It is with great interest that we read the paper by Yoshida et al. It provided further insight into the relationship between the function of the heart, hyperglycemia and insulin resistance in younger cohorts. While heavily studied in older cohorts, younger cohorts were relatively absent from studies. The authors reported that cumulative fasting glucose and insulin resistance were associated with midlife diastolic dysfunction. However, we suggest that further dimensions of glycemic exposure should be explored to provide a more accurate assessment of cardiometabolic effects of hyperglycemia on the heart.
The approach of Yoshida et al. in calculating the area under the curve is good at quantifying mean exposure, but fails to account for rapid changes. Current relevant findings show that fluctuating glucose levels are associated with endothelial dysfunction, prolonged inflammation, and oxidative stress on the heart. , Moreover, higher long-term glycemic variability has been linked to adverse heart failure outcomes, even when mean glucose remains within target ranges. This effect may be equal to, or more potent than sustained hyperglycemia. Postprandial glucose spikes have also been associated with decreased vascular function even in euglycemic men, in the long term. , These rapid changes generate reactive oxygen species, which alter the structural integrity of the heart muscle, affecting microvascular tone and calcium handling. Further inquiry into continuous blood glucose level monitoring could expose earlier or stronger associations with cardiac dysfunction than cumulative fasting measures alone.
Another important concept is metabolic memory. It has been shown that transient changes in blood glucose levels cause epigenetic changes that continue to damage the heart, even after glucose level stabilization. These changes include persistent DNA methylation and continued pro-oxidant gene expression. , This can provide further reasoning as to why individuals develop diastolic dysfunction, despite later regulating blood glucose levels. Measuring longitudinal molecular markers like circulating methylation signatures would help provide an answer to these persistent effects.
In conclusion, the work of Yoshida et al. is a foundational study to observe and provide further view into early diastolic dysfunction of the heart. This study, when paired with additional in-depth analysis of glycemic variability, may prove consequential in early detection of diastolic dysfunction. Such work is especially beneficial in lower-income countries such as ours, Egypt, where populations might not afford treatment of advanced or advancing heart disease.
Conflict of interest
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
