Insulin Resistance, Elevated Glomerular Filtration Fraction, and Renal Injury

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1996-07, Vol.28 (1), p.127-132
• Main Authors: Dengel, Donald R, Goldberg, Andrew P, Mayuga, Ronaldo S, Kairis, Gretchen M, Weir, Matthew R
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure; Body Composition; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Data Interpretation, Statistical; Female; Glomerular Filtration Rate; Glucose - metabolism; Humans; Hypertension - metabolism; Hypertension - physiopathology; Insulin Resistance; Kidney Diseases - etiology; Life Style; Male; Medical sciences; Middle Aged; Obesity - metabolism; Obesity - physiopathology; Oxygen Consumption; Renal Circulation
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.28.1.127

The development of insulin resistance may be an early step in the development of hypertension; however, the mechanism for this process is not known. The worsening of insulin resistance and hypertension could increase both systemic and glomerular capillary pressures and predispose an individual to renal injury. The purpose of this study was to examine the relationship of insulin resistance to glomerular hemodynamics and dietary salt intake in 10 older (68 plus/minus 6 years), obese (body mass index, 31 plus/minus 4 kg/m), mildly hypertensive (151 plus/minus 8/82 plus/minus 2 mm Hg), sedentary subjects without clinical evidence of diabetes or renal disease. They were studied on separate days with radioisotopic renal clearances (glomerular filtration rate by Tc-diethylenetriaminepentaacetic acid urinary clearance; renal plasma flow by Iodine-hippuran serum disappearance) and a two-dose (40 and 100 mU/m per minute) hyperinsulinemic euglycemic clamp for measurement of glucose disposal after 2 weeks of a 3-g and 2 weeks of a 10-g sodium diet. Glomerular filtration rate (68.1 plus/minus 7.7 to 78.0 plus/minus 6.6 mL/min per 1.73 m, P = .08) and glomerular filtration fraction (0.21 plus/minus 0.02 to 0.22 plus/minus 0.02, P = .5) did not change significantly after dietary salt was increased. During low dietary salt intake, there was an inverse relationship between glomerular filtration fraction and glucose disposal rate (milligrams per kilogram fat-free mass per minute) at both low (r = -.70, P = .04) and high (r = -.83, P = .006) insulin levels. However, these relationships were attenuated during salt loading. This suggests that a greater degree of insulin resistance, not increased dietary salt, may predispose older mildly hypertensive subjects to renal injury by worsening renal hemodynamics through the elevation of glomerular filtration fraction and resultant glomerular hyperfiltration. (Hypertension. 1996;28:127-132.)