Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for Cardiovascular Control

Abstract

Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experimental hypoglycemia (2.8 mmol/L) for 120 min. Cardiac vagal baroreflex function was assessed using the modified Oxford method before the initiation of the hypoglycemic-hyperinsulinemic clamp protocol and during the last 30 min of hypoglycemia. During hypoglycemia, compared with baseline euglycemic conditions, 1) baroreflex sensitivity decreases significantly (19.2 ± 7.5 vs. 32.9 ± 16.6 ms/mmHg, P < 0.005), 2) the systolic blood pressure threshold for baroreflex activation increases significantly (the baroreflex function shifts to the right; 120 ± 14 vs. 112 ± 12 mmHg, P < 0.005), and 3) the maximum R-R interval response (1,088 ± 132 vs. 1,496 ± 194 ms, P < 0.001) and maximal range of the R-R interval response (414 ± 128 vs. 817 ± 183 ms, P < 0.001) decrease significantly. These findings indicate reduced vagal control and impaired cardiovascular homeostasis during hypoglycemia.

© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Timing of the baroreflex assessment (modified Oxford) relative to the plasma glucose levels (mean ± SD) during the hypoglycemic-hyperinsulinemic clamp protocol. The straight line represents the target glucose level (2.8 mmol/L).

Figure 2

Baroreflex function from a representative subject measured by the modified Oxford method during baseline euglycemia (circles) and hypoglycemia (triangles). Data points represent the corresponding values of SBP and cardiac interval (R-R) during the pharmacologically induced blood pressure change. For baroreflex assessment, R-R is plotted as a function of SBP between the lowest and the highest SBP values. The linear portion (arrows) of the sigmoid function describes BRS (see research design and methods). During hypoglycemia, BRS is decreased, maximal R-R interval is decreased, and the sigmoidal baroreflex function curve shifts to the right.

Figure 3

Baroreflex function measured by the modified Oxford method during baseline euglycemia (circles) and hypoglycemia (triangles). Group average values for the threshold and saturation blood pressures and corresponding cardiac intervals (R-R) are displayed for each glycemic condition. A sigmoidal curve is fitted to these group data for both glycemic conditions. Horizontal error bars denote the SD of blood pressure, and the vertical error bars denote the SD of the R-R interval. During hypoglycemia, the baroreflex threshold shifts to higher blood pressures (arrow 1), the R-R interval at the blood pressure saturation point decreases (arrow 2), and the R-R interval range is lower (double-headed arrows 3). Data for BRS (the slope of the linear portion of the baroreflex sigmoid curve) showing a significant decrease with hypoglycemia are reported in Table 1. *P < 0.005 for the difference in the baroreflex blood pressure threshold, hypoglycemia vs. baseline. †P < 0.001 for the difference in maximum R-R interval at the blood pressure saturation point, hypoglycemia vs. baseline. **P < 0.001 for the difference in R-R interval ranges, hypoglycemia vs. baseline.