RAAS-blockade in type II diabetes: added effects of a low sodium diet and diuretics.

The worldwide incidence of diabetic nephropathy consequently to type II
diabetes is increasing. Pathophysiology is complex and only partly explained.
An increased extracellular volume associated with hypertension and albuminuria
is tought to play an important role in the process. We hypothesize that
modulation of extracellular volume by meanings of dietary sodium restriction or
diuretic use in addition to a standardized blockade of the Renin Angiotensin
System can potentiate antihypertensive and antialbuminuric therapy.

Determinination of the added effects of dietary sodium restriction or diuretic
use to antihypertensive and antialbuminuric therapy.

The research consists of a cross-over design in which both the sodium intake
and diuretic is randomized. The cross-over is preceded by a pre-randomistaion
phase with a duration of 4-12 weeks. During this phase patients will be adhered
to the standard therapy of 40mg lisinopril 1dd1. This phase is followed by the
cross-over phase consisting 4 periods of 6 weeks. Patients will be randomized
for both the low (50 mmol) and high sodium (200 mmol) intake and 25 mg
hydrochlorothiazide or placebo use. Total study extent is 28 to 36 weeks
dependent on the dureation of the pre-randomisation phase.

Study includes two interventions:

Patients will be randomized to low and high sodium intake in a cross-over design
Patients will be randomized to 25 mg hydrochlorothiazide or placobo

Both hydrochlorothiazide and lisinopril both are broadly prescribed, type II
diabetic patients included. Sodiumbromide has potential adverse events, but in
the dose we use none have been reported. A sodium restricted diet may be
burdensome but is has no particular risks. Patient burden consists of 6-8
visits to the outpatient clinic and a total of 10 24 hours urine collections.
During each visit 10-20 ml of blood will be withdrawn and bloodpressure is
measured in supine position for a period of 15 minutes.