I003: Determinants of intrarenal RAS activation in type 2 diabetes

• Published in: American journal of hypertension Vol. 13; no. S2; pp. 175A - 176A
• Main Authors: Price, D.A., Lansang, M.C., Osei, S.Y., Fisher, N.D.L., Laffel, L.M.B., Hollenberg, N.K.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2000
• Subjects: AGT; AngII; diabetes; RAS; RBF
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(00)01150-X

Our recent study revealed a variable but striking enhancement of renal vasodilator responses to blockers of the renin angiotensin system (RAS) in subjects with Type 2 diabetes mellitus (DM). As this vasodilator response may reflect the level of intrarenal activation of RAS, and thus a risk of nephropathy, we explored possible determinants to this response. We studied 12 Type 2 diabetics, age range of 35–62 yr., 5 with microalbuminuria in balance on a low sodium diet. PAH and insulin clearances were measured at baseline to assess renal plasma flow (RPF) and glomerular filtration rate (GFR). Each subject then received 150 mg Irbesartan, and renal function was measured every 45 min. for the 4-hr study. The average vasodilator response to Irbesartan was 173.5 ± 33 ml/min (range −13 to 431 ml/min). The above table depicts average ± SEM baseline values and the Rand p values for correlations with the RPF response to Irbesartan. There was good correlation between the change in RPF and basal RPF suggesting the contribution of angiotensin II (AngII) is substantial early in the course of diabetic nephropathy. Body mass index (BMI) was well correlated to renal response suggesting an important role for obesity perhaps via adipocyte production of AGT and/or insulin resistance controlling hepatic production of AGT. BMI and basal RPF may be determinants of the level of intrarenal RAS activation and thus an indicator of risk of nephropathy. The enhancement was less than that in diabetics with gross proteinuria we have studied in the past (215 ± 41 ml/min) suggesting that renal injury activates the renin system. Age (Yr) 49.9 ± 2.7 R = .51, p = 0.1 Duration of DM (Yr) 7.8 ± 1.311 R = .39, p = .2 Glucose 1.58 ± 9.4 R = .35, p = 0.3 HbA1C 8.8 ± 0.6 R = .05, p = 9 Albumin excretion/24 hr 52 ± 17.5 R = .08, p = 0.8 RPF (ml/min) 651 ± 47 R = .81, p = 0.002 BMI (kg/m2) 33.5 ± 2.0 R = .70, p = .02