Effect of experimental hyperglycaemia on renal haemodynamics in prediabetic patients with and without AT1 receptor blockade.
OBJECTIVE
To prevent diabetic nephropathy, knowledge about early renal impairment caused by a disturbed glucose homoeostasis is essential. The purpose of our study was to investigate haemodynamic changes of the kidney in subjects with impaired glucose tolerance (prediabetics, IGT) during experimental hyperglycaemia and the effect of angiotensin receptor blockade.


METHODS
In our prospective case control study, we measured renal haemodynamics in 13 non-albuminuric males with normal kidney function and IGT (diagnosed by an oral glucose tolerance test, OGTT) and in 13 matched controls with a normoglycemic response in the OGTT. Glomerular filtration rate (GFR) was assessed by determination of sinistrin clearance; renal plasma flow (RPF) by para-aminohippuric acid clearance. All measurements were performed at rest and during hyperglycaemic stress testing (clamp technique; target blood glucose approximately 170 mg dL(-1)). We examined renal effects of valsartan (4 weeks 160 mg day(-1)) at rest and during experimental hyperglycaemia. Metabolic (glycosylated haemoglobin, adiponectin) and inflammatory (high sensitive C-reactive protein) parameters were compared with and without valsartan in both groups.


RESULTS
During experimental hyperglycaemia, GFR and RPF decreased significantly more in prediabetics compared with controls. Under valsartan, the hyperglycaemia induced decrease of GFR and RPF was blunted in part by valsartan. Hs-CRP and HbA1c were significantly higher in prediabetics when compared with controls and improved both under valsartan. Adiponectin was lower in prediabetics and increased significantly under valsartan.


CONCLUSIONS
Hyperglycaemia induces impairments of renal haemodynamics as well as inflammatory and metabolic parameters in subjects with impaired glucose tolerance, which improve under valsartan.
Technische Universitaet Muenchen, Munich, Germany. helga.frank@lrz.tum.de
Helga
H
Frank
Stefan
S
Pscherer
Danilo
D
Fliser
Uwe
U
Heemann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D005919:Glomerular Filtration Rate; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan; D055815:Young Adult
D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine