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Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetes
Author(s) -
Nielsen S.,
Hove K. Y.,
Dollerup J.,
Poulsen P. L.,
Christiansen J. S.,
Schmitz O.,
Mogensen C. E.
Publication year - 2001
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.2001.00169.x
Subject(s) - losartan , endocrinology , medicine , renal function , angiotensin ii , filtration fraction , renal blood flow , insulin , placebo , blood pressure , chemistry , alternative medicine , pathology
Aim: 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 [ 125 I]‐iothalamate), renal plasma flow (RPF, determined using [ 131 I]‐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.), HbA 1c 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.