Effect of acute hyperglycaemia on sodium handling and excretion of nitric oxide metabolites, bradykinin, and cGMP in Type 1 diabetes mellitus.
OBJECTIVE
The aim of this study was to evaluate the effect of acutely induced hyperglycaemia on renal sodium handling and to explore the role of the bradykinin-nitric oxide-cGMP signalling pathway.


METHODS
We compared 20 Type 1 diabetic (DM1) patients without microalbuminuria with 15 weight-, age-, and sex-matched healthy controls (C). Clearances of para-aminohippuric acid (CPAH), inulin (Cin), lithium, sodium, and urinary nitrite/nitrate (NOx), cGMP and bradykinin excretion rates were measured in two 90-min periods: a glycaemic clamp-induced euglycaemia (5 mmol/l-period I) and hyperglycaemia (12 mmol/l-period II) (Study 1) and during time-controlled euglycaemia (5 mmol/l-period I and 5 mmol/l-period II) to avoid the effects of time and volume load (Study 2).


RESULTS
Cin and CPAH were not significantly different during euglycaemia (period I of Study 1) in DM1 and controls, whereas fractional excretion of sodium was decreased in DM1 (1.84 +/- 0.75 vs. 2.36 +/- 0.67%; P < 0.05) due to an increase in fractional distal tubular reabsorption of sodium (94.01 +/- 1.94 vs. 92.24 +/- 2.47%; P < 0.05). A comparison of changes during Study 1 and Study 2 revealed acute hyperglycaemia did not change renal haemodynamics significantly, while fractional distal tubular reabsorption of sodium increased (DM1: P < 0.05; C: P < 0.01) and fractional excretion of sodium decreased (P < 0.01) in both groups. The urinary excretion rates of NOx were comparable during euglycaemia in DM1 and C. While in C, they significantly increased during Study 1 (period I: 382 +/- 217 vs. period II: 515 +/- 254 nmol/min; P < 0.01) and Study 2 (period I: 202.9 +/- 176.8 vs. period II: 297.2 +/- 267.5 nmol/min; P < 0.05) as a consequence of the water load, no changes were found in DM1. The urinary excretion of bradykinin was lower in DM1 compared with C (0.84 +/- 0.68 vs. 1.20 +/- 0.85 micro g/min; P < 0.01) during euglycaemia; it was not affected by hyperglycaemia. There were no significant differences between DM1 and C and in cGMP urinary excretion rates following hyperglycaemia.


CONCLUSIONS
This study demonstrates that DM1 without renal haemodynamic alterations is associated with impaired renal sodium handling. Moreover, we did not find a relationship between the renal excretion rates of vasoactive mediators and sodium handling due to hyperglycaemia.
Simková
R
R
Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, the Czech Republic. renata.simkova@medicon.cz
Kazdová
L
L
Karasová
L
L
Simek
S
S
Pelikánová
T
T
D000042:Absorption / Q000502:physiology; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001920:Bradykinin / Q000652:urine*; D006152:Cyclic GMP / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D004231:Diuresis / Q000502:physiology; D015309:Glucose Clamp Technique / Q000379:methods; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000032:analysis; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D014554:Urination / Q000502:physiology; D014867:Water / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D014867:Water; D009569:Nitric Oxide; D012964:Sodium; D006152:Cyclic GMP; D001920:Bradykinin