Summary
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]
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- IDDM:
-
insulin-dependent diabetes mellitus
- CSII:
-
continuous subcutaneous insulin infusion
- CT:
-
conventional treatment (2, 3 or multiple injections daily)
- BMT:
-
basement membrane thickness
- AER:
-
urinary albumin excretion rate
- CI:
-
confidence interval
References
Pirart J (1978) Diabetes mellitus and its degenerative complications. A prospective study of 4400 patients observed between 1947 and 1973. Diabetes Care 1: 168–188
Wisemann, M, Viberti GC, Mackintosh D, Jarrett RF, Keen H (1984) Glycaemia, arterial pressure and microalbuminuria in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 26: 401–405
Mathiesen ER, Saurbrey N, Hommel E, Parving HH (1986) Prevalence of microalbuminuria in children with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 29: 640–643
Bangstad H-J, Hanssen KF, Kierulf P et al. (1987) Elevated albumin excretion rate is common among poorly controlled adolescent insulin dependent diabetics. Diabetes Res 6: 43–46
Mortensen HB, Martinelli K, N0rgaard K et al. (1990) A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Diabetic Med 7: 887–897
Joner G, Brinchmann-Hansen O, Torres CG, Hanssen KF (1993) A nationwide cross-sectional study of retino-pathy and microalbuminuria in young Norwegian type 1 (insulin-dependent) diabetic patients. Diabetologia 35: 1049–1055
Nørgaard K, Storm B, Graae M, Feldt-Rasmussen B (1988) Elevated albumin excretion and retinal changes in children with type 1 diabetes are related to long-term poor blood glucose control. Diabetic Med 6: 325–328
Bangstad H-J, Hanssen KF, Dahl-J0rgensen K, Aagenæs Ø (1989) Microalbuminuria is associated with long term poor glycemic control in adolescent insulin dependent diabetics. Diabetes Res 12: 71–74
Walker JD, Close CF, Jones SL et al. (1992) Glomerular structure in type I (insulin-dependent) diabetic patients with normo- and microalbuminuria. Kidney Int 41: 741–748
Bangstad H-J, Østerby R, Dahl-Jørgensen K et al. (1993) Early glomerulopathy is present in young type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 36: 523–529
Dahl-Jørgensen K, Hanssen KF, Kierulf P, Bjøro T, Sandvik L, Aagenæs Ø (1988) Reduction of urinary albumin excretion after 4 years of continuous subcutaneous insulin-infusion in insulin-dependent diabetes mellitus. The Oslo study. Acta Endocrinol 117: 19–25
Feldt-Rasmussen B, Mathiesen ER, Deckert T (1986) Effect of 2 years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet I: 1300–1304
Reichard P, Nilsson B-Y, Rosenquist U (1993) The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 329: 304–309
Eshøj O, Feldt-Rasmussen B, Larsen ML, Mogensen CE (1987) Comparison of overnight, morning and 24-hour collections in the assesment of diabetic microalbuminuria. Diabetic Med 4: 531–533
Bangstad H-J, Kofoed-Enevoldsen A, Dahl-Jørgensen K, Hanssen KF (1992) Glomerular charge selectivity and the influence of improved blood glucose control in type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 35: 1165–1169
Deckert T, Feldt-Rasmussen B, Djurup R, Deckert M (1988) Glomerular size and charge selectivity in insulin-dependent diabetes mellitus. Kidney Int 33: 100–106
østerby R (1973) Morphometric studies of the peripheral glomerular basement membrane in early juvenile diabetes II. Topography of the initial lesions. Diabetologia 9: 108–114
Gundersen HJG, Bendtsen TF, Korbo L et al. (1988) Some new, simple and efficient sterological methods and their use in pathological research and diagnosis. APMIS 96: 379- 394
Bilous RW, Mauer SM, Sutherland DER, Najarian JS, Goetz FC, Steffes MW (1989) The effect of transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 321: 80–85
Barbosa J, Steffes M, Connett J, Mauer M (1992) Hyper-glycemia is causally related to diabetic renal lesions. Diabetes 41: 9 (Abstract)
Silbiger S, Crowley S, Shan Z, Brownlee M, Satriano J, Schlondorff D (1993) Nonenzymatic glycation of mesangial matrix and prolonged exposure of mesangial matrix to elevated glucose reduces collagen synthesis and proteoglycan charge. Kidney Int 43: 853–864
Brownlee M, Spiro RG (1979) Glomerular basement membrane metabolism in the diabetic rat: in vivo studies. Diabetes28: 121–125
Ledbetter S, Copeland EJ, Noonan D, Vogeli G, Hassel JR (1990) Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. Diabetes 39: 196–203
Cagliero E, Roth T, Roy S, Lorenzi M (1991) Characteristics and mechanisms of high-glucose-induced overexpression of basement membrane components in cultured human endo-thelial cells. Diabetes 40: 102–110
Roy S, Sala R, Cagliero E, Lorenzi M (1990) Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 87: 404–408
Poulson R, Kurkinen M, Prockop DJ, Boot-Handford RP (1988) Increased steady-state levels of laminin Bl mRNA in kidneys of long term streptozotozin-diabetic rats. J Biol Chem 263: 1072–1076
Brownlee M, Vlassara H, Cerami A (1984) Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Int Med 101: 527–537
The Diabetes Control and Complications Trial research group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329: 977–986
østerby R (1992) Glomerular structural changes in type 1 (insulin-dependent) diabetes mellitus: causes, consequences and prevention. Diabetologia 35: 803–812
Feldt-Rasmussen B, Mathiesen ER (1984) Variability of urinary albumin excretion in incipient diabetic nephropathy. Diabetic Nephropathy 3: 101–103
Mogensen CE, Chachati A, Christensen CK et al. (1986) Microalbuminuria: an early marker of renal involvement in diabetes. Uremia Invest 9: 85–95
Mogensen CE, Hansen KW (1992) Blood pressure elevation versus abnormal albuminuria in the genesis and prediction of renal disease in diabetes. Diabetes Care 15: 1192–1204
Chavers BM, Bilous RW, Ellis EN, Steffes MW, Mauer SM (1989) Glomerular lesions and urinary albumin excretion in type 1 diabetes without overt proteinuria. N Engl J Med 320: 966–970
Dahl-Jørgensen K, Bjøro T, Kierulf P, Sandvik L, Bangstad H-J, Hanssen KF (1992) Long-term glycemic control and kidney function in insulin-dependent diabetes mellitus. Kidney Int 41: 920–923
Dahl-Jørgensen K, Brinchmann-Hansen O, Hanssen KF et al. (1986) Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo study. BMJ 293: 1195–1199
Chantelau E, Spraul M, Miihlhauser I, Gause R, Berger M (1989) Long-term safety, efficacy and side-effects of continuous subcutaneous insulin infusion treatment for type 1 (insulin-dependent) diabetes mellitus: a one centre experience. Diabetologia 32: 421–426
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bangstad, H.J., Dahl-Jørgensen, K., Hanssen, K.F. et al. Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy. Diabetologia 37, 483–490 (1994). https://doi.org/10.1007/s001250050136
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/s001250050136