Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients

OBJECTIVE - The aim of the present study was to evaluate the hemodynamic ef fects of acute hyperglycemia in type 2 diabetic patients and to see whether these effects are related to changes in nitric oxide (NO) availability. RESEARCH DESIGN AND METHODS - Twenty newly diagnosed complication-free diet -treated type 2 diabetic patients participated in the study. All patients u nderwent 3 hyper glycemic glucose clamps in random order: 1) the control st udy was performed with plasma glucose clamped at 18 mmol/l for 2 h; 2) the octreotide study with plasma insulin blocked at basal levels during the cla mp; and 3) the L-arginine study with L-arginine (1 g/min) infused during th e last 30 min of the clamp. A group of 8 patients also underwent a glutathi one infusion (600 mg as an intravenous bolus followed by 5 mg/min infusion) during the clamp. RESULTS- During hyperglycemia, there were significant increments of systoli c (sBP) (from 115.5 +/- 9.1 to 120.3 +/- 8.2 mmHg, P < 0.01) and diastolic (dBP) (from 70.3 +/- 7.8 to 79.7 +/- 5.3 mmHg, P < 0.01) blood pressure, as well as heart rate (from 75.2 +/- 7.8 to 80.8 +/- 5.4 beats/min, P < 0.01) and plasma catecholamines (P < 0.05). Squatting ratios, a measure of the b aroreflex activity, significantly deteriorated after hyperglycemia (P ( 0.0 1). The infusion of octreotide, used to avoid the possible confounding infl uence of insulin, did not change the hemodynamic effects of hyperglycemia. Glutathione, a free radical scavenger, completely prevented the vascular ef fects of hyperglycemia. L-arginine produced a fall in sBP and dBP to baseli ne values and normalized squatting ratios. CONCLUSIONS- Acute hyperglycemia in newly diagnosed type 2 diabetic patient s causes significant hemodynamic changes that are independent of endogenous insulin and are prevented by glutatione and reversed by L-arginine, sugges ting an interference with endogenous NO availability. These observations co uld help explain the adverse cardiovascular effects of hyperglycemic spikes .