Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetes.
OBJECTIVE
The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design.


METHODS
Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 +/- 7 years (mean +/- s.d.), HbA1c 8.1 +/- 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo.


RESULTS
Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 +/- 11/8 vs. 130/76 +/- 12/6 mmHg, p < 0.05). A significant decline in GFR (133 +/- 23 vs. 140 +/- 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 +/- 3.5 vs. 26.2 +/- 3.6%, p < 0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 +/- 0.53 vs. 2.98 +/- 0.93 mg/kg/min) and insulin-stimulated states (6.84 +/- 2.52 vs. 6.97 +/- 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 +/- 0.34 vs. 1.33 +/- 0.18, mg/kg/min, p < 0.01) and during insulin stimulation (2.89 +/- 0.75 vs. 2.40 +/- 0.62 mg/kg/min, p < 0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups.


CONCLUSIONS
Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients.
Nielsen
S
S
Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Aarhus, Denmark. Nielsen.Soren@dadlnet.dk
Hove
K Y
KY
Dollerup
J
J
Poulsen
P L
PL
Christiansen
J S
JS
Schmitz
O
O
Mogensen
C E
CE
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015309:Glucose Clamp Technique; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D019808:Losartan