INSULIN-RESISTANCE, ELEVATED GLOMERULAR-FILTRATION FRACTION, AND RENAL INJURY

The development of insulin resistance may be an early step in the deve lopment of hypertension; however, the mechanism for this process is no t known. The worsening of insulin resistance and hypertension could in crease both systemic and glomerular capillary pressures and predispose an individual to renal injury. The purpose of this study was to exami ne the relationship of insulin resistance to glomerular hemodynamics a nd dietary salt intake in 10 older (68+/-6 years), obese (body mass in dex, 31+/-4 kg/m(2)), mildly hypertensive (151+/-8/82+/-2 mm Hg), sede ntary subjects without clinical evidence of diabetes or renal disease. They were studied on separate days with radioisotopic renal clearance s (glomerular filtration rate by Tc-99m-diethylenetriaminepentaacetic acid urinary clearance; renal plasma flow by I-131-hippuran serum disa ppearance) and a two-dose (40 and 100 mU/m(2) per minute) hyperinsulin emic euglycemic clamp for measurement of glucose disposal after 2 week s of a 3-g and 2 weeks of a 10-g sodium diet. Glomerular filtration ra te (68.1+/-7.7 to 78.0+/-6.6 mL/min per 1.73 m(2), P=.08) and glomerul ar filtration fraction (0.21+/-0.02 to 0.22+/-0.02, P=.5) did not chan ge significant ly after dietary salt was increased. During low dietary salt intake, there was an inverse relationship between glomerular fil tration fraction and glucose disposal rate (milligrams per kilogram fa t-free mass per minute) at both low (r=-.70, P=.04) and high (r=-.83, P=.006) insulin levels, However, these relation ships were attenuated during salt loading. This suggests that a greater degree of insulin re sistance, not increased dietary salt, may predispose older mildly hype rtensive subjects to renal injury by worsening renal hemodynamics thro ugh the elevation of glomerular filtration fraction and resultant glom erular hyperfiltration.