The aim of this study was to analyze the role of ACE gene insertion/deletion (I/D) and PC-1 gene K121Q polymorphisms in the changes of glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric Type 1 diabetic patients. This is a 10.2+/-2.0-year prospective study of 30 normotensive normoalbuminuric Type 1 diabetic patients. UAER (immunoturbidimetry), GFR ((51)Cr-EDTA single injection technique), GHb (ion exchange chromatography), and BP levels were measured at baseline and at 1.7+/-0.6-year intervals. The presence of ACE gene I/D and PC-1 gene K121Q polymorphisms was determined by polymerase chain reaction (PCR) and restriction enzyme techniques. Three patients developed diabetic nephropathy (DN), all carriers of allele D. The presence of allele D was the only predictor (R(2)=.15, F=4.92, P=.035) of the observed GFR decline (-0.29+/-0.34 ml/min/month, P<.05). UAER increased during the study (log UAER=0.0275+/-0.042 microg/min/month, P=.002) and was associated with baseline UAER levels only (R(2)=.17, F=5.72, P=.024). A significant increase (P<.05) in cases of hypertension and retinopathy were observed in ID/DD (n=19) and not in II patients (n=11). Patients with the KQ/QQ genotype (n=8) presented a significant increase (P=.045) in new cases of retinopathy. In conclusion, the presence of the ACE gene D allele in this sample of normoalbuminuric normotensive Type 1 diabetic patients was associated with a higher proportion of microvascular complications and hypertension.