Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients.
OBJECTIVE
The aim of the present study was to evaluate the hemodynamic effects of acute hyperglycemia in type 2 diabetic patients and to see whether these effects are related to changes in nitric oxide (NO) availability.


METHODS
Twenty newly diagnosed complication-free diet-treated type 2 diabetic patients participated in the study. All patients underwent 3 hyperglycemic glucose clamps in random order: 1) the control study 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 clamp; and 3) the L-arginine study with L-arginine (1 g/min) infused during the last 30 min of the clamp. A group of 8 patients also underwent a glutathione infusion (600 mg as an intravenous bolus followed by 5 mg/min infusion) during the clamp.


RESULTS
During hyperglycemia, there were significant increments of systolic (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 baroreflex activity, significantly deteriorated after hyperglycemia (P < 0.01). The infusion of octreotide, used to avoid the possible confounding influence of insulin, did not change the hemodynamic effects of hyperglycemia. Glutathione, a free radical scavenger, completely prevented the vascular effects of hyperglycemia. L-Arginine produced a fall in sBP and dBP to baseline values and normalized squatting ratios.


CONCLUSIONS
Acute hyperglycemia in newly diagnosed type 2 diabetic patients causes significant hemodynamic changes that are independent of endogenous insulin and are prevented by glutatione and reversed by L-arginine, suggesting an interference with endogenous NO availability. These observations could help explain the adverse cardiovascular effects of hyperglycemic spikes.
Marfella
R
R
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy. dagiugli@tin.it
Nappo
F
F
De Angelis
L
L
Paolisso
G
G
Tagliamonte
M R
MR
Giugliano
D
D
D000328:Adult; D001120:Arginine; D001794:Blood Pressure; D001810:Blood Volume; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D005978:Glutathione; D006339:Heart Rate; D006439:Hemodynamics; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D015282:Octreotide
D007328:Insulin; D001120:Arginine; D005978:Glutathione; D015282:Octreotide; D009638:Norepinephrine; D004837:Epinephrine