Glycemic Variability in Patients with Type 2 Diabetes Mellitus (T2DM): The Role of Melatonin in a Crossover, Double-Blind, Placebo-Controlled, Randomized Study

Abstract

Background: Glycemic variability in patients with type 2 diabetes mellitus (T2DM) may be associated with chronic complications of the disease. Melatonin is a hormone that plays a crucial role in biological rhythms. Previous studies have indicated that individuals with T2DM often exhibit reduced melatonin production. In this study, our objective was to investigate whether nighttime melatonin supplementation could mitigate glycemic variability in these patients. Methods: Crossover, double-blind, placebo-controlled, randomized study. A total of 30 patients were enrolled in this study. The study included 15 participants who followed the intervention sequence of placebo (7 days)—washout (7 days)—melatonin (3 mg) (7 days), and another 15 participants who followed the sequence of melatonin (3 mg) (7 days)—washout (7 days)—placebo (7 days). During the final three days of the first and third weeks, the participants measured their pre- and postprandial capillary blood glucose levels. This study was reported according to the CONSORT 2010 statement: extension to randomized crossover trials. Results: There was a significant absolute difference in the breakfast blood glucose levels (p = 0.016) on Day 7. The use of melatonin determined a greater positive variation between pre- and postprandial glycemia than the placebo. The difference in glycemic amplitude between post-dinner Day 6 and pre-breakfast Day 7 was also significantly higher in the melatonin group (p = 0.032). Conclusions: Melatonin increased glycemic variability in individuals with type 2 diabetes mellitus (T2DM). These results can be attributed to the residual daytime effects of melatonin, prospective proximal effects, and damage to the prospective distal effects of exogenous melatonin. Therefore, caution should be exercised when administering melatonin supplementation to patients with T2DM, taking into consideration factors such as dosage, duration of use and genetic considerations.

Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice

“…One study enrolled 30 patients with type 2 diabetes and gave them melatonin therapy for 7 days. The results showed that melatonin supplementation increased glycemic variability in patients with T2DM (Martorina and Tavares, 2023). However, some studies have suggested that melatonin is effective in treating diabetes.…”

“…Meanwhile, we found that energy metabolism imbalance was the main cause of diabetes-induced hippocampal damage, including carbon metabolism (TCA cycle, glycolysis/gluconeogenesis, pyruvate metabolism), purine metabolism, biosynthesis of amino Correlation analysis of DEPs-DRMs showed that melatonin may be a critical target for DP to alleviate DCI. Abnormal melatonin secretion affects blood glucose levels (Martorina and Tavares, 2023) and circadian rhythm. Hyperglycemia and circadian rhythm disorder are risk factors for DCI (Barone et al, 2021;Liu et al, 2023).…”