Effect of strict glycemic control on renal hemodynamic response to amino acids and renal enlargement in insulin-dependent diabetes mellitus

Background. Many patients with insulin-dependent diabetes mellitus have an increase in the glomerular filtration rate and renal enlargement early in the course of their disease. Both these changes may be risk factors for the later development of diabetic nephropathy. Their cause is not known, but they could be due to augmented renal responses to the increase in plasma amino acid concentrations that occurs when dietary protein intake is high, a factor known to increase glomerular filtration and renal blood flow in normal subjects. Methods. We measured the glomerular filtration rate and renal plasma flow after an overnight fast and during an infusion of amino acids in 12 patients with insulin-dependent diabetes mellitus and 9 normal subjects. The diabetic patients were studied when they were hyperglycemic, when they were euglycemic after an insulin infusion for 36 hours, and after intensive insulin therapy for 3 weeks. Kidney volume was measured by ultrasonography before and after the period of intensive insulin therapy. Results. The glomerular filtration rate and renal plasma flow were normal after fasting when the patients were hyperglycemic (mean [±SE] fasting plasma glucose level, 11.5±0.7 mmol per liter). After the amino acid infusion, these values increased more in the patients (glomerular filtration rate, 2.65±0.07 ml per second per 1.73 m² of body-surface area; renal plasma flow, 13.30±0.68 ml per second per 1.73 m²; P<0.05 for both) than in the normal subjects (2.25±0.08 and 11.20±0.65 ml per second per 1.73 m², respectively). The 36-hour infusion of insulin in the diabetic patients did not alter the glomerular filtration rate or renal plasma flow either before or during the amino acid infusion. After three weeks of intensive insulin therapy (fasting plasma glucose level, 5.3±0.2 mmol per liter), the glomerular filtration rate and renal plasma flow after the amino acid infusion (2.33±0.03 and 11.30±0.43 ml per second per 1.73 m², respectively) were similar to those in the normal subjects. The kidney volumes in the normal subjects and the patients with diabetes were 219±14 and 312±14 ml per 1.73 m², respectively (P<0.01); the volume decreased to 267±22 ml per 1.73 m² (P<0.001) in the diabetic patients after three weeks of intensive insulin therapy, which was not significantly different from the volume in the normal subjects (P=0.1). Conclusions. Conventionally treated diabetic patients who have normal renal function while fasting have augmented renal hemodynamic responses to increased plasma amino acid concentrations. The concomitant decrease in these hemodynamic responses and in kidney size with strict glycemic control suggests that these phenomena are related and influenced by the metabolic state. (N Engl J Med 1991;324:1626–32.).