Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy

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Abstract
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, mor-phometric methods were used. The blood glucose control improved significantly (p = 0.01) during the study in the CSII-group as glycated haemoglobin (HbAlc) 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 HbAlc 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/mesan-gial volume fraction (p = 0.006) and matrix star volume (p = 0.04). Furthermore, a positive correlation between mean HbAlc during the study and change from baseline in BMT (r = 0.70, p = 0.001) and ma-trix/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. [Diabetologia (1994) 37: 483-490]