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Context: Heart rate variability (HRV), an index of cardiac vagal activity, is decreased in individuals with metabolic disease. The relationship between decreased HRV and metabolic disease is unclear. Objective: The objective of this study was to determine whether experimentally induced glucose intolerance decreases HRV in a circadian relevant manner in healthy individuals. Design: This was a within-subject, randomized design study with subjects infused for 48 h with saline (50 ml/h) or 15% glucose (200 mg/m2·min). HRV was evaluated using time domain measurements taken over the 48-h period. Blood pressure and heart rate were monitored, and blood samples were taken. Setting: This study was performed at the General Clinical Research Center of the Hospital of the University of Pennsylvania. Patients: Sixteen healthy subjects (eight men and eight women; 18–30 yr old; mean body mass index, 21.7 ± 1.6 kg/m2) were studied. Results: After glucose infusion, mean plasma glucose was increased by 16.8% (P &amp;lt; 0.0001), and plasma insulin was increased by 99.4% (P &amp;lt; 0.0001) compared with after saline infusion. Significant decreases in homeostasis model assessment indicated a decrease in insulin sensitivity (saline, 0.52 + 0.13; glucose, 0.34 + 0.12; P &amp;lt; 0.0001). The nocturnal root mean square successive difference, an index of cardiac vagal activity, was significantly decreased (P &amp;lt; 0.01), and nocturnal HR (P &amp;lt; 0.001) and blood pressure were significantly elevated (saline, 107.4 ± 2.7; glucose, 112.5 ± 3.3 mm Hg; P &amp;lt; 0.05) compared with the saline control. The change in homeostasis model assessment due to glucose infusion was significantly correlated with the change in root mean square successive difference (r = 0.48; P &amp;lt; 0.01). Conclusions: Prolonged mild hyperinsulinemia disrupts the circadian rhythm of cardiac autonomic activity. Early changes in the neural control of cardiac activity may provide a potential mechanism mediating the pathophysiological link between impaired glucose tolerance and cardiovascular disease.

the journal of clinical endocrinology and metabolism/journal of clinical endocrinology and metabolism

Prolonged (48-Hour) Modest Hyperinsulinemia Decreases Nocturnal Heart Rate Variability and Attenuates the Nocturnal Decrease in Blood Pressure in Lean, Normotensive Humans