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

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 tumour necrosis factor-α [TNF-α]), 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-α (r = 0.38, p = 0.006). In a linear regression model, fasting glucose (β = 0.39, p = 0.003) and hs-CRP (β = 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.