C75-16 Melatonin and Cardiometabolic Outcomes in Diabetes: A Systematic Review of Experimental and Clinical Evidence

Abstract Rationale Melatonin, widely used as a sleep aid, has effects beyond sleep regulation, influencing circadian rhythms, oxidative stress, vascular function, and inflammation. It directly modulates pancreatic β-cell function and glucose transporter activity, affecting insulin secretion and glycemic control. Preclinical and clinical studies demonstrate cardioprotective benefits, including improved myocardial injury, antioxidant capacity, and vascular integrity, particularly in diabetic and postoperative contexts. However, mechanistic and genetic data suggest melatonin may impair insulin secretion in susceptible individuals. Given these mixed cardiovascular and metabolic effects, understanding melatonin’s role is critical for safe and effective use in patients with diabetes. Results Five studies met the inclusion criteria: two animal experiments, two randomized clinical trials, and one mechanistic human study. In diabetic mice and rats (n = 40 each), melatonin at 3 mg/kg and 10 mg/kg improved cardiovascular injury markers. In mice, melatonin reduced cardiomyocyte toxicity and vascular detachment, inhibited IL-1β, stabilized vascular pericytes, and up-regulated anti-senescence pathways (p 0.05). In rats, melatonin enhanced total antioxidant capacity and nitric oxide levels, normalized biochemical markers, and restored cardiac and renal histology (p 0.05).In a randomized postoperative trial (≈60 CABG patients), nightly melatonin (5-10 mg) improved left-ventricular ejection fraction and antioxidant status while lowering TNF-α and lipid peroxidation (p 0.05). In a separate double-blind trial of 50 adults with type 2 diabetes, melatonin improved anthropometric indices and blood pressure; however, it did not improve the atherogenic index of plasma, indicating no measurable benefit on lipid-related cardiovascular risk. A mechanistic study showed MTNR1B risk-allele carriers had reduced insulin secretion, further impaired by melatonin. Conclusion Current evidence suggests that melatonin exerts cardioprotective, antioxidant, and anti-inflammatory effects in diabetic and postoperative settings, improving cardiac function and oxidative balance. Experimental models consistently demonstrate reversal of diabetes-induced myocardial and vascular injury, while clinical trials indicate potential metabolic and vascular benefits with good tolerability. However, genetic predisposition influencing melatonin receptor signaling may alter glycemic responses, warranting caution in individuals with impaired insulin secretion. Larger, multi-center randomized trials are needed to confirm melatonin’s cardiovascular and metabolic effects in diabetic. Future studies should stratify participants by MTNR1B genotype, optimize dosing and treatment duration, and evaluate long-term outcomes such as heart failure progression, glycemic control, and survival to clarify melatonin’s therapeutic role in cardio-metabolic disease. This abstract is funded by: none