IMPROVEMENT OF BLOOD-GLUCOSE CONTROL IN IDDM PATIENTS RETARDS THE PROGRESSION OF MORPHOLOGICAL-CHANGES IN EARLY DIABETIC NEPHROPATHY

We investigated in a randomized, prospective study the influence of improved blood glucose control during 2-3 years in young insulin-dependent diabetic (IDDM) patients with microalbuminuria, which is indicative of early nephropathy. Patients were randomized either to intensive treatment by continuous subcutaneous insulin infusion (CSII) (n = 9) or CT (n = 9). Kidney biopsies were taken at baseline and after 26-34 months. End points were structural changes in the glomeruli. Sensitive, quantitative, morphometric methods were used. The blood glucose control improved significantly (p = 0.01) during the study in the CSII-group as glycated haemoglobin (HbA(1c)) fell from 10.1% ([95% CI] 8.9-11.3) to 8.6% (7.9-9.2), but not in the CT-group, 10.1% (8.3-11.9) vs 9.7% (8.7-10.8). Mean HbA(1c) during the study period was significantly lower in the CSII-group than in the CT-group, 8.7% (8.1-9.3) vs 9.9% (8.5-11.3), p = 0.04. Basement membrane thickness (BMT) increased in both groups, most (CT vs CSII, p = 0.03) in the CT-group: 140 nm (50-230) vs CSII: 56 nm (27-86). In the CT-group only an increase was seen in matrix/mesangial volume fraction (p = 0.006) and matrix star volume (p = 0.04). Furthermore, a positive correlation between mean HbA(1c) during the study and change from baseline in BMT (r = 0.70, p = 0.001) and matrix/glomerular volume fraction (r = 0.33,p = 0.09, NS) was demonstrated. Albumin excretion rate correlated significantly to BMT and most of the matrix parameters. The present study shows that during a period of only 2.5 years, a close relationship between the level of mean blood glucose and progression of glomerular morphological changes in early diabetic nephropathy can be demonstrated.