July 1, 1994
View Full PaperPlasma Endothelin Levels and Vascular Effects of Intravenous l-Arginine Infusion in Subjects with Uncomplicated Insulin-Dependent Diabetes Mellitus
Key Result
Intravenous l-arginine infusion produced similar vascular responses in men with uncomplicated type 1 diabetes and controls, despite lower baseline plasma endothelin in diabetics (1.7 vs 2.1 pmol/l; P<0.05).
Structured PICO
Does intravenous l-arginine infusion alter vascular effects and endothelial mediators differently in men with uncomplicated insulin-dependent diabetes mellitus compared to non-diabetic subjects?
P
Population
20 men, comprising 10 with uncomplicated type 1 diabetes and 10 non-diabetic controls, evaluated for vascular effects of l-arginine.
I
Intervention
Intravenous l-arginine infusion
C
Comparator
Intravenous isotonic saline infusion
O
Outcome
Plasma endothelin levels and vascular effects (plasma cyclic GMP, l-citrulline, blood pressure, extracellular fluid volume)surrogate
Intravenous l-arginine produces similar vascular effects in men with uncomplicated type 1 diabetes and healthy controls, despite lower baseline endothelin levels in diabetic patients.
Main Result
Absolute Event Rate: 5.7% vs 4.6%
p-value: p=0.09
Limitations
- Whether the vascular effects of l-arginine are due to an increase in NO synthesis remains unclear
Abstract
Uncomplicated insulin-dependent diabetes mellitus is associated with generalized vasodilatation. This vasodilatation is believed to contribute to the development of microvascular complications. The endothelium plays an important role in the regulation of vascular tone. 2. To investigate the role of endothelial mediators, we measured plasma endothelin levels and studied the vascular effects of intravenous l-arginine (the precursor of NO) in 10 male type 1 diabetic patients and 10 non-diabetic subjects. 3. The baseline plasma endothelin level was significantly lower in the diabetic patients mean 1.7 (SD 0.5) versus 2.1 (0.4) pmol/l; P 0.05 than in the control subjects. 4. During l-arginine infusion, plasma cyclic GMP (the second messenger for NO) increased in the control subjects from 5.1 (2.9) to 6.9 (2.9) nmol/l; P 0.05 versus saline and in the diabetic patients from 4.6 (1.8) to 5.7 (2.2) nmol/l; P = 0.09. l-Citrulline (a by-product of NO synthesis from l-arginine) increased in both groups. The responses to l-arginine were not significantly different between the control subjects and the diabetic patients. The plasma atrial natriuretic peptide level did not change in either group during infusion of l-arginine or of an equal volume of isotonic saline. 5. Blood pressure decreased slightly during l-arginine administration in both groups. In control subjects, the extracellular fluid volume in the lower leg increased during l-arginine infusion as compared with saline; in the diabetic patients both l-arginine and saline increased the extracellular fluid volume. 6. In conclusion, the vascular effects of l-arginine are similar in men with uncomplicated insulin-dependent diabetes mellitus and in control subjects. Whether these effects are due to an increase in NO synthesis remains unclear. The increase in extracellular fluid volume during saline infusion in diabetic patients suggests an increase in microvascular permeability in