4. Discussion
ASCVD, prediabetes, diabetes, T2DM, dyslipidemia
PREDIABETES, DIABETES, DYSLIPIDEMIA, ARTERIAL STIFFNESS, EVENTS, ASCVD, ENDOTHELIAL DYSFUNCTION
In this 14-week randomized placebo-controlled trial, we evaluated for the first time, the efficacy of carnosine supplementation in the improvement of endothelial function, arterial stiffness, and indicators of high ASCVD risk in patients with prediabetes and T2DM. Our main outcome adds to the body of emerging evidence demonstrating that 2 g/day carnosine supplementation had no effect on endothelial dysfunction, blood pressure, markers of cardiovascular risk, arterial stiffness, lipid profile, hepatic health indicators, or renal outcomes compared to placebo in patients with prediabetes and T2DM with good glycemic control. As previously reported, carnosine was well-tolerated and we did not observe any significant side effects [Carnosine is considered a potential therapeutic option that could mitigate the development of cardiovascular events associated with diabetes [A recently published review provided evidence regarding the effect of carnosine on endothelial function, but highlighted the need for human studies [Another finding of this study was that the use of carnosine was not associated with the improvement of either central or peripheral blood pressure and pulse pressure and heart rate, while there is a body of emerging evidence on the anti-hypertensive property of carnosine [Several animal studies have investigated the effect of carnosine supplementation on lipid parameters and have shown dyslipidemia improvement and reduction of oxidation and glycation of LDL-C following carnosine treatment in both diabetic and non-diabetic rodents [Despite the findings from animal studies that carnosine supplementation resulted in improvement in kidney and liver parameters, we did not find any significant effect of carnosine on fibroScanThe present study has several strengths, the main one being that it was the first time that we examined the effectiveness of carnosine supplementation on cardiovascular outcomes using gold-standard endoPAT and Complior devices and other cardiometabolic indicators in individuals with prediabetes and T2DM. Additionally, this study included a population with prediabetes and T2DM. Considering the mentioned strengths, the present study also has some limitations. Firstly, we are aware that the small sample size in our study may have an impact on the analytical power. To prevent bias, all patients were sequentially recruited using strict inclusion/exclusion criteria. Secondly, the moderate dropout rate (12.2%) may have led to a breach of the randomization principles, altering the effect size. To this end, although an intention-to-treat analysis would be favorable, we conducted per-protocol analysis which is preferred in trials with small sample size [