Variabilidade glicêmica em pacientes com diabetes mellitus tipo 2 (DMT2): o papel da melatonina em um estudo crossover, duplo cego, placebo controlado, randomizado.

Abstract

Type 2 diabetes mellitus (DMT2) is a disease characterized by chronic hyperglycemia. Melatonin, a hormone that signals the phase of our circadian rhythm, plays a key role in biological rhythms. Previous studies have shown that patients with DMT2 have a deficiency in the production of melatonin. The role of this substance in the hyperglycemia of patients with T2DM has been widely studied. However, we believe that melatonin may influence the circadian rhythm of glucose variation more than its average. In this work, we tried to evaluate whether the supplementation of 3mg of melatonin at 21:00 could reduce the variation of capillary glycemia in patients with T2DM. For this, we designed a crossover, double blind, placebo controlled and randomized study. 30 patients participated in this study. 15 of them followed the intervention sequence: placebo (7 days) - washout (7 days) - melatonin (7 days), and another 15: melatonin (7 days) - washout (7 days) - placebo (7 days). On the 5th, 6th and 7th days of the first and third week, the patients measured pre- and postprandial capillary glycemia, a total of 6 measurements per day. In the seventh, the absolute variation between pre and post-prandial breakfast glucose levels was greater when patients used melatonin. In addition, the range of glycemic variation between the sixth day after dinner and the seventh day fasting was greater when patients used melatonin. There are two theoretical ways to explain the first result: Melatonin inhibits G protein-coupled cellular receptors during the night. In the morning, after the drop in serum levels, this intracellular pathway could become hypersensitive and suddenly increase the production of insulin counter-regulatory hormones. Another possible explanation for this result is the possible residual effect of exogenous melatonin in the morning, which, by inhibiting insulin, can generate a hyperglycemic response to the diet.. Melatonin acts directly to suppress Clock/Bmal1 complex activity. A prolonged inhibitory effect on this complex could lead to abnormal, erratic synchronization in the biological clock and glycemic amplitude. This study concluded, therefore, that the short-term use of melatonin can alter the glycemic variability of patients with T2DM. Future, longer-term studies are needed to investigate the role of this hormone in the glycemic variability of these patients.