Hyperglycemia: A determinant of cardiac autonomic dysfunction in youth with obesity across the spectrum of glycemic regulation

Authors: EL-AYASH, HEBA - Children'S Nutrition Research Center (CNRC); PUYAU, MAURICE - Children'S Nutrition Research Center (CNRC); BACHA, FIDA - Children'S Nutrition Research Center (CNRC)

Submitted to: Pediatric Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2023
Publication Date: 6/13/2023
Citation: El-Ayash, H., Puyau, M., Bacha, F. 2023. Hyperglycemia: A determinant of cardiac autonomic dysfunction in youth with obesity across the spectrum of glycemic regulation. Pediatric Obesity. Article e13063. https://doi.org/10.1111/ijpo.13063.
DOI: https://doi.org/10.1111/ijpo.13063

Interpretive Summary: Heart rate variability (HRV) is a measure of early change in heart function related to the autonomic nervous system. Decrease in HRV is related to cardiovascular events in adult studies. It is also found to be worse in youth with type 2 diabetes compared with peers without diabetes. It is not clear what drives this abnormality in vascular function in childhood, and whether it is present before the diagnosis of diabetes. Researchers in Houston studied 94 adolescents, at average age of 15 years. These children included those with overweight and with normal weight and were along the spectrum of glucose regulation from normal glucose control to early abnormalities in glucose to full diabetes. This work showed that youth with impaired glucose regulation have evidence of cardiac autonomic dysfunction. This dysfunction is mainly related to glucose elevation and to inflammation, rather than insulin resistance (which the researchers had shown to be related to vessel stiffness). This suggests that changes in the autonomic nervous system are evident in the early stages of impaired sugar regulation in children, and that different mechanisms lead to different aspects of vascular disease in youth-onset obesity.

Technical Abstract: To characterize the determinants of heart rate variability (HRV) in youth with obesity across the glycemia spectrum. A total of 94 adolescents, 15 +/- 2.1 years (21 with normal weight, 23 with overweight-normal glucose tolerance, 26 with prediabetes and 24 with type 2 diabetes [T2D]) underwent an assessment of body composition (dual-energy x-ray absorptiometry), 2-h oral glucose tolerance test with the calculation of indices of glycemia and insulin sensitivity (IS), inflammatory markers (high-sensitivity C-reactive protein [hs-CRP] and tumor necrosis factor-a [TNF-a]), and HRV by peripheral arterial tonometry. The HRV frequency-domain index (low-frequency to high-frequency ratio [LF/HF]), an estimate of the ratio between sympathetic and parasympathetic activity, increased across the glycemic spectrum, and was highest in T2D compared with the other three groups (p = 0.004). LF/HF correlated with %body fat (r = 0.22, p = 0.04); fasting (r = 0.39, p < 0.001), 2-h (r = 0.31, p = 0.004), and area under the curve glucose (r = 0.32, p = 0.003); hs-CRP (r = 0.33, p = 0.002) and TNF-a (r = 0.38, p = 0.006). In a linear regression model, fasting glucose (B = 0.39, p = 0.003) and hs-CRP (B = 0.21, p = 0.09) contributed to the variance in Ln LF/HF independent of IS, %body fat, age, sex, race-ethnicity and Tanner stage (R2 = 0.23, p = 0.013). Youth with impaired glucose regulation have evidence of cardiac autonomic dysfunction with decreased HRV, and sympathetic overdrive (increased LF/HF). This dysfunction is mainly related to glycemia and systemic inflammation.