore examined plasma melatonin profiles in diabetics with and without evidence of autonomic neuropathy and in normal matched controls. The physiological increase in nocturnal plasma melatonin concentration was not observed in diabetics neuropaths. There was no consistent pattern in the diabetics without neuropathy; only three out of the eight subjects in this group had a sustained nocturnal increase in melatonin. Normal diurnal variation of plasma cortisol was present in all groups of subjects. The present study shows that diabetic patients with evidence of autonomic neuropathy lack the normal circadian changes of plasma melatonin concentration. This provides confirmation for the control of pineal function via the sympathetic nervous system in man. The impaired melatonin profiles observed in diabetic patients without apparent autonomic neuropathy suggest that a subclinical state of sympathetic denervation may exist in this group of diabetics.

Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men

“…Although there was no significant difference in plasma melatonin between the lean and T2DM groups, this comparison is less meaningful than the comparison between weight-matched obese non-diabetic and T2DM groups, due to the effects of obesity per se described above. Reduced amplitude melatonin rhythms have been previously reported in T2DM patients with autonomic neuropathy [26], [27] and retinopathy [28]. A further study has reported a small decrease in serum melatonin across the 24-hour diurnal cycle in T2DM patients [29]; however, many of these individuals were extremely obese (mean BMI  = 44 for T2DM versus 34 for non-T2DM ) and there were no other participant details provided, making interpretation of the data extremely difficult.…”

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

“…This antagonism is in line with the fact that, in man, the low insulin levels at night and high levels during the day coincide with elevated nocturnal melatonin concentrations and reduced levels during the day [37]. In addition, diabetic patients are largely devoid of a circadian melatonin rhythm [38,39]. Altogether, the cited findings clearly indicate that melatonin-insulin interactions, which are modulated and regulated by catecholamines, particularly norepinephrine [40–46], play an important role in glucose metabolism.…”

Melatonin, mitochondria, and the metabolic syndrome

“…A further important aspect concerns the contrasting findings of impairments of insulin secretion by the overexpressed MT2 G allele and the observed reduced melatonin levels in patients with diabetes [110,[116][117][118][119][120]. The reduction in melatonin levels should presumably be considered as a primary change that is associated with the initiation and/or progression of the disease.…”